OVERDOSE

Human Overdosage Experience

Sustained Release Formulation: There has been very limited experience with overdosage of bupropion HCl sustained release tablets; three cases were reported during clinical trials in depressed patients. One patient ingested 3000 mg of bupropion sustained release tablets and vomited quickly after the overdose; the patient experienced blurred vision and lightheadedness. A second patient ingested a “handful” of bupropion HCl sustained release tablets and experienced confusion, lethargy, nausea, jitteriness, and seizure. A third patient ingested 3600 mg of bupropion sustained release tablets and a bottle of wine; the patient experienced nausea, visual hallucinations, and “grogginess.” None of the patients experienced further sequelae.

Immediate Release Formulation: There has been extensive experience with overdosage of the immediate-release formulation of bupropion. Thirteen overdoses occurred during clinical trials. Twelve patients ingested 850 to 4200 mg and recovered without significant sequelae. Another patient who ingested 9000 mg of the immediate-release formulation of bupropion and 300 mg of tranylcypromine experienced a grand mal seizure and recovered without further sequelae.

Since introduction, overdoses of up to 17,500 mg of the immediate release formulation of bupropion have been reported. Seizure was reported in approximately one third of all cases. Other serious reactions reported with overdoses of the immediate release formulation of bupropion alone included hallucinations, loss of consciosness, and sinus tachycardia. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported when the immediate release formulation of bupropion was party of multiple drug overdoses.

Although most patients recovered without sequelae, deaths associated with overdoses of the immediate release formulation of bupropion alone have been reported rarely in patients ingesting massive doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

Management of OVERDOSE

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. EEG monitoring is also recommended for the next 48 hours post ingestion. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients.

Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the management of bupropion overdoses. No specific antidotes for bupropion are known.

Due to the dose-related risk of seizures with bupropion HCl, hospitalization following suspected overdose should be be considered. Based on studies in animals, it is recommended that seizures be treated with intravenous benzodiazepine administration and other supportive measures, as appropriate.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.

CONTRAINDICATIONS

Immediate Release and Sustained Release Tablets

Bupropion HCl is contraindicated in patients with a seizure disorder.

Buproprion HCl is contraindicated in patients treated with other medications that contain bupropion because the incidence of seizure is dose-dependent.

Bupropion HCl is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated for bulimia with bupropion HCl immediate-relase formulation.

The concurrent administration of bupropion HCl and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion HCl.

Bupropion HCl is contraindicated in patients who have shown an allergic response to bupropion or the other ingredients that make up bupropion HCl.