MHRA Contraindicates Domperidone in Phaeochromocytoma

Domperidone is now contraindicated in patients with confirmed or suspected phaeochromocytoma because of the risk of severe hypertension, the Medicines and Healthcare products Regulatory Agency (MHRA) has said in a new drug safety update. The update follows a European review of domperidone safety data that identified four reports of severe hypertension in these patients. The contraindication affects a widely prescribed drug: domperidone is dispensed at an average of 222,000 items a year across NHS England, according to prescribing data cited in the safety update. Although no such reports of severe hypertension had been received via the UK's Yellow Card reporting site, the UK's Pharmacovigilance Expert Advisory Committee of the Commission on Human Medicines considered the findings of the European review and agreed with its recommendations. The MHRA advised that healthcare professionals and patients be made aware of the change, which will be reflected in updated product information. Recommendations for Clinicians and Patients Patients with confirmed or suspected phaeochromocytoma should stop taking domperidone immediately and be switched to an alternative treatment, the agency said. It said clinicians should also be aware that domperidone can unmask phaeochromocytomas, so if a patient taking it has an episode of severe hypertension, further investigations for phaeochromocytoma should be considered. The MHRA advised prescribers that if indicated, domperidone should be used at the lowest effective dose for the shortest possible duration. Maximum treatment duration should not usually exceed one week. Patients should be advised to seek medical attention immediately if they experience symptoms of severe high blood pressure including persistent headache, blurred vision, shortness of breath, and chest pain. Phaeochromocytoma and Domperidone: The Background Phaeochromocytomas are rare neuroendocrine tumours arising from the catecholamine-producing chromaffin cells of the adrenal medulla. Global prevalence is estimated at 19.8 per 1,000,000 people. They are often diagnosed incidentally after imaging for other conditions. Around one in three cases arises as part of an inherited genetic disorder, such as multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, familial paraganglioma syndromes, or neurofibromatosis type 1. Symptoms include headache, heavy sweating, palpitations, tremor, facial pallor, nausea and vomiting, and feeling anxious or panicky. They tend to occur unpredictably, often in sudden attacks lasting from a few minutes to an hour, sometimes increasing in frequency, duration, and severity as the tumour enlarges. Extreme blood pressure elevations increase the risk of heart attacks, strokes, and organ failure. Most phaeochromocytomas can be successfully surgically removed. Alpha-blocker treatment is usually given for several weeks pre-operatively, sometimes along with beta-blockers, to counteract the effects of excess catecholamines and stabilise heart rate and blood pressure. About 10% of tumours become metastatic and may need chemotherapy or radiotherapy after surgery. Domperidone is a peripherally selective dopamine D ₂ receptor antagonist used primarily as an antiemetic to suppress nausea and vomiting, and as a prokinetic to increase peristalsis and relieve abdominal pain and discomfort due to gastroparesis. It has poor penetration across the blood–brain barrier, so achieves this without significant central nervous system (CNS) effects. This gives it a favourable CNS safety profile compared with metoclopramide. It also acts to increase prolactin, so is sometimes used to boost low breast milk production. The drug is licensed for use in adults and in children 12 years and above. Known adverse effects include an increased risk of arrhythmias and cardiac arrest, particularly in people over 60 or those taking doses higher than 30 mg per day. There may be interactions with some antibiotic and antifungal drugs. The agency asked healthcare professionals, patients, and caregivers to report suspected adverse drug reactions associated with domperidone via the Yellow Card scheme. Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.