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does not interfere with drug metabolism, but provides a target for enzyme inducers such as
phenytoin and carbamazepine, or inhibitors such as sodium valproate.

Gabapentin

Gabapentin may occasionally be useful as a second-line treatment of focal seizures. It is of no
use in other seizure types. The initial dose is 300400 mg/day and the titration rate consists of
weekly dose increases of 300–400 mg up to 2400–3600mg/day in first instance. In view of its
short elimination half-life a three times daily dosage is recommended.

Gabapentin is not metabolised, exhibits no protein binding and does not induce hepatic
enzymes. Its potential for drug interaction is small and, to date, no clinically significant
interaction with other drugs has been reported. Gabapentin may, therefore, be a useful add-on
drug in people with a high risk of drug interactions. There is no need to measure levels as a
guide to dosing.

Side effects of gabapentin are mainly related to the CNS and these include drowsiness,
dizziness, diplopia, ataxia and headaches. Gabapentin is associated with weight gain,
particularly at high doses. It may also occasionally worsen seizures, particularly myoclonic
seizures. Gabapentin treatment has not been associated with any serious idiosyncratic reaction
to date.

Lamotrigine

Lamotrigine is a first-line drug for people with focal seizures and with generalised seizures.

The recommended starting dose as monotherapy is 25 mg/day. If the person is taking
concomitant sodium valproate then the starting dose should be 25 mg/day on alternate days.
The maximum recommended dose as monotherapy is 400500 mg/day in two divided doses
but no more than 200 mg/day if the person is taking concomitant valproate. Treatment should
be slowly titrated upwards over a period of several weeks as too rapid titration may be
associated with an increased incidence of adverse events, particularly skin rash.

Lamotrigine does not seem to interact with other concomitantly administered AEDs, although
it may increase levels of an active metabolite of carbamazepine. Hepatic enzyme inducers,
however, increase lamotrigine clearance, reducing its half-life. Hence, higher doses of
lamotrigine need to be used with concomitant enzyme inducing drugs such as phenytoin and
carbamazepine. Inhibitors of hepatic enzymes, such as sodium valproate, block the metabolism
of lamotrigine so that reduced doses of lamotrigine have to be used if both drugs are given
together. Oral contraceptives containing oestrogen may increase the metabolism of lamotrigine.

Headaches, drowsiness, ataxia, diplopia, insomnia, nausea and dizziness are the most common
acute adverse effects of lamotrigine, particularly during dose escalation. A skin rash is the
commonest idiosyncratic side effect and affects up to 5% of people exposed to it. The incidence
is higher when lamotrigine is used in combination with sodium valproate or if larger initial
doses of lamotrigine are used. Rarely, it may cause more severe idiosyncratic reactions,
including toxic epidermal necrolysis, Stevens-Johnson syndrome, aplastic anaemia and liver
failure.

Phenytoin

Phenytoin is now a last resort option for focal and tonic-clonic seizures in view of its chronic
toxicity and kinetic profile. Phenytoin is one of a handful of drugs that switches from