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Major depressive disorder (Aplenzin, Forfivo XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL): Treatment of major depressive disorder (MDD).
Seasonal affective disorder (Aplenzin, Wellbutrin XL): Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).
Smoking cessation (Buproban and Zyban): As an aid to smoking cessation treatment.
Hypersensitivity to bupropion or any component of the formulation; seizure disorder; history of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives, including benzodiazepines, barbiturates, or antiepileptic drugs; use of MAO inhibitors (concurrently or within 14 days of discontinuing either bupropion or the MAO inhibitor)
Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban: Additional contraindications: Initiation of bupropion in a patient receiving linezolid or intravenous methylene blue
Aplenzin, Wellbutrin XL: Additional contraindications: Other conditions that increase seizure risk, including arteriovenous malformation, severe head injury, severe stroke, CNS tumor, CNS infection
Forfivo XL: Additional contraindications: Patients receiving other dosage forms of bupropion
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use or use within 14 days of thioridazine; concurrent use with other dosage forms of bupropion
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. Short-term studies did not show an increase in the risk of suicidal thoughts or behavior with antidepressant use in adults older than 24 years; there was a reduction in risk with antidepressant use in adults 65 years and older. Appropriately monitor patients of all ages who are started on antidepressant therapy and closely observe them for clinical worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the health care provider.
Smoking cessation treatmentSerious neuropsychiatric events have occurred in patients taking bupropion for smoking cessation. The majority of reactions occurred during bupropion treatment; some occurred during treatment discontinuation. A causal relationship is uncertain, as depressed mood may be a symptom of nicotine withdrawal. Some cases also occurred in patients taking bupropion who continued to smoke.
Weigh the risks of bupropion against the benefits of its use. Bupropion has been demonstrated to increase the likelihood of abstinence from smoking for as long as 6 months compared with treatment with placebo. The health benefits of quitting smoking are immediate and substantial.
Observe all patients for neuropsychiatric reactions. Instruct the patient to contact a healthcare provider if such reactions occur.
Depression: Oral: Note: Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used.
Immediate release hydrochloride salt: Initial: 100 mg twice daily; after 3 days may increase to the usual dose of 100 mg 3 times a day; if no clinical improvement after several weeks, may increase to a maximum dose of 450 mg daily in 3 or 4 divided doses; do not exceed 150 mg in a single dose
Sustained release hydrochloride salt: Initial: 150 mg daily in the morning; if tolerated, after 3 days, may increase to a target dose of 150 mg twice daily; if no clinical improvement after several weeks, may increase to a maximum dose of 200 mg twice daily
Extended release:
Hydrochloride salt (Wellbutrin XL): Initial: 150 mg once daily in the morning; if tolerated, as early as day 4, may increase to 300 mg once daily (maximum dose: 300 mg/day; however, guidelines suggest up to 450 mg/day may be used [APA 2010]). Note: Forfivo XL may only be used after initial dose titration with other bupropion products.
Hydrochloride salt (Forfivo XL): Switching from Wellbutrin immediate release, SR, or XL to Forfivo XL: Patients receiving 300 mg daily of bupropion hydrochloride for at least 2 weeks and requiring a dose increase or patients already taking 450 mg daily of bupropion hydrochloride may switch to Forfivo XL 450 mg once daily.
Hydrobromide salt (Aplenzin): Initial: 174 mg once daily in the morning; may increase as early as day 4 of dosing to 348 mg once daily (target dose); maximum dose: 522 mg daily.
Switching from hydrochloride salt formulation (eg, Wellbutrin immediate release, SR, XL, or Forfivo XL) to hydrobromide salt formulation (Aplenzin):
Bupropion hydrochloride 150 mg daily is equivalent to bupropion hydrobromide 174 mg once daily
Bupropion hydrochloride 300 mg daily is equivalent to bupropion hydrobromide 348 mg once daily
Bupropion hydrochloride 450 mg daily is equivalent to bupropion hydrobromide 522 mg once daily
Seasonal affective disorder (SAD): Initial: 150 mg once daily (Wellbutrin XL) or 174 mg once daily (Aplenzin) in the morning; if tolerated, may increase after 1 week to 300 mg once daily (Wellbutrin XL) or 348 mg once daily (Aplenzin) in the morning.
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. Doses >300 mg daily (Wellbutrin XL) or >348 mg daily (Aplenzin) have not been studied in SAD (maximum: Wellbutrin XL 300 mg daily; Aplenzin 522 mg daily).
