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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(byoo PROE pee on)
Generic Available (U.S.)
Yes: Excludes bupropion hydrobromide tablet, sustained release hydrochloride tablet
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Aplenzin™: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm085915.pdf
Wellbutrin®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089824.pdf
Wellbutrin SR®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089826.pdf
Wellbutrin XL®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM172744.pdf
Zyban®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089835.pdf
REMS Components
Medication Guide
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder, including seasonal affective disorder (SAD); adjunct in smoking cessation
Use: Unlabeled/Investigational
Attention-deficit/hyperactivity disorder (ADHD); depression associated with bipolar disorder
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to adverse events observed in some animal studies, bupropion is classified as pregnancy category C. A significant increase in major teratogenic effects has not been observed following exposure to bupropion during pregnancy; however, the risk of spontaneous abortions may be increased (additional studies are needed to confirm). The long-term effects on development and behavior have not been studied.Pregnancy itself does not provide protection against depression. The ACOG recommends that therapy with antidepressants during pregnancy be individualized and should incorporate the clinical expertise of the mental health clinician, obstetrician, primary care provider, and pediatrician. If treatment is needed, consider gradually stopping antidepressants 10-14 days before the expected date of delivery to prevent potential withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. Bupropion has also been evaluated for smoking cessation during pregnancy; current recommendations suggest that pharmacologic treatments be considered only after other therapies have failed. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers, 2009).
Lactation
Enters breast milk/not recommended (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Bupropion and its metabolites are excreted into breast milk, although neither bupropion nor its metabolites have been detected in the plasma of breast-fed infants. Adverse events have not been reported in older breast-fed infants; however, a seizure was noted in one 6-month old infant (a causal effect could not be confirmed). Breast-feeding is not recommended by the manufacturer.
Contraindications
Hypersensitivity to bupropion or any component of the formulation; seizure disorder; history of anorexia/bulimia; use of MAO inhibitors within 14 days; patients undergoing abrupt discontinuation of ethanol or sedatives (including benzodiazepines); patients receiving other dosage forms of bupropion
Warnings/Precautions
Boxed warnings:
• Neuropsychiatric effects (use in smoking cessation): See “Concerns related to adverse effects” below.
• Suicidal thinking/behavior (use in treating psychiatric disorders): See “Major psychiatric warnings” below.
Major psychiatric warnings (use in treating psychiatric disorders):
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Bupropion is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Bupropion is not FDA approved for bipolar depression.
Concerns related to adverse effects:
• CNS stimulation: May cause CNS stimulation (restlessness, anxiety, insomnia) or anorexia.
• Cognitive impairment: May cause motor or cognitive impairment in some patients, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Delayed hypersensitivity reactions: Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported.
• Neuropsychiatric effect (use in smoking cessation): [U.S. Boxed Warning]: Serious neuropsychiatric events, including depression, suicidal thoughts, and suicide, have been reported with use; some cases may have been complicated by symptoms of nicotine withdrawal following smoking cessation. Smoking cessation (with or without treatment) is associated with nicotine withdrawal symptoms and the exacerbation of underlying psychiatric illness; however, some of the behavioral disturbances were reported in treated patients who continued to smoke. Neuropsychiatric symptoms (eg, mood disturbances, psychosis, hostility) have occurred in patients with and without pre-existing psychiatric disease; many cases resolved following therapy discontinuation although in some cases, symptoms persisted. Monitor all patients for behavioral changes and psychiatric symptoms (eg, agitation, depression, suicidal behavior, suicidal ideation); inform patients to discontinue treatment and contact their healthcare provider immediately if they experience any behavioral and/or mood changes.
• Seizures: The risk of seizures is dose-dependent and increased in patients with a history of seizures, anorexia/bulimia, head trauma, CNS tumor, severe hepatic cirrhosis, abrupt discontinuation of sedative-hypnotics or ethanol, medications which lower seizure threshold (antipsychotics, antidepressants, theophyllines, systemic steroids), stimulants, or hypoglycemic agents. Risk of seizures may also be increased by chewing ,crushing, or dividing long-acting products. Risk may be reduced by limiting the daily dose to bupropion hydrochloride ≤450 mg or bupropion hydrobromide 522 mg. Gradually increase dose incrementally to reduce risk. Discontinue and do not restart in patients experiencing a seizure.
• Sexual dysfunction: The incidence of sexual dysfunction with bupropion is generally lower than with SSRIs.
• Weight loss: May cause weight loss; use caution in patients where weight loss is not desirable.
Disease-related concerns:
• ADHD (unlabeled use): All children diagnosed with ADHD who may be candidates for stimulant medications should have a thorough cardiovascular assessment to identify risk factors for sudden cardiac death prior to initiation of drug therapy.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, history of hypertension, or coronary artery disease; treatment-emergent hypertension (including some severe cases) has been reported, both with bupropion alone and in combination with nicotine transdermal systems.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced dose and/or frequency recommended.
• Renal impairment: Use with caution in patients with renal impairment; consider a reduction in dosing frequency.
Special populations:
• Elderly: Use with caution in the elderly; may be at greater risk of accumulation during chronic dosing. Reduced dose recommended.
Dosage form specific issues:
• Extended release tablet: Insoluble tablet shell may remain intact and be visible in the stool.
Other warnings/precautions:
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Adverse Reactions
Frequencies, when reported, reflect highest incidence reported with sustained release product.
>10%:
Cardiovascular: Tachycardia (11%)
Central nervous system: Headache (25% to 34%), insomnia (11% to 20%), dizziness (6% to 11%)
Gastrointestinal: Xerostomia (17% to 26%), weight loss (14% to 23%), nausea (1% to 18%)
Respiratory: Pharyngitis (3% to 13%)
1% to 10%:
Cardiovascular: Palpitation (2% to 6%), arrhythmias (5%), chest pain (3% to 4%), hypertension (2% to 4%; may be severe), flushing (1% to 4%), hypotension (3%)
Central nervous system: Agitation (2% to 9%), confusion (8%), anxiety (5% to 7%), hostility (6%), nervousness (3% to 5%), sleep disturbance (4%), sensory disturbance (4%), migraine (1% to 4%), abnormal dreams (3%), irritability (2% to 3%), somnolence (2% to 3%), pain (2% to 3%), memory decreased (≤3%), fever (1% to 2%), CNS stimulation (1% to 2%), depression
Dermatologic: Rash (1% to 5%), pruritus (2% to 4%), urticaria (1% to 2%)
Endocrine & metabolic: Menstrual complaints (2% to 5%), hot flashes (1% to 3%), libido decreased (3%)
Gastrointestinal: Constipation (5% to 10%), abdominal pain (2% to 9%), diarrhea (5% to 7%), flatulence (6%), anorexia (3% to 5%), appetite increased (4%), taste perversion (2% to 4%), vomiting (2% to 4%), dyspepsia (3%), dysphagia (≤2%)
Genitourinary: Polyuria (2% to 5%), urinary urgency (≤2%), vaginal hemorrhage (≤2%), UTI (≤1%)
Neuromuscular & skeletal: Tremor (3% to 6%), myalgia (2% to 6%), weakness (2% to 4%), arthralgia (1% to 4%), arthritis (2%), akathisia (≤2%), paresthesia (1% to 2%), twitching (1% to 2%), neck pain
Ocular: Blurred vision (2% to 3%), amblyopia (2%)
Otic: Tinnitus (3% to 6%), auditory disturbance (5%)
Respiratory: Upper respiratory infection (9%), cough increased (1% to 4%), sinusitis (1% to 5%)
Miscellaneous: Infection (8% to 9%), diaphoresis (5% to 6%), allergic reaction (including anaphylaxis, pruritus, urticaria)
<1%, postmarketing, and/or case reports (limited to life-threatening or important): Accommodation abnormality, aggression, akinesia, alopecia, amnesia, anaphylactic shock, anemia, angioedema, aphasia, ataxia, atrioventricular block, bronchospasm, bruxism, colitis, coma, coordination abnormal, cystitis, deafness, delayed hypersensitivity, delirium, delusions, depersonalization, derealization, diplopia, dysarthria, dyskinesia, dyspareunia, dysphoria, dystonia, dysuria, edema, EEG abnormality, emotional lability, erythema multiforme, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal syndrome, extrasystoles, facial edema, gastric reflux, gastrointestinal hemorrhage, glossitis, glycosuria, gum hemorrhage, gynecomastia, hallucinations, hepatic damage, hepatitis, hirsutism, hyper-/hypoglycemia, hyper-/hypokinesia, hypertonia, hypoesthesia, hypomania, impotence, intestinal perforation, intraocular pressure increased, jaundice, , leukocytosis, leukopenia, libido increased, liver function abnormal, lymphadenopathy, manic reaction, MI, muscle weakness, musculoskeletal chest pain, mydriasis, myoclonus, neuralgia, neuropathy, painful erection, pancreatitis, pancytopenia, paranoia, pneumonia, photosensitivity, postural hypotension, pulmonary embolism, rhabdomyolysis, salpingitis, sciatica, seizures (dose-related), SIADH, stomach ulcer, Stevens-Johnson syndrome, stomatitis, stroke, suicidal ideation, syncope, tardive dyskinesia, thrombocytopenia, tongue edema, urinary incontinence, urinary retention, vasodilation
