bupropion hydrochloride
Wellbutrin, Wellbutrin SR

Available forms
Available by prescription only
Tablets: 75 mg, 100 mg
Tablets (sustained-release): 100 mg, 150 mg, 200 mg

Indications and dosages
 Depression. Adults: Initially, 100 mg P.O. b.i.d. or 75 mg P.O. t.i.d. If needed, increase after 3 days to usual dosage of 100 mg P.O. t.i.d. If no response occurs after several weeks of therapy, consider increasing dosage to 150 mg t.i.d. Maximum, 450 mg daily. For sustained-release tablets, start with 150 mg P.O. q morning; increase to target dosage of 150 mg P.O. b.i.d. as tolerated as early as day 4 of dosing. If no response after several weeks of therapy, increase to 200 mg b.i.d. Maximum, 400 mg daily.

Pharmacodynamics
Antidepressant action: Mechanism of action is unknown. Bupropion doesn’t inhibit MAO; it’s a weak inhibitor of norepinephrine, dopamine, and serotonin reuptake.

Pharmacokinetics
Absorption: Only 5% to 20% is bioavailable in animal studies.
Distribution: At plasma levels up to 200 mcg/ml, drug appears to be about 80% bound to plasma proteins.
Metabolism: Metabolism is probably hepatic; several active metabolites have been identified. With prolonged use, the active metabolites probably accumulate in plasma, and their level may exceed that of the parent compound. Appears to induce its own metabolism.
Excretion: Excretion is primarily renal; elimination half-life of parent compound in single-dose studies ranges from 8 to 24 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, in patients with seizure disorders, and in patients who have taken an MAO inhibitor within previous 14 days. Also contraindicated in patients taking the smoking cessation drug Zyban (also bupropion) and in those with a history of bulimia or anorexia nervosa because of an increased risk of seizures. Use cautiously in patients with recent MI, unstable heart disease, and renal or hepatic impairment.

Interactions
Drug-drug. Levodopa, MAO inhibitors, phenothiazines, recent and rapid withdrawal of benzodiazepines, tricyclic antidepressants: Increase risk of adverse effects, including seizures. Monitor patient closely.
Drug-lifestyle. Alcohol use: Alters seizure threshold. Discourage alcohol use.
Sun exposure: Photosensitivity reactions may occur. Advise patient to take precautions.

Adverse reactions
CNS: headache, seizures, anxiety, confusion, delusions, euphoria, hostility, impaired sleep quality, insomnia, sedation, tremor, akinesia, akathisia, agitation, dizziness, syncope, fatigue, fever.
CV: arrhythmias, hypertension, hypotension, palpitations, tachycardia.
EENT: auditory disturbances, blurred vision.
GI: dry mouth, taste disturbance, increased appetite, constipation, dyspepsia, nausea, vomiting, anorexia, diarrhea.
GU: impotence, menstrual complaints, urinary frequency, urine retention.
Metabolic: weight changes, hyperglycemia.
Musculoskeletal: arthritis.
Skin: pruritus, rash, cutaneous temperature disturbance, excessive diaphoresis.
Other: chills, decreased libido.

Effects on lab test results
• May increase glucose level.

Overdose and treatment
Overdose may cause labored breathing, salivation, arched back, ptosis, ataxia, and seizures.
 If ingestion was recent, empty the stomach using gastric lavage or induce emesis with ipecac, as appropriate; follow with activated charcoal. Treatment should be supportive. Control seizures with I.V. benzodiazepines; stuporous, comatose, or convulsing patients may need intubation. The benefits of dialysis, hemoperfusion, or diuresis are unknown.

Special considerations
• Consider the inherent risk of suicide until depression improves significantly. High-risk patients should be supervised closely at start of therapy. To reduce risk of intentional overdose, prescribe the smallest quantity of tablets consistent with good management.
• Gradual increase of drug (no more than 75 to 100 mg daily every 2 to 3 days) reduces the risk of seizures, agitation, motor restlessness, and insomnia.  ALERT Bupropion is the active ingredient in different trade name drugs that are used for separate indications. Be sure the patient is not already taking Zyban before prescribing.
• Patients with bipolar disorder have an increased risk of manic episodes when taking an antidepressant.
• Investigational uses of drug include treatment of bipolar depression and attention deficit hyperactivity disorder in children.
Pregnant patients
• Safety hasn’t been established in pregnant women. Use drug only when absolutely necessary, and use pregnancy registry for monitoring outcomes: 1-800-336-2176.
Breast-feeding patients
• Because of the risk of serious adverse reactions in the infant, breast-feeding during therapy isn’t recommended.
Pediatric patients
• Safety in children younger than age 18 hasn’t been established.

Patient education
• Advise patient to take drug regularly as scheduled and to take each day’s amount in three divided doses, preferably at 6-hour intervals, to minimize risk of seizures.
• Warn patient to avoid alcohol, which may increase the risk of seizures.
• Advise patient to avoid activities that require alertness and coordination until CNS effects of drug are known.
• Tell patient not to chew, divide, or crush sustained-release tablets.
• Instruct patient not to take Zyban with Wellbutrin or other medications, including OTC medications, without medical approval.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use