Smoking cessation (Zyban, Buproban): Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should continue for 7 to 12 weeks (maximum dose: 300 mg daily).
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 to 12 weeks, may consider ongoing maintenance therapy based on individual patient risk:benefit. Efficacy of maintenance therapy (300 mg daily) 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.
Dosing conversion between hydrochloride salt immediate (Wellbutrin), sustained (Wellbutrin SR), and extended release (Wellbutrin XL, Forfivo XL) 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.
Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to allow for the detection of re-emerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (APA 2010).
Manufacturer 's labeling:
Aplenzin: In patients receiving 348 mg once daily, taper dose down to 174 mg once daily for 2 weeks prior to discontinuing.
Wellbutrin XL: In patients receiving 300 mg once daily, taper dose down to 150 mg once daily for 2 weeks prior to discontinuing.
MAO inhibitor recommendations:
Switching to or from an MAO inhibitor antidepressant:
Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat depression and initiation of bupropion.
Allow 14 days to elapse between discontinuing bupropion and initiation of an MAO inhibitor intended to treat depression.
Use with reversible MAO inhibitors (such as linezolid or IV methylene blue):
Do not initiate bupropion in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.
If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving bupropion and potential benefits outweigh potential risks, discontinue bupropion promptly and administer linezolid or IV methylene blue. Monitor for increased risk of hypertensive reactions for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume bupropion 24 hours after the last dose of linezolid or IV methylene blue.
Depression: Oral (hydrochloride salt): Initial: 37.5 mg of immediate release tablets twice daily or 100 mg daily of sustained release tablets; increase by 37.5 to 100 mg every 3 to 4 days as tolerated to a maximum dose of 300 mg daily (in divided doses). There is evidence that the elderly respond at 150 mg daily 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 daily sustained release), increased as needed up to 300 mg daily in divided doses (300 mg daily for sustained release) (Rabins 2007).
Smoking cessation: Refer to adult dosing.
Discontinuation of therapy: Refer to adult dosing.
MAO inhibitor recommendations: Refer to adult dosing.
ADHD (off-label use): Oral (hydrochloride salt): Children and Adolescents: 1.4 to 6 mg/kg/day (Barrickman 1995; Conners 1996)
MAO inhibitor recommendations: Refer to adult dosing.
Use with caution; manufacturer 's labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations. Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Zyban product labeling defines renal impairment as GFR <90 mL/minute.
Forfivo XL: Use is not recommended.
Mild impairment (Child-Pugh score 5 to 6): Use with caution; manufacturer 's labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations.
Forfivo XL: Use is not recommended.
Moderate to severe impairment, including severe hepatic cirrhosis (Child-Pugh score 7 to 15): Use with extreme caution; maximum dose:
Aplenzin: 174 mg every other day
Buproban: Severe hepatic cirrhosis: 150 mg every other day
Forfivo XL: Use is not recommended.
Wellbutrin: 75 mg once daily
Wellbutrin SR: 100 mg once daily or 150 mg every other day
Wellbutrin XL, Zyban: 150 mg every other day
May be taken without regard to meals. The manufacturer states that tablets should be swallowed whole; do not crush, chew, or divide.
Extended release: Administer once daily with at least 24 hours between successive doses.
Immediate release: Administer 3 to 4 times daily with at least 6 hours between successive doses; do not exceed 150 mg in a single dose.
Sustained release: Administer 2 times daily with at least 8 hours between successive doses.
Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Wellbutrin, Wellbutrin XL, Zyban: Protect from light and moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as hydrochloride:
Wellbutrin: 75 mg [DSC], 100 mg [DSC]
Generic: 75 mg, 100 mg
Tablet Extended Release 12 Hour, Oral:
Generic: 100 mg, 150 mg
Tablet Extended Release 12 Hour, Oral, as hydrochloride:
Budeprion SR: 100 mg [DSC] [contains tartrazine (fd&c yellow #5)]
Budeprion SR: 150 mg [DSC]
Buproban: 150 mg [DSC]
Wellbutrin SR: 100 mg, 150 mg, 200 mg
Zyban: 150 mg
Generic: 100 mg, 150 mg, 200 mg
Tablet Extended Release 24 Hour, Oral, as hydrobromide:
Aplenzin: 174 mg, 348 mg, 522 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Budeprion XL: 300 mg [DSC] [contains fd&c red #40, tartrazine (fd&c yellow #5)]
Forfivo XL: 450 mg
Wellbutrin XL: 150 mg, 300 mg
Generic: 150 mg, 300 mg
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Monitor therapy
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. Consider therapy modification
Antihepaciviral Combination Products: May decrease the serum concentration of BuPROPion. Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): May enhance the adverse/toxic effect of BuPROPion. Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Monitor therapy
Citalopram: BuPROPion may enhance the adverse/toxic effect of Citalopram. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion, and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Consider therapy modification
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Monitor therapy
CYP2B6 Inducers (Moderate): May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Efavirenz: May decrease the serum concentration of BuPROPion. Management: Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Monitor therapy
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy
FLUoxetine: BuPROPion may enhance the adverse/toxic effect of FLUoxetine. BuPROPion may increase the serum concentration of FLUoxetine. Monitor therapy
FluvoxaMINE: BuPROPion may enhance the adverse/toxic effect of FluvoxaMINE. BuPROPion may increase the serum concentration of FluvoxaMINE. Monitor therapy
Ioflupane I 123: BuPROPion may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy
Isavuconazonium Sulfate: May decrease the serum concentration of BuPROPion. Monitor therapy
Lopinavir: May decrease the serum concentration of BuPROPion. Concentrations of the active metabolite, hydroxybupropion, may also be decreased. Management: Monitor bupropion response closely. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving lopinavir. Monitor therapy
Lorcaserin: BuPROPion may enhance the serotonergic effect of Lorcaserin. This could result in serotonin syndrome. Management: Seek alternatives to this combination when possible. Consider therapy modification
Lumacaftor: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of BuPROPion. Avoid combination
Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy
Nilotinib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
OCT2 Substrates: BuPROPion may increase the serum concentration of OCT2 Substrates. Monitor therapy
PARoxetine: BuPROPion may enhance the adverse/toxic effect of PARoxetine. BuPROPion may increase the serum concentration of PARoxetine. Monitor therapy
Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification
Propafenone: May increase the serum concentration of CYP2D6 Inhibitors (Moderate). Monitor therapy
Ritonavir: May decrease the serum concentration of BuPROPion. Mixed effects on concentrations of the active hydroxybupropion metabolite have been reported. Management: Monitor for decreased bupropion effects. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving ritonavir. Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination
Thiotepa: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
TraMADol: CYP2D6 Inhibitors (Moderate) 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. Monitor therapy
Tricyclic Antidepressants: BuPROPion may decrease the metabolism of Tricyclic Antidepressants. Management: Seek alternatives when possible. Monitor patients receiving these combinations closely for increased serum concentrations (when testing is available) and toxic effects of the tricyclic antidepressant. Exceptions: Amoxapine; Protriptyline. Consider therapy modification
Vortioxetine: BuPROPion may enhance the adverse/toxic effect of Vortioxetine. BuPROPion may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with bupropion. Following cessation of bupropion, the vortioxetine dose should be returned to the normal level. Consider therapy modification
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; blood pressure (baseline and periodically especially when used in conjunction with nicotine transdermal replacement); renal and hepatic function
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).
May interfere with urine detection of amphetamine/methamphetamine (false-positive). Decreased prolactin levels.
>10%:
Cardiovascular: Tachycardia (11%)
Central nervous system: Headache (25% to 34%), agitation (2% to 32%), dizziness (6% to 22%), insomnia (11% to 20%)
Dermatologic: Diaphoresis (5% to 22%)
Endocrine & metabolic: Weight loss (14% to 23%)
Gastrointestinal: Xerostomia (17% to 28%), nausea (1% to 18%)
Ophthalmic: Blurred vision (2% to 15%)
Respiratory: Pharyngitis (3% to 13%)
1% to 10%:
Cardiovascular: Palpitations (2% to 6%), cardiac arrhythmia (5%), chest pain (3% to 4%), hypertension (2% to 4%; may be severe), flushing (1% to 4%), hypotension (3%)