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2A6 (minor), 2B6 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (strong)
Drug Interactions
Alcohol (Ethyl): May enhance the adverse/toxic effect of BuPROPion. Specifically, seizure threshold may be lowered. BuPROPion may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may decrease during treatment. Management: Patients receiving bupropion should be advised to minimize or avoid alcohol consumption due to possible lower alcohol tolerance, and lower seizure threshold associated with heavy alcohol consumption/abrupt discontinuation of heavy consumption. Risk D: Consider therapy modification
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP2B6 Inducers (Strong): May increase the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2B6 Inhibitors (Moderate): May decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2B6 Inhibitors (Strong): May decrease the metabolism of CYP2B6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Lopinavir: May decrease the serum concentration of BuPROPion. Concentrations of the active metabolite, hydroxybupropion, may also be decreased. Risk C: Monitor therapy
MAO Inhibitors: May enhance the neurotoxic (central) effect of BuPROPion. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Quazepam: May increase the serum concentration of CYP2B6 Substrates. Risk C: Monitor therapy
Ritonavir: May decrease the serum concentration of BuPROPion. Mixed effects on concentrations of the active hydroxybupropion metabolite have been reported. Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Tricyclic Antidepressants: BuPROPion may decrease the metabolism of Tricyclic Antidepressants. Exceptions: Amoxapine; Protriptyline. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, gotu kola, kava kava (may increase CNS depression).
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Aplenzin™, Wellbutrin XL®: Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Aminoketone antidepressant structurally different from all other marketed antidepressants; like other antidepressants the mechanism of bupropion's activity is not fully understood. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Metabolite inhibits the reuptake of norepinephrine. The primary mechanism of action is thought to be dopaminergic and/or noradrenergic.
Pharmacodynamics/Kinetics
Absorption: Rapid
Distribution: Vd: ~20-47 L/kg (Laizure, 1985)
Protein binding: 84%
Metabolism: Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion.
Half-life:
Distribution: 3-4 hours
Elimination: 21 ± 9 hours; Metabolites: Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours
Extended release (Aplenzin™): 21 ± 7 hours; Metabolites: Hydroxybupropion: 24 ± 5 hours; Erythrohydrobupropion: 31 ± 8 hours; Threohydrobupropion: 51 ± 9 hours
Time to peak, serum:
Bupropion: Immediate release: Within 2 hours; Sustained release: Within 3 hours; Extended release: ~5 hours
Metabolite: Hydroxybupropion: Immediate release: ~3 hours; Extended release, sustained release: ~6-7 hours
Excretion: Urine (87%, primarily as metabolites); feces (10%, primarily as metabolites)
Dosage
Oral:
Children and Adolescents: ADHD (unlabeled use): Hydrochloride salt: 1.4-6 mg/kg/day
Adults:
Depression:
Immediate release hydrochloride salt: 100 mg 3 times/day; begin at 100 mg twice daily; may increase to a maximum dose of 450 mg/day
Sustained release hydrochloride salt: 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
Extended release:
Hydrochloride salt: Initial: 150 mg/day in the morning; may increase as early as day 4 of dosing to 300 mg/day; maximum dose: 450 mg/day
Hydrobromide salt (Aplenzin™): Target dose: 348 mg/day in the morning. Patients not previously on bupropion: Initial: 174 mg/day in the morning; may increase as early as day 4 of dosing to 348 mg/day; maximum dose: 522 mg/day. Note: 174 mg strength currently not available; 348 mg tablet cannot be split.
