Anti-obesity (combination) Pregnancy: §4.6: should not be used during pregnancy or in women currently attempting to become pregnant (no or limited human data; naltrexone showed reproductive toxicity in animals). Naltrexone and bupropion and their metabolites are excreted in human milk — should not be used during breast-feeding.

Naltrexone with bupropion

Brand names: Mysimba

A modified-release oral combination of the opioid antagonist naltrexone and the antidepressant/smoking-cessation agent bupropion, used as an adjunct to diet and exercise for weight management in adults with obesity or overweight with comorbidities.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Maintenance from week 4 onwards: two tablets in the morning and two tablets in the evening (naltrexone 8 mg / bupropion 90 mg prolonged-release tablets), reached by a 4-week escalation

Route: Oral — swallow whole with water, preferably with food; do not cut, chew or crush

Frequency: Twice daily (morning and evening)

Max: Two tablets taken twice daily, a total daily dose of 32 mg naltrexone hydrochloride and 360 mg bupropion hydrochloride

eMC §4.2 (Mysimba 8 mg/90 mg prolonged-release tablets). Dose escalation over 4 weeks: week 1 — one tablet in the morning; week 2 — one tablet in the morning and one tablet in the evening; week 3 — two tablets in the morning and one tablet in the evening; week 4 and onwards — two tablets in the morning and two tablets in the evening. The need for continued treatment should be evaluated after 16 weeks and re-evaluated annually. Missed dose: do not take an additional dose — take the prescribed next dose at the usual time. Elderly: use with caution in patients over 65 years; not recommended in patients over 75 years. Hepatic impairment: contraindicated in severe impairment; not recommended in moderate impairment; in mild impairment the maximum recommended daily dose is two tablets (one in the morning and one in the evening), initiating with one tablet in the morning for the first week and escalating from week 2 — assess degree of impairment using the Child-Pugh score. Paediatric population: safety and efficacy below 18 years have not been established — should not be used in children and adolescents below 18.

Dose adjustments

Renal

§4.2: contraindicated in end-stage renal failure. In moderate or severe renal impairment the maximum recommended daily dose is two tablets (one tablet in the morning and one tablet in the evening); it is recommended to initiate with one tablet in the morning for the first week and escalate to one tablet morning and one tablet evening from week 2 onwards. Dose reduction is not necessary in mild renal impairment. For individuals at elevated risk of renal impairment, in particular patients with diabetes or elderly individuals, eGFR should be assessed prior to initiating therapy.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients
Uncontrolled hypertension
Current seizure disorder or a history of seizures; known central nervous system tumour
Acute alcohol or benzodiazepine withdrawal; history of bipolar disorder
Any concomitant treatment containing bupropion or naltrexone
Current or previous diagnosis of bulimia or anorexia nervosa
Current dependence on chronic opioids or opiate agonists (e.g. methadone), or acute opiate withdrawal
Concomitant monoamine oxidase inhibitors — at least 14 days should elapse between stopping an MAOI and starting treatment
Severe hepatic impairment; end-stage renal failure

Side effects

Nausea (very common)
Constipation (very common)
Vomiting (very common)
Headache (very common)
Dizziness, dry mouth, tremor, dysgeusia, lethargy, somnolence (common)
Anxiety and insomnia (common); increased heart rate, palpitations, hot flush, hypertension/increased blood pressure (common)
Seizure (rare); suicidal ideation, suicide attempt and suicidal behaviour (frequency not known) — see §4.4

Clinical monograph

How it works

The two agents act centrally on appetite-regulating pathways, with bupropion stimulating hypothalamic neurones and naltrexone blocking an opioid-mediated feedback loop, together reducing appetite and food intake.

Prescribing in practice

Because bupropion lowers the seizure threshold, the combination is contraindicated in epilepsy or conditions predisposing to seizures, and must not be used with opioids or in opioid dependence owing to the naltrexone component.
It is contraindicated with monoamine oxidase inhibitors and in uncontrolled hypertension, and can raise blood pressure and heart rate.
Review for adequate weight loss after an initial period and discontinue if the response is insufficient, while monitoring mood given bupropion's psychiatric effects.

Monitoring

Monitor blood pressure and heart rate, weight response, and mood or behavioural changes including any suicidal ideation.

Counselling the patient

Swallow the tablets whole with the dose built up gradually, and do not take with a high-fat meal.
Do not take any opioid painkillers while on this medicine and tell healthcare staff you take it before any procedure.
Report low mood, agitation or thoughts of self-harm.

Evidence & guidelines

Naltrexone-bupropion is licensed for weight management as an adjunct to lifestyle measures, with trials showing modest additional weight loss; NICE has appraised its place in therapy.

Reference: NICE TA494; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways