Trade Names:Aplenzin- Tablets, ER 174 mg as hydrobromide- Tablets, ER 348 mg as hydrobromide- Tablets, ER 522 mg as hydrobromide
Trade Names:Budeprion SR (12 h)- Tablets, sustained-release 100 mg as hydrochloride- Tablets, sustained-release 150 mg as hydrochloride
Trade Names:Budeprion XL (24 h)- Tablets, ER 300 mg as hydrochloride
Trade Names:Wellbutrin- Tablets 75 mg as hydrochloride- Tablets 100 mg as hydrochloride
Trade Names:Wellbutrin SR (12 h)- Tablets, sustained-release 100 mg as hydrochloride- Tablets, sustained-release 150 mg as hydrochloride- Tablets, sustained-release 200 mg as hydrochloride
Trade Names:Wellbutrin XL (24 h)- Tablets, ER 150 mg as hydrochloride- Tablets, ER 300 mg as hydrochloride
Trade Names:Zyban- Tablets, ER 150 mg as hydrochlorideratio-Bupropion SR (Canada)Sandoz Bupropion SR (Canada)
Exact mechanism of antidepressant or smoking deterrent activity is unknown, but it is presumed to be mediated by noradrenergic and/or dopaminergic mechanisms.
Steady state achieved in about 8 days.
Immediate-release: T max within 2 h.
Sustained-release (SR): T max approximately 3 h.
ER (XL, Aplenzin ): T max approximately 5 h.
Bupropion is 84% protein bound. Vd is 1,950 L.
Extensively metabolized by hydroxylation or oxidation in the liver. CYP2B6 is involved in formation of hydroxybupropion (50% as potent as bupropion). The other 2 main metabolites are threohydrobupropion and erythrohydrobupropion, which are 20% as potent as bupropion.
87% excreted in urine, 10% in feces, and 0.5% as unchanged drug; elimination half-life is about 21 h (bupropion), about 20 h (hydroxybupropion), about 37 h (threohydrobupropion), and about 33 h (erythrohydrobupropion).
Elimination of major metabolites may be reduced. Dose adjustment may be necessary.Hepatic Function Impairment
Elimination of hydroxybupropion is reduced in patients with alcoholic liver disease. Bupropion C max increased 70%, AUC increased 3-fold, and mean half-life increased to 29 h in patients with severe hepatic impairment. Mean half-life for active metabolites increased 2- to 5-fold in patients with severe hepatic impairment.Elderly
May be at risk of accumulation of bupropion and its metabolites.Gender
AUC was approximately 13% higher in males.
Treatment of major depressive disorder (MDD); smoking cessation ( Zyban only).
Prevention of seasonal major depressive episodes in patients with seasonal affective disorder ( Wellbutrin XL only).
Treatment of neuropathic pain and enhancement of weight loss (bupropion SR); treatment of attention deficit hyperactivity disorder.
Seizure disorder; current or prior diagnosis of bulimia or anorexia nervosa; concurrent treatment with or within 14 days of discontinuation of MAOIs; concurrent treatment with multiple bupropion products (eg, coadministration of Zyban for smoking cessation and Wellbutrin for depression); abrupt discontinuation of alcohol or sedatives; hypersensitivity to bupropion or any other component of the product.
100 mg twice daily initially; may increase to 100 mg 3 times daily after 3 days (max daily dose, 450 mg; max single dose, 150 mg).SR
150 mg once daily initially; may increase to 150 mg twice daily as early as day 4 of therapy (max daily dose, 400 mg; max single dose, 200 mg).XL
150 mg once daily initially; may increase to 300 mg once daily as early as day 4 of therapy (max daily dose, 450 mg).Aplenzin
174 mg once daily in the morning initially; may increase to 348 mg once daily as early as day 4 of therapy (max daily dose, 522 mg) (174 mg tablet not currently marketed; expected launch in mid-year 2009).Smoking DeterrentAdults Initial dose
PO 150 mg once daily for first 3 days, increasing to 150 mg twice daily. Do not exceed 300 mg/day. Initiate treatment while patient is still smoking. Patient should set target date to quit smoking within the first 2 wk of treatment; continue treatment for 7 to 12 wk.Maintenance dose
PO Clinical data are not available regarding long-term treatment for smoking cessation. Whether to continue treatment beyond 12 wk must be determined for individual patients.Combination treatment
PO Bupropion may be used in combination with a nicotine transdermal system for smoking cessation.Hepatic Function Impairment (Severe Hepatic Cirrhosis)Adults Immediate-release
PO Do not exceed 75 mg once daily.SR
PO Do not exceed 100 mg once daily or 150 mg every other day.XL
PO Do not exceed 150 mg every other day.Aplenzin
PO Do not exceed 174 mg every other day.Zyban
PO 150 mg every other day.Seasonal Affective DisorderAdults
PO 150 mg initially as a single dose in the morning. The dose may be increased to 300 mg after 1 wk.
