UMEM Educational Pearls

Title: Bupropion Toxicity

Keywords: Bupropion, Seizure, Cardivascular instability (PubMed Search)

Posted: 6/2/2016 by Kathy Prybys, MD (Updated: 6/3/2016)
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Bupropion (Wellbutrin, Zyban) is one of the most frequently prescribed antidepressants and smoking cessation agents. A lesser incidence of undesirable side effects such as weight gain and sexual dysfunction when compared to other antidepressants lends to its popularity. Bupropion's mechanism of action is only partially understood but it is known to be a norepinephine dopamine reuptake inhibitor and anticholinergic receptor blocker at certain nicotinic receptors. Bupropion has a monocyclic structure similar to amphetamines. Seizures are a major concern in overdose. When first released, Bupropion was initially withdrawn from the market due to its narrow therapeutic window with seizures occurring at doses as low as 450 mg.

Seizures are dose dependent and all types can occur. Incidence increases dramatically with higher doses. Benzodiazepines are first-line therapy.
Most patients experience seizure within 8 hours however, seizures can occur up to 24 hours after ingestion even without preceding symptoms.
Longer acting forms: SR, XL, ER cause prolonged toxicity and activated charcoal should be administered in the absence of contraindications (depressed mental status, lack of airway protection, seizure).
Myocardial sodium channel blocking properties occur and sodium bicarbonate should be administered when this occurs.
Cardiovascular effects including tachycardia, prolonged QT interval, QRS widening, arrhythmia, and cardiovasular collapse.
Bupropion is extremely lipid soluble and intravenous lipids should be considered in severe poisonings. Intralipid has been successfully used in several cases of Bupropion poisoning with cardiovascular instability or severe CNS symptom with good outcomes.

References

Life threatening Bupropion ingestion, Is there a role for intravenous fat emulsion? Livshits Z, Feng L, et al. Basic & Clinical Toxicology & Pharmacology, 2011, 109. 418-22.

Incidence and onset of delayed seizures after overdoses of extended release Bupropion. Starr P, Klein-Schwartw W, et al. Am Journal EM, 2009 Oct(27)8: 911-15.