Switching from hydrochloride salt formulation (eg, Wellbutrin® immediate release, SR®, XL®) to hydrobromide salt formulation (Aplenzin™): Note: Patients being treated twice daily with bupropion hydrochloride would be switched to the equivalent once daily dose of bupropion hydrobromide.
Bupropion hydrochloride 150 mg is equivalent to bupropion hydrobromide 174 mg
Bupropion hydrochloride 300 mg is equivalent to bupropion hydrobromide 348 mg
Bupropion hydrochloride 450 mg is equivalent to bupropion hydrobromide 522 mg
SAD (Wellbutrin XL®): Initial: 150 mg/day in the morning; if tolerated, may increase after 1 week to 300 mg/day
Note: Prophylactic treatment should be reserved for those patients with frequent depressive episodes and/or significant impairment. Initiate treatment in the Autumn prior to symptom onset, and discontinue in early Spring with dose tapering to 150 mg/day for 2 weeks
Smoking cessation (Zyban®): Initiate with 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should continue for 7-12 weeks
Note: Therapy should begin at least 1 week before target quit date. Target quit dates are generally in the second week of treatment. If patient successfully quits smoking after 7-12 weeks, may consider ongoing maintenance therapy based on individual patient risk:benefit. Efficacy of maintenance therapy (300 mg/day) has been demonstrated for up to 6 months. Conversely, if significant progress has not been made by the seventh week of therapy, success is unlikely and treatment discontinuation should be considered.
Elderly: Depression: Hydrochloride salt: 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. Note: Patients with Alzheimer's dementia-related depression may require a lower starting dosage of 37.5 mg once or twice daily (100 mg/day sustained release), increased as needed up to 300 mg/day in divided doses (300 mg/day for sustained release)
Dosing conversion between hydrochloride salt (eg, Wellbutrin®) immediate, sustained, and extended release products: Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for sustained (twice daily) or extended (once daily) release products.
Dosing adjustment/comments in renal impairment: Use with caution and consider a reduction in dosing frequency; limited pharmacokinetic information suggests elimination of bupropion and/or the active metabolites may be reduced.
Moderate-to-severe renal impairment: Bupropion exposure was approximately twofold higher compared to normal subjects following a 150 mg single dose administration.
End-stage renal failure: Per the manufacturer, the elimination of hydroxybupropion and threohydrobupropion are reduced in patients with end-stage renal failure.
Dosing adjustment in hepatic impairment:
Note: The mean AUC increased by ~1.5-fold for hydroxybupropion and ~2.5-fold for erythro/threohydrobupropion; median Tmax was observed 19 hours later for hydroxybupropion, 31 hours later for erythro/threohydrobupropion; mean half-life for hydroxybupropion increased fivefold, and increased twofold for erythro/threohydrobupropion in patients with severe hepatic cirrhosis compared to healthy volunteers.
Mild-to-moderate hepatic impairment: Use with caution and/or reduced dose/frequency
Severe hepatic cirrhosis: Use with extreme caution; maximum dose:
Aplenzin™: 174 mg every other day
Wellbutrin®: 75 mg/day
Wellbutrin SR®: 100 mg/day or 150 mg every other day
Wellbutrin XL®: 150 mg every other day
Zyban®: 150 mg every other day
Administration: Oral
May be taken without regard to meals. Zyban® and extended release tablets (hydrochloride and hydrobromide salt formulations) should be swallowed whole; do not crush, chew, or divide. The insoluble shell of the extended-release tablet may remain intact during GI transit and is eliminated in the feces. Data from the manufacturer states that dividing Wellbutrin SR® tablets resulted in an increased rate of release at 15 minutes: “However, the divided tablet retained its sustained-release characteristics with similar increases of released bupropion at each sampling point beyond 15 minutes when compared to the intact Wellbutrin SR® tablet...” Bupropion is hydroscopic and therefore should be stored in a dry place. Splitting of large quantities in advance of administration is not advised since loss of potency may result. If necessary, splitting should be done cleanly without crushing.
Monitoring Parameters
Body weight; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks
When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter, 2008).
Reference Range
Therapeutic levels (trough, 12 hours after last dose): 50-100 ng/mL
Test Interactions
May interfere with urine detection of amphetamine/methamphetamine (false-positive). Decreased prolactin levels.