Store immediate-release tablets at 59° to 77°F. Protect from light and moisture. Store SR tablets, Budeprion XL tablets, and Zyban at 68° to 77°F. Store Wellbutrin XL and Aplenzin tablets at 59° to 86°F.
Adverse neuropsychiatric reactions or reduced alcohol tolerance may occur.Amantadine, levodopa
Incidence of bupropion adverse reactions may be increased.Antidepressants, antipsychotics, systemic steroids, theophylline
May lower seizure threshold.Carbamazepine, phenobarbital, phenytoin, rifampin
May decrease bupropion serum concentrations.Cyclosporine
Cyclosporine concentrations may be reduced.Drugs metabolized by CYP2D6 (eg, desipramine, flecainide, fluoxetine, haloperidol, imipramine, metoprolol, nortriptyline, paroxetine, propafenone, risperidone, sertraline, thioridazine)
Plasma levels of these agents may be elevated by bupropion. Use with caution and adjust the dose as needed.Efavirenz, nelfinavir, ritonavir
Plasma levels of bupropion may be decreased, increasing the risk of adverse reactions.Guanfacine
Risk of bupropion toxicity may be increased.Inhibitors of CYP2B6 (cimetidine, clopidogrel, cyclophosphamide, orphenadrine, thiotepa, ticlopidine)
May increase bupropion plasma levels and risk of adverse reactions.Linezolid, MAOIs, selegiline
May increase risk of acute bupropion toxicity. Discontinue MAOIs at least 14 days before starting bupropion.Nicotine patch
Coadministration may cause hypertension.Theophylline, warfarin, and other drugs extensively metabolized
Plasma concentrations of these agents may increase following smoking cessation because of deinduction of hepatic enzymes.
None well documented.
Tachycardia (11%); palpitation (6%); cardiac arrhythmia (5%); flushing, hypertension (4%); hot flashes, hypotension (3%); edema (at least 1%); syncope (1%); AV block, extrasystoles, MI, orthostatic hypotension, phlebitis, pulmonary embolism, third-degree heart block (postmarketing).
Headache (34%); agitation (32%); insomnia (31%); dizziness (22%); tremor (21%); sedation (20%); disturbed concentration (9%); akinesia/bradykinesia, anxiety, confusion (8%); hostility (6%); fatigue, nervousness (5%); asthenia, decreased appetite, impaired sleep quality, migraine, sensory disturbances (4%); abnormal dreams, decreased libido, decreased memory, feeling jittery, irritability, somnolence (3%); CNS stimulation, paresthesia (2%); ataxia/incoordination, decreased sexual function, depression, dyskinesia, dystonia, hallucinations, increased libido, mania/hypomania, myoclonus, seizure (at least 1%); delusions (1%); abnormal EEG, aggression, aphasia, coma, delirium, dysarthria, euphoria, extrapyramidal syndrome, hypokinesia, manic reaction, neuralgia, neuropathy, paranoid ideation, paresthesia, restlessness, unmasking tardive dyskinesia (postmarketing).
Sweating (22%); rash (8%); pruritus (4%); urticaria (2%); nonspecific rashes (at least 1%); alopecia, angioedema, erythema multiforme, exfoliative dermatitis, hirsutis, Stevens-Johnson syndrome (postmarketing).
Blurred vision (15%); nasopharyngitis (13%); pharyngitis (11%); tinnitus (6%); auditory disturbance (5%); amblyopia, diplopia (3%); deafness, increased IOP, mydriasis (postmarketing).
Dry mouth (28%); constipation (26%); anorexia, nausea (18%); abdominal pain (9%); diarrhea (7%); flatulence (6%); increased appetite, taste perversion, vomiting (4%); dyspepsia, gustatory disturbance (3%); dysphagia (2%); stomatitis (at least 1%); colitis, esophagitis, GI hemorrhage, gum hemorrhage, intestinal perforation, pancreatitis, stomach ulcer (postmarketing).
