Bupropion + Naltrexone

Bupropion + Naltrexone puts two older medicines into each tablet. One component, bupropion, modifies dopamine and noradrenaline activity and the other, naltrexone, occupies opioid receptors; the developers argue that together they dampen appetite and the brain’s reward response to food. British authorisation is for Mysimba prolonged-release tablets (naltrexone 8 mg/bupropion 90 mg) in adults with a BMI of 30 or above, or between 27 and 30 where type 2 diabetes, dyslipidaemia or well-controlled high blood pressure is present. A lower-calorie diet and more exercise are part of the licence.

The listing gives 8 mg naltrexone hydrochloride with 90 mg bupropion hydrochloride in a tablet, sold as 30, 60, 90 or 120. Mysimba prolonged-release tablets must be swallowed whole and never cut, chewed or crushed; for the imported tablets, the release formulation and instructions should be confirmed with a pharmacist before Mysimba dosing guidance is applied. Printing on the strip may follow the labelling rules of another country, though both ingredients ought to be named. The Mysimba SmPC is the reference to use, and a clinician who can monitor progress makes weight management safer.

Bupropion + Naltrexone is introduced gradually. One tablet is taken in the morning in week 1, a second is added in the evening in week 2, and week 3 becomes two in the morning with one in the evening. From week 4 the schedule is two tablets at breakfast and two in the evening, which amounts to the daily maximum of 32 mg naltrexone and 360 mg bupropion. Water is the drink of choice, ideally with food, and a missed dose is left, not doubled. For people with moderate or severe kidney impairment, or mild liver impairment, the SmPC caps the dose at a single tablet in the morning and another in the evening. Moderate liver impairment and an age above 75 are both reasons the SmPC advises against it. Weight loss below 5 per cent at 16 weeks ends treatment, and the benefit is reassessed every year.

Mysimba is contraindicated in uncontrolled hypertension, current or previous seizures, a known CNS tumour, acute alcohol or benzodiazepine withdrawal, a history of bipolar disorder, and current or previous bulimia or anorexia nervosa. The list continues with continuing opioid therapy, acute opioid withdrawal, an MAOI taken within the past fortnight, another medicine with bupropion or naltrexone in it, severe liver failure and end-stage kidney disease. The SmPC does not advise use in pregnancy or while breastfeeding. Any seizure during treatment means the medicine is stopped for good.

Before the first tablet and from time to time afterwards, blood pressure and pulse are checked. Naltrexone blocks opioid receptors, so trying to overcome it with a large opioid dose risks overdose. Bupropion relies mainly on CYP2B6 for clearance and blocks CYP2D6, so levels of certain antidepressants, antipsychotics, metoprolol and tamoxifen may change. Tramadol, theophylline and systemic corticosteroids all raise the chance of a seizure. Low mood, suicidal thoughts or odd changes in behaviour during treatment with Bupropion + Naltrexone mean contacting a doctor without delay.

Very common effects are nausea, constipation, headache and vomiting; dizziness is common, as are insomnia, dry mouth, anxiety and higher blood pressure. NICE examined the combination in appraisal TA494 and concluded that it should not be recommended for the NHS. A prescriber will go over your health and your medicines, decide whether Bupropion + Naltrexone is suitable, and explain what degree of weight loss would justify going on.