Pharmacy Information for Providers

The Advanced Health Formulary is a list of medications that are covered for Advanced Health members. Some medications listed on the formulary require a prior authorization to ensure the least costly alternatives for treatment are utilized, and the condition being treated is funded for coverage by Oregon Health Plan.

Any medication may be requested for coverage, regardless of formulary status, through the prior authorization process.

Submission of a prior authorization request is not a guarantee of coverage, as certain requirements and criteria must be met in order for a prior authorization request to be approved.

Any prescription over $500 requires a prior authorization, even if the medication is on the Advanced Health Formulary.

Advanced Health is a mandatory generic plan, therefore, generic medications must be used when commercially available.

Mental Health medications are covered directly by the State Medical Assistance Program (MAP, previously known as the Division of Medical Assistance Programs or DMAP) as part of the mental health (or 7/11) carve-out.

Please contact Advanced Health Customer Service at (541) 269-7400 if you have any questions or need assistance.

For general formulary questions or any other questions, you can also email Advanced Health Pharmacy Department at ahpharmacy@advancedhealth.com. Please do NOT include member PHI.

Mail-Order Medications:

Please contact Postal Prescription Services (PPS) at 800-552-6694 to establish a new member profile. Advanced Health members are enrolled under “Doctors of the Oregon Coast” plan. New member profile and prescription transfer requests may be made by phone. PPS Customer New Prescription Request PPS Mail-Order Quick Reference Guide

THIS SECTION IS CURRENTLY UNDER CONSTRUCTION

Attention Deficit/Hyperactivity Disorders in Children

Guideline Note

Prioritized List Guideline Note
Extracted from the February 1, 2021 Prioritized List
GUIDELINE NOTE 20, ATTENTION DEFICIT/HYPERACTIVITY DISORDERS IN CHILDREN
Line 121

Use of ICD-10-CM F90.9, Attention deficit/hyperactivity disorder, unspecified type, in children age 5 and under, is appropriate only when the following apply:
• Child does not meet the full criteria for the full diagnosis because of their age.
• For children age 3 and under, when the child exhibits functional impairment due to hyperactivity that is clearly in excess of the normal activity range for age (confirmed by the evaluating clinician’s observation, not only the parent/caregiver report), and when the child is very limited in his/her ability to have the sustained periods of calm, focused activity which would be expected for the child’s age.

For children age 5 and under diagnosed with disruptive behavior disorders, including those at risk for ADHD, first line therapy is evidence-based, structured “parent-behavior training. Second line therapy is pharmacotherapy.
For children age 6 and over who are diagnosed with ADHD, pharmacotherapy alone or pharmacotherapy with psychosocial/behavioral treatment are included on this line for first line therapy.

The development of this guideline note was informed by a HERC coverage guidance. See
https://www.oregon.gov/oha/HPA/DSIHERC/Pages/Evidence-based-Reports.aspx
https://www.oregon.gov/oha/HPA/DSI-HERC/PrioritizedList/2-1-

Short Acting Stimulant Drug Use Criteria

Long Acting Stimulant Drug Use Criteria

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Neutropenia

Guideline Note

Acute Pain

Guideline Note

Ketoralac Drug Use Criteria

Click HERE for a printable PDF

Ketorolac
Created: 6/8/17
Reviewed: 5/13/19
Includes:
Toradol© Ketorolac
*This policy applies only to oral ketorolac tablets prescribed for outpatient use. Injectable ketorolac administered at the provider office is not included as part of this drug use criteria for coverage.
GUIDELINE FOR USE:
1. Is the medication being used to treat a funded condition for coverage by Oregon Health Plan?
a. If yes, continue to 2
b. If no, deny as below the line.
2. Is the medication being used to treat kidney stones?
a. If yes, go to 3.
b. If no, deny as nonformulary and recommend use of a formulary NSAID such as ibuprofen, naproxen, diclofenac or meloxicam.
3. Is the dose prescribed less than 40mg/day and duration does not exceed 5 days and no contraindications to therapy exist (see below section on Contraindications)?
a. If yes, approve for 5 days of therapy.
b. If no, deny as not meeting criteria. Off label use of medications is not a covered benefit on OHP.
Rationale:
Due to the high risk of adverse events associated with ketorolac and the availability of safer alternative therapies, ketorolac will only be covered when the above drug use criteria are met. Ketoralac should not be used in pediatric patients less than 17 years of age.
FDA Approved Indication:
Ketorolac is indicated for the short-term (≤ 5 days) management of moderate to severe acute pain requiring analgesia at the opioid level. Oral Ketorolac is only indicated as continuation treatment following IV or mg dosing of Ketorolac, if necessary. The total combined duration of use of Ketorolac tablets and injection should not exceed 5 days. Ketorolac is not indicated for use in pediatric patients
and is not indicated for minor or chronic painful conditions. Increasing the dose of ketorolac beyond labeled recommendations will not provide better efficacy but will increase the risk of developing serious adverse events.
Mechanism of Action:
Ketorolac reversibly inhibits the COX-1 and COX-2 enzymes which results in decreased formation of prostaglandin precursors.
Dosing:
20mg followed by 10mg every 4 to 6 hours as needed; maximum 40mg/day.
Contraindications:
• Hypersensitivity to ketorolac, aspirin, other NSAIDs,
• Active or history of peptic ulcer disease
• Recent or history of GI bleeding or perforation
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Advanced renal disease or risk of renal failure (due to volume depletion)
• Prophylactic analgesic before any major surgery
• Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis,
incomplete hemostasis, or high risk of bleeding
• Concurrent use with aspirin, other NSAIDs, probenecid, or pentoxifylline
• Epidural or intrathecal administration (injection only)
• Use in the setting of coronary artery bypass graft (CABG)surgery
• Labor and delivery
References:
1. Ketorolac (systemic); Drug Information. UptoDate. Accessed April 18, 2019.
____________________________________________________________________________________________
Approved by WOAH P&T on August 28, 2017; Approved by Advanced Health Pharmacy and Therapeutics
Committee May 13, 2019

Alzheimer’s

Donepezil Drug Use Criteria

Click HERE for a printable PDF

Donepezil Drug Use Criteria
Created: September 2011
Reviewed: 4/22/2019
Includes:
Aricept© Donepezil
GUIDELINE FOR USE:
1. Is the patient being treated for dementia of the Alzheimer’s type?
a. If yes, go to 2
b. If no, deny as not meeting criteria. Donepezil is an FDA approved for treatment of mild,
moderate and severe dementia of the Alzheimer’s type.
2. Is the requested dosing consistent with the FDA approved prescribing information for the patient’s
disease severity?
a. If yes, go to 3
b. If no, deny as not meeting criteria. Off label use of medication is not a covered benefit on OHP.
3. Does the patient have any contraindications to donepezil therapy?
a. If yes, deny as not meeting criteria. Medication should be prescribed consistent with the FDA
package insert.
b. If no, approve for 12 fills.
Rationale:
To promote the use of donepezil for FDA approved indications and dose consistent with the FDA approved
prescribing information.
FDA Approved Indications:
Donepezil is indicated for the treatment of mild, moderate and severe dementia of the Alzheimer’s type.
Mechanism of Action:
Donepezil is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer’s type.
Dosing:
Mild to moderate Alzheimer’s disease: 5 to 10 mg once daily
Moderate to severe Alzheimer’s disease: 10 to 23 mg once daily
Contraindications:
Known hypersensitivity to donepezil or to piperidine derivatives
References:
1. Aricept© (Donepezil) prescribing information. Revised 12/2018

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/2019

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19

Atrial Fibrillation

Direct Oral Anticoagulants Drug Use Criteria

Click HERE for a printable PDF

Direct Oral Anticoagulants Drug Use Criteria

Created: October 2016

Reviewed: 4/22/19

Includes:

Xarelto©        Rivaroxaban

Pradaxa©       Dabigatran

Eliquis©          Apixaban

Savaysa©       Edoxaban

This drug use criteria will be used to determine ongoing coverage of the direct oral anticoagulants following the initial three months of therapy allowed through the Advanced Health formulary.

Guideline for Use:

  1. Does the member have an OHP funded condition?
    1. If yes, continue to question 2.
    2. If no, deny as BTL.
  1. Does the member have a diagnosis for any of the recommended FDA approved indications (DVT or PE treatment, secondary prevention of recurrent DVT or PE, prophylaxis of DVT in knee or hip replacement surgery, or prevention of stroke or systemic embolism in nonvalvular atrial fibrillation), AND is the appropriate dose of medication being prescribed consistent with the FDA approved prescribing information?
    1. If yes, continue to question 3
    2. If no, deny as not meeting criteria. Use of medications for off label indications is considered experimental and not a covered benefit on OHP.

**Note to reviewer: Please coordinate with prescriber prior to denying authorization request for inappropriate dosing to change to FDA approved dosing regimen.

Indications and Dosing

Xarelto© Pradaxa© Eliquis© Savaysa©
Deep vein thrombosis (DVT) or pulmonary embolism (PE) treatment 15 mg twice daily for 21 days followed by 20 mg once daily 150 mg twice daily following 5-10 days of parenteral anticoagulation 10 mg twice daily for 7 days followed by 5 mg twice daily 60 mg once daily following 5-10 days of parenteral anticoagulation
Reduction in risk of recurrent DVT/PE 20 mg once daily after initial 6 months of therapy 150 mg twice daily 2.5 mg twice daily after initial 6 months of therapy Not indicated
Nonvalvular atrial fibrillation 20 mg once daily 150 mg twice daily 5 mg twice daily 60 mg once daily
Postoperative DVT prophylaxis (hip and knee replacement surgery) 10 mg once daily

· Minimum: 10 days

· Maximum: 35 days

110 mg on day 1 then 220 mg once daily (hip replacement only)

