(a) Varies with mono- or adjunctive therapy; see manufacturer's recommendations.
(b) Avoid if major seizures are accompanied by absence seizures or myoclonic jerks.
(c) Lamotrigine may be effective, particularly if used with sodium valproate.
(d) Alone or in combination with clonazepam, which may be synergistic.
Pharmacokinetics. Carbamazepine is extensively metabolised; one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t/2 of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy.
Standard tablets are taken twice a day, but with higher doses a three or four times a day regimen may be necessary. Rectal and liquid formulations are available, but there is no i.v. preparation.
Uses. Carbamazepine is used for secondary generalised and partial seizures, and primary generalised seizures. Because another antiepilepsy drug (phenytoin) was sometimes beneficial in trigeminal neuralgia, carbamazepine was tried in this condition, for which it is now the drug of choice
Adverse effects include CNS symptoms (reversible blurring of vision, diplopia, dizziness and ataxia) and depression of cardiac AV conduction. Alimentary symptoms, skin rashes, blood disorders and liver and kidney dysfunction also occur. Osteomalacia by enhanced metabolism of vitamin D (enzyme induction) occurs over years; so also does folate deficiency. Enzyme induction reduces the efficacy of combined and progestogen-only contraceptives. Carbamazepine impairs cognitive function less than phenytoin.
Oxcarbazepine, like its analogue carbamazepine, acts by blocking voltage-sensitive sodium channels. It is rapidly and extensively metabolised in the liver; the tl/2 of the parent drug is 2 h but that of its principal metabolite (which also has therapeutic activity) is 11 h. Unlike carbamazepine, it does not form an epoxide which may explain why oxcarbazepine has fewer unwanted effects. Oxcarbazepine is a selective inducer of a cytochrome isoenzyme that metabolises the oral contraceptive and a 50 microgram oestrogen preparation is necessary for contraception. It does not induce hepatic enzymes in general.
Oxcarbazepine is as effective as carbamazepine, sodium valproate and phenytoin in the treatment of partial and secondary generalised seizures, for which it is used either as monotherapy or add on therapy.
The most common chronic adverse effect is hyponatraemia, but this is usually mild, asymptomatic and of no clinical significance. Routine serum monitoring of the plasma sodium is indicated only where there is special risk, e.g. patients taking diuretics or the elderly.
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