PS-R01-9: THE PERILS OF GRAPEFRUIT: A POTENTIALLY LETHAL INTERACTION WITH VERAPAMIL

Abstract

Objective: Hereby we describe a case of severe toxicity induced by a standard dose of slow-release verapamil Design and Methods: Review of the patient's records and of the relevant literature. Results (Case Description): A 57-year old woman had been diagnosed with hypertension by her family physician, but her management had been complicated with intolerance to multiple antihypertensive drugs. On the occasion of a family conflict, she developed a hypertensive crisis, with a holocranial headache, tremor and palpitations, but no symptoms of ischemia on the EKG. After discharge from the Emergency Room she was referred to our Outpatient Hypertension Clinic in order to rule out secondary hypertension. For the workup, and in order to avoid interference with the renin-angiotensin-aldosterone system she was switched to slow-release verapamil 120 mg twice a day. One month afterwards the workup was completed: primary aldosteronism, pheochromocytoma/paraganglioma, renovascular hypertension and Cushing's syndrome had been ruled out. Her BP was adequately controlled with verapamil, with ABPM confirmation, and her tolerance was good. Considering her multiple drug intolerances, we decided to keep her on verapamil. Four months afterwards, the patient was brought back to the Emergency Room with severe hypotension and bradycardia, extreme asthenia, generalized rubor and diaphoresis, with normal lab tests except for mild creatinine elevation in the context of dehydration. Her SBP was 74 mmHg, with DBP not measurable, and HR 39 lpm; the EKG showed Wenckebach 2:1 AV block. After 48 hr in the Emergency Room with saline infusion and basic support measures the patient was discharged and referred again to our Clinic for reevaluation. A verapamil overdose was suspected, but the patient was adamant that she had always taken verapamil exactly as prescribed. A detailed anamnesis revealed that the patient had put on some weight the previous month and decided to lose it with a novelty diet based on the intake of about 2 liters of grapefruit fruit daily plus protein. She was switched to indapamide 2.5 mg daily with good tolerance and adequate BP control. Conclusions: Grapefruit juice contains 6’-7’dihydrohybergamottin, a powerful inhibitor of the key drug metabolizing enzyme CYP3A4, potentially causing accumulation of many common drugs such as verapamil, statins, ticagrelor, sildenafil, amiodarone or cisapride, and related toxicity. We need to remember that prescription drugs do not only interact among themselves but also with herbal remedies and common foodstuffs such as grapefruit.