No

Antidepressant, Dopamine-Reuptake Inhibitor

Treatment of depression; adjunct in smoking cessation

B

Seizure disorder; anorexia/bulimia; use of monoamine oxidase inhibitors within 14 days; hypersensitivity to bupropion

Seizure risk is increased at total daily dosage >450 mg, individual dosages >150 mg, or by sudden, large increments in dose. The risk of seizures is increased in patients with a history of seizures, head trauma, CNS tumor, abrupt discontinuation of sedative-hypnotics or alcohol, medications which lower seizure threshold, stimulants, or hypoglycemic agents. May cause CNS stimulation (restlessness, anxiety, insomnia) or anorexia. Use with caution in patients where weight loss is not desirable. The incidence of sexual dysfunction with bupropion is generally lower than with SSRIs.

>10%:

Cardiovascular: Tachycardia

Central nervous system: Agitation, insomnia, headache, dizziness, sedation

Gastrointestinal: Nausea, vomiting, xerostomia, constipation

Neuromuscular & skeletal: Tremor

Ocular: Blurred vision

Respiratory: Rhinitis

Miscellaneous: Diaphoresis

1% to 10%:

Cardiovascular: Hypertension, palpitations

Central nervous system: Anxiety, nervousness, confusion, hostility, abnormal dreams

Dermatologic: Rash, acne, dry skin

Endocrine & metabolic: Hyper- or hypoglycemia

Gastrointestinal: Anorexia, diarrhea, dyspepsia

Neuromuscular & skeletal: Arthralgia, myalgia

Otic: Tinnitus

Symptoms of overdose include labored breathing, salivation, arched back, ataxia, convulsions, sedation, coma, and respiratory depression especially with coingestion of alcohol; bupropion may cause sinus tachycardia and seizures

Treatment is supportive following initial decontamination with activated charcoal (lavage with massive and recent doses). Treat seizures with I.V. benzodiazepines and supportive therapies; dialysis may be of limited value after drug absorption because of slow tissue to plasma diffusion.

CYP2B6 and 2D6 enzyme substrate, CYP3A3/4 enzyme substrate (minor)

Carbamazepine, cimetidine, phenobarbital, and phenytoin may increase the metabolism (decrease clinical effect) of bupropion

Cimetidine may inhibit the metabolism (increase clinical/adverse effects) of bupropion

Toxicity of bupropion is enhanced by levodopa and phenelzine (MAOI)

Use with caution in individuals receiving other agents that may lower seizure threshold (antipsychotics, antidepressants, theophylline, abrupt discontinuation of benzodiazepines, systemic steroids)

Antidepressant structurally different from all other previously marketed antidepressants; like other antidepressants the mechanism of bupropion's activity is not fully understood; weak inhibitor of the neuronal uptake of serotonin, norepinephrine, and dopamine

Onset of effect: >2 weeks to therapeutic effect

Absorption: Rapidly absorbed from GI tract

Distribution: V_d: 19-21 L/kg

Protein binding: 82% to 88%

Metabolism: Extensively in the liver to multiple metabolites

Half-life: 14 hours

Time to peak serum concentration: Oral: Within 3 hours

Oral:

Depression:

Immediate release: 100 mg 3 times/day; begin at 100 mg twice daily; may increase to a maximum dose of 450 mg/day

Sustained release: Initial: 150 mg/day in the morning; may increase to 150 mg twice daily by day 4 if tolerated; target dose: 300 mg/day given as 150 mg twice daily; maximum dose: 400 mg/day given as 200 mg twice daily

Smoking cessation: Initiate with 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should continue for 7-12 weeks

Elderly: Depression: 50-100 mg/day, increase by 50-100 mg every 3-4 days as tolerated; there is evidence that the elderly respond at 150 mg/day in divided doses, but some may require a higher dose

Dosing adjustment/comments in renal or hepatic impairment: Patients with renal or hepatic failure should receive a reduced dosage initially and be closely monitored

Alcohol: Additive CNS effects, avoid use

Monitor body weight

Therapeutic levels (trough, 12 hours after last dose): 50-100 ng/mL

Decreased prolactin levels

None; this is not a tricyclic type antidepressant and will not enhance pressor response of epinephrine

A common adverse effect is significant dry mouth (>10%); normal salivary flow will occur with cessation of drug therapy

Depression: Take as directed, in equally divided doses, do not take in larger dose or more often than recommended. Do not discontinue without consulting prescriber. Do not use excessive alcohol or OTC medications not approved by prescriber. May cause drowsiness, clouded sensorium, restlessness, or agitation (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); or impotence (reversible). Report persistent CNS effects (agitation, confusion, anxiety, restlessness, insomnia, psychosis, hallucinations, seizures); muscle weakness or tremor; skin rash or irritation; chest pain or palpitations, abdominal pain or blood in stools; yellowing of skin or eyes; difficulty breathing, bronchitis, or unusual cough.

Smoking cessation: Use as directed, do not take extra doses. Do not combine narcotic patches with use of Zyban™ unless approved by prescriber. May cause dry mouth and insomnia (these may resolve with continued use). Report any difficulty breathing, unusual cough, dizziness, or muscle tremors.

Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Be aware that drug may cause seizures; dose should not be increased by more than 50 mg/day once weekly

Tablet: 75 mg, 100 mg

Tablet, sustained release: 100 mg, 150 mg

Tablet, sustained release (Zyban™): 150 mg

Branconnier RJ, Cole JO, Ghazvinian S, et al, "Clinical Pharmacology of Bupropion and Imipramine in Elderly Depressives," J Clin Psychiatry, 1983, 44(5 Pt 2):130-3.

Davidson J, "Seizures and Bupropion: A Review," J Clin Psychiatry, 1989, 50(7):256-61.

Hayes PE and Kristoff CA, "Adverse Reactions to Five New Antidepressants," Clin Pharm, 1986, 5:471-80.

Jennison TA, Brown P, Crossett J, et al, "A High-Performance Liquid Chromatographic Method for Quantitating Bupropion in Human Plasma or Serum," J Anal Toxicol, 1995, 19(2):69-72.

Kane JM, Cole K, Sarantakos S, et al, "Safety and Efficacy of Bupropion in Elderly Patients: Preliminary Observations," J Clin Psychiatry, 1983, 44(5 Pt 2):134-6.

Van Wyck FJ, Manberg PJ, Miller LL, et al, "Overview of Clinically Significant Adverse Reactions to Bupropion," J Clin Psychiatry, 1983, 44(5 Pt 2):191-6.