Bupropion Hydrochloride

Pronunciation

Class: Antidepressants, Miscellaneous
VA Class: CN609
Chemical Name: ±-1-(3-Chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone Hydrochloride
Molecular Formula: C13H18ClNO•ClH
CAS Number: 31677-93-7
Brands: Wellbutrin, Zyban

Warning(s)

  • Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders
  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.1 142 143 161 162 168 Bupropion is not approved for use in pediatric patients.1 142 143 168 (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.161 162

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.161 162 167

  • Appropriately monitor and closely observe all patients who are started on bupropion therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.1 142 143 162 161 167 168 (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders under Cautions.)

  • Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment
  • Serious neuropsychiatric symptoms (e.g., depression, suicidal ideation, suicide attempt, completed suicide) have been reported in patients receiving bupropion for smoking cessation.182 183 184 185 186 187 (See Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment under Cautions.)

  • Symptoms have occurred in patients with and without preexisting psychiatric disease; some patients experienced worsening of their psychiatric illness.182 183 184 185

  • Depressed mood may be a symptom of nicotine withdrawal;182 183 184 185 186 however, some symptoms occurred in bupropion-treated patients who continued to smoke.182 183 184 185 186 187

  • Most symptoms occurred during bupropion therapy, but some were reported following discontinuance of drug.182 183 184 185

  • Monitor all patients receiving bupropion for smoking cessation for neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, and suicide-related events (including ideation, behavior, and attempted suicide).182 183 184 185

  • Patients should discontinue bupropion and immediately contact their clinician if agitation, hostility, depressed mood, or changes in thinking or behavior not typical for the patient occur, or if patient develops suicidal ideation or behavior.182 183 184 185

  • Symptoms resolved upon drug discontinuance in many cases, but persisted in a few cases.182 183 184 185 186 187 Provide ongoing monitoring and supportive care until symptoms resolve.182 183 184 185

  • Weigh risks of bupropion for smoking cessation against benefits.182 183 184 185 186 187 Bupropion shown to increase likelihood of abstinence from smoking for up to 6 months compared with placebo.182 183 184 185 186 187 Health benefits of quitting smoking are immediate and substantial.182 183 184 185 186 187

REMS:

FDA approved a REMS for bupropion to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of bupropion and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antidepressant and smoking deterrent; aminoketone derivative.1 43 142 143 168

Uses for Bupropion Hydrochloride

Major Depressive Disorder

Treatment of major depressive disorder.1 127 128 129 131 132 142 168 179 180

May be useful (alone or in combination with other antidepressants) in patients with refractory depression.179 180

Seasonal Affective Disorder

Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD; also referred to as winter depression).168 169 170 171

Slideshow: How to Manage Antidepressant Side Effects

Smoking Cessation

Adjunct in the cessation of smoking (alone or in combination with nicotine replacement therapy).143 145 146 147 152 (See Cardiovascular Effects under Cautions and see also Smoking Cessation and Specific Drugs under Interactions.)

Depression Associated with Bipolar Disorder

Treatment of patients with bipolar depression (bipolar disorder, depressive episode).2 77 78 85 86 102 154

American Psychiatric Association (APA) considers bupropion one of several second-line agents for use when first-line agents are ineffective or not tolerated.154

Attention Deficit Hyperactivity Disorder (ADHD)

Used in a limited number of children2 44 79 80 134 156 157 158 and adults in the management of ADHD.2 44 76 126

Panic Disorder

Ineffective in the treatment of panic disorder and concomitant phobic disorder,2 44 99 134 but may improve symptoms of panic and depression in patients with major depression who have superimposed panic symptoms.44

Bulimia Nervosa

Not recommended by APA for bulimia nervosa because associated with seizures in purging bulimic patients.153

Bupropion Hydrochloride Dosage and Administration

General

  • Appropriately monitor and closely observe all patients receiving bupropion for any indication for clinical worsening, suicidality, or unusual changes in behavior, particularly during initial therapy or following any change (increase or decrease) in dosage.161 162 167 182 183 184 (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

  • Monitor all patients receiving bupropion for smoking cessation for serious neuropsychiatric symptoms or worsening of preexisting psychiatric illness.182 183 184 185 186 187 (See Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment in Boxed Warning and also under Cautions.)

