Bupropion

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Internet Database 12 References

Introduction

• Tradename: Wellbutrin.

Indications

• depression, especially with anergia &/or hypersomnia

• start 100 mg PO BID
• after 4-7 days, can increase to 100 mg TID
• max 150 mg/dose, 450 mg/day
• average effective dose 300-450 mg/day
• sustained release (Wellbutrin SR)

• start 150 mg PO QAM
• may increase to 150 mg PO BID

• attention-deficit hyperactivity disorder ( ADHD) in adults
• smoking cessation ( sustained release):

• start 150 mg QAM for 3 days
• increase to 150 mg PO BID for 7-12 days to 7 weeks
• last dose no later than 5 pm
• max dose 150 mg PO BID
• quit date should be 1 week after starting therapy to achieve steady-state level
• stop if no progress in smoking cessation by 7th week

• sexual dysfunction in women [6]
• good choice for depression in Parkinson's disease
• neuropathic pain [9]
• seasonal affective disorder (Wellbutin XL)

Contraindications

• seizures
• bulimia
• anorexia
• use of monoamine oxidase ( MAO) inhibitor within past 14 days

• Caution:

• allow 8 hours between doses
• avoid alcohol
• safety of use in children < 18 years of age has NOT been established
  

• pregnancy category = b
• safety in lactation = -

Dosage

• adults

• start: 100 mg PO BID
• maximum 450 mg QD, 150 mg/dose
• usual dose 250-300 mg/day divided BID- TID

• 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 with renal impairment: (& hepatic impairment)

• use reduced dose
• use with caution

Pharmacokinetics

• bioavailability is low (5%), not affected by food
• peak plasma levels 2 hours after oral dose (5 hours for XL)
• > 80% bound to plasma proteins
• metabolites accumulate in patients with renal or hepatic dysfunction
• active metabolite hydroxybupropion

• 1/2life > 24 hours
• LD50 in mice 1/2 that of bupropion

• therapeutic window of 50-100 ng/mL
• no correlation between dose & response or plasma levels
• inhibits cyt P450 2D6, thus may increase plasma levels of drugs metabolized by cyt P450 2D6
  

• elimination via kidney
• 1/2life = 9.6-21 hours
• protein binding = 80 %
• elimination by hemodialysis = -
• elimination by peritoneal dialysis = -

Adverse-effects

• common (> 10%)

• agitation, anxiety, restlessness, insomnia, confusion, constipation, anorexia, dizziness, dry mouth, increased sweating, nausea/vomiting, tremor, weight loss

• less common (1-10%)

• psychosis & hallucinations, skin rash, blurred vision, chills, fatigue

• uncommon (< 1%)

• fainting, drowsiness, seizures*

• other

• insomnia, agitation, headache, tinnitus, rash, diarrhea, tachycardia, akathisia, impotence, hostility, agitation, depression, suicidal ideation [14]

• 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]
  

• drug adverse effects of antidepressants

Drug-interactions

• L-dopa: higher incidence of adverse effects
• monoamine oxidase inhibitors

• acute toxicity may be enhanced
• discontinue MAO inhibitors at least 14 days before starting bupropion

• concurrent use of alcohol, tricyclic antidepressants ( TCA) fluoxetine ( Prozac) or phenothiazines lowers seizure threshold
• cimetidine & ritonavir decrease bupropion metabolism
• bupropion may increase metabolism of:

• carbamazepine
• phenytoin
• phenobarbital
• cimetidine
  

• drug interaction(s) of antidepressants with benzodiazepines

Laboratory

• specimen:

• plasma ( heparin)
• bupropion is unstable in human plasma
• freeze soon after collection
• stable frozen for 6 months

• methods: HPLC, TLC, GC, RIA

Mechanism-of-action

• monocyclic antidepressant
• inhibits reuptake of norepinephrine & dopamine

More General Terms

• norepinephrine & dopamine reuptake inhibitor (NDRI)

Internet Database

PubChem: 444
PubChem: 62884
PubChem: 657316

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#: [1] (subscription needed) [2]
13. Prescriber's Letter 13(9): 2006 Drug Treatment of Seasonal Affective Disorder (SAD) Detail-Document#: [3] (subscription needed) [4]
14. FDA Safety Alert Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics) [5]
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 [6]

bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)