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bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)

Tradename: Wellbutrin. Indications: 1) depression, especially with anergia &/or hypersomnia a) start 100 mg PO BID b) after 4-7 days, can increase to 100 mg TID c) max 150 mg/dose, 450 mg/day d) average effective dose 300-450 mg/day e) sustained release (Wellbutrin SR) 1] start 150 mg PO QAM 2] may increase to 150 mg PO BID 2) attention-deficit hyperactivity disorder (ADHD) in adults 3) smoking cessation (sustained release)* a) start 150 mg QAM for 3 days b) increase to 150 mg PO BID for 7-12 days to 7 weeks c) last dose no later than 5 pm d) max dose 150 mg PO BID double rate of smoking cessation [20] e) quit date should be 1 week after starting therapy to achieve steady-state level f) stop if no progress in smoking cessation by 7th week 4) sexual dysfunction in women [6] - may be used in combination with SSRI [26] - erectile dysfunction in men with comorbid depression (NEJM) [26] 5) good choice for depression in Parkinson's disease 6) neuropathic pain [9] 7) seasonal affective disorder (Wellbutin XL) 8) mania [16] * avoid for smoking cessation [22] - risk of neuropsychiatric disorders cited Contraindications: 1) seizures 2) bulimia 3) anorexia 4) use of monoamine oxidase (MAO) inhibitor within past 14 days Caution: 1) allow 8 hours between doses 2) avoid alcohol 3) safety of use in children < 18 years of age has NOT been established Dosage: 1) adults - start: 100 mg PO BID - maximum 450 mg QD, 150 mg/dose - usual dose 250-300 mg/day divided BID-TID 2) elderly patients: - start: 50-100 mg/day - increase by 50-100 mg every 3-4 days as tolerated - usual effective dose: 150 mg QD Tabs: 75 & 100 mg Sustained release: - Wellbutrin SR: 75, 100 & 150 mg. (BID dosing) - Wellbutrin XL: 150, 300 mg (QD dosing) Alpenzin is the hydrobromide salt of bupropion Dosage adjustment in renal failure: (& hepatic impairment) 1) use reduced dose 2) use with caution Pharmacokinetics: 1) bioavailability is low (5%), not affected by food 2) peak plasma levels 2 hours after oral dose (5 hours for XL) 3) > 80% bound to plasma proteins 4) metabolites accumulate in patients with renal or hepatic dysfunction 5) active metabolite hydroxybupropion a) 1/2life > 24 hours b) LD50 in mice 1/2 that of bupropion 6) therapeutic window of 50-100 ng/mL 7) no correlation between dose & response or plasma levels 8) inhibits cyt P450 2D6, thus may increase plasma levels of drugs metabolized by cyt P450 2D6 Adverse effects: 1) common (> 10%) - agitation, anxiety, restlessness, insomnia, confusion, constipation, anorexia, dizziness, dry mouth, increased sweating, nausea/vomiting, tremor, weight loss 2) less common (1-10%) - psychosis & hallucinations, skin rash, blurred vision, chills, fatigue 3) uncommon (< 1%) - fainting, drowsiness, seizures* 4) other - insomnia, agitation, headache, tinnitus, rash, diarrhea, tachycardia, akathisia, impotence, hostility, agitation, depression, suicidal ideation [14]# - no excess risk for depression or self-harm [17] - not associated with increased cardiovascular risk [18] - reduced risk for combined outcome of stroke, MI, & cardiovascular death (RR=0.45) [18] - not associated with excess risk for neuropsychiatric events when used for smoking cessation [19] - less likely than venlafaxine to cause GI distress [25] 5) overdose results in: - seizures (most common) - prolongation of the QT interval * increased potential with daily doses of 450-600 mg/day limit single doses to < 150 mg & daily doses to < 300 mg [3] # risk of serious side effects on mood, behavior, or thinking lower than previously suspected [21] Drug interactions: 1) L-dopa: higher incidence of adverse effects 2) monoamine oxidase inhibitors a) acute toxicity may be enhanced b) discontinue MAO inhibitors at least 14 days before starting bupropion 3) concurrent use of alcohol, tricyclic antidepressants (TCA) fluoxetine (Prozac) or phenothiazines lowers seizure threshold 4) cimetidine & ritonavir decrease bupropion metabolism 5) bupropion may increase metabolism of: a) carbamazepine b) phenytoin c) phenobarbital d) cimetidine 5) no known interaction with warfarin [25] Laboratory: 1) specimen: a) plasma (heparin) b) bupropion is unstable in human plasma c) freeze soon after collection d) stable frozen for 6 months 2) methods: HPLC, TLC, GC, RIA Mechanism of action: 1) monocyclic antidepressant 2) inhibits reuptake of norepinephrine & dopamine

