By: Richard P. Barna, Pharm. D., R.Ph.
Is Warfarin a thing of the past? With four new target-specific oral anticoagulants (TSOACs) now available, numerous therapeutic options exist for treatment and prophylaxis against venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in addition to atrial fibrillation. The availability of dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) offer the clinician the option of utilizing a therapeutic agent that requires no routine monitoring, no dietary restrictions, and few drug-drug interactions compared with Warfarin without compromising efficacy. How do these agents really stack up and what do you need to know about using these drugs in the elderly? Dabigatran’s approval by the FDA in 2010 represented the first new anticoagulant to reach the market in 50 years. This drug exerts its anticoagulant effect by blocking the activity of factor IIa. This drug is approved for anticoagulation in individuals with atrial fibrillation who do not have a mechanical heart valve as well as for the treatment and reduction in risk of recurrence of VTE. For all indications, for individuals with a CrCl above 30 mL/min, the drug should be dosed at 150 mg orally twice daily.
For non-valvular atrial fibrillation (NVAF), for patients with CrCl between 15-30 mL/min, the dose should be 75 mg orally twice daily. Capsules should not be crushed, opened, broken or chewed when administering this medication. Monitor patients for heartburn and dyspepsia as these gastrointestinal adverse effects are common with therapy. Rivaroxaban, apixaban, and edoxaban are all direct-acting inhibitors of factor Xa. Regarding rivaroxaban, this medication is indicated as an anticoagulant in NVAF and for treatment and prophylaxis of VTE. For atrial fibrillation, this medication is administered at a dose of 20 mg (if CrCl>50 mL/min) or 15 mg (if the CrCl is between 15-50 mL/min) orally once daily with the evening meal, as food increases the absorption of this medication; use should be avoided in patients with CrCl less than 15 mL/min. For treating VTE and reducing the risk of recurrence, the drug is dosed at 15 mg orally twice daily with food for the first 21 days of therapy followed by 20 mg orally once daily for the remainder of the treatment period. A dose of 10 mg once daily is used for prophylaxis of DVT following hip or knee replacement surgery.
For VTE treatment and prophylaxis, use should be avoided in individuals with a CrCl less than 30 mL/min. Apixaban shares the same mechanism of action and indications as rivaroxaban. This medication is dosed 5 mg BID; 2.5 mg BID for patients with two or more of the following: age 80 years and older, weight 60 kg or less, serum creatinine 1.5 mg/dL or greater for patients with NVAF. For VTE prevention post-hip or knee replacement, dosing should be 2.5 mg PO twice daily for 35 days [hip] or 12 days [knee] starting 12 to 24 hrs. post-operatively. Finally for DVT/PE treatment, 10 mg BID for seven days, then 5 mg BID, or DVT/PE prevention of recurrence 2.5 mg BID after at least six months of treatment. Edoxaban is the newest drug in this class that received approved in January 2015. This agent is similar to rivaroxaban and apixaban in indications and mechanism. This medication is dosed 60 mg orally once daily for treatment of NVAF, DVT and PE. The medication shouldn’t be used in patients with CrCl above 95 mL/min and a reduced dose of 30 mg orally once daily is indicated for patients with CrCl 15-50 mL/min for atrial fibrillation and treatment of DVT and PE, respectively. Comparing all of the new TSOACs, the clinician should be mindful of the differences in cost, need for dosage adjustment in patients with renal dysfunction, and bleeding risks, all of which are pivotal characteristics of concern for the elderly population.
No head-to-head clinical trials are currently available to provide comparative efficacy. In evaluating a patient for candidacy for one of these newer agents, the clinician must consider whether the individual is a candidate for a TSOAC, whether they have comorbid illnesses that would preclude use of the agent under consideration, and finally the patient’s ability to comply with and afford the medication. Importantly, specific antidotes for the management of bleeding with these medications are in development but are not currently available. Warfarin, with all its limitations, including drug-drug interactions, dietary issues, and need for therapeutic monitoring, may still be a reasonable choice for some individuals.