Makindo Medical Notes

⚠️ Important: Carbamazepine is associated with severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), especially in patients of Han Chinese or Thai origin carrying the HLA-B*1502 allele. Genetic screening is recommended in high-risk groups. It may also worsen absence and myoclonic seizures.

📖 About

• Carbamazepine is an anticonvulsant and mood stabiliser.
• It is also the drug of choice in the UK for trigeminal neuralgia.
• It is a potent inducer of cytochrome P450 enzymes, reducing the efficacy of many co-administered drugs.
• Always check the BNF for up-to-date prescribing guidance.

⚙️ Mode of Action

• Blocks voltage-gated sodium channels in neuronal membranes → stabilises hyperexcited nerve tissue.
• Reduces repetitive neuronal firing and prevents seizure propagation.
• Weak effect on calcium channels and neurotransmitter modulation.
• Potent hepatic enzyme inducer (CYP3A4).

🩺 Indications & Typical Dose

• Epilepsy: focal seizures (with or without secondary generalisation), generalised tonic–clonic seizures. Avoid in absence/myoclonic epilepsy.
• Trigeminal neuralgia: first-line drug in the UK.
• Bipolar disorder: sometimes used as a mood stabiliser (less common than lithium or valproate).

💊 Dosing – Carbamazepine (PO, UK practice; verify with BNF/datasheet)

🧪 Monitoring

• Baseline: FBC, U&E (esp. sodium), LFTs, BMI, pregnancy test if appropriate.
• During therapy: FBC, U&E, LFTs periodically (risk of agranulocytosis, hyponatraemia, hepatotoxicity).
• Drug levels: not routine; check if poor control, toxicity suspected, or adherence concerns. Therapeutic range: 4–12 mg/L (20–50 µmol/L).
• Toxicity: usually >12 mg/L (50 µmol/L) → ataxia, diplopia, drowsiness.

⚠️ Side Effects

• Common: nausea, dizziness, drowsiness, diplopia, ataxia, headache, blurred vision, rash.
• Serious: aplastic anaemia, agranulocytosis, SIADH → hyponatraemia (esp. elderly), hepatic dysfunction, pancreatitis.
• Skin reactions: urticaria, severe hypersensitivity (SJS/TEN) — especially in Asians with HLA-B*1502 allele.
• Pregnancy: teratogenic (↑ risk of neural tube defects, craniofacial anomalies).

⚠️ Cautions

• Ethnicity: screen Han Chinese and Thai patients for HLA-B*1502 before initiation.
• CNS depression may impair driving or machine operation.
• Use caution in elderly (risk of SIADH/hyponatraemia).
• Gradual withdrawal required to avoid seizure rebound.

🔄 Interactions

• Enzyme induction: reduces efficacy of oral contraceptives, anticoagulants (warfarin), ciclosporin, antivirals, many others.
• Inhibitors (↑ carbamazepine levels): macrolides (erythromycin, clarithromycin), diltiazem, verapamil, azole antifungals.
• Other AEDs: complex bidirectional interactions with phenytoin, valproate, lamotrigine.

🚫 Contraindications

• Worsens absence and myoclonic epilepsy.
• History of bone marrow suppression.
• Concomitant use with MAOIs.
• Cardiac conduction disorders (e.g. AV block).
• Acute porphyria.

📚 References

• BNF: Carbamazepine
• NICE CG137: Epilepsies: diagnosis and management