Carbamazepine
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Carbamazepine is an anticonvulsant medication that is chemically similar to the tricyclic antidepressant drugs. It's indications include:
Mechanism of action
Carbamazepine (like phenytoin) binds to and blocks sodium channels increasing their refractory period. This prevent high-frequency repetitive neuronal firing.
Monitoring
Baseline FBC, LFT and U&E and at 6 months.
Plasma carbamazepine levels after 1–2 weeks. Routine monitoring of levels is not advised but levels should be checked in certain circumstances such as suspected toxicity or pregnancy.
A number of drugs inhibit the metabolism or elimination of carbamazepine and may cause a sharp increase in carbamazepine levels with increased risk of toxicity. These include:
- epilepsy (focal seizures, primary and secondary generalised tonic-clonic seizures)
- neuropathic pain (e.g. trigeminal neuralgia, diabetic neuropathy)
- bipolar disorder
- adjunct in acute alcohol withdrawal
Carbamazepine may exacerbate seizures in patients with the following seizure types:
- absence seizures
- myoclonic seizures (including juvenile myoclonic epilepsy)
- Tonic or atonic seizures
- Dravet syndrome
- Lennox-Gastaut syndrome
- Myoclonic-atonic seizures
Mechanism of action
Carbamazepine (like phenytoin) binds to and blocks sodium channels increasing their refractory period. This prevent high-frequency repetitive neuronal firing.
Side effects
Common or very common side effects:- Dizziness and ataxia
- Drowsiness
- Dry mouth
- Eosinophilia
- Fatigue
- Fluid imbalance
- Gastrointestinal discomfort
- Headache
- Hyponatraemia (syndrome of inappropriate ADH secretion)
- Leucopenia (rarely agranulocytosis)
- Movement disorders
- Nausea
- Oedema
- Skin reactions (rarely Steven-Johnson syndrome)
- Thrombocytopenia
- Vision disorders (especially diplopia)
- Vomiting
- Weight gain
Hyponatraemia & diuretics
Hyponatraemia occurs in 20% of patients taking carbamazepine. Avoid giving carbamazepine with diuretics as there is an increased risk of hyponatraemia.
Hyponatraemia occurs in 20% of patients taking carbamazepine. Avoid giving carbamazepine with diuretics as there is an increased risk of hyponatraemia.
Teratogenicity
An increased risk of major congenital malformations has been seen with carbamazepineContra-indications
- Acute porphyrias
- AV conduction abnormalities (unless paced)
- History of bone-marrow depression
- Taking a monoamine oxidase inhibitor (increased risk of serotonin syndrome)
Monitoring
Baseline FBC, LFT and U&E and at 6 months.
Plasma carbamazepine levels after 1–2 weeks. Routine monitoring of levels is not advised but levels should be checked in certain circumstances such as suspected toxicity or pregnancy.
Drug interactions
Carbamazepine (like phenytoin) is a cytochrome P450 inducer wnd may accelerate the metabolism of several drugs including:- Azole antifungals: resulting in reduced levels of voriconazole and itraconazole.
- Ciclosporin: resulting in reduced levels of ciclosporin.
- Clozapine: resulting in reduced plasma concentration of clozapine
- Corticosteroids (systemic): resulting in their reduced effect.
- Direct acting oral anti-coagulants (DOACs; rivaroxaban, dabigatran, apixaban, and edoxaban) may lead to reduced plasma concentrations of DOACs, which carries the risk of thrombosis. Closer monitoring is recommended.
- Doxycycline: resulting in reduced effect.
- Oestrogens and progestogens: resulting in reduced effect of oral contraceptives.
- Thyroid hormones: requirements for thyroid hormones in hypothyroidism may be increased.
- Tricyclic antidepressants: resulting in their reduced effect.
- Simvastatin: consider increasing dose of simvastatin; statins metabolized by the same route as simvastatin may also have their levels reduced.
- Warfarin: resulting in reduced anticoagulant effect.
A number of drugs inhibit the metabolism or elimination of carbamazepine and may cause a sharp increase in carbamazepine levels with increased risk of toxicity. These include:
- Acetazolamide.
- Antidepressants: fluoxetine, fluvoxamine, paroxetine, trazodone.
- Azole antifungals.
- Antivirals: protease inhibitors for HIV treatment (for example ritonavir).
- Cimetidine.
- Ciprofloxacin.
- Clarithromycin.
- Danazol.
- Dextropropoxyphene.
- Diltiazem.
- Erythromycin.
- Isoniazid.
- Olanzapine.
- Omeprazole
- Verapamil.
- Vigabatrin.