BUPROPION
Synonyms
Wellbutrin®, Zyban®, Contrave® (combination with naltrexone), amfebutamone
Description
Used in treatment of depression and attention deficit hyperactivity disorders, and as an aid to smoking cessation.
Available in Canada as sustained release (SR) and extended release (XL) tablets. Immediate release (IR) formulations
are also available in the US.
Toxicity
Bupropion commonly causes sinus tachycardia,
hypertension, agitation and GI symptoms. Large
overdoses can result in seizures (single or multiple),
QRS prolongation, ventricular dysrhythmias and
cardiac arrest. Cardiac arrest is often fatal.
Aggressive GI decontamination and early transfer to
an ECMO centre should be considered in large
overdoses.
Mechanism of Toxicity
A cathinone derivative, structurally similar to
amphetamines and bath salts. Bupropion and its
active metabolite inhibit reuptake of dopamine and
norepinephrine (minimally inhibits serotonin
reuptake). No significant anticholinergic or
monoamine oxidase inhibitor activity. Mechanism for
seizures and cardiotoxicity is unclear. QRS widening
may be due to cardiac myocyte gap junction inhibition
rather than sodium channel blockade.
See Case Reports.
Toxic Dose
Variable.
Adult: In a review of bupropion overdoses in 385
patients, 12-57 years, seizures were reported in 11%
of patients. Doses associated with seizures ranged
from 600 mg up to 18 g; seizures were most common
with > 2.5 g bupropion alone or when bupropion,
irrespective of dose, was taken with other stimulants.
Deaths attributed to bupropion alone have typically
involved large ingestions resulting in multiple
uncontrolled seizures rapidly progressing to
ventricular dysrhythmias, cardiogenic shock, and
cardiac arrest. However, as little as 1.5 g SR in an
adult has resulted in recurrent, prolonged seizures
and cardiac arrest. Patient recovered following
resuscitation and ICU supportive care.
With therapeutic doses up to 450 mg per day,
incidence of seizures is approximately 0.4%. In a
review of unintentional bupropion medication errors in
491 adults, the risk of having a seizure with doses
ranging from 600 -1200 mg was 0.6% (median time
was 9.6 hrs post ingestion; range 2 hrs -21.5 hrs post
ingestion).
Pediatric: Ingestion of > 10 mg/kg in young children
can result in toxicity.
US poison control centres reported 6,000 pediatric
bupropion exposures over a 7-year period. With
doses up to 10 mg/kg, a few children developed
tachycardia, irritability, drowsiness, ataxia,
hallucinations, lethargy and tremor. Seizures occurred
Poison Management Manual (PMM)
BC Drug and Poison Information Centre, Vancouver, BC
604-682-5050 or 1-800-567-8911 www.dpic.org
July 2019
in a single patient in this dose range. Occurrence of
seizures or coma increased with higher doses and
when the ingested dose was unknown. Authors
recommended referral to a healthcare facility if the
ingested dose was greater than 10 mg/kg (a single
tablet in a small child) or if the dose was unknown.
Case Reports
A 23-year-old ingested 15 g bupropion XL and by 4
hours post ingestion had HR 135, BP 140/72 with
confusion, diaphoresis, abnormal movements,
hypertonicity, clonus, and had a 30-second
generalized tonic-clonic seizure. He was intubated on
arrival to ER. ECG showed sinus tachycardia, QRS
114 ms, terminal R wave in aVR. QRS continued to
widen despite repeated boluses of sodium
bicarbonate and BP worsened. ECMO was started at
9.5 hours post ingestion and continued for 42 hours.
By day 5, patient was walking independently and
recovered without sequelae.
A 41-year-old ingested 18 g bupropion XL and
presented to hospital within 2 hours post ingestion.
Ten hours post ingestion patient had 2 seizures; by
11 hours post ingestion patient developed apnea and
asystole after a 3rd seizure. Following resuscitation,
ECG showed QRS 0.156 sec which initially
responded to sodium bicarbonate boluses. Recurrent
QRS widening over the next 10 hours was followed
by another cardiac arrest. Patient was resuscitated
but remained unresponsive requiring pressor support.
By 36 hours post ingestion patient had suffered 2
more cardiac arrests; resuscitation was discontinued.
A 31-year-old ingested 13.5 g bupropion SR with
ethanol and by 6 hours post ingestion exhibited
agitation, tachycardia, hypertension, tremor, dystonia,
hyperreflexia and clonus. Coma, recurrent seizures
and wide complex tachycardia developed requiring
sedation, intubation and ventilation. Patient recovered
with intensive care.
A 14-year-old ingested 1.5-3 g bupropion and by 5-6
hours post ingestion developed vomiting, drowsiness,
slurred speech, hallucinations and sinus tachycardia.
