Bupropion + Naltrexone

Bupropion + Naltrexone combines two medicines that act on appetite and reward pathways in the brain. Bupropion affects dopamine and noradrenaline, while naltrexone blocks opioid receptors; taken together they reduce hunger and help with control over eating. The UK SmPC limits use to adults aged 18 or over, as an addition to a reduced-calorie diet and more physical activity, who start with a body mass index of 30 kg/m² or more, or of 27 to under 30 kg/m² with at least one weight-related condition such as type 2 diabetes, dyslipidaemia or controlled high blood pressure.

Bupropion + Naltrexone is offered in a single strength: a prolonged-release tablet containing 8 mg naltrexone hydrochloride and 90 mg bupropion hydrochloride, available in packs of 30, 60, 90 or 120 tablets. At the full maintenance dose of four tablets a day, a pack of 120 lasts about 30 days. The tablets supplied are an imported generic, so packaging may differ from the UK-branded carton.

Treatment starts low and is increased over four weeks to limit nausea. In week one, one tablet is taken in the morning; in week two, one in the morning and one in the evening; in week three, two in the morning and one in the evening; from week four, two tablets twice a day. The SmPC sets the maximum at four tablets daily (32 mg naltrexone and 360 mg bupropion). Tablets are swallowed whole with water, preferably with food, and must not be cut, crushed or chewed. A missed dose is simply skipped. Progress is checked after 16 weeks, and treatment should stop if at least 5% of starting body weight has not been lost; continuing use is reassessed every year. Lower maximum doses apply in kidney or mild liver impairment, and extra caution is needed over 65.

The branded product in the UK is Mysimba 8 mg/90 mg prolonged-release tablets, with the licence held by Orexigen Therapeutics Ireland. Under UK rules it falls into the POM category and is supplied only on prescription. NICE technology appraisal TA494 does not recommend this combination for managing overweight and obesity, so it is not routinely available on the NHS. The prescriber decides whether it is a suitable option after checking blood pressure, pulse and medical history.

Bupropion + Naltrexone is contraindicated in people with uncontrolled high blood pressure, epilepsy or any past seizure, a brain tumour, bipolar disorder, current or past bulimia or anorexia nervosa, severe liver impairment, end-stage kidney failure, and sudden withdrawal from alcohol or benzodiazepines. It cannot be used by people dependent on opioids, including methadone, or alongside any other medicine containing bupropion or naltrexone. At least 14 days must pass after stopping an MAO inhibitor. Bupropion inhibits the liver enzyme CYP2D6, which can raise levels of some antidepressants, antipsychotics and beta-blockers such as metoprolol, and may weaken tamoxifen. Medicines that lower the seizure threshold, such as tramadol, theophylline and systemic steroids, need care, and people with diabetes may need their glucose-lowering treatment adjusted.

Nausea is the most frequent complaint, especially during the build-up. Constipation, vomiting, headache, dizziness, dry mouth and difficulty sleeping are also common. Blood pressure and pulse can rise and are monitored during treatment. Bupropion carries a dose-related risk of seizures; anyone who has a fit must stop and not restart. Low mood, agitation or thoughts of self-harm should be reported straight away, as antidepressant-type drugs have been linked with suicidal thinking. Drowsiness or blackouts have occurred, so take care with driving, particularly in the first weeks of Bupropion + Naltrexone.