Mysimba (Naltrexone/Bupropion): How It Works, Dosage, Side Effects and Results

Mysimba is a prescription tablet for weight management that combines two medicines, naltrexone and bupropion. It is taken twice a day and acts on areas of the brain that control appetite. This guide covers who it is licensed for, how it is taken, its side effects and warnings, and what the trials found, using the UK product information and NICE guidance.

What Is Mysimba?

A naltrexone and bupropion tablet licensed in the UK for weight management in adults.

Mysimba is a prolonged-release tablet containing naltrexone 8 mg and bupropion 90 mg. It holds a UK marketing authorisation (PLGB 50742/0001).

Its Summary of Product Characteristics (SmPC) licenses it, alongside a reduced-calorie diet and more physical activity, for weight management in adults aged 18 and over with a body mass index (BMI) of:

• 30 kg/m² or more, or

• 27 to 29.9 kg/m² with at least one weight-related condition, such as type 2 diabetes, abnormal blood fats or controlled high blood pressure.

It is not for children or adolescents under 18.

How Does Mysimba Work?

Its two medicines act on the brain's hunger and reward areas; the exact mechanism is not fully understood.

The SmPC says the exact way it reduces appetite is not fully understood. It combines:

• Naltrexone, which blocks a type of opioid receptor (mu-opioid).

• Bupropion, a weak inhibitor of the reuptake of dopamine and noradrenaline in the brain.

Together they act on two areas of the brain: the hypothalamus, which regulates hunger, and the reward system linked to food. Bupropion stimulates appetite-regulating nerve cells in the hypothalamus, and naltrexone blocks a feedback loop that would otherwise dampen that effect. Animal studies suggest the two together reduce food intake more than either alone.

It works differently from weekly injections such as Wegovy and Mounjaro, which copy gut hormones.

Mysimba Dosage

One tablet a day in week 1, building to two tablets twice a day from week 4.

The dose is built up over 4 weeks:

• Week 1: one tablet in the morning.

• Week 2: one tablet in the morning and one in the evening.

• Week 3: two tablets in the morning and one in the evening.

• Week 4 onwards: two tablets in the morning and two in the evening, the maximum.

Swallow the tablets whole with some water, preferably with food, and do not cut, chew or crush them. If you miss a dose, do not take an extra one; take the next dose at the usual time.

For people with moderate or severe kidney problems or mild liver problems, the maximum is two tablets a day (one in the morning, one in the evening). It is not recommended with moderate liver problems, should be used with caution over 65 and is not recommended over 75.

The 16-Week Rule

Stop after 16 weeks if less than 5% of starting weight has been lost.

The SmPC says treatment should be stopped after 16 weeks if you have not lost at least 5% of your starting body weight. If you continue, the need for treatment is reviewed each year.

What the Trials Found

In NB-301, average weight change over 56 weeks was -5.4% with Mysimba and -1.3% with placebo.

Four phase 3 trials tested naltrexone/bupropion in 4,536 adults alongside lifestyle changes. In NB-301, the SmPC reports an average weight change of -5.4% with naltrexone/bupropion and -1.3% with placebo over 56 weeks, and 31% of people on it lost at least 5% of their body weight, against 12% on placebo. People who completed all 56 weeks lost more on average (-8.1% against -1.8%).

With intensive behavioural counselling (NB-302) the average was -8.1% against -4.9% on placebo, and in people with type 2 diabetes (NB-304) the effect was smaller (-3.7%).

These are averages across trials, not a prediction for one person. In the trials, 23.8% of people on naltrexone/bupropion stopped because of side effects, against 11.9% on placebo.

Mysimba Side Effects

Most common: nausea, constipation, vomiting, headache, dizziness and dry mouth.

The SmPC lists the most frequent side effects as nausea, constipation and vomiting (each very common, more than 1 in 10 people), plus headache (very common), dizziness and dry mouth (common).

Other common side effects include trouble sleeping, anxiety, tremor, changes in taste, tiredness, ringing in the ears, a fast heartbeat or palpitations, hot flushes, raised blood pressure, stomach pain, sweating, itching, hair loss and rash.

Report suspected side effects to the MHRA Yellow Card scheme.

Important Warnings

Watch for mood changes and suicidal thoughts; seizure risk; blood pressure checks; never with long-term opioids.

• Mood and suicidal thoughts: bupropion is used for depression in some countries. No suicides or suicide attempts were reported in the weight trials up to 56 weeks, but suicidal thoughts have been reported since it came onto the market. Seek medical advice immediately for worsening mood, suicidal thoughts or unusual changes in behaviour, especially early on and after dose changes.

• Seizures: bupropion carries a dose-related risk of seizures. Seizures happened in about 0.06% of people in the trials. Mysimba should be stopped and not restarted after a seizure. Keep alcohol to a minimum or avoid it.

• Blood pressure and pulse should be checked before starting and regularly during treatment, and it should be stopped if they rise significantly and stay raised.

• Opioids: naltrexone blocks opioid painkillers. Mysimba must not be taken with long-term opioid treatment, and trying to overcome the block with large doses of opioids is very dangerous. It can also make opioid-containing cough, cold and anti-diarrhoea medicines less effective. After stopping, you may be more sensitive to lower doses of opioids.

• Other medicines: bupropion slows the breakdown of medicines processed by the liver enzyme CYP2D6, including some antidepressants, antipsychotics and beta-blockers such as metoprolol, so their doses may need adjusting. Tell your prescriber about every medicine you take.

• Allergic reactions: stop taking it and see a doctor if you get a rash, itching, hives, chest pain, swelling or shortness of breath. For severe swelling of the face or throat or difficulty breathing, call 999.

Who Should Not Take Mysimba

Not with seizures, bipolar disorder, eating disorders, uncontrolled high blood pressure, opioid dependence or MAOIs.

The SmPC lists these contraindications:

• Allergy to naltrexone, bupropion or any other ingredient.

• Uncontrolled high blood pressure.

• A current seizure disorder or any history of seizures, or a known brain or spinal cord tumour.

• Sudden withdrawal from alcohol or benzodiazepines.

• A history of bipolar disorder, or a current or past diagnosis of bulimia or anorexia nervosa.

• Taking any other medicine containing bupropion or naltrexone.

• Dependence on long-term opioids or opiate agonists such as methadone, or acute opiate withdrawal.

• Taking a monoamine oxidase inhibitor (MAOI), or within 14 days of stopping one.

• Severe liver problems or end-stage kidney failure.

It should not be used during pregnancy, by women trying to become pregnant, or while breastfeeding.

Is Mysimba Available on the NHS?

NICE does not recommend it for managing overweight and obesity on the NHS.

NICE technology appraisal TA494, published in December 2017, does not recommend naltrexone/bupropion for managing overweight and obesity in adults on the NHS. People who started it on the NHS before the guidance can continue until they and their clinician decide to stop. Privately, it needs a prescription after a prescriber has checked that it is suitable.

Scientific References

1. Mysimba 8 mg/90 mg prolonged-release tablets - Summary of Product Characteristics.
2. Naltrexone-bupropion for managing overweight and obesity (TA494) - Recommendations.
3. MHRA Yellow Card scheme.

Frequently Asked Questions