Use of Target-Specific Oral Anticoagulants for Venous Thromboembolism

Case

A 69-year-old man presents to the emergency department (ED) with lower left leg pain and swelling, and is diagnosed with a deep vein thrombus (DVT). Of note, the patient has a history of 2 unprovoked DVTs and his home medications include warfarin 5 mg daily.

Laboratory test results:

• Serum creatinine: 1.2 mg/dL (estimated creatinine clearance 59 mL/min)
• International normalized ratio: 2.8
• Alanine transaminase, total bilirubin, and complete blood count: within normal limits.

The hematology team is consulted. The team concludes that the patient failed warfarin treatment, so they switch him to rivaroxaban 15 mg twice a day for 21 days, followed by 20 mg daily. Insurance coverage is confirmed and thorough medication counseling is provided, including educating the patient to take doses with food.

Two days after the patient’s ED visit, he presents to the family medicine clinic with an intolerable pruritic erythematous papular rash over his trunk and arms, and requests a different medication. The physician asks for your recommendation regarding the patient’s oral anticoagulation therapy.

Answer

Given the patient’s history of recurrent venous thromboembolism (VTE), lifelong oral anticoagulation is recommended.¹ It appears that the patient is experiencing pruritus following rivaroxaban initiation. In the RECORD 13 studies, pruritus occurred in 2.1% of patients receiving rivaroxaban 10 mg daily compared with 1.8% of patients receiving enoxaparin 40 mg once daily.²

Fortunately, apixaban, dabigatran, and edoxaban are also FDA-approved for VTE prevention and treatment.^3-5 The Online Table displays the prescribing recommendations for using target-specific oral anticoagulants for VTE prevention and treatment.^2-5 According to FDA-approved labeling, use of dabigatran and edoxaban for acute VTE treatment requires 5 to 10 days of parenteral anticoagulation.^4-5 Given this patient’s intolerable pruritus, difficulty affording enoxaparin injections, and insurance plan preference for apixaban, rivaroxaban is discontinued and apixaban 10 mg twice daily is initiated. In 1 week, patient returns to the clinic noting resolution of his rash and he is transitioned to apixaban 5 mg twice daily.^2-5

Table: FDA-Approved VTE Prescribing Recommendations for Target-Specific Oral Anticoagulants ^2-5

Drug

Indication

Recommended Dosage

Dosage Adjustments

Avoid Use

Apixaban

(Eliquis)

VTE treatment

10 mg twice daily for 7 days, followed by 5 mg orally twice daily

Reduce dose by 50% if used concomitantly with strong CYP3A4 and P-gp inhibitors

• With concomitant strong CYP3A4 and P-gp inducers
• For patients with severe hepatic impairment

VTE prevention

2.5 mg twice daily following a minimum of 6 months of treatment for DVT or PE

Avoid use with concomitant strong dual CYP3A4 and P-gp inhibitors for patients already receiving 2.5 mg twice daily

Dabigatran

(Pradaxa)

VTE treatment and prevention

150 mg twice daily

after 5 to 10 days of parenteral anticoagulation

Dosing recommendations cannot be provided for patients with CrCl <30 mL/min or those on dialysis

• For patients with CrCl <50 mL/min with concomitant use of P-gp inhibitors
• With concomitant P-gp inducers (eg, rifampin)

Edoxaban

(Savaysa)

VTE treatment and prevention

60 mg daily after 5 to 10 days of parenteral anticoagulation

30 mg daily in patients with CrCl 15 to 50 mL/min, patients who weigh less than or equal to 60 kg, or patients who are taking certain concomitant P-gp inhibitor medications (eg, verapamil and quinidine or short-term concomitant administration of azithromycin, clarithromycin, erythromycin, oral itraconazole, or oral ketoconazole)

• With concomitant use of rifampin
• Not recommended for patients with moderate or severe hepatic impairment (Child-Pugh B and C) as they may have intrinsic coagulation abnormalities
• For patients with CrCl <15 mL/min

Rivaroxaban

(Xarelto)

VTE treatment

15 mg twice daily with food for the first 21 days, then transition to 20 mg daily with food for remaining treatment

• For patients with CrCl <30 mL/min
• With concomitant use of combined P-gp and strong CYP3A4 inhibitors
• With concomitant use of combined P-gp and strong CYP3A4 inducers
• For patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy

VTE prevention

20 mg once daily with food

^{CrCl = creatinine clearance; CYP3A4 = cytochrome P450 3A4; DVT = deep vein thrombosis; P-gp = P-glycoprotein; VTE = venous thromboembolism.}

Dr. Hawes is a clinical pharmacist practitioner at the UNC Family Medicine Center and clinical assistant professor at the UNC School of Medicine Department of Family Medicine in Chapel Hill, North Carolina.

References

• Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e419S-e494S.
• Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2011.
• Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2012.
• Pradaxa [package insert].Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2010.
• Savaysa [package insert]. Parsippany, NJ: Daiichi Sankyo, Inc; 2015.