Menstrual complaints, urinary frequency (5%); impotence (3%); dysmenorrhea, urinary retention, urinary urgency, vaginal hemorrhage (2%); nocturia (at least 1%); UTI (1%); abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, vaginitis (postmarketing).
Altered PT or INR, anemia, ecchymosis, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, thrombocytopenia (postmarketing).
Hepatitis, liver damage (postmarketing).
Weight loss (23%); weight gain (14%); glycosuria (postmarketing).
Myalgia (6%); arthralgia (4%); arthritis, pain in extremity (3%); akathisia, muscle spasm, twitch (2%); arthralgia, muscle rigidity, muscle weakness, myalgia, rhabdomyolysis (postmarketing).
Upper respiratory tract infection (9%); sinusitis (5%); cough (4%); pneumonia (postmarketing).
Infection (9%); upper respiratory tract complaints (5%); chest pain (4%); pain (3%); bronchitis, fever (2%); anaphylactic shock, delayed hypersensitivity, fever with rash, hyperglycemia, hypoglycemia, serum sickness–like reactions, SIADH, symptoms of delayed hypersensitivity (postmarketing).
Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children, adolescents, and young adults with MDD and other psychiatric disorders. When considering the use of any antidepressant, balance this risk with clinical need. Closely observe all patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior during the initial few months of therapy or at times of increases or decreases in dose. Advise families and caregivers of the need for close observation and communication with the health care provider.
Monitor all patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy or at times of increases or decreases in dose. The following symptoms may represent precursors to suicidality and should be reported to the health care provider immediately if noted or suspected: aggressiveness, agitation, anxiety, hostility, hypomania, impulsivity, insomnia, irritability, mania, panic attacks, and psychomotor restlessness. Monitor all patients with hepatic or renal impairment for possible adverse reactions that could indicate high drug and/or metabolite levels. Monitor BP in patients receiving combination of bupropion and nicotine replacement. Frequently assess patient for response to treatment. Periodically review therapy to determine if therapy needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.
Category C .
Excreted in breast milk.
Safety and efficacy not established.
Use with caution. Because elderly patients are more likely to have decreased renal function, use care in dose selection and consider monitoring renal function.
Use with caution; reduce frequency and/or dose as needed.
Use with caution in patients with hepatic impairment. Consider reduced frequency and/or dose (reduced frequency of dosing for Zyban ). Use with extreme caution in patients with severe hepatic cirrhosis; a reduced dose and/or frequency is required.
May impair judgment, thinking, or motor skills.
A substantial proportion of patients will experience restlessness, agitation, anxiety, and/or insomnia; treatment with a sedative/hypnotic agent or discontinuation of therapy may be required. Gradual escalation of dose may minimize symptoms.
Anaphylactoid reactions characterized by pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported.
Has been associated with decreased appetite and weight loss; consider anorectic and/or weight-reducing potential of bupropion when determining treatment for depressed patient with weight loss as a major presenting symptom of the depression.
Hypertension requiring treatment may occur in patients receiving bupropion alone and in combination with nicotine replacement therapy. Use bupropion with caution in patients with unstable heart disease or recent history of MI.
Neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbances, paranoia, and confusion, have been reported; may abate with dose reduction or withdrawal of drug.
Inform patients that the same active ingredient (bupropion) is found in Aplenzin , Budeprion SR , Budeprion XL , Wellbutrin , Wellbutrin SR , Wellbutrin XL, and Zyban .
May precipitate mania in bipolar patients or activate latent psychosis in other patients.
May occur. Dose-related risk; sudden and large increases in dose may contribute to increased risk. Use with caution in patients with history of head trauma, seizure, CNS tumors, or severe hepatic cirrhosis; in patients taking other drugs known to increase risk of seizures; in cases of excessive use of alcohol, or addiction to opiates, cocaine, or other stimulants; patients taking anorectics; and diabetic patients treated with oral hypoglycemics or insulin. Discontinue use and do not restart bupropion in patients who experienced a seizure while on treatment.
A major depressive episode may be the initial presentation of bipolar disorder. Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.
Suicidal ideation is inherent in depression and may persist until significant remission occurs. Closely supervise high-risk patients during initial drug therapy. Prescribe smallest quantity of medication consistent with good patient management in order to reduce risk of overdose.
Cardiac arrest; death accompanied by bradycardia, cardiac failure, and uncontrolled seizures prior to death; ECG changes or arrhythmias; hallucinations; loss of consciousness; seizures; sinus tachycardia.
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