PB0142 - Drug-drug interaction in a patient with concomitant use of strong CYP3A4 and P-gp inhibitor amiodarone and direct oral anticoagulant rivaroxaban

Background: Patients with atrial fibrillation (AF), in addition to therapy with direct oral anticoagulants such as rivaroxaban for the prevention of stroke, may need additional therapy with anti-arrhythmic drugs such as amiodarone. Concomitant use of both drugs is recommended by the European Society of Cardiology and European Heart Rhythm Association guidelines without contraindication based on ROCKET AF study.

Aims: To present the case of concomitant use of rivaroxaban and amiodarone which resulted with strong drug-drug interaction (DDI).

Methods: A 74-year-old woman with the multiple comorbidities (arterial hypertension, AF, osteoarthritis, osteoporosis, post COVID) presented to Emergency Department (ED) with syncope and the weakness of right side of the body, lower angle of the mouth, difficulty speaking, and headache which developed during the regular clinical examination by rheumatologist. In chronic therapy she had amiodarone, torasemid, bisoprolol hydrochlorothiazide, leflunomide, pantoprazole, calcitriol and Ca citrate and rivaroxaban (1x20 mg). Clinical pharmacologist evaluated potential DDI between all drugs in use.

Results: Computed tomography (CT) has shown intracerebral haematoma measuring 4.2 cm and visible blood into ventricular system. CT angiography has not shown signs of AV malformation or aneurism. Laboratory diagnostics has revealed rivaroxaban concentration of 928 ng/mL (peak therapeutic range 184-383 ng/mL). 24 hours after discontinuation rivaroxaban concentration was 45 ng/mL and in the next 24 hours 0 ng/mL. Pharmacogenomics analysis showed that patient was intermediary metabolizer (genotype combination CYP3A4*22 *1/*1 and CYP3A5*3 *3/*3) of medications-supstrates CYP3A requiring average doses

Conclusion(s): This case report has shown strong DDI between rivaroxaban and amiodarone. Both metabolise via CYP 3A4 pathway and are P-gp substrates. Although ROCKET AF study indicated no clinical effect in concomitant use of these drugs, re-evaluation of the recommendations should be considered in terms of avoiding combination of strong inhibitors of CYP 3A4 and P-gp and rivaroxaban.