Carbamazepine

Aka: Carbamazepine, Tegretol

1. Indication
   1. Simple Partial Seizures
   2. Complex Partial Seizures
   3. Generalized Tonic Clonic Seizures
   4. Trigeminal Neuralgia
   5. Bipolar Disorder
      1. Frequently reserved for use as a second agent
   6. Resistant Schizophrenia
   7. Restless Leg Syndrome
   8. Psychosis in Dementia
   9. Post-Traumatic Stress Disorder
2. Contraindications
   1. MAO inhibitor use within last 14 days
   2. Bone Marrow depression
   3. Pregnancy
   4. Asian patients who are positive for HLA-B1502
      1. Risk of Steven's Johnson: 5% if HLA-B1502 positive
      2. Also associated with Toxic Epidermal Necrolysis
      3. FDA has issued a black box warning
      4. Man (2007) Epilepsia 48(5):1015-8
3. Adverse Effects: Dose related
   1. Gradual tolerance to side effects (slowly titrate)
   2. Headache
   3. Lethargy or Fatigue
   4. Nausea and Vomiting
   5. Tremor
   6. Nystagmus
   7. Ataxia
   8. Diplopia
4. Adverse Effects: Other
   1. Morbilliform rash
   2. Leukopenia
   3. Agranulocytosis
   4. Aplastic Anemia
   5. Cardiac conduction abnormality (increases A-V delay)
   6. Hyponatremia
      1. Occurs in up to 40% of patients
      2. Elderly are at higher risk of SIADH
   7. Liver failure
   8. Osteoporosis
   9. Serum Sickness
   10. Stevens-Johnson Syndrome
   11. Toxic Epidermal Necrolysis
5. Drug Interactions (Numerous)
   1. Substrate of Cytochrome P450 2C8/9
   2. Substrate of Cytochrome P450 3A4
   3. Induces Cytochrome P450 1A2
   4. Induces Cytochrome P450 2B6
   5. Induces Cytochrome P450 2C8/9
   6. Induces Cytochrome P450 2C19
   7. Induces Cytochrome P450 3A4
6. Dose: General
   1. Titrate dose to serum concentration and effect
   2. Target serum concentration: 4-12 mcg/ml
      1. Observe closely for concentration 8 mcg/ml or higher
   3. Toxic serum concentration: >15 mcg/ml
7. Dose: Adults
   1. Seizure Disorder
      1. Initial: 200 mg orally twice daily
      2. Increase by 200 mg/day increments weekly
      3. Target: 800-1200 mg/day divided three to four time daily
   2. Trigeminal Neuralgia
      1. Initial: 100 mg orally twice daily
      2. Increase by 100 mg/day increments weekly
      3. Target: 400-800 mg/day divided twice daily
   3. Bipolar Disorder
      1. Initial: 200 mg twice daily
      2. Increase by 200 mg as often as daily in acute mania as tolerated
         1. Slower titration results in fewer side effects
      3. Target: 200-1600 mg per day
      4. Target serum level: 4 to 12 mcg/ml
8. Dose: Elderly
   1. Initial: 100 mg orally twice daily
   2. Increase by 100 mg/day increments weekly
   3. Target: 400-1000 mg/day divided three to four times daily
9. Monitoring
   1. Routine labs
      1. Obtain monthly for first 2 months, then every 3 to 12 months
      2. Complete Blood Count with Platelet Count
      3. Liver Function Tests
   2. HLA-B1502
      1. Indicated before starting in asian patients
      2. See contraindications above
   3. Serum Carbamazepine level
      1. Initial: Every 1-2 weeks
      2. Later: Every 3-6 months
      3. Also check before and after dose changes
   4. Other tests previously monitored with Carbamazepine use
      1. Serum Iron
      2. Urinalysis
      3. Serum Sodium
      4. Blood Urea Nitrogen
      5. Thyroid Stimulating Hormone