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Tabulated list of adverse reactions: The safety profile of naltrexone/bupropion (NB) summarised in Table 4 as follows is based on clinical studies performed with the fixed-dose combination (adverse reactions at an incidence of at least 0.1% and twice that of placebo) and/or post-marketing data sources. The list of terms in Table 5 provides information on the adverse reactions of the individual components naltrexone (N) and bupropion (B) identified in their respective approved SmPCs for different indications.
The frequencies of adverse reactions are ranked according to the following: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). (See Tables 4 and 5.)
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Click on icon to see table/diagram/imageDescription of selected adverse reactions: Seizures: The incidence of seizure in naltrexone/bupropion over the course of the clinical program was 0.06% (2/3,239 subjects). Among the group of subjects treated with naltrexone/bupropion, both cases of seizures were considered as serious and led to treatment discontinuation (see Precautions). There were no cases of seizures in the placebo group.
Gastrointestinal adverse reactions: The vast majority of subjects treated with naltrexone/bupropion who experienced nausea reported the event within 4 weeks of starting treatment. Events were generally self-limited; the majority of events resolved within4 weeks and almost all resolved by week 24. Similarly, the majority of events of constipation in subjects treated with naltrexone/bupropion were reported during the dose escalation phase. The time to resolution of constipation was similar between subjects treated with naltrexone/bupropion and subjects treated with placebo. Approximately half of the subjects treated with naltrexone/bupropion who experienced vomiting first reported the event during the dose escalation phase. Time to resolution for vomiting was typically rapid (within one week) and almost all events resolved within 4 weeks. The incidence of these common gastrointestinal adverse reactions in naltrexone/bupropion versus placebo was as follows: nausea (31.8% vs. 6.7%), constipation (18.1% vs. 7.2%), and vomiting (9.9% vs. 2.9%). The incidence of severe nausea, severe constipation, and severe vomiting was low, but was higher in subjects treated with naltrexone/bupropion compared to subjects treated with placebo (severe nausea: naltrexone/bupropion (1.9%), placebo (<0.1%); severe constipation: naltrexone/bupropion (0.6%), placebo (0.1%); severe vomiting: naltrexone/bupropion (0.7%), placebo (0.3%)). No events of nausea, constipation, or vomiting were considered serious.
Other frequent adverse reactions: The majority of subjects treated with naltrexone/bupropion who reported dizziness, headache, insomnia, or dry mouth, first reported these events during the dose escalation phase. Dry mouth may be associated with toothache and dental caries; in the subset of patients with dry mouth, a higher incidence of toothache and dental caries were observed in subjects treated with naltrexone/bupropion compared to subjects treated with placebo. The incidence of severe headache, severe dizziness, and severe insomnia was low, but was higher in subjects treated with naltrexone/bupropion compared to subjects treated with placebo (severe headache: naltrexone/bupropion (1.1%), placebo (0.3%); severe dizziness: naltrexone/bupropion (0.6%), placebo (0.2%); severe insomnia: naltrexone/bupropion (0.4%), placebo (<0.1%)). No events of dizziness, dry mouth, headache, or insomnia in subjects treated with naltrexone/bupropion were considered serious.
Elderly patients: Elderly patients may be more sensitive to some of the central nervous system-related adverse reactions of naltrexone/bupropion (primarily dizziness and tremor). There is an increased incidence of gastrointestinal disorders with higher age categories. Common events leading to withdrawal among elderly were nausea, vomiting, dizziness, constipation.
Type 2 diabetes: Patients with type 2 diabetes treated with naltrexone/bupropion demonstrated a higher incidence of gastrointestinal adverse reactions, primarily nausea, vomiting, and diarrhoea, than subjects without diabetes. Patients with type 2 diabetes may be more prone to these events due to concomitant medicinal product use (e.g., metformin) or may be more likely to have underlying gastrointestinal disorders (e.g., gastroparesis) predisposing to gastrointestinal symptoms.
Renal impairment: Patients with moderate renal impairment had a higher incidence of gastrointestinal and central nervous system-related adverse reactions, thus these patients generally had lower tolerability of naltrexone/bupropion at a total daily dose of 32 mg naltrexone hydrochloride/360 mg bupropion hydrochloride, which is thought to be due to higher plasma concentrations of active metabolites. The types of tolerability events were similar to the events observed in patients with normal renal function (see Dosage & Administration, Precautions, and Pharmacology: Pharmacokinetics under Actions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
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