Patient Education
Be aware that bupropion is marketed under different names and should not be taken together; Zyban® is for smoking cessation. Excessive use or abrupt discontinuation of alcohol or sedatives may lower seizure threshold.
Depression: Take in equally divided doses. Do not use alcohol. May cause drowsiness, clouded sensorium, headache, restlessness, agitation, nausea, vomiting, dry mouth, weight loss, constipation, or impotence (reversible). Report persistent CNS effects (eg, agitation, confusion, anxiety, restlessness, insomnia, psychosis, hallucinations, seizures); suicide ideation; muscle weakness or tremor; skin rash or irritation; chest pain or palpitations, abdominal pain or blood in stools; yellowing of skin or eyes; or respiratory difficulty, bronchitis, or unusual cough.
Smoking cessation: May cause dry mouth and insomnia (these may resolve with continued use). Report any respiratory difficulty, unusual cough, dizziness, changes in behavior, agitation, anxiety, suicide ideation, seizures, or muscle tremors.
Geriatric Considerations
Limited data available about the use of bupropion in the elderly; two studies have found it equally effective when compared to imipramine. Its side effect profile (minimal anticholinergic and blood pressure effects) may make it useful in persons who do not tolerate traditional cyclic antidepressants. A single and multiple dose pharmacokinetic study suggested that accumulation of bupropion and its metabolites may occur in the elderly.
Additional Information
Risk of seizures: When using bupropion hydrochloride immediate release tablets, seizure risk is increased at total daily dosage >450 mg, individual dosages >150 mg, or by sudden, large increments in dose. Data for the immediate-release formulation of bupropion revealed a seizure incidence of 0.4% in patients treated at doses in the 300-450 mg/day range. The estimated seizure incidence increases almost 10-fold between 450 mg and 600 mg per day. Data for the sustained release dosage form revealed a seizure incidence of 0.1% in patients treated at a dosage range of 100-300 mg/day, and increases to ~0.4% at the maximum recommended dose of 400 mg/day.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: There are relatively few cardiovascular side effects compared to tricyclic antidepressants. However, several case reports include cardiovascular complications, including hypotension and MI. Use with caution in patients with recent MI or unstable angina. Recent information suggests that hypertension, in some cases severe and requiring acute treatment, has been reported in patients receiving bupropion alone, and especially when bupropion is used in conjunction with nicotine replacement therapy. Monitoring of blood pressure is recommended in patients receiving the combination of bupropion and nicotine replacement, particularly in those with hypertension and/or significant coronary artery disease.
Cardiovascular Considerations
Recent information suggests that hypertension, in some cases severe and requiring acute treatment, has been reported in patients receiving bupropion alone, and especially when bupropion is used in conjunction with nicotine replacement therapy. These events have been observed in both patients with and without evidence of pre-existing hypertension. Data from a comparative study of sustained-release bupropion, nicotine transdermal system (NTS), the combination of sustained-release bupropion and NTS, and placebo suggest a higher incidence of treatment-emergent hypertension (>6%) in patients treated with the combination of sustained-release bupropion and NTS. The majority of these patients had evidence of pre-existing hypertension. Monitoring of blood pressure is recommended in patients receiving the combination of bupropion and nicotine replacement, particularly in those with hypertension and/or significant coronary artery disease. Possible potential problems need to be balanced against the very substantial benefits of smoking cessation.
ADHD: Cardiovascular evaluation: In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) issued a statement in April 2008 (Vetter, 2008) recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment (including a combination of a thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death) prior to initiation of drug therapy. Although not mandatory, physicians should consider obtaining an ECG. These recommendations are based on the Food and Drug Administration (FDA) reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children, however, may be detrimental in certain patients with underlying cardiovascular disease. None of the medications have been shown to cause heart conditions or proven to have caused sudden cardiac death.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Abnormal taste, significant xerostomia (normal salivary flow resumes with discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Part of the mechanism of bupropion is to block reuptake of norepinephrine along with dopamine. Because of the potential for norepinephrine elevation within CNS synapses, it is suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way.
Mental Health: Child/Adolescent Considerations
Attention-deficit/hyperactivity disorder (ADHD): Bupropion hydrochloride 1.4-5.7 mg/kg/day (mean: 3.3 mg/kg/day) was utilized in 15 ADHD subjects 7-17 years of age (Barrickman, 1995); 72 children with ADHD (6-12 years of age) received 3-6 mg/kg/day (Conners, 1996); adolescents with conduct disorder and substance use disorder were titrated to a maximum fixed daily dose of 300 mg (Riggs, 1998). The immediate-release dosage form was studied in clinical trials for indications other than depression in 104 pediatric patients. This limited exposure does not allow for assessment of the safety of bupropion in pediatric patients. Bupropion 100–350 mg/day (mean: 3.5 ± 0.8 mg/kg/day) was given to 57 children and adolescents 9–18 years of age with ADHD in a randomized controlled trial to assess whether it prevented smoking in nonsmokers for ≤6.5 years (mean: 12 months). Bupropion was not found to be superior to placebo for smoking prevention in youth with ADHD. Adverse effects were similar in bupropion and placebo groups (Monuteaux, 2007).
A pharmacokinetic study of bupropion SR, showed the mean half-life and threohydrobupropion metabolite of bupropion were significantly shorter in children 11-17 years of age compared to adults. The AUC were 19% and 80% higher for bupropion and its metabolite (respectively). This indicates it may be preferable to dose bupropion SR twice daily in children (Daviss, 2005).
Barrickman LL, Petty PJ, Allen AJ, et al, “Bupropion Versus Methylphenidate in the Treatment of Attention-Deficit Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 1995, 34(5):649-57.
Conners CK, Casat CD, Gualtieri CT, et al, “Bupropion Hydrochloride in Attention Deficit Disorder With Hyperactivity,” J Am Acad Child Adolesc Psychiatry, 1996, 35(10):1314-21.
Daviss WB, Perel JM, Birmaher B, et al, “Steady-State Clinical Pharmacokinetics of Bupropion Extended-Release in Youths,” J Am Acad Child Adolesc Psychiatry, 2006, 45(12):1503-9.
Monuteaux MC, Spencer TJ, Faraone SV, et al, “A Randomized, Placebo-Controlled Clinical Trial of Bupropion for the Prevention of Smoking in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder,” J Clin Psychiatry, 2007, 68(7):1094-101.
Riggs PD, Leon SL, Mikulich SK, et al, “An Open Trial of Bupropion for ADHD in Adolescents With Substance Use Disorders and Conduct Disorder,” J Am Acad Child Adolesc Psychiatry, 1998, 37(12):1271-8.
Mental Health: Comment
Bupropion is an activating antidepressant that may be particularly useful for individuals whose depression is associated with fatigue and poor concentration. It is also used as an adjunct in smoking cessation and may benefit those with ADHD. While some evidence suggests that it is less likely to induce mania when used in individuals with bipolar disorder, the trials suggesting this are flawed. It is not associated with withdrawal symptoms so it can be stopped abruptly. Sexual dysfunction, seen commonly with the SSRI, is less problematic with bupropion.
Nursing: Physical Assessment/Monitoring
Perform careful cardiovascular assessment prior to initiating therapy. Monitor blood pressure at beginning of therapy and periodically throughout. Monitor for clinical worsening; neuropsychiatric symptoms, such as changes in behavior, hostility, agitation, and depression; and suicidality, especially at the beginning of therapy or when dose changes occur. Taper dosage slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hydrochloride: 75 mg [generic for Wellbutrin®], 100 mg [generic for Wellbutrin®]
Wellbutrin®: 75 mg, 100 mg
Tablet, extended release, oral, as hydrobromide:
Aplenzin™: 174 mg, 348 mg, 522 mg
Tablet, extended release, oral, as hydrochloride: 100 mg [generic for Wellbutrin SR®], 150 mg [generic for Wellbutrin SR®], 150 mg [generic for Wellbutrin XL®], 150 mg [generic for Zyban®], 200 mg [generic for Wellbutrin SR®], 300 mg [generic for Wellbutrin XL®]
Budeprion SR®: 100 mg [contains tartrazine; generic for Wellbutrin SR®]
Budeprion SR®: 150 mg [generic for Wellbutrin SR®]
Budeprion XL®: 150 mg [generic for Wellbutrin XL®]
Budeprion XL®: 300 mg [contains tartrazine; generic for Wellbutrin XL®]
Buproban®: 150 mg [generic for Zyban®]
Wellbutrin XL®: 150 mg, 300 mg
Tablet, sustained release, oral, as hydrochloride:
Wellbutrin SR®: 100 mg, 150 mg, 200 mg
Zyban®: 150 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 12-hour (Buproban)
150 mg (30): $49.99
Tablet, 12-hour (BuPROPion HCl (Smoking Deter))
150 mg (60): $116.00
Tablet, 12-hour (Wellbutrin SR)
100 mg (60): $227.99
150 mg (60): $225.99
200 mg (60): $428.01
Tablet, 12-hour (Zyban)
150 mg (60): $209.99
Tablet, 24-hour (Aplenzin)
348 mg (30): $209.98
522 mg (30): $499.94
Tablet, 24-hour (Budeprion XL)
150 mg (60): $105.98
Tablet, 24-hour (BuPROPion HCl)
300 mg (30): $132.98
Tablets (BuPROPion HCl)
75 mg (90): $61.99
100 mg (90): $79.99
Tablets (Wellbutrin)
75 mg (90): $235.28
100 mg (90): $311.29
References
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Academy of Pediatrics/American Heart Association, “Clarification of Statement on Cardiovascular Evaluation and Monitoring of Children and Adolescents With Heart Disease Receiving Medications for ADHD: May 16, 2008,” J Dev Behav Pediatr, 2008, 29(4):335.