Major Depressive Disorder

  • Increase dosages gradually to minimize the risk of seizures and other adverse effects; do not exceed recommended maximum individual doses or daily dosages.1 142 168 (See Prescribing Limits and see Seizures under Warnings.)

  • Maximum antidepressant effects of therapy may not be evident until ≥4 weeks of treatment.1 142 168

  • Sustained therapy may be required; monitor periodically for need for continued therapy.1 142 168

Administration

Oral Administration

Conventional Tablets

Initially, administer orally twice daily in the morning and evening, then increase to 3 times daily, preferably with 6 or more hours separating doses (e.g., in the morning, at midday, and in the evening).1 23 24 141

Dosages ≥300 mg should be administered as divided doses that do not exceed 150 mg per dose.1 If components of a larger dosage include 4 whole tablets of 100 mg each, administer the divided doses 4 times daily separated by 4 or more hours so that no individual dose exceeds 150 mg.1

Avoid bedtime administration of evening dose to decrease incidence of insomnia.1 142 152

Extended-release Tablets

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, administer orally once daily in the morning, then increase to twice daily, in the morning and evening.142 Dosages >150 mg should be administered as divided doses twice daily, preferably with 8 or more hours separating the doses.142 143 Avoid bedtime administration of evening dose to decrease incidence of insomnia.183

Extended-release, film-coated tablets (e.g., Zyban): Administer orally once daily for the first 3 days, then usually increase to twice daily administration with 8 or more hours separating the doses.143 Avoid bedtime administration of evening dose to decrease incidence of insomnia.182

Extended-release tablets (Wellbutrin XL): Administer orally once daily in the morning, with an interval of 24 hours separating the doses.168

Do not chew, divide, or crush the extended-release tablets (e.g., Zyban, Wellbutrin SR, Wellbutrin XL); tablets should be swallowed whole.142 143 168

The shell of the extended-release tablet (Wellbutrin XL) does not dissolve and may be passed in the stool.168

Dosage

Available as bupropion hydrochloride; dosage expressed in terms of the salt.1

Pediatric Patients

ADHD
Oral

Children weighing ≥20 kg: Initially, 1 mg/kg daily in 2–3 divided doses.156 After 3 days, titrate up to 3 mg/kg daily in 2–3 divided doses by day 7, then up to 6 mg/kg daily in 2–3 divided doses or 300 mg (whichever is smaller) by third week of therapy.156

Alternatively, may give initial dose of 37.5 or 50 mg twice daily with titration over 2 weeks up to a maximum of 250 mg daily (300–400 mg daily in adolescents).157

Pediatric dosage for ADHD generally has ranged from 50–100 mg 3 times daily for conventional tablets or 100–150 mg twice daily for extended-release tablets.158

Adults

Major Depression
Therapy with Conventional Tablets
Oral

Initially, 100 mg twice daily.1 Alternatively, dosage may be initiated at 75 mg 3 times daily.23 24 141

If clinical improvement not apparent after >3 days, may increase to 100 mg 3 times daily.1 23 24 141 142

Dosages >300 mg should not be considered until completion of several weeks of therapy; if no improvement is apparent, then the dosage may be increased to 150 mg 3 times daily.1 142 Dosage should not be increased by more than 100 mg every 3 days.1 23 24 141 142

If no improvement after appropriate trial at 450 mg daily, the drug should be discontinued.1 23 24 141

Therapy with Extended-release Tablets
Oral

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, 150 mg once daily in the morning.142 If tolerated, may increase to 150 mg twice daily as early as fourth day of therapy.142 Dosages >300 mg daily should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to 200 mg twice daily.1 142

