Endocrine Abstracts

Introduction/Aim: New oral anticoagulant drugs such as the factor Xa inhibitor rivaroxaban are often preferred to the classic coumarins because they do not need frequent blood-test monitoring and have fever interactions with other drugs and foodstuffs. They are not, however, interaction free. Rivaroxaban is metabolized by oxidative degradation catalyzed by CYP3A4/5 and CYP2J2; it is also a substrate of the P-gp and ABCG2 efflux transporter proteins. CYP3A4 activity enhancers such as phenytoin, carbamazepine, phenobarbital, rifampin, and the herbal antidepressant St. John’s wort may decrease the efficacy of factor Xa inhibitors and increase the risk of thrombosis and embolism. We hereby report the case of a patient who presented recurrence of deep vein thrombosis (DVT) complicated with severe pulmonary embolism in spite of treatment with rivaroxaban, associated with the intake of Saint John’s wort.

Methods: Review of the patient’s record and the relevant literature.

Results: A 54 year old, non-smoker female patient with type 2 diabetes, obesity, sedentarism, hypertension and dyslipidaemia had recurrent episodes of DVT in both calves, and had been diagnosed of factor V Leiden deficiency. Treatment with acenocoumarol was prescribed, but her INR values were erratic; moreover she had several episodes of minor bleeding, and her treatment was switched to rivaroxaban 2.5 mg/12 h + AAS 100 mg/day. The patient remained asymptomatic for two years. Afterwards, the patient was admitted to the Emergency Room with sudden-onset dyspnea, tachypnea, tachycardia, hypotension, diffuse pleuritic chest pain, cyanosis and sincope. She had noticed tenderness, redness and swelling in her right calf during the previous week. Chest auscultation showed disseminated sibilant rales, and her pulse oximetry was 91%. DVT and pulmonary embolism were suspected and confirmed by calf ultrasonography and thoracic CT scan. Intravenous heparin therapy was begun along with support measures, and the patient was discharged on subcutaneous low molecular weight heparin after five days. When questioned again before discharge, she revealed self-medication with a non-prescription St. John’s wort (Hypericum perforatum) preparation over the previous 3 weeks, motivated by depressive symptoms related to family issues.

Conclusions: Depression is a frequent comorbidity of DVT and the use of non-prescription herbal antidepressants such as Saint John’s wort is often not reported by the patients. Saint John’s wort may treble the activity of CYP3A4 and impair the effect of factor Xa inhibitors such as rivaroxaban with potentially serious consequences. The awareness of this interaction among the prescribing physicians is low and should be enhanced.