Carbamazepine

 Common indications

• Epilepsy, as a first choice treatment for focal seizures with and without secondary generalisation and for primary generalised seizures.
• Trigeminal neuralgia, as first choice treatment to control pain and reduce frequency and severity of attacks.
• Bipolar disorder, as an option for prophylaxis in patients resistant to or intolerant of other medication.

 

Mechanisms of action

• The mechanism of action of carbamazepine is incompletely understood. It appears to inhibit neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability (see Phenytoin). 
• This may inhibit spread of seizure activity in epilepsy, control neuralgic pain by blocking synaptic transmission in the trigeminal nucleus and stabilise mood in bipolar disorder by reducing electrical ‘kindling’ in the temporal lobe and limbic system.

 

Important adverse effects

• The most common dose-related adverse effects are gastrointestinal upset (e.g. nausea and vomiting) and neurological effects (particularly dizziness and ataxia). 
• Carbamazepine hypersensitivity affects about 10% of people taking the drug and most commonly manifests as a mild maculopapular skin rash. 
• Antiepileptic hypersensitivity syndrome affects about 1 in 5000 people taking carbamazepine or phenytoin, usually within 2 months of starting treatment. Clinical features include severe skin reactions (e.g. Stevens–Johnson syndrome, toxic epidermal necrolysis), fever and lymphadenopathy with systemic (e.g. haematological, hepatic, renal) involvement and mortality of about 10%. 
• Other common adverse effects include oedema and hyponatraemia due to an antidiuretic hormone-like effect.

 

Warnings

• Carbamazepine exposure in utero is associated with neural tube defects, cardiac and urinary tract abnormalities and cleft palate. 
• Women with epilepsy planning pregnancy should discuss treatment with a specialist and start taking high-dose folic acid supplements before conception. 
• Prior antiepileptic hypersensitivity syndrome is a contraindication to both carbamazepine and phenytoin, due to potential cross-sensitivity. 
• Carbamazepine should be prescribed with caution in patients with hepatic, renal or cardiac disease, due to increased risk of toxicity.