Stephan Moll, MD writes… Is there a dose change or limitation for the use of Xarelto® (rivaroxaban) in very obese or underweight patients?
Xarelto® is FDA approved for venous thromboembolism (VTE) at 15 mg bid x 3 weeks and then 20 mg qd thereafter, independent of body weight.
Xarelto Package Insert
The Xarelto® package insert states that “Extremes in body weight (<50 kg or >120 kg) did not influence [in phase 1 studies] (< 25%) rivaroxaban exposure” (link here).
Janssen’s Public Statement
This is what Janssen’s Xarelto website says (link here): “Q: Does the dose of Xarelto® need to be adjusted according to a patient’s body weight? A: No dose adjustment of Xarelto® for body weight was required in patients participating in phase 2 and phase 3 clinical trials [ref 1-5]. In phase 1 trials, extremes in body weight (<50 kg or >120 kg) did not significantly influence (<25%) Xarelto® exposure. Moreover, outcomes analyses in the EINSTEIN DVT and PE trials indicated that the safety and efficacy of Xarelto® were consistent irrespective of body weight [ref 6,7]”.
My Clinical Approach
As limited patients with extreme body weights were studied in the phase 3 rivaroxaban trials (and the other NOACs, for that matter) , I am hesitant to use the drug in the very heavy and very light patients. Warfarin is my treatment of choice in these patients. However, if a very overweight patient really wants to use rivaroxaban, I obtain a trough and a 2 ½ hour peak plasma anti-Xa level to make sure that the level is roughly in the anticipated anti-Xa range – peak and trough ranges from “real-world” patients have been published [ref 8]. I would not increase or decrease rivaroxaban dose based on plasma levels, but would use another anticoagulant (warfarin) if the obese or underweight patient was not in the desired anti-Xa range.
- The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499‐2510.
- The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297.
- Büller HR et al. A dose-ranging study evaluating once‐daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose‐Ranging Study. Blood. 2008;112(6):2242-2247.
- Agnelli G et al. Treatment of proximal deep‐vein thrombosis with the oral direct Factor Xa inhibitor rivaroxaban (BAY 59‐7939): the ODIXa–DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep‐Vein Thrombosis) study. Circulation. 2007;116(2):180-187.
- Patel MR et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883‐891.
- Online supplement to: The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297. Link here. Accessed Sept 9, 2014.
- Online supplement to: The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510. Link here. Accessed Sept 9, 2014.
- Francart SJ et al. Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peal and trough plasma levels. Thromb Haemost. 2014 Jan 9;111(5):1153-69 [Epub ahead of print].
Disclosure: I have consulted for Janssen, Daiichi, Boehringer Ingelheim.
Last updated: Sept 9th, 2014