Patient had two single seizures within the first 24
hours. At 18 hours post ingestion, patient experienced
a brief self-limiting episode of extreme agitation and
combativeness. Patient recovered without sequelae.
A 17-year-old ingested 2 tablets of 300 mg and had a
single seizure at 11.5 hrs post ingestion. Patient
recovered without sequelae.
 BUPROPION - 2
Pharmacokinetics
Well absorbed. Peak plasma levels (therapeutic
dosing) reached within 3 hours following ingestion of
SR form; 5 hours after XL form; and 1.5 hours after IR
form. Peak may be delayed following overdose.
Pharmacobezoars and empty tablet shells have been
seen in emesis as late as 7-8 hours post ingestion.
Extensively metabolized to active metabolites.
Elimination half-life of bupropion with therapeutic
dosing is 21 hours (range 8-36 hours); half-life of
active metabolites ranges from 20-37 hours.
Clinical Effects
 Inhalation: Insufflation of crushed tablets can
result in seizures; most occur within first 8 hours.
Sinus tachycardia is present in most patients who
seize.
 Injection: Injection can result in systemic signs.
Severe skin lesions and vascular complications
have been reported. Inadvertent intra-arterial
injection of bupropion and cocaine into the
vertebral artery resulted in a fatal brainstem
infarct.
 Ingestion:
General: Vomiting, seizures, agitation, tremor,
hallucinations, sinus tachycardia and QTc
prolongation are common and may be delayed.
Seizures are often delayed; usually within 18
hours of exposure. Single seizures are most
common; seizures are typically brief with no long-
term sequelae. Multiple seizures may occur;
status epilepticus is uncommon except in large
overdoses. Neurologic effects such as agitation,
tremors, hallucinations often are observed prior
to seizure activity.
With large overdoses multiple seizures can
progress rapidly to cardiovascular toxicity and
death.
HEENT: Mydriasis (common); pupils may be
fixed and dilated in large overdoses.
CVS: Sinus tachycardia (common), prolonged
QTc interval (common, may be delayed).
Hypertension and hypotension (less common)
can also occur. Widened QRS complex,
ventricular dysrhythmias, cardiogenic shock,
asystole and death may occur following large
overdoses. Cardiac arrest from bupropion is
often fatal. QRS widening may be due to
inhibition of cardiac myocyte gap junction
inhibition rather than sodium channel blockade.
Neurologic: Lethargy (common), agitation
(common), tremors (common), generalized
seizures (common, may be delayed), status
epilepticus (large overdoses). With large
overdoses multiple seizures can progress rapidly
to cardiovascular toxicity and death. Pupils may
be fixed and dilated in large overdoses.
In one study, 40/41 patients developed
neurologic symptoms such as agitation, tremors,
and hallucinations prior to having a seizure.
Poison Management Manual (PMM)
BC Drug and Poison Information Centre, Vancouver, BC
604-682-5050 or 1-800-567-8911 www.dpic.org
July 2019
Confusion, dizziness, hallucinations (auditory,
visual) paresthesias, slurred speech,
extrapyramidal symptoms and psychosis may
also be seen.
GI: Vomiting (common), nausea, empty tablet
shells can appear in emesis or stool.
Fluid/Lytes/Acid-Base: Hypokalemia,
hypophosphatemia, metabolic acidosis.
Musculoskeletal: Choreoathetosis, increased
muscle tone, clonus, dystonia.
Lab: False positive urine toxicology screen for
amphetamines.
Treatment
1. 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.
2. Symptomatic patients should be monitored for at
least 12 hours after resolution of symptoms.
3. Activated charcoal may be useful several hours
after ingestion. For large overdoses, aggressive
GI decontamination should be considered. If
patient needs to be intubated for management
of agitation or seizures, WBI should be started
once airway is protected.
4. Protect airway and assist ventilation as needed.
Consider early intubation for control of agitation
or seizures.
5. Maintain fluid and electrolyte balance.
6. Monitor vital signs; obtain an initial ECG and
electrolytes. Monitor blood gases in
symptomatic patients. Repeat ECG; QRS and
QT prolongation may be delayed.
7. Sinus tachycardia rarely requires treatment. QTc
prolongation should be closely monitored and
electrolytes corrected as needed.
8. Hypotension unresponsive to IV fluids may
require vasopressors. Hypertension does not
usually require treatment.
9. Agitation and seizures should be treated
aggressively with IV benzodiazepines. Consider
early intubation and sedation with propofol or
midazolam infusion for patients with more than a
single seizure. Avoid phenytoin as it is not
effective and may worsen cardiac toxicity.
 BUPROPION - 3

