Dosing Tips

• XL formulation has replaced immediate release and SR formulations as the preferred option

• XL is best dosed once a day, whereas SR is best dosed twice daily, and immediate release is best dosed 3 times daily

• Dosing higher than 450 mg/day (400 mg/day SR) increases seizure risk

• Patients who do not respond to 450 mg/day should discontinue use or get blood levels of bupropion and its major active metabolite 6-hydroxy-bupropion

• If levels of parent drug and active metabolite are low despite dosing at 450 mg/day, experts can prudently increase dosing beyond the therapeutic range while monitoring closely, informing the patient of the potential risk of seizures and weighing risk-benefit ratios in difficult-to-treat patients

• When used for bipolar depression, it is usually as an augmenting agent to mood stabilizers, lithium, and/or atypical antipsychotics

• For smoking cessation, may be used in conjunction with nicotine replacement therapy

• Do not break or chew SR or XL tablets as this will alter controlled release properties

• The more anxious and agitated the patient, the lower the starting dose, the slower the titration, and the more likely the need for a concomitant agent such as trazodone or a benzodiazepine

• If intolerable anxiety, insomnia, agitation, akathisia, or activation occur either upon dosing initiation or discontinuation, consider the possibility of activated bipolar disorder and switch to a mood stabilizer or an atypical antipsychotic

Overdose

• Rarely lethal; seizures, cardiac disturbances, hallucinations, loss of consciousness

Long-Term Use

• For smoking cessation, treatment for up to 6 months has been found effective

• For depression, treatment up to 1 year has been found to decrease rate of relapse

Habit Forming

• No

• Can be abused by individuals who crush and then snort or inject it

How to Stop

• Tapering is prudent to avoid withdrawal effects, but no well-documented tolerance, dependence, or withdrawal reactions

Pharmacokinetics

• Inhibits CYP450 2D6

• Parent half-life 10–14 hours

• Metabolite half-life 20–27 hours

Drug Interactions

• Tramadol increases the risk of seizures in patients taking an antidepressant

• Can increase tricyclic antidepressant levels; use with caution with tricyclic antidepressants or when switching from a TCA to bupropion

• Use with caution with MAO inhibitors, including 14 days after MAOIs are stopped (for the expert)

• Via CYP450 2D6 inhibition, bupropion could theoretically interfere with the analgesic actions of codeine, and increase the plasma levels of some beta blockers and of atomoxetine

• Via CYP450 2D6 inhibition, bupropion could theoretically increase concentrations of thioridazine and cause dangerous cardiac arrhythmias

Other Warnings/Precautions

• Use cautiously with other drugs that increase seizure risk (TCAs, lithium, phenothiazines, thioxanthenes, some antipsychotics)

• Bupropion should be used with caution in patients taking levodopa or amantadine, as these agents can potentially enhance dopamine neurotransmission and be activating

• Do not use if patient has severe insomnia

• Use with caution in patients with bipolar disorder unless treated with concomitant mood-stabilizing agent

• When treating children, carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment and make sure to document this in the patient’s chart

• Distribute the brochures provided by the FDA and the drug companies

• Warn patients and their caregivers about the possibility of activating side effects and advise them to report such symptoms immediately

• Monitor patients for activation of suicidal ideation, especially children and adolescents

• Discontinuing smoking may lead to pharmacokinetic or pharmacodynamic changes in other drugs the patient is taking, which could potentially require dose adjustment

Do Not Use

• Zyban or Aplenzin in combination with each other or with any formulation of Wellbutrin

• If patient has history of seizures

• If patient is anorexic or bulimic, either currently or in the past, but see Pearls

• If patient is abruptly discontinuing alcohol or sedative use

• If patient has had recent head injury

• If patient has a nervous system tumor

• If patient is taking an MAO inhibitor (except as noted under Drug Interactions)

• If patient is taking thioridazine

• If there is a proven allergy to bupropion

BUPROPION: SPECIAL POPULATIONS

Renal Impairment

• Lower initial dose, perhaps give less frequently

• Drug concentration may be increased

• Patient should be monitored closely

Hepatic Impairment

• Lower initial dose, perhaps give less frequently

• Patient should be monitored closely

• In severe hepatic cirrhosis, bupropion XL should be administered at no more than 150 mg every other day

Cardiac Impairment

• Limited available data

• Evidence of rise in supine blood pressure

• Use with caution

Elderly

• Some patients may tolerate lower doses better

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Safety and efficacy have not been established

• May be used for ADHD in children or adolescents

• May be used for smoking cessation in adolescents

• Preliminary research suggests efficacy in comorbid depression and ADHD

• Dosage may follow adult pattern for adolescents

• Children may require lower doses initially, with a maximum dose of 300 mg/day