Interactions

drug interactions drug adverse effects (more general classes)

Related

bupropion in blood bupropion in body fluid bupropion in serum/plasma bupropion in tissue bupropion in urine bupropion measurement

General

norepinephrine & dopamine reuptake inhibitor (NDRI)

Properties

MISC-INFO: elimination route KIDNEY 1/2life 9.6-21 HOURS therapeutic-range 25-100 UG/ML protein-binding 80% elimination by hemodialysis - peritoneal dialysis - pregnancy-category B safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  5. Prescriber's Letter 8(4):23 2001
  6. Prescriber's Letter 8(6):34 2001
  7. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  8. Journal Watch 21(20):162, 2001 Hayes et al, Ann Intern Med 135:423, 2002
  9. Journal Watch 22(1):10, 2002 Semenchunk et al, Neurology 57:1583, 2001
  10. Prescriber's Letter 9(3):13-14 2002
  11. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  12. Prescriber's Letter 10(10):57 2003 Detail-Document#: 191003 (subscription needed) http://www.prescribersletter.com
  13. Prescriber's Letter 13(9): 2006 Drug Treatment of Seasonal Affective Disorder (SAD) Detail-Document#: 220904 (subscription needed) http://www.prescribersletter.com
  14. FDA Safety Alert Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170090.htm
  15. Stahl SM et al A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor Prim Care Companion J Clin Psychiatry. 2004; 6(4):159-166 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/ http://www.bmj.com/content/347/bmj.f5704http://www.bmj.com/content/347/bmj.f5704
  16. Deprecated Reference
  17. Thomas KH et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: Prospective cohort study. BMJ 2013 Oct 11; 347:f5704. PMID: 24124105 http://www.bmj.com/content/347/bmj.f5704
  18. Mills EJ et al Cardiovascular Events Associated with Smoking Cessation Pharmacotherapies: A Network Meta-Analysis. Circulation. Dex 9, 2013 PMID: 24323793 http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.003961.abstract - Samet J Smoking Cessation: Benefits versus Risks of Using Pharmacotherapy to Quit. Circulation. Dex 9, 2013 PMID: 24323794 http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.006928.abstract
  19. Anthenelli RM et al Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo- controlled clinical trial. The Lancet. April 22, 2016 PMID: 27116918 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2930272-0/abstract
  20. Fossati R, Apolone G, Negri E et al A double-blind, placebo-controlled, randomized trial of bupropion for smoking cessation in primary care. Arch Intern Med. 2007 Sep 10;167(16):1791-7. PMID: 17846399
  21. FDA Safety Alert. Dec 16, 2016 Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533517.htm - FDA Safety Aommunication. Dec 16, 2016 FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm
  22. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  23. Clayton AH, Croft HA, Horrigan JP et al. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry 2006 Jul 18; 67:736. PMID: 16841623
  24. Patel K, Allen S, Haque MN et al. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol 2016 Apr; 6:99. PMID: 27141292 Free PMC Article
  25. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  26. NEJM Knowledge+ Psychiatry

Component-of

bupropion/dextromethorphan (Auvelity) bupropion/naltrexone (Contrave)