10. Wide complex tachycardia (QRS > 0.1 sec)
should be treated initially with IV sodium
bicarbonate boluses. QRS widening may not
respond to sodium bicarbonate boluses as the
mechanism is thought to be due to myocyte gap
junction inhibition rather than sodium channel
blockade.
11. 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).
13. IV lipid emulsion therapy can be considered for
cardiogenic shock or cardiac arrest refractory to
standard ACLS protocols in centres 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.
See Lipid Emulsion Antidote monograph.
14. Hemodialysis is not useful in enhancing
elimination of bupropion but may be required in
critically ill patients.

12. Early referral to a centre with ECMO capabilities

should be considered with large overdoses.

Key Points
 Asymptomatic patients should have continuous cardiac monitoring and monitoring of vital signs for a
minimum of 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 intubation, aggressive GI decontamination and early transfer to an ECMO centre should be considered
in large overdoses.

 Delayed and recurrent dose-related seizures are common (first seizure may be delayed for up to 18 hours).
Seizures following insufflation usually occur within the first 8 hours.

 Treatment is symptomatic and supportive with aggressive management of agitation and seizures using IV
benzodiazepines, barbiturates, propofol. Consider early intubation and sedation with propofol or midazolam
infusion for patients with more than a single seizure.

 Sinus tachycardia and QTc interval prolongation are common, may be delayed and rarely require treatment.

 QRS prolongation, life-threatening dysrhythmias, cardiogenic shock, asystole and death can occur following
large overdoses.

 QRS prolongation should be managed initially with IV sodium bicarbonate boluses. However, it may not
respond to bicarbonate as the mechanism may not be due to sodium channel blockade.

 Standard supportive measures (ACLS protocols, sodium bicarbonate boluses) should be used but are
unlikely to be effective.

 ECMO may be helpful for patients not responding to standard ACLS protocols.

 If ECMO is unavailable, IV lipid emulsion therapy should be considered. Note: Lipid emulsion therapy can
result in acute pancreatitis, interfere with some lab investigations, and impede performance of ECMO or
hemodialysis.

Poison Management Manual (PMM)

BC Drug and Poison Information Centre, Vancouver, BC
604-682-5050 or 1-800-567-8911 www.dpic.org
July 2019