Carbamazepine

Carbamazepine is a mood stabilizer and antiepileptic used in the treatment of epilepsy and bipolar disorder. It is used in the treatment of acute mania and mixed episodes of bipolar I disorder.

Is highly protein bound.

  • Blocks α subunit of VSNaC
  • ?possible actions on K and Ca channels

Sedation, dizziness, fatigue, nausea, leukopenia in 7%,

  • Agranulocytosis or aplastic anemia (1/10,000 to 1/125,000): monitor for fever, bruising, petechiae etc
  • GGT ↑ common; hepatotoxicity rare
  • Higher risk of serious cutaneous reactions in pts with Human Leukocyte Antigens (HLA)- A*3101 and HLA-B*1502
  • Allelic frequency varies by ethnic group
    • Consider genetic screening in at-risk population before starting Rx

The dose range for carbamazepine is between 100-1200mg (using the CR formulation), and it is usually dosed BID. Carbamazepine can be increased by 100 mg every 2-3 days as tolerated, up to an initial target dose of at least 300 mg/day. After at least 5 days at this target dose (to allow steady state to be achieve), a carbamazepine level should be drawn 12 hours after the last dose. If the level is:

  • <17 μmol/L, then the dose should be increased by 100 mg/day and another level should be drawn in 5 days
  • 17-54 μmol/L, then the dose can be maintained
  • >54 μmol/L, then the dose should be reduced by 100 mg/day and another level should be drawn in 5 days

Note that carbamazepine induces its own metabolism thus drawing levels repeatedly for the same dose will be necessary over the first few weeks, making dose adjustments as necessary.

  • Serum levels:
    • Substrate for CYP 3A4 (autoinduction): monitor blood level weekly for the first 8 weeks
  • Blood level correlates poorly with therapeutic effect
  • Signs of high blood level: diplopia, poor coordination, sedation

Carbamazepine is a strong inducer of CYP3A4 and P-glycoprotein (P-gp). Induces CYP 1A2, 3A4, 2C9, 2B6

Carbamazepine has many drug-drug interactions, more side effects in the elderly. Side effects include weight gain, neurotoxicity (dose dependent: diplopia, drowsiness, blurred vision, cognitive impairment), transaminitis, SIADH, blood dyscrasias, AV node delays, bradycardia. Hypersensitivity rashes are uncommon.