Carbamazepine

Usage

  • A first-line choice for focal seizures, focal seizures which become bilateral convulsive seizures, and Childhood epilepsy with Centro temporal spikes.
  • Carbamazepine may worsen seizures in the primary generalised epilepsies such as CAE and JME.

Resources

Side effects

Common side effects:

  • Incoordination (e.g. gait unsteadiness) or drowsiness can occur when a patient first starts carbamazepine. These are usually transient side effects (unsteadiness resolves over days to a couple of weeks) and dose can continue to be increased gradually. Commencing slowly lessens these side effects.
  • Rash: in particular Steven-Johnsons Syndrome (SJS), is the most important adverse effect to watch for. Rash will usually occur within 4-6 weeks.Development of rash on carbamazepine warrants immediate medical review. Particularly concerning signs to look out for are red eyes, mucosal involvement, and blistering. Suspected SJS requires appropriate (usually inpatient) medical management. Research has shown an increased risk of SJS in people of Han Chinese ethnicity with the HLA-B1502 allele. Care should be taken when considering carbamazepine in this population and HLA-B1502 testing is recommended before starting the drug in particular ethnic populations (Han Chines, Filipinos, Malaysians, South Asians Indians, and Thai). The Epilepsy Society Australia is one source of further information.


Other notable side effects:

  • Neutropenia
  • Transaminitis. Mild nonprogressive transaminitis does not necessarily require drug cessation.
  • Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH)
  • All anticonvulsants are potentially teratogenic and this is often dose related (see section: AED Prescribing - Pregnancy)
  • For a complete list of adverse effects, appropriate formularies should be consulted.

Dosing

  • The initiation and escalation dose depend upon age, weight, syndrome, seizure frequency and intensity, and side effect profile.
  • Unfortunately, one dose regime does not fit all.
  • A Paediatric Neurologist should be consulted if there is uncertainty.
  • ‘Start low and go slow.’ Rash is more of a risk when starting with high doses and rapid dose increase. A slow introduction is also preferable to minimise drowsiness or incoordination.

Commonly used regime

  • In children, an introduction of 5mg/kg/day in two doses increasing over 3-4 wks to 10-20 mg/kg/day in 2 doses provides a reasonable guideline.
  • Some patients may be controlled on a lower dose. In the young child, the dosage may be changed to three times a day.
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs. Consult appropriate formularies for higher weights and in the adult range.
  • These dosages are only a guideline and appropriate formularies should be consulted as needed.

Preparations

  • Tablets 400mg CR, 200mg CR, 100mg, 200mg, Suspension 20mg/ml.
  • Tds dosing can achieve steadier levels with carbamazepine syrup in the young child. Carbamazepine is usually avoided in the first year of life due to poor absorption.

Monitoring and levels

  • Most would do a baseline LFT and FBC prior to commencing the drug and then repeat in 4-6 wks. Further tests as clinically indicated.
  • Drug levels are done for a reason and the timing of the test depends on the indication; e.g. trough for efficacy, peak for toxicity. 
  • Levels can be useful to titrate dosage, manage potential drug interactions and assess for toxicity.

Interactions | Precautions

  • Tegretol is an enzyme inducer and therefore can lower valproate and phenytoin levels.
  • It will also reduce the efficacy of the oral contraceptive pill.
  • Avoid macrolides – particularly erythromycin – as it can alter carbamazepine levels and cause toxicity, including hyponatremia.