Mysimba

Mysimba holds naltrexone and bupropion together in a single prolonged-release tablet. Bupropion acts on dopamine and noradrenaline pathways, while naltrexone blocks opioid receptors, and the SmPC suggests that, acting together in the hypothalamus and in the reward circuits of the brain, they reduce appetite and the pull of food as a reward. It also admits that the exact mechanism is not fully understood.

The licence is for adults aged 18 and over, as an addition to a reduced-calorie diet and more physical activity, where the starting body mass index is 30 kg/m2 or higher, or between 27 and below 30 kg/m2 when at least one weight-related condition such as type 2 diabetes, dyslipidaemia or controlled hypertension is also present. The tablets are meant as one part of a wider plan and do not replace changes in eating and activity.

Only one tablet strength is available, 8 mg of naltrexone with 90 mg of bupropion, supplied as 30, 60, 90 or 120. UK-licensed Mysimba comes in packs of 28 or 112 tablets; the stock listed here is imported, so its carton and leaflet may differ from the UK ones. Mysimba tablets are swallowed whole and are never split, chewed or crushed, so anyone holding an imported pack should read its leaflet, or ask a pharmacist, before assuming it behaves in the same way.

Dosing is stepped up over four weeks, starting with one tablet in the morning in week 1, adding one in the evening in week 2, moving to two in the morning and one in the evening in week 3 and reaching two in the morning and two in the evening from week 4, which is the daily limit of four tablets. Water is the drink of choice, ideally with food, and a missed tablet is not made up with an extra one. Treatment has to stop after 16 weeks if less than 5% of the starting weight has been lost, and for people who go on, the SmPC expects the benefit to be reassessed every year. Moderate or severe kidney impairment and mild liver impairment cap the dose at one tablet morning and evening, and the SmPC does not recommend the tablets in moderate liver impairment or in people over 75.

Mysimba is contraindicated in uncontrolled high blood pressure, in epilepsy or any previous seizure, with a tumour of the brain or spinal cord, during sudden withdrawal from alcohol or benzodiazepines, with a history of bipolar disorder, and in current or past bulimia or anorexia nervosa. Also excluding it are severe liver failure, end-stage kidney disease, another medicine that contains bupropion or naltrexone, an MAOI taken within the last 14 days, and opioid use of any continuing kind, including methadone and acute opioid withdrawal. It is also not for use in pregnancy, when a pregnancy is being planned or during breastfeeding.

Blood pressure and pulse are monitored, since rises, and a hypertensive crisis during the climb to full dose, have been reported, and the risk of seizure grows with dose and with alcohol, head injury and certain other medicines, so a seizure means stopping for good. Naltrexone blocks opioids, which can make opioid painkillers and cough or diarrhoea medicines less effective, and bupropion inhibits CYP2D6, which can raise levels of metoprolol, tricyclic antidepressants and antipsychotics and reduce the effect of tamoxifen. Serotonin syndrome is a possibility if it is combined with an SSRI or SNRI. Nausea, constipation, vomiting and headache are very common, and dizziness, dry mouth, poor sleep, jitteriness, shaking, altered taste, tinnitus, sweating, itching, hair loss, palpitations and a rise in blood pressure are common. Because drowsiness is possible, take care before driving. NICE examined the combination in TA494 and did not recommend it, and the prescriber decides whether Mysimba is right for you and whether treatment should continue.