Extended-release tablets (Wellbutrin XL): Initially, 150 mg once daily.168 If tolerated, may increase to 300 mg once daily as early as fourth day of therapy.168 Dosages >300 mg should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to 450 mg once daily.168

When switching from conventional or extended-release, film-coated tablets (e.g., Wellbutrin SR) to extended-release tablets (Wellbutrin XL), administer same total daily dose when possible.168

Seasonal Affective Disorder
Therapy with Extended-release Tablets
Oral

Extended-release tablets (Wellbutrin XL): Initiate therapy in autumn prior to onset of depressive symptoms; continue treatment through the winter and taper and discontinue in early spring.168 169 Individualize timing of initiation and duration of therapy based on patient’s historical pattern of seasonal depressive episodes.168

Initially, 150 mg once daily in the morning.168 If tolerated, may increase dosage after 1 week to 300 mg once daily.168 If this dosage is not tolerated, reduce dosage to 150 mg once daily.168

Usual target dosage: 300 mg once daily in the morning.168

For patients receiving 300 mg once daily during the autumn-winter period, taper dosage to 150 mg once daily for 2 weeks prior to discontinuance.168

Smoking Cessation
Therapy with Extended-release, Film-coated Tablets
Oral

Initially, 150 mg daily for the first 3 days of therapy.143 145 152 Initiate 1–2 weeks prior to discontinuance of cigarette smoking.143 145 152

Maintenance, 150 mg twice daily.143 145 Continue therapy for 7–12 weeks; evaluate need for prolonged therapy after that period based on individual patient assessment.143 152

Cessation of smoking is unlikely in patients who do not show substantial progress toward abstinence after 7 weeks of therapy, so such therapy should be discontinued at that time in these patients.143

Combination Therapy with Extended-release Tablets and Transdermal Nicotine Patches
Oral

Initially, 150 mg daily, and after 3 days increase to 150 mg twice daily while still smoking.143

After about 1 week of therapy, when the patient is scheduled to stop smoking, initiate transdermal nicotine therapy at a dosage of 21 mg/24 hours.143

Taper transdermal nicotine to 14, then to 7 mg/24 hours during the eighth and ninth weeks of therapy, respectively.143

Depression Associated With Bipolar Disorder
Oral

Dosages generally range from 75–400 mg in conjunction with a mood-stabilizing agent (e.g., carbamazepine, lithium, valproate).2

ADHD
Therapy with Conventional Tablets
Oral

Initially, 150 mg daily.2 May be titrated up to 450 mg daily.2

Prescribing Limits

Adults

Major Depression
Oral

Conventional tablets: Maximum 450 mg daily (not >150 mg per dose).1

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Maximum 400 mg daily (not >200 mg per dose).142

Extended-release tablets (Wellbutrin XL): Maximum 450 mg daily.168

Seasonal Affective Disorder
Oral

Extended-release tablets (e.g., Wellbutrin XL): Dosages >300 mg daily have not been studied.168

Smoking Cessation
Oral

Extended-release, film-coated tablets (e.g., Zyban): 300 mg daily (not >150 mg per dose).143

Special Populations

Hepatic Impairment

Maximum Dosage for Major Depression and Seasonal Affective Disorder in Severe Hepatic Cirrhosis1142168

Dosage Form

Maximum Dosage

Conventional tablets

75 mg once daily1

Extended-release, film-coated tablets (e.g., Wellbutrin SR)

100 mg once daily or 150 mg every other day142

Extended-release tablets (Wellbutrin XL)

150 mg every other day168

Smoking cessation in patients with severe hepatic cirrhosis: Maximum 150 mg every other day as extended-release, film-coated tablets (e.g., Zyban).143

Major depression, seasonal affective disorder, or smoking cessation in patients with mild to moderate hepatic impairment (e.g., mild to moderate hepatic cirrhosis): Reduce dosage and/or frequency of administration as required.1 142 143 168 (See Hepatic Impairment under Cautions.)