Central nervous system: Confusion (8%), anxiety (3% to 7%), hostility (6%), nervousness (3% to 5%), sensory disturbance (4%), sleep disorder (4%), migraine (1% to 4%), abnormal dreams (3%), memory impairment ( ≤3%), drowsiness (2% to 3%), irritability (2% to 3%), pain (2% to 3%), akathisia ( ≤2%), central nervous system stimulation (1% to 2%), paresthesia (1% to 2%), twitching (1% to 2%), dystonia ( ≥1%), depression
Dermatologic: Skin rash (1% to 8%), pruritus (2% to 4%), urticaria (1% to 2%)
Endocrine & metabolic: Weight gain (9%), menstrual disease (2% to 5%), decreased libido (3%), hot flash (1% to 3%)
Gastrointestinal: Constipation (5% to 10%), abdominal pain (2% to 9%), diarrhea (5% to 7%), flatulence (6%), anorexia (3% to 5%), increased appetite (4%), dysgeusia (2% to 4%), vomiting (2% to 4%), dyspepsia (3%), dysphagia ( ≤2%)
Genitourinary: Urinary urgency ( ≤2%), vaginal hemorrhage ( ≤2%), urinary tract infection ( ≤1%)
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, pruritus, urticaria)
Infection: Infection (8% to 9%)
Neuromuscular & skeletal: Tremor (3% to 6%), myalgia (2% to 6%), weakness (2% to 4%), arthralgia (1% to 4%), arthritis ( ≤2%), dyskinesia ( ≥1%), neck pain
Otic: Tinnitus (3% to 6%), auditory disturbance (5%)
Renal: Polyuria (2% to 5%)
Respiratory: Upper respiratory infection (9%), sinusitis (1% to 5%), cough (1% to 4%)
Miscellaneous: Fever (1% to 2%)
<1% (Limited to important or life-threatening): Abnormal accommodation, akinesia, alopecia, amnesia, anaphylactic shock, anaphylactoid reaction, anemia, angioedema, angle-closure glaucoma, aphasia, ataxia, atrioventricular block, cerebrovascular accident, colitis, coma, complete atrioventricular block, cystitis, deafness, delayed hypersensitivity, delirium, delusions, depersonalization, derealization, diplopia, drug-induced Parkinsons disease, dysarthria, dyspareunia, dysphoria, dysuria, edema, EEG pattern changes, erythema multiforme, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal reaction, extrasystoles, facial edema, gastric ulcer, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, glossitis, glycosuria, gynecomastia, hallucination, hepatic injury, hepatic insufficiency, hepatitis, hirsutism, hyperglycemia, hyperkinesia, hypertonia, hypoglycemia, hypokinesia, hypomania, impotence, increased intraocular pressure, increased libido, intestinal perforation, jaundice, leukocytosis, leukopenia, lymphadenopathy, manic behavior, myasthenia, mydriasis, myocardial infarction, myoclonus, neuralgia, neuropathy, orthostatic hypotension, painful erection, pancreatitis, pancytopenia, paranoia, pneumonia, psychiatric signs and symptoms, pulmonary embolism, rhabdomyolysis, salpingitis, sciatica, seizure (dose-related), SIADH, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, suicidal ideation, syncope, tardive dyskinesia, thrombocytopenia, tongue edema, urinary incontinence, urinary retention, vasodilatation
Elimination of bupropion and/or major metabolites may be reduced.
Elimination of hydroxybupropion is reduced in patients with alcoholic liver disease. Bupropion Cmax increased 70%, AUC increased 3-fold, and mean half-life increased to 29 hours in patients with severe hepatic impairment. Mean half-life for active metabolites increased 2- to 5-fold in patients with severe hepatic impairment.
May be at risk of accumulation of bupropion and its metabolites.
AUC was approximately 13% higher in men.
Major psychiatric warnings (use in treating psychiatric disorders):
- Suicidal thinking/behavior (use in treating psychiatric disorders): [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 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 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patients 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.
- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. 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.
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).
- Hypersensitivity reactions: Anaphylactoid/anaphylactic reactions have occurred, with symptoms of pruritus, urticaria, angioedema, and dyspnea. Serious reactions have been (rarely) reported, including erythema multiforme, Stevens-Johnson syndrome and anaphylactic shock. Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported.
- Hypertension: May elevate blood pressure and cause hypertension. Events have been observed in patients with or without evidence of preexisting hypertension. The risk is increased when used concomitantly with monoamine oxidase inhibitors, nicotine replacement, or other drugs that increase dopaminergic or noradrenergic activity. Assess blood pressure before treatment and monitor periodically.
- Neuropsychiatric effect (use in smoking cessation): [US Boxed Warning]: Serious neuropsychiatric events have occurred in patients taking bupropion for smoking cessation, including changes in mood (eg, depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, suicidal ideation, suicide attempt and completed suicide. The majority occurred during bupropion treatment; some occurred during treatment discontinuation. A causal relationship is uncertain as depressed mood may be a symptom of nicotine withdrawal. Some cases also occurred in patients taking bupropion who continued to smoke. However, subsequent controlled trials in patients with or without psychiatric disorders have not identified significant differences in neuropsychiatric effects for patients taking bupropion, varenicline, nicotine patches, or placebo (Anthenelli 2016; Cinciripini 2013). Observe all patients taking bupropion for neuropsychiatric reactions. Instruct patients to contact a health care provider if neuropsychiatric reactions occur.
