Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Orexigen Therapeutics Ireland Limited, 2nd Floor, Palmerston House, Fenian Street, Dublin 2, Ireland
Mysimba is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, for the management of weight in adult patients (≥18 years) with an initial Body Mass Index (BMI) of
Treatment with Mysimba should be discontinued after 16 weeks if patients have not lost at least 5% of their initial body weight (see section 5.1).
Upon initiating treatment, the dose should be escalated over a 4-week period as follows:
The maximum recommended daily dose of Mysimba is two tablets taken twice daily for a total dose of 32 mg naltrexone hydrochloride and 360 mg bupropion hydrochloride. The need for continued treatment should be evaluated after 16 weeks (see section 4.1) and reevaluated annually.
If a dose is missed, patients should not take an additional dose, but take the prescribed next dose at the usual time.
Naltrexone/bupropion should be used with caution in patients over 65 years of age and is not recommended in patients over 75 years of age (see sections 4.4, 4.8 and 5.2).
Naltrexone/bupropion is contraindicated in patients with end-stage renal failure (see section 4.3). In patients with moderate or severe renal impairment, the maximum recommended daily dose for naltrexone/bupropion is two tablets (one tablet in the morning and one tablet in the evening) (see sections 4.4, 4.8 and 5.2). It is recommended that patients with moderate or severe renal impairment initiate treatment with one tablet in the morning for the first week of treatment, and escalate to one tablet in the morning and one tablet in the evening from week 2 onwards. Dose reduction is not necessary in patients with mild renal impairment. For individuals who are at elevated risk for renal impairment, in particular patients with diabetes or elderly individuals, estimated glomerular filtration rate (eGFR) should be assessed prior to initiating therapy with naltrexone/bupropion.
Naltrexone/bupropion is contraindicated in patients with severe hepatic impairment (see section 4.3). Naltrexone/bupropion is not recommended in patients with moderate hepatic impairment (see sections 4.4 and 5.2). In patients with mild hepatic impairment, the maximum recommended daily dose for naltrexone/bupropion is two tablets (one tablet in the morning and one tablet in the evening) (see sections 4.4 and 5.2). It is recommended that patients with mild hepatic impairment initiate treatment with one tablet in the morning for the first week of treatment, and escalate to one tablet in the morning and one tablet in the evening from week 2 onwards. Degree of hepatic impairment should be assessed using the Child-Pugh score.
The safety and efficacy of naltrexone/bupropion in children and adolescents below 18 have not yet been established. Therefore, naltrexone/bupropion should not be used in children and adolescents below 18.
Oral use. The tablets should be swallowed whole with some water. The tablets should preferably be taken with food (see section 5.2). The tablets should not be cut, chewed, or crushed.
There is no clinical experience with overdose with combined use of bupropion and naltrexone. The maximum daily dose of combined use of bupropion and naltrexone administered in clinical trials contained 50 mg naltrexone hydrochloride and 400 mg bupropion hydrochloride. The most serious clinical implications of combined use of bupropion and naltrexone overdose are likely related to bupropion.
Acute ingestion of doses in excess of 10 times the maximum therapeutic dose of bupropion (equivalent to approximately in excess of 8 times the recommended daily dose of naltrexone/bupropion) has been reported. Seizure was reported in approximately one third of these overdose cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances (including QRS prolongation) or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.
Although most subjects recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in subjects ingesting large doses of the drug.
There is limited experience with overdose of naltrexone monotherapy in humans. In one study, subjects received 800 mg naltrexone hydrochloride daily (equivalent to 25 times the recommended daily dose of naltrexone/bupropion) for up to one week showing no evidence of toxicity.
An adequate airway, oxygenation, and ventilation should be ensured. Cardiac rhythm and vital signs should be monitored. EEG monitoring is also recommended for the first 48 hours post-ingestion. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended.
Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the management of combined use of bupropion and naltrexone overdoses. No specific antidotes for combined use of bupropion and naltrexone are known.
Due to the dose-related risk of seizures with bupropion, hospitalisation following suspected overdose with naltrexone/bupropion should be considered. Based on studies in animals, it is recommended that seizures be treated with intravenous benzodiazepine administration and other supportive measures, as appropriate.
30 months.
Do not store above 30°C.
PVC/PCTFE/PVC/Aluminium blisters.
Pack sizes: 28, 112 tablets.
Not all pack sizes may be marketed.
No special requirements.
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