Renal Impairment

Active metabolites may accumulate; reduce dosage and/or frequency of administration as required.1 142 143 168 177 (See Renal Impairment under Cautions.)

Smoking cessation in patients undergoing hemodialysis: Some clinicians recommend a dosage of 150 mg every 3 days as extended-release, film-coated tablets (e.g., Zyban).177

Cautions for Bupropion Hydrochloride

Contraindications

  • Seizure disorders.1 142 143 152 168

  • Current or past diagnosis of anorexia nervosa or bulimia.1 21 22 24 39 142 143 152 168

  • Contraindicated in patients receiving any other bupropion formulation (e.g., for smoking cessation, antidepressant use) because risk of seizures is dose-dependent.1 142 143 168

  • Patients undergoing abrupt discontinuance of alcohol or sedatives (including benzodiazepines).1 142 143 168

  • Patients currently receiving, or having recently received (i.e., within 2 weeks), MAO inhibitor therapy.1 142 152 168

  • Hypersensitivity to the drug or any ingredient in the formulation.1 142 168

Warnings/Precautions

Warnings

Seizures

Seizures reported;1 6 19 20 24 52 142 143 168 risk of seizures may be higher with sudden and large increases in dosage.1 8 (See Dosage and Administration.)

Risk factors include patient factors (e.g., history of head trauma or prior seizure, CNS tumor, presence of severe hepatic cirrhosis), clinical situations (excessive use of alcohol or sedatives [e.g., benzodiazepines], abrupt withdrawal from alcohol or other sedatives, addiction to opiates, cocaine, or stimulants, use of OTC stimulants and anorectics, diabetes treated with oral hypoglycemics or insulin), and concomitant drugs that lower seizure threshold.1 8 142 143 168 (See Interactions: Specific Drugs.)

If patients experience a seizure during therapy, discontinue drug and do not restart.1 142 143 168

Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.1 142 143 161 162 167 168 181 However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.161 162 167

Appropriately monitor and closely observe patients receiving bupropion for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.1 142 143 161 162 167 168 (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.161 167 Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.1 142 143 161 162 167 168 (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.1 142 143 168 161

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.1 142 143 161 168

Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment

Serious neuropsychiatric symptoms, including mood changes (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, reported in patients receiving bupropion for smoking cessation.182 183 184 185 186 187 (See Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment in Boxed Warning.)

Monitor all patients receiving bupropion for smoking cessation for such neuropsychiatric symptoms.182 183 184 185

Patients and caregivers that patients should stop taking bupropion and immediately contact their clinician if agitation, hostility, depressed mood, or changes in thinking or behavior not typical for the patient occur, or if patient develops suicidal ideation or behavior.182 183 184 185 Symptoms resolved upon drug discontinuance, in many cases but persisted in a few cases.182 183 184 185 186 187 Provide ongoing monitoring and supportive care until symptoms resolve.182 183 184 185 186

Weigh possible risk of serious adverse effects with bupropion against health benefits of smoking cessation (e.g., reduced risk of developing pulmonary disease, cardiovascular disease, and cancer).182 183 184 185 186 187

Bipolar Disorder

May unmask bipolar disorder.1 142 143 161 168 (See Activation of Mania or Psychosis under Cautions.) Bupropion is not approved for use in treating bipolar depression.1 142 143 168

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.1 142 143 161 168

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., pruritus, urticaria, angioedema, dyspnea) have been reported;1 142 143 168 however, causality has not been established.145 Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.1 142 143 168

Possible arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity.1 142 143 168

Major Toxicities

Hepatotoxicity

Abnormal hepatic function (e.g., jaundice, hepatitis) infrequently reported during postmarketing surveillance; causal relationship not established.1 40 142 143 168 However, increased incidence of hepatic hyperplastic nodules and hepatocellular hypertrophy observed in rats receiving large doses and various histologic changes and mild hepatocellular injury observed in dogs administered large doses of the drug.1 142 143 168

