As a clinical pharmacist, you are in a key position to prevent direct oral anticoagulant (DOAC) dosing errors. Advocate for a pharmacist-to-dose protocol, recent evidence suggests this can reduce DOAC errors by almost half. Require an indication for DOAC orders and when documenting home DOACs to verify appropriate dosing. And include other key factors within your protocol...
- Obesity. Give the usual dose up to 120 kg or a BMI of 40. If a DOAC is preferred for patients with a higher weight, prescribe apixaban (Eliquis) or rivaroxaban (Xarelto) at usual doses based on limited data. Otherwise, choose warfarin.
- Kidney impairment. For atrial fibrillation, generally use a lower dose.
- For instance, think of “ABC” with apixaban. Reduce the dose for patients with 2 of these 3 features (Age over 80, Body weight under 60 kg, or serum Creatinine over 1.5 mg/dL).
- And reduce rivaroxaban for CrCl under 50 mL/min. On the other hand, don’t extend atrial fibrillation dosing “rules” to venous thromboembolism (VTE) treatment, this may undertreat acute thrombosis. In this case, only lower edoxaban (Savaysa) doses, there’s no evidence for reducing other DOACs.
- But avoid dabigatran (Pradaxa) for CrCl below 30 mL/min, or rivaroxaban (Xarelto) below 15 mL/min.
- For patients on dialysis, consider cautious use of apixaban (Eliquis) at the usual dose if a DOAC is preferred for atrial fibrillation or VTE.
- Interactions. Apixaban and rivaroxaban are metabolized by CYP3A4, and absorption of all 4 DOACs is affected by P-glycoprotein (P-gp).
- For example, reduce apixaban 5 or 10 mg by half when it’s used with a strong CYP3A4 and P-gp inhibitor (itraconazole, ritonavir, etc). Avoid rivaroxaban in this case.
- At discharge from hospital, address DOAC doses that may have been adjusted. Also note durations and dose changes, such as when to step down from apixaban 10 mg BID to 5 mg BID for patients starting VTE treatment.
REFERENCES
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Bikdeli B, Zahedi Tajrishi F, Sadeghipour P, Talasaz AH, Fanikos J, Lippi G, Siegal DM, Eikelboom JW, Monreal M, Jimenez D, Connors JM, Ageno W, Barnes GD, Piazza G, Angiolillo DJ, Parikh SA, Kirtane AJ, Lopes RD, Bhatt DL, Weitz JI, Mehran R, Krumholz HM, Goldhaber SZ, Lip GYH. Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review. JAMA Cardiol. 2022 Jul 1;7(7):747-759. Available at: https://jamanetwork.com/journals/jamacardiology/article-abstract/2793119
Camm AJ, Cools F, Virdone S, Bassand JP, Fitzmaurice DA, Arthur Fox KA, Goldhaber SZ, Goto S, Haas S, Mantovani LG, Kayani G, Grierson Turpie AG, Antoon Verheugt FW, Kakkar AK; GARFIELD-AF Investigators. Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants. J Am Coll Cardiol. 2020 Sep 22;76(12):1425-1436. Available at: https://www.sciencedirect.com/science/article/pii/S0735109720361052?via%3Dihub
Martin KA, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021 Aug;19(8):1874-1882. Available at: https://onlinelibrary.wiley.com/doi/10.1111/jth.15358