Pharm

Bupropion

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Bupropion, Wellbutrin, Zyban, Norepinephrine Dopamine Reuptake Inhibitor, NDRI

  • Background
  1. Cost: $67 per month
  • Indications
  1. Tobacco Cessation (Zyban)
    1. May be used in combination with Nicotine Replacement
    2. Not considered first-line therapy for adolescents
  2. Reasonable second line Antidepressant
    1. Selective Serotonin Reuptake Inhibitor (SSRI) Failure
    2. Adjunctive therapy in combination with SSRI
  • Precautions
  1. FDA Pregnancy Category C
  2. FDA Black Box Warning
    1. Increased risk of Suicidality in patients with Major Depression
  1. Predictors of quitting with Bupropion
    1. Higher dose (Bupropion 300 mg/day)
    2. Male gender
    3. Prior Tobacco abstinence previously
    4. Abstinence for >2 weeks with current attempt
  2. Quit Rates (Study: n=893 over 10 weeks)
    1. Note these rates are higher than with other studies
    2. Placebo: 20% quit
    3. Transdermal Nicotine (21 mg): 32% quit
    4. Bupropion SR 150 mg bid: 46% quit
    5. Bupropion and Transdermal Nicotine: 51% quit
  3. Reference
    1. (1997) Med Lett Drugs Ther 39(1007):77-8 [PubMed]
    2. Dale (2001) Chest 119:1357-64 [PubMed]
  • Mechanism
  1. Monocyclic aminoketone
  2. Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
    1. Marked Norepinephrine reuptake inhibitor effect
    2. Some selective Dopamine reuptake inhibitor effect
  3. Smoking Cessation effect
    1. Enhances Dopamine levels in the mesolimbic system
      1. Reduces desire for nicotine dramatically
    2. Affects noradrenergic Neurons in the locus ceruleus
      1. Reduces nicotine withdrawal symptoms
  1. Elderly: 100 mg PO bid
  2. Usual dosing
    1. Initial: 100 mg PO bid for 4 days
    2. Next: 100 mg PO tid
    3. Maximum: 150 mg PO tid
  1. Protocol (May substitute 2 of Wellbutrin 75 mg)
    1. Start: Bupropion 150 mg PO qd for 3 days
    2. Then: Bupropion 150 mg PO bid for 7-12 weeks
  2. General
    1. Stop smoking during second week of medication
    2. Stop Bupropion if unable to quit by 7 weeks
    3. Cost: $186/10 week supply (wholesale)
    4. Minimum of 8 hours between doses
    5. More is not better
    6. Swallow pills whole (not crushed, divided or chewed)
  • Pharmacokinetics
  1. Serum Half Life: 15 hours
  2. Therapeutic Blood Level: 50-100 ng/ml
  • Drug Interactions
  1. Prozac associated with panic and Psychosis
  2. Increased toxicity with:
    1. MAO inhibitor
    2. Ritonavir
  3. Carbamazepine (Tegretol) increases metabolism
  • Contraindications
  1. Seizure disorder
  2. Concurrent psychiatric medications
    1. MAO inhibitor (allow 14 day interval between these two medication classes)
    2. Ritonavir
    3. Other forms of Bupropion (Wellbutrin, Zyban)
  3. Eating Disorder
    1. Anorexia Nervosa
    2. Bulimia
  4. Pregnancy
  5. Uncontrolled Hypertension
  1. Very Activating, Agitation
    1. Good choice in withdrawn people
    2. Decreases in 1-2 weeks after starting medication
    3. Consider starting with Benzodiazepine and tapering
  2. Insomnia (35-40%)
  3. Dry Mouth (10%)
  4. Restlessness
  5. Tremor
  6. Gastrointestinal upset
  7. Headache
  8. Appetite suppression and weight loss
    1. Avoid in Eating Disorders
  9. Lowers Seizure threshold
    1. Avoid if concurrent Seizure disorder
    2. Seizure Incidence
      1. Regular release: 1%
        1. Increased with dose >150 mg/dose or 450 mg/day
      2. Sustained release: 0.1%
        1. Increased with dose >200 mg/dose or 400 mg/day
    3. Minimize risk by limiting dose to 150 mg q6 hours
  1. Findings
    1. Tachycardia (23%)
    2. Nausea and Vomiting (14%)
    3. Seizures (11%)
      1. Occur up to 14 hours after ingestion (esp. sustained release products)
      2. May occur with Overdose >600 mg (but typically occurs with Overdose >2500 mg)
      3. Prolonged and recurrent Seizures may occur with extended release preparations
      4. Treat Seizures with Benzodiazepines (other antiepileptics in Status Epilepticus are not indicated)
      5. If intubated, Propofol is preferred for sedation
    4. Intraventricular conduction abnormalities (Wide QRS, Prolonged QTc)
      1. May occur with large Overdoses
      2. Give 1-2 ampules bicarbonate IV frequently until QRS narrows (goal pH 7.45-7.55)
  2. Management
    1. Consider Intravenous Lipid Emulsion (Intralipid) in severe cases (e.g. cardiac toxicity)
    2. Supportive care
  3. References
    1. Nordt and Shoenberger in Herbert (2019) EM:Rap 19(3): 8-9
    2. Yen (2015) Crit Dec Emerg Med 29(10):18-23
  • Advantages
  1. No Anticholinergic Toxicity
  2. No Antihistaminergic activity
  3. No cardiac toxicity
  4. No sexual side effects
  1. Zyban Advantage Plan
    1. Free 3 month program to users of product
  2. Tobacco Cessation counseling course
  • References
  1. Sundberg (1995) Depression Primary Care, PGM, p. 45-57
  2. Mallin (2002) Am Fam Physician 65(6):1107-17 [PubMed]