bupropion (Wellbutrin, Zyban, Budeprion SR, Aplenzin, Buproban, Wellbutrin SR, Wellbutrin XL, Forfivo XL)
Classes: Antidepressants, Other; Smoking Cessation Aids; Antidepressants, Dopamine Reuptake Inhibitors
Dosing and uses of Wellbutrin, Zyban (bupropion)
Adult dosage forms and strengths
tablet (Wellbutrin)
- 75mg
- 100mg
tablet, sustained-release (Wellbutrin SR)
- 100mg
- 150mg
- 200mg
tablet, extended-release (Wellbutrin XL)
- 150mg
- 300mg
tablet, extended-release (Aplenzin)
- 174mg
- 348mg
- 522mg
tablet, extended-release (Forfivo XL)
- 450mg
tablet, extended-release (Zyban)
- 150mg
Major Depressive Disorder
Immediate-release
- Initial: 100 mg PO q12hr; may increase to 100 mg PO q8hr as early as day 4; may consider increasing dose up to maximum 150 mg q8hr after several weeks if no clinical improvement observed with 100 mg q8hr
- Alternatively, may initiate with 75 mg PO q8hr
Sustained-release
- Initial: 150 mg PO qDay; may increase to 150 mg q12hr after 3 days
- May increase to no more than 200 mg q12hr after more than 4 weeks if no clinical improvement observed with 150 mg q12hr
Extended-release
- Initial: 150 mg PO qDay; may increase to 300 mg qDay on day 4
- May increase not to exceed 450 mg qDay after more than 4 weeks if no clinical improvement observed with 300 mg qDay; Forfivo may be used only after titrating initially with other bupropion products
Aplenzin
- Initial: 174 mg PO qDay; after 4 days, may increase to usual adult target dose of 348 mg PO qDay
- May increase not to exceed 522 mg qDay after more than 4 weeks
Forfivo XL
- 450 mg PO qDay without regard to food
- Can be used in patients who have been receiving 300 mg/day of another bupropion formulation for at least 2 weeks and who require a dosage of 450 mg/day
- Patients who are currently being treated with other bupropion products at 450 mg/day can be switched to equivalent dose of Forfivo XL once daily
Dosing considerations (Depression)
- Extended-release: When switching to XL, give the same total daily dose at the indicated frequencies: 3 times daily for immediate-release, twice daily for sustained-release, and once daily for extended-release
- Forfivo XL: Do not initiate treatment with Forfivo XL; use another bupropion formulation for initial dose titration
- Switching from hydrochloride salt formulation to hydrobromide salt (Aplenzin): 150 mg/day hydrochloride salt = 174 mg/day hydrobromide salt; 300 mg/day hydrochloride salt = 348 mg/day hydrobromide salt; 450 mg/day hydrochloride salt = 522 mg/day hydrobromide salt
Seasonal Affective Disorder
Wellbutrin XL: 150 mg PO qDay; may increase to 300 mg qDay
Aplenzin (bupropion hydrobromide): 174 mg PO qDay initially (equivalent to 150 mg bupropion HCl); after 1 week, may increase to usual target dose of 348 mg/day (equivalent to 300 mg bupropion HCL)
Dosing considerations (SAD)
- Initiate treatment in the autumn prior to onset of seasonal depressive symptoms and continue through the winter season
Smoking Cessation
Zyban: 150 mg PO qDay for 3 days, THEn
Increase to 150 mg q12hr; should continue treatment for 7-12 weeks; if patient successfully quits after 7-12 weeks, consider ongoing maintenance therapy based on individual patient risk/benefit
Dosing considerations (Smoking Cessation)
- Begin therapy 1 week before target quit date (usually second week of treatment)
- May be used in combination with nicotine patch
ADHD (Off-label)
Initial: 150 mg/day PO
Titrate to 150-450 mg/day based on tolerability and efficacy; may administer in divided doses or in ER or SR formulations
Neuropathic Pain (Off-label)
150 mg bupropion SR PO twice daily for 6 weeks
Dosing Modifications
Hepatic impairment
- Mild to moderate: Use caution; consider reducing dose or frequency; Fortivo XL not recommended
- Moderate to severe (Buproban, Wellbutrin XL, Zyban): Not to exceed 150 mg every other day
- Moderate to severe (Aplenzin): Not to exceed 174 mg every other day
- Moderate to severe (Wellbutrin): 75 mg once daily
- Moderate to severe (Wellbutrin SR): 100 mg once daily or 150 mg every other day
- Moderate to severe (Zyban): 150 mg every other day
- Elderly: Lower dose/frequency may be required because of decreased renal/hepatic clearance
Renal impairment
- Use caution; consider dose reduction
Pediatric dosage forms and strengths
tablet (Wellbutrin)
- 75mg
- 100mg
tablet, sustained-release (Wellbutrin SR)
- 100mg
- 150mg
- 200mg
tablet, extended-release (Wellbutrin XL)
- 150mg
- 300mg
tablet, extended-release (Aplenzin)
- 174mg
- 348mg
- 522mg
tablet, extended-release (Forfivo XL)
- 450mg
ADHD (Off-label)
Immediate-release
- Initial: 3 mg/kg/day or 150 mg/day PO
- Titrate to 6 mg/kg/day or 300 mg/day, maximum
- Single dose should not exceed 150 mg; may administer as divided doses for safety and effectiveness (eg, BID for children and TID for adolescents)
Extended-release
- Initial: Up to 3 mg/kg/day or 150 mg/day PO
- Titrate to 6 mg/kg/day or 300 mg/day, maximum
Sustained-release
- Initial: Up to 3 mg/kg/day or 150 mg/day PO
- Titrate to 6 mg/kg/day or 300 mg/day, maximum
Wellbutrin, Zyban (bupropion) adverse (side) effects
>10%
Headache (25-34%)
Dry mouth (17-28%)
Nausea (1-18%)
Weight loss (15-20%)
Insomnia (11-20%)
Agitation (2-32%)
Dizziness (6-22%)
Pharyngitis (3-13%)
1-10%
Constipation (5-10%)
Infection (8-9%)
Abdominal pain (2-9%)
Anxiety (5-7%)
Diarrhea (5-7%)
Tinnitus (3-6%)
Tremor (3-6%)
Nervousness (3-5%)
Anorexia (3-5%)
Palpitation (2-6%)
Myalgia (2-6%)
Sweating (2-5%)
Rash (1-5%)
Sinusitis (1-5%)
Weight gain (4%)
Chest pain (3-4%)
Urinary frequency (2%)