· Minimum:10 days

· Maximum: 35 days

Not indicated for knee replacement

2.5 mg twice daily

· Knee: 12 days

· Hip: 35 days

Not indicated

Duration of therapy

Provoked DVT/PE

· Surgery

· Nonsurgical transient risk factors: estrogen therapy, pregnancy, leg injury, flight >8h

· 3 months
Unprovoked DVT/PE · Low to moderate bleeding risk: extended               anticoagulation therapy (no stop date)

· High bleeding risk: 3 months

VTE associated with cancer: LMWH is the preferred agent over VKA, Pradaxa, Xarelto, Eliquis, or Savaysa · Extended anticoagulation therapy (no stop date)
  1. Does the member have any conditions in which the DOACs are not recommended or contraindicated? See chart below.
    1. If yes, deny as not meeting criteria. Warfarin or LMWH are alternatives
    2. If no, approve for appropriate duration of therapy for FDA approved indication medication is prescribed to treat.
Xarelto© Pradaxa© Eliquis© Savaysa©
Contraindication -Active bleeding -Active bleeding

-Mechanical prosthetic heart valve

-Active bleeding -Active bleeding
Use not recommended -Age <18-year-old -Prosthetic heart valves -Severe renal impairment (CrCl <15 ml/min) -Hepatic impairment (Child-Pugh B and C) -Hepatic disease associated with coagulopathy -Pregnancy -Nursing mothers -Age <18 years old -Bioprosthetic heart valve -Severe renal impairment (CrCl <15 ml/min) -Pregnancy -Nursing mothers -Age <18 years old -Prosthetic heart valve -Nursing mothers -Pregnancy -Severe hepatic impairment (Child-Pugh C) -Severe renal impairment (CrCl <15 ml/min) -Age <18 years old -Mechanical heart valve -Moderate to severe mitral stenosis -CrCl >95 ml/min (nonvalvular atrial fibrillation)

-Nursing mothers

-Moderate to severe hepatic impairment (Child-Pugh B and C)

Drug-Drug Interactions -Anticoagulants

-Combined P-gp and strong CYP3A4 inhibitors and inducers

-Anticoagulants

-Rifampin

-Anticoagulants

-Combined strong CYP3A4 and P-gp inhibitors and inducers

-Anticoagulants

-Rifampin

*Example of potential drug-drug interactions:

Strong CYP3A4 and P-gp Inducers: carbamazepine, phenytoin, rifampin, St. John’s wort

Strong CYP3A4 and P-gp Inhibitors: cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, ketoconazole, clarithromycin, diltiazem, quinidine, tacrolimus, grapefruit juice

*Note: The International society on Thrombosis and Haemostatis (ISTH) 2016 guideline suggests avoiding the use of DOACs in patients with BMI >40 kg/m2 or weight >120 kg due to lack of clinical data in this population. If used in patients with BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an anti-factor Xa assay or mass spectrometry. If drug level is below expected range, ISTH recommends changing to Vitamin K antagonist. Advanced Health will not restrict access to DOAC medication based on BMI or weight, however, a note will be sent to the requesting provider alerting them to the lack of clinical data in this population.

Dosing Adjustments

Xarelto© Pradaxa© Eliquis© Savaysa©
DVT or PE treatment 30 mg once daily (CrCl 15 to 50 ml/min or body weight ≤60 kg)
Reduction in risk of recurrent DVT/PE 15 mg once daily (CrCl 15 to 50 ml/min)
Nonvalvular atrial fibrillation 15 mg once daily (CrCl 15 to 50 ml/min) 75 mg twice daily (CrCL 15-30 ml/min) 2.5 mg twice daily (2 or more of the following: age ≥80, weight ≤60 kg, or serum creatinine ≥1.5 mg/dl) 30 mg once daily (CrCl 15 to 50 ml/min)

Rationale:

Due to high cost of therapy and potential for serious adverse events, drug use criteria help to promote safe, evidence-based prescribing of the direct oral anticoagulants.

FDA Approved Indications:

Xarelto© (rivaroxaban) is FDA indicated for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), reduction in the risk of recurrence of DVT and PE, reduction of risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation, and prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Savaysa© (edoxaban) if FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and the treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant.

Pradaxa© (dabigatran) is FDA indicated for the reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment of DVT and PE following 5-10 days of initial therapy with a parenteral anticoagulant, reduction  in the risk of recurrence of DVT and PE, and DVT and PE prophylaxis in patients that have undergone hip replacement surgery.

Eliquis© (apixaban) is FDA indicated for reduction of risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery, treatment of DVT and PE, and reduction in the risk of recurrent DVT and PE.

References:

  1. Xarelto© Prescribing Information. Last updated 8/2016
  2. Savaysa© Prescribing Information. Last updated 9/2016
  3. Pradaxa© Prescribing Information. Last updated 11/2015
  4. Eliquis© Prescribing Information. Last updates 7/2016
  5. Kearin C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST 2016; 149(2):315-352
  6. International Society on Thrombosis Haemostasis (ISTH) 2016 Guideline

Approved by Advanced Health Pharmacy and Therapeutics Committee 4/22/19