Human overdose experience: 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.
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.
Naltrexone: 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.
Overdose management: 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.