- Ocular effects: May cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.
- Psychosis: May cause delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion; most common in depressed patients and patients with a diagnosis of bipolar disorder. Symptoms may abate with dose reduction and/or withdrawal of treatment.
- Seizures: May cause a dose-related risk of seizures. Use is contraindicated in patients with a history of seizures or certain conditions with high seizure risk (eg, history of anorexia/bulimia or patients undergoing abrupt discontinuation of ethanol, benzodiazepines, barbiturates, or antiepileptic drugs). Aplenzin and Wellbutrin XL are also contraindicated in patients with certain conditions with high seizure risk (eg, arteriovenous malformation, severe head injury, severe stroke, CNS tumor and CNS infection). Use caution with concurrent use of antipsychotics, antidepressants, theophylline, systemic corticosteroids, stimulants (including cocaine), anorexiants, or hypoglycemic agents, or with excessive use of ethanol, benzodiazepines, sedative/hypnotics, or opioids. Use with caution in seizure-potentiating metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia). The dose-dependent risk of seizures may be reduced by gradual dose increases and by not exceeding the maximum daily dose. Do not coadminister with other bupropion-containing formulations; Forfivo XL is contraindicated in patients receiving other dosage forms of bupropion. Permanently discontinue if seizure occurs during therapy. Chewing, crushing, or dividing long-acting products may increase seizure risk.
- 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 (off-label 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; consider a reduction in dose and/or frequency; Forfivo XL is not recommended in patients with hepatic impairment.
- Mania/hypomania: May precipitate a manic, mixed, or hypomanic episode; risk is increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Screen patients for a history of bipolar disorder and the presence of risk factors including a family history of bipolar disorder, suicide, or depression. Bupropion is not FDA approved for bipolar depression.
- Renal impairment: Use with caution in patients with renal impairment; consider a reduction in dose and/or frequency; Forfivo XL is not recommended in patients with renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Use with caution in the elderly; may be at greater risk of drug accumulation during chronic dosing. Consider a reduction in dose.
Dosage form specific issues:
- Extended release tablet: Insoluble tablet shell may remain intact and be visible in the stool.
Other warnings/precautions:
- Electroconvulsive therapy (ECT): May increase the risks associated with electroconvulsive therapy (ECT); consider discontinuing, when possible, prior to ECT treatment (APA 2010).
C
Adverse events have been observed in some animal reproduction studies. Bupropion and its metabolites were found to cross the placenta in in vitro studies (Earhart 2012). An increased risk of congenital malformations has not been observed following maternal use of bupropion during pregnancy; however, data specific to cardiovascular malformations is inconsistent. The long-term effects on development and behavior have not been studied. The ACOG recommends that antidepressant therapy during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009). There is insufficient information related to the use of bupropion to recommend use in pregnancy (ACOG 2010).
Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.
Aminoketone antidepressant structurally different from all other marketed antidepressants; like other antidepressants the mechanism of bupropions 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.
Rapid
Vd: ~20 to 47 L/kg (Laizure 1985)
Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion.
Urine (87%, primarily as metabolites); feces (10%, primarily as metabolites)
1 to 2 weeks
Bupropion: Immediate release: Within 2 hours; Sustained release: Within 3 hours; Extended release: ~5 hours (Forfivo XL: 5 hours [fasting]; 12 hours [fed])
Metabolite: Hydroxybupropion: Immediate release: ~3 hours; Extended release, sustained release: ~6 to 7 hours
1 to 2 days
Distribution: 3 to 4 hours
Elimination: ~21 hours after chronic dosing (range: 12 to 30 hours); Metabolites (after a single dose): 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
84%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, abdominal pain, tremors, nightmares, nausea, vomiting, constipation, dry mouth, insomnia, pharyngitis, sweating a lot, lack of appetite, or tablet shell in stool. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), confusion, seizures, anxietyideas of murder, forceful actions, psychosis, behavioral changes, hallucinations, irritability, panic attacks, mood changes, agitation, severe headache, severe dizziness, passing out, seizures, excessive weight gain or loss, angina, tachycardia, abnormal heartbeat, tinnitus, polyuria, enlarged lymph nodes, difficulty moving, severe joint pain, severe muscle pain, vision changes, eye pain, eye irritation, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.