General Precautions

CNS Effects

Agitation,1 3 5 6 7 8 45 46 47 51 52 53 54 142 168 insomnia,1 3 5 7 45 46 47 51 52 53 142 143 152 168 and anxiety1 3 54 142 168 have been reported.1 Insomnia may be minimized by avoidance of bedtime administration or reduction of dosage.1 142 143 168

Neuropsychiatric manifestations, including confusion, delusions, hallucinations, psychosis, disturbances in concentration, and paranoia, reported in patients receiving bupropion in depression trials.182 183 184 185 Similar types of neuropsychiatric manifestations reported during postmarketing experience in patients receiving the drug for smoking cessation.182 183

Activation of Mania or Psychosis

Possible activation of mania or hypomania in bipolar disorder patients (see Bipolar Disorder under Cautions); activation of latent psychosis may occur in susceptible patients.1 142 143 168

Metabolic Effects

Possible anorexia and weight loss (exceeding 2.27 kg);1 19 29 30 52 caution in patients in whom weight loss is a presenting manifestation of depression.1 143 168

Cardiovascular Effects

Hypertension (sometimes severe) has occurred with bupropion therapy either alone or in combination with transdermal nicotine in patients with and without pre-existing hypertension.1 Safety in patients with recent history of MI or unstable heart disease not established.1 142 143 168

Electroconvulsive Therapy (ECT)

Possible increased duration of motor and EEG seizures in certain patients.44 94 104 Some clinicians suggest that ECT can be safely performed 48 hours after discontinuance of bupropion.44

Specific Populations

Pregnancy

Category B.1 142 143 168 Bupropion pregnancy registry at 800-336-2176.1 142 143 168

Lactation

Distributed into milk; discontinue nursing or drug.1 2 64 142 143 168

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 142 143 168

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).1 142 143 161 162 168 However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.181 No suicides occurred in these pediatric trials.1 142 143 161 162 168 181

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use.1 142 143 162 168 162 161 167 181 (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

Has been used in a limited number of children 7–16 years of age for attention deficit disorder without unusual adverse effect.2 44 79 80 134 158

Has been used as extended-release preparation in adolescents for smoking cessation.152 (See Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment in Boxed Warning and also under Cautions.)

Geriatric Use

Use with caution;1 possible decreased clearance.1 142 143 No substantial differences in safety and efficacy relative to younger adults.1 2 142 143 168

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.162 161 (See Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders in Boxed Warning and also under Cautions.)

Hepatic Impairment

Use with extreme caution in patients with severe hepatic cirrhosis and caution in patients with hepatic impairment (e.g., mild to moderate hepatic cirrhosis); reduced frequency and/or dosage and close monitoring for adverse effects required.1 142 143 168 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution; active metabolites may accumulate.1 142 143 168 177 Monitor closely for adverse effects (e.g., seizures); reduction in dosage and/or frequency may be necessary.1 142 143 168 177

Common Adverse Effects

Agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, tremor.1 3 6 7 19 44 47 50 134 142 143 152 168

Interactions for Bupropion Hydrochloride

Metabolized principally by CYP2B6; may also inhibit CYP2D6 and induce other hepatic microsomal enzymes.1 142 143 168

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered serum concentrations of bupropion) with drugs that induce or inhibit CYP2B6.1 142 143 168

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: potential pharmacokinetic interaction (increased plasma substrate concentrations).1 142 143 168

Substrates of hepatic microsomal enzymes: potential pharmacokinetic interaction (altered substrate metabolism).1 142 143 168

Smoking Cessation

Smoking may induce enzymes and increase metabolism of some drugs.149 150 151 Therefore, cessation of smoking (with or without adjunctive use of bupropion) may result in decreased enzyme induction and altered metabolism of some drugs (e.g., theophylline, warfarin); consider dosage adjustment.143

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible neuropsychiatric effects or reduced alcohol tolerance1 142 143

Possible increased risk of seizures with excessive use of alcohol or abrupt withdrawal from alcohol1 142 143