Barrickman LL, Petty PJ, Allen AJ, et al, “Bupropion Versus Methylphenidate in the Treatment of Attention-Deficit Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 1995, 34(5):649-57.
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.
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Conners CK, Casat CD, Gualtieri CT, et al, “Bupropion Hydrochloride in Attention Deficit Disorder With Hyperactivity,” J Am Acad Child Adolesc Psychiatry, 1996, 35(10):1314-21.
Davidson J, “Seizures and Bupropion: A Review,” J Clin Psychiatry, 1989, 50(7):256-61.
Fiore MC, Jaen CR, Baker TB, et al, Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008. Available at http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf.
Fiore M, Jaen CR, Baker TB, et al, “A Clinical Practice Guideline for Treating Tobacco Use and Dependence: 2008 Update. A U.S. Public Health Service Report,” Am J Prev Med, 2008, 35(2):158-76.
GlaxoSmithKline [data on file], “Wellbutrin® SR, GAZZ/96/0006/00, Study Report Synopsis, 1996, 1-8.
Hayes PE and Kristoff CA, “Adverse Reactions to Five New Antidepressants,” Clin Pharm, 1986, 5:471-80.
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Kavoussi RJ, Segraves RT, Hughes AR, et al, “Double-Blind Comparison of Bupropion Sustained Release and Sertraline in Depressed Outpatients,” J Clin Psychiatry, 1997, 58(12):532-7.
Laizure SC, DeVane CL, Stewart JT, et al, “Pharmacokinetics of Bupropion and Its Major Basic Metabolites in Normal Subjects After a Single Dose,” Clin Pharmacol Ther, 1985, 38(5):586-9.
Leverich GS, Altshuler LL, Frye MA, et al, “Risk of Switch in Mood Polarity to Hypomania or Mania in Patients with Bipolar Depression During Acute and Continuation Trials of Venlafaxine, Sertraline, and Bupropion as Adjuncts to Mood Stabilizers,” Am J Psychiatry, 2006, 163(2):232-9.
McIntyre RS, Mancini DA, McCann S, et al, “Topiramate Versus Bupropion SR When Added to Mood Stabilizer Therapy fpr the Depressive Phase of Bipolar Disorder: A Preliminary Single-Blind Study,” Bipolar Disord, 2002, 4(3):207-13.
National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health , “Attention Deficit Hyperactivity Disorder, The NICE Guideline on Diagnosis and Management of ADHD in Children, Young People and Adults,” National Clinical Practice Guideline Number 72, 2008:1-664. Available at www.nice.org.uk/cg072
Nissen SE, “ADHD Drugs and Cardiovascular Risk,” N Engl J Med, 2006, 354(14):1445-8.
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Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.
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Riggs PD, Leon SL, Mikulich SK, et al, “An Open Trial of Bupropion for ADHD in Adolescents With Substance Use Disorders and Conduct Disorder,” J Am Acad Child Adolesc Psychiatry, 1998, 37(12):1271-8.
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International Brand Names
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Last full review/revision May 2011
Content last modified May 2011
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