Carbamazepine (Tegretol)

 

 

HALF-LIFE: Initially 25-65 hours, then 15 hours after 2-4 weeks
STARTING DOSE: 200mg PO BID
TARGET DOSING RANGE: 400mg-600mg PO BID
BEST TIME TO DOSE: Any
HOW TO DOSE:
>Initial 200mg PO BID
>Increase by 200mg/d every 3-4 days to target dose
>Max dose 800mg PO BID
PREGNANCY: AVOID
BREASTFEEDING: AVOID

 

FDA INDICATIONS:
1) Seizures
2) Trigeminal Neuralgia
3) Acute mania associated with Bipolar Disorder (Equetro)

 

Mechanism of Action

  • Blocks voltage sensitive sodium channels

 

 

Notable Adverse Effects

  • Leukopenia
  • Thrombocytopenia
  • Rare Aplastic Anemia (fever, fatigue, pallor, bleeding gums)
  • Risk of Aplastic Anemia increased by coadministration with clozapine
  • Rare Agranulocytosis
  • Rash (increased risk of SJ/TEN in Asians with HLA-B1502 allele (recommend testing for this allele prior to prescribing carbamazepine to individuals of Asian descent)
  • Syndrome of Inappropriate ADH (Hyponatremia)
  • Very rare hepatotoxicity
  • Rashes are common (up to 5% of patients)
  • Slows cardiac conduction
  • Elevated GGT (not concerning unless >3x normal limit)
  • Sedation
  • Fatigue
  • Nausea
  • Dizziness
  • Ataxia
  • diplopia
  • muscle incoordination
  • nystagmus

 

Drugs that may increase carbamazepine levels:

 

Cimetidine

Ciprofloxacin

Diltiazem

Fluoxetine

Fluvoxamine

Doxycycline

Erythromycin (and other macrolide antibiotics)

Fluconazole

Grapefruit juice

Isoniazid (INH)

Ketoconazole

TCAs

Valproate

Warfarin

Norfloxacin

Verapamil

 

Drugs whose blood levels are decreased by carbamazepine:

 

Atypical antipsychotics (olanzapine, risperidone, clozapine)

Benzodiazepines

Doxycycline

Ethosuximide

Fentanyl

Glucocorticoids

Haloperidol

Methadone

Oral contraceptives

Phenothiazines

Phenytoin

Sertraline

TCAs

Theophylline

 

Additional Information

  • Reports of CNS toxicity (dizziness, diplopia) associated with combination of carbamazepine and lamotrigine 
  • Metabolized primarily by CYP3A4 and also induces its own metabolism by inducing CYP3A4
  • Induces multiple other CYP450 isozymes as well as P-Glycoprotein
  • May test positive (false positive) for tricyclics (TCAs)

References

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  4. J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.