Date of report 14 Feb 2020
Reported case interaction between
Ritonavir and Rivaroxaban
Ritonavir and Rivaroxaban
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Rivaroxaban, lamotrigine, levetiracetam, gemfibrozil, pantoprazole and terbinafine
Clinical case description
52-year-old Caucasian male with HIV infection diagnosed in 1984. Receiving salvage therapy including darunavir/ritonavir 600 mg/100 mg twice daily, lamivudine 150 mg twice daily, tenofovir 300 mg once daily, etravirine 200 mg twice daily and raltegravir 400 mg twice daily, which resulted in virological HIV suppression (<20 copies/ml). In January 2012, the patient presented a fracture of the right malleolus, which led to surgery. The postoperative period was uneventful and the patient returned home with a prescription for rivaroxaban 10 mg once daily for six weeks. Two weeks after the start of anticoagulant treatment the rivaroxaban plasma level was 253 μg/l (expected peak concentration 125μg/l for 10 mg once daily). The patient was informed of the elevated result and was advised to halve the dosage of rivaroxaban. No additional rivaroxaban measurements were performed. At the end of February 2012, while on a work trip in Mexico, the patient called his HIV physician to complain about acute bloody diarrhoea. At this point, the patient was advised immediately to stop rivaroxaban and to go to the emergency unit. The patient was treated with intravenous hydration and ciprofloxacin 500 mg twice daily with complete resolution of the bloody diarrhoea. Alternative causes for the gastrointestinal bleeding were excluded. Since the treatment for the prevention of venous thromboembolism was almost completed, no other anticoagulant was further prescribed. This case was publshed in Swiss Med Wkly. 2014 Jan 22;144:w13906. doi: 10.4414/smw.2014.13906 by Lakatos B et al.
Clinical Outcome
Drug Interaction Probability Scale (DIPS)
Editorial Comment
It is not recommended to use ritonavir in patients receiving rivaroxaban, due to the risk of increased bleeding. Inhibition of CYP3A and P-gp lead to increased plasma levels and pharmacodynamic effects of rivaroxaban which may lead to an increased bleeding risk. Coadministration of rivaroxaban (10 mg single dose) and ritonavir (600 mg every 12 hours) increased rivaroxaban AUC and Cmax by 153% and 55%. Norvir Summary of Product Characteristics, AbbVie Ltd, September 2016.