Navigation

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

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