INDEX

    Bupropion Overdose

    Toxicology

    Last Updated Mar 03, 2020
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    Context

    • Bupropion is a commonly prescribed psychotropic medication for the treatment of depression, attention deficit hyperactivity disorders, smoking cessation and weight loss.
    • Bupropion is only available in Canada as sustained release (SR) and extended release (XL) formulations.
    • Immediately release (IR) formulations are available in the US.

    Typical Signs and Symptoms

    • Signs and symptoms can vary by route of exposure.
    • Bupropion commonly causes sinus tachycardia, hypertension, agitation and GI symptoms.
    • Large overdoses (>5g) can result in seizures (single, multiple, status epilepticus), QRS prolongation, ventricular dysrhythmias and cardiac arrest. Cardiac arrest is often fatal.
    • Inhalation/Insufflation of crushed tablets can result in seizures and sinus tachycardia.
    • Injection: Injection can result in systemic signs. Severe skin lesions and vascular complications have been reported.
    • Ingestion:
      •  Common
        • Typically present with features of sympathomimetic toxidrome including agitation, seizures, tachycardia (usually sinus), hypertension, mydriasis.
        • Seizures are usually generalized, may be single or multiple (and may be delayed), but are usually abrupt in onset and short in duration.
      • Less common
        • QRS and QT interval widening, cardiovascular collapse, status epilepticus (refractory to standard treatment), cardiac arrest.
      • Uncommon
        • Severe bupropion overdoses can mimic the findings of brain death.
        • Some patients may present with drowsiness or obtundation, in the absence of sympathomimetic features.
    • ECG Changes
      • Sinus tachycardia
      • QTc prolongation
      • QRS interval prolongation (may be delayed)
      • Right axis deviation
    • Ventricular dysrhythmias after large overdoses can include ventricular tachycardia, ventricular fibrillation, and asystole.

    Typical Course

    • Bupropion XL is the only form available in Canada. Peak levels are reached at 5 hours (therapeutic use) though may be substantially longer in overdose.
    • Bupropion is suspected to form pharmacobezoars and clump within the upper GI system, further prolonging absorption.
    • Metabolites of bupropion are active and may be more toxic than the parent drug.
    • Symptom onset is usually within 4-6 hours, though severe toxicity may be delayed up to 18-24 hours (or longer).
    • Severe cardiovascular toxicity may develop late, though usually within 24 hours.
    • Symptoms usually resolve within 18 hours in mild cases, and up to 48 hours in severe cases.

    Mechanism of Toxicity

    • Bupropion is a derivative of cathinone, and structurally similar to amphetamines and bath salts.
    • Bupropion and its active metabolite inhibit reuptake of dopamine and norepinephrine (minimally inhibits serotonin reuptake).
    • There is no significant anticholinergic or monoamine oxidase inhibitor activity.
    • The precise mechanism for seizures and cardiotoxicity is unclear. QRS widening may be due to cardiac myocyte gap junction inhibition rather than sodium channel blockade (as with other antidepressants).

    Toxic Dose

    • Not established.
    • Doubling of therapeutic dosage (as low as 600 mg) may result in seizures. The risk of seizure with therapeutic dosing (up to 450 mg/day) is 0.4%.
    • Seizures are most common with doses > 2.5 g.
    • Serious toxicity can be expected with doses > 6 g, and fatalities usually involve doses > 9 g.

    Diagnosis

    • Serum levels are not readily available and do not correlate with toxicity or outcome.

    Clinical Pitfalls

    • False positive urine immunoassay for amphetamines has been reported with bupropion.

    Recommended Treatment

    It is strongly recommended that the BC Drug and Poison Information Centre (DPIC) be contacted at 1-800-567-8911

    General

    • Asymptomatic patients should have continuous cardiac monitoring and monitoring of vital signs for 18 hours. An ECG should be done on presentation and prior to discharge.
    • Children ingesting more than 10 mg/kg or adults ingesting 600 mg or more should be observed and monitored in a health care facility.
    • Symptomatic patients should be monitored for at least 12 hours after resolution of symptoms.
    • Early and/or prophylactic intubation can be considered for control of agitation or seizures.

    Decontamination

    • For large overdoses (> 2.5 g) Aggressive GI decontamination should be considered. If the patient needs to be intubated for management of agitation or seizures, Whole Bowel Irrigation should be started once airway is protected.
    • Activated charcoal may be useful several (4-6) hours after ingestion as bupropion is known to clump and/or form bezoars in the upper GI system.
    • It is strongly recommended that decontamination options be discussed with DPIC.

    Agitation, Seizures, Neurological toxicity

    • Agitation and seizures should be treated aggressively with IV benzodiazepines.
    • Early intubation and sedation with propofol or midazolam infusions should be considered for patients with multiple seizures or severe agitation.
    • Phenytoin should be avoided as it is ineffective and may worsen cardiac toxicity.

    Management of cardiovascular toxicity

    • Sinus tachycardia and hypertension rarely requires treatment.
    • QTc prolongation should be closely monitored and electrolytes corrected as needed.
    • Hypotension unresponsive to IV fluids should be treated with vasopressors.
    • Wide complex tachycardia (QRS > 0.1 sec) should be treated initially with IV sodium bicarbonate boluses, though this may be ineffective.
    • For severe cardiovascular toxicity, hypotension, or cardiogenic shock, standard supportive measures (ACLS protocols, sodium bicarbonate boluses) should be used but are unlikely to be effective. Lipid emulsion therapy or ECMO should be considered (see below).

    Intravenous Lipid Emulsion

    • IV lipid emulsion therapy can be considered for cardiogenic shock or cardiac arrest refractory to standard ACLS protocols in centers where ECMO is not available.
    • Note: Lipid emulsion therapy can result in acute pancreatitis, interfere with a number of lab investigations, and impede performance of ECMO or hemodialysis.

    Extracorporeal Membrane Oxygenation (ECMO)

    • Referral to a centre with ECMO capabilities should be considered with large overdoses (> 6-9 g).

    Hemodialysis

    • Hemodialysis is not effective, though may be necessary in critically ill patients.

    Quality Of Evidence?

    Justification

    Low quality of evidence. Confined to case reports/case series.

    Low

    Related Information

    Reference List

    1. Buehler M, et al. Adverse effects associated with adult unintentional ingestion of bupropion reported to four US Poison Centers. Clin Tox 2018: 56 (10): 925-6


    2. Bruccoleri RE, Burns MM. A literature review of the use of sodium bicarbonate for the treatment of QRS widening. J Med Tox 2016;12:121-129.


    3. Caillier, B., Pilote, S., Castonguay, A., Patoine, D., Ménard‐Desrosiers, V., Vigneault, P., . . . Drolet, B. (2012). QRS widening and QT prolongation under bupropion: A unique cardiac electrophysiological profile. Fundamental & Clinical Pharmacology, 26(5), 599-608. doi:10.1111/j.1472-8206.2011.00953.x


    4. Chhabra, N., DesLauriers, C., Wahl, M., & Bryant, S. M. (2018). Management of severe bupropion poisoning with intravenous lipid emulsion. Clinical Toxicology, 56(1), 51-54. doi:10.1080/15563650.2017.1337909


    5. Ovakim D, Briggs M, Phillips K, Fedoruk L. Two cases bupropion-related cardiogenic shock treated with early institution of extracorporeal membrane oxygenation. (poster). Presented at ACMT 2019 Annual Scientific Meeting, San Francisco. J Med Tox 2019:15: 60 (abstract 024).


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