Minimize or avoid alcohol consumption 1 142 143 168

Amantadine

Potential increased incidence of adverse effects (e.g., nausea/vomiting, excitement/restlessness, postural tremor)1 2 44 55 142 143

Use with caution; initiate bupropion therapy with lower dosage and increase gradually in small increments1 142 143

Antiarrhythmic agents, class 1C (e.g., flecainide, propafenone)

Possible decreased metabolism of antiarrhythmic agent144

Use with caution;144 consider dosage reduction of antiarrhythmic agent1 142

Antidepressants

Possible lowering of seizure threshold; increased risk of seizures1 142 143

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143

Antidepressants, SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline)

Possible decreased metabolism of SSRI1 142 143 144 168

Possible decreased metabolism of bupropion168

Use with caution;144 168 consider dosage reduction of SSRI1 142 168

Antidepressants, tricyclic (TCAs) (e.g., desipramine, imipramine, nortriptyline)

Possible decreased TCA metabolism144 168

Use with caution;144 168 consider dosage reduction of TCA1 142 168

Antipsychotic agents (e.g., haloperidol, risperidone, thioridazine)

Possible lowering of seizure threshold; increased risk of seizures1 142 143

Possible decreased metabolism of antipsychotic144

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143

Use with caution;144 consider dosage reduction of antipsychotic agent1 142

β-Adrenergic blocking agents (e.g., metoprolol)

Possible decreased metabolism of β-blocker144

Use with caution;144 consider dosage reduction of β-blocker1 142

Benzodiazepines

Increased risk of seizures with excessive use or abrupt discontinuance1 142 143

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually1 142 143

Carbamazepine

Possible increased metabolism of bupropion1 138 142 143

Use with caution1 138 142 143

Cimetidine

Possible decreased metabolism of bupropion1 138 142 143

Use with caution1 138 142 143

Corticosteroids (systemic)

Possible lowering of seizure threshold; increased risk of seizures1 142 143

Use with extreme caution; initiate therapy with lower dosages and increase gradually1 142 143

Cyclophosphamide

Potential altered metabolism of bupropion142 143

Efavirenz

Possible decreased metabolism of bupropion1 142 143 168 173

Lamotrigine

Pharmacokinetic interactions unlikely1 142 143 168 172

Levodopa

Potential increased incidence of adverse effects (e.g., nausea/vomiting, excitement/restlessness, postural tremor)1 2 44 55 142 143

Use with caution; initiate therapy with lower bupropion dosage and increase gradually in small increments1 142 143

MAO inhibitors (e.g., phenelzine)

Possible enhanced acute toxicity of bupropion1 2 142 168

Concurrent administration is contraindicated; at least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion1 142 168

Nelfinavir

Possible decreased metabolism of bupropion1 142 143 168 173

Nicotine

Possible increased risk of hypertension143

Orphenadrine

Potential altered metabolism of bupropion142 143

Phenobarbital

Possible increased metabolism of bupropion1 138 142 143

Use with caution1 138 142 143

Phenytoin

Possible increased metabolism of bupropion1 138 142 143

Use with caution1 138 142 143

Ritonavir

Possible decreased metabolism of bupropion1 142 143 168 173

Theophylline

Possible lowering of seizure threshold; increased risk of seizures1 142 143

Use with extreme caution; initiate therapy with lower bupropion dosage and increase gradually1 142 143

Thiotepa

Potential altered metabolism of bupropion142 143

Warfarin

Possible altered PT/INR; infrequently associated with hemorrhagic or thrombotic complications1 142 143

Bupropion Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well-absorbed from the GI tract following oral administration.60 Peak plasma concentrations usually occur within 2, 3, or 5 hours after oral administration of conventional or extended-release tablets of Wellbutrin SR or Wellbutrin XL, respectively.1 59 61 90 130 142 143 168

At steady state, conventional and extended-release tablets (Wellbutrin SR, Wellbutrin XL) are essentially bioequivalent.142 168

Food

Food does not appear to substantially affect the peak plasma concentration or extent of absorption achieved with extended-release tablets.142 143 168