Vaginal hemorrhage (2%)
Pruritus (2-4%)
Vomiting (2-4%)
Arthralgia (1-4%)
Flushing (1-4%)
Migraine (1-4%)
Decreased memory (<3%)
Irritability (2-3%)
Somnolence (2-3%)
Dysphagia (<2%)
Arthritis (2%)
Paresthesia (1-2%)
Fever (1-2%)
Twitch (1-2%)
Seizures (0.4% [<450 mg/day], >3% [>450 mg/day]; may be increased risk with concomitant ECT)
Frequency not defined
Confusion
Cystitis
Erythema
Ataxia
Coma
EEG abnormality
Euphoria
Gastric reflux
Postmarketing reports
Nervous system: Abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, completed suicide, delirium, delusions, dysarthria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia
Warnings
Black box warnings
Not FDA approved for bipolar depression
Suicidality
- In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients >24 years
- Slight decrease in suicidal thinking was seen in adults >65 years
- In children and young adults, risks must be weighed against the benefits of taking antidepressants
- Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
- The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
- Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy; this drug is not approved for use in pediatric patients
Use for smoking cessation
- Serious neuropsychiatric events, including, but not limited to, depression, suicidal ideation, suicide attempt, and completed suicide, have been reported in patients taking bupropion for smoking cessation
Contraindications
Hypersensitivity to bupropion or other ingredients
History of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives including anticonvulsants, barbiturates, or benzodiazepines
Coadministration of any other medications that contain bupropion, because seizures are dose dependent
Aplenzin contraindications
- Seizure disorder or conditions that increase seizure risk (arteriovenous malformation, severe head injury, CNS tumor, CNS infection, severe stroke, anorexia nervosa or bulimia (current or prior diagnosis)
Coadministration with MAOIs
- Coadministration may cause serotonin syndrome
- Do not use concomitantly or initiate bupropion within 14 days of stopping an MAOI
- Conversely, at least 14 days should be allowed after stopping bupropion before starting an MAOI antidepressant
- Starting bupropion in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue bupropion immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first
Cautions
Caution in severe hepatic cirrhosis (do not exceed 150 mg every other day), mild-moderate hepatic impairment, head trauma and prior seizure history, CNS tumor, concomitant meds lowering seizure threshold
Observe patients for neuropsychiatric symptoms, such as changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide (see Black box warnings); therapy may cause delusions, hallucinations, psychosis, paranoia, confusion, and concentration disturbance; symptoms may abate with dose reduction
Potential risk of hepatotoxicity
Assess blood pressure before initiating treatment with sustained release formulation, and monitor periodically during treatment; risk of hypertension is increased if sustained release formulation is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity; use caution in patients with cardiovascular disease
May cause weight loss; use caution if weight loss not desirable
May cause CNS depression and impair ability to operate heavy machinery
Extended-release: Do not administer less than 8 hr apart
Seizure risk is dose-related; can minimize risk by limiting daily dose to 522 mg and gradually increasing dose; discontinue permanently in patients who experience seizures
May cause sexual dysfunction
Screen patients for bipolar disorder and monitor for these symptoms; may precipitate manic, hypomanic or mixed episodes in patients with bipolar disorder
Instruct patients to contact a healthcare professional if neuropsychiatric reactions occur
Perform thorough cardiovascular assessment to identify risk factors of sudden cardiac death in pediatric ADHD patients
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy; use caution
False-positive urine immunoassay screening tests for amphetamines have been reported; confirmatory test (eg, gas chromatography, mass spectrometry) will distinguish bupropion from amphetamines
Bupropion hydrobromide extended-release tablets are intended for oral use only; inhalation of crushed tablets or injection of dissolved bupropion reported; seizures and/or cases of death reported when administered intranasally or by parenteral injection
Abuse warning
- XL and SR tablets are intended for oral use only
- Inhaling crushed tablets or injecting dissolved tablets has been reported to cause seizures and/or death
Pregnancy and lactation
Pregnancy category: C
Lactation: Enters breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Wellbutrin, Zyban (bupropion)
Mechanism of action
Not well understood; structurally unrelated to SSRIs, TCAs, MAOIs; does not inhibit the activity of monoamine oxidase or the reuptake of serotonin
Norepinephrine dopamine reuptake inhibitor; may act through dopaminergic or noradrenergic pathways
Absorption
Peak serum time: 2 hr (immediate-release); 3 hr (extended-release)
Distribution
Protein bound: 84%
Vd: 20-47 L/kg
Metabolism
Hepatic, via CYP2B6
Metabolites: Hydroxybupropion (50% potency of parent compound)
Elimination
Half-life: 8-24 hr (immediate-release); 21 +/- 7 hr (extended-release)
Excretion: Urine (87%); feces (10%)
Administration
Oral Administration
Swallow extended/sustained-release tablets whole; do not chew, crush, or split; this may lead to adverse effects including seizures