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

Possible 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 the 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 most commonly occurs within 4-6 weeks but can occur at any time.
    • Development of rash on carbamazepine warrants an 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 HLA testing in New South Wales can be done via a blood test using the Immunogenetics Request Form available here.


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 below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

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 approach.
  • 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 up to weights of 30-40kgs.
  • ‘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.

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.
  • 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 HLA testing in New South Wales can be done via a blood test using the Immunogenetics Request Form available here.

 

Information last reviewed: 3/05/2023.