Distribution

Extent

Bupropion and its metabolites are distributed into milk.2 64

Plasma Protein Binding

≥80% bound to human albumin.1 142 143 168

Elimination

Metabolism

Extensively metabolized in the liver1 57 60 61 130 142 143 to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion.1 142 143 168

Elimination Route

Excreted in urine (87%) and feces (10%), principally as metabolites.1 61 130 142 143 168

Half-life

The half-life in the terminal phase (t½β) averages about 14 hours following single doses; 1 57 61 90 130 139 with multiple dosing, t½β reportedly averages 21 hours.139 142

Special Populations

Hepatic impairment can decrease elimination of the drug.143

Renal impairment may decrease elimination of major metabolites.1 142 143 168 177

Stability

Storage

Oral

Conventional Tablets

15–25°C; protect from light and moisture.1

Extended-release Tablets

Extended-release, film-coated tablets (e.g., Wellbutrin SR, Zyban): tight, light-resistant containers at 20–25°C.142 143

Extended-release tablets (Wellbutrin XL): tight, light-resistant containers at 25°C (may be exposed to temperatures ranging from 15–30°C).168

Actions

  • Chemically unrelated to tricyclic, tetracyclic, or other currently available antidepressants (e.g., SSRIs);1 43 142 143 168 also chemically unrelated to nicotine or other agents currently used in treatment of nicotine dependence.143

  • Mechanism of antidepressant action is unclear; noradrenergic pathways appear to be principally involved.1 2 115 142 168

  • Mechanism of action as an adjunct in the cessation of smoking is unclear; noradrenergic and/or dopaminergic effects presumably are involved.143 145 146

  • Produces less frequent anticholinergic effects, cardiovascular effects, antihistaminic effects, and weight gain compared with tricyclic antidepressants at usual dosages.2 23 44 104 127 128 133

Advice to Patients

  • Importance of providing copy of written patient information (medication guide) each time bupropion is dispensed.182 183 184 185

  • Risk of suicidality with antidepressants; importance of patients, families, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.1 142 143 167 168 162 161 167 Advise patients to read the medication guide explaining risks of suicidality before starting bupropion and each time the prescription is refilled.182 183 184 185

  • Risk of serious neuropsychiatric symptoms, including changes in mood (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, when used for smoking cessation.182 183 184 185 186 187 Advise patients to read the medication guide explaining the risk of such symptoms before starting bupropion and each time the prescription is refilled.182 183 184 185

  • Importance of advising patients and caregivers that patients using bupropion for smoking cessation should stop drug and immediately contact clinician if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.182 183 184 185

  • Importance of advising patients that it usually takes several weeks of antidepressant therapy before they will start to feel better.183 184 185 Advise patients not to stop taking the drug if a response is not evident right away.183 184 185

  • Importance of avoiding concurrent therapy with preparations containing bupropion for use as an adjunct in smoking cessation (e.g., Zyban) and preparations used for treatment of major depressive disorder or seasonal affective disorder (e.g., various Wellbutrin formulations and generic formulations).182 183 184 185

  • Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until the effects on the individual are known.1 142 143 168

  • Importance of minimizing or avoiding consumption of alcohol; use of alcohol or abrupt cessation of use may alter the seizure threshold.1 142 143 168

  • Risk of seizures, particularly in patients with certain medical problems, those taking certain drugs concomitantly, and those receiving higher dosages (see Seizures under Cautions).182 183 184 185 Advise patients to stop taking the drug and immediately notify their clinician if they have a seizure.182 183 184 185

  • Risk of anaphylactoid and other sensitivity reactions.182 183 184 185 Advise patients to stop taking bupropion and notify their clinician immediately if they develop signs of a severe allergic reaction (e.g., rash, itching, hives, fever, swollen lymph glands, painful sores in mouth or around eyes, swelling of lips or tongue, chest pain, difficulty breathing).182 183 184 185

  • Risk of high blood pressure, which can be severe.182 185 Risk may be higher during concurrent use of nicotine replacement therapy (e.g., nicotine patch) for smoking cessation.182 185

  • Importance of informing patients that the shell of the extended-release tablet (Wellbutrin XL) does not dissolve and may be passed in the stool.168

  • Importance of not crushing or chewing extended-release tablets.142 143 168

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1 142 143 168

  • Importance of women notifying clinicians if they are or plan to become pregnant or plan to breast-feed.1 142 143 168

  • Importance of informing patients of other important precautionary information.1 142 143 168 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupropion Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

150 mg*

Wellbutrin XL

GlaxoSmithKline

300 mg*

Wellbutrin XL

GlaxoSmithKline

Tablets, extended-release, film-coated

100 mg*

Bupropion Hydrochloride SR

Wellbutrin SR

GlaxoSmithKline

150 mg*

Bupropion Hydrochloride SR

Wellbutrin SR

GlaxoSmithKline

Zyban (available as 60-tablet Advantage Pack or refill)

GlaxoSmithKline

200 mg*

Bupropion Hydrochloride SR

Wellbutrin SR

GlaxoSmithKline

Tablets, film-coated

75 mg*

Bupropion Hydrochloride

Wellbutrin

GlaxoSmithKline

100 mg*

Bupropion Hydrochloride

Wellbutrin

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aplenzin 174MG 24-hr Tablets (SANOFI-AVENTIS U.S.): 30/$155.98 or 90/$445.95

Aplenzin 348MG 24-hr Tablets (SANOFI-AVENTIS U.S.): 30/$245.99 or 90/$706.00

Aplenzin 522MG 24-hr Tablets (SANOFI-AVENTIS U.S.): 30/$560.00 or 90/$1,629.99

Budeprion XL 150MG 24-hr Tablets (TEVA PHARMACEUTICALS USA): 60/$105.98 or 180/$295.93

Budeprion XL 300MG 24-hr Tablets (TEVA PHARMACEUTICALS USA): 30/$135.00 or 90/$371.96

BuPROPion HCl 100MG 12-hr Tablets (WATSON LABS): 60/$75.99 or 180/$195.97

BuPROPion HCl 100MG Tablets (MYLAN): 30/$29.99 or 90/$79.97

BuPROPion HCl 150MG 12-hr Tablets (WATSON LABS): 60/$105.98 or 180/$295.96

BuPROPion HCl 200MG 12-hr Tablets (WATSON LABS): 60/$129.99 or 180/$339.97

BuPROPion HCl 300MG 24-hr Tablets (WATSON LABS): 30/$137.99 or 90/$367.97

BuPROPion HCl 75MG Tablets (MYLAN): 90/$74.99 or 270/$210.98

BuPROPion HCl (XL) 150MG 24-hr Tablets (ANCHEN PHARMACEUTICALS): 30/$100.00 or 90/$279.97

Bupropion HCl XL 150MG 24-hr Tablets (WATSON LABS): 60/$106.99 or 180/$298.96

Wellbutrin 100MG Tablets (GLAXO SMITH KLINE): 90/$311.29 or 270/$904.92

Wellbutrin 75MG Tablets (GLAXO SMITH KLINE): 90/$235.28 or 270/$682.93

Wellbutrin SR 100MG 12-hr Tablets (GLAXO SMITH KLINE): 60/$227.99 or 180/$648.97

Wellbutrin SR 150MG 12-hr Tablets (GLAXO SMITH KLINE): 60/$229.98 or 180/$662.96

Wellbutrin SR 200MG 12-hr Tablets (GLAXO SMITH KLINE): 60/$441.01 or 180/$1,279.02

Wellbutrin XL 150MG 24-hr Tablets (VALEANT): 30/$230.97 or 90/$629.94

Wellbutrin XL 300MG 24-hr Tablets (VALEANT): 30/$290.00 or 90/$825.99

Zyban 150MG 12-hr Tablets (GLAXO SMITH KLINE): 60/$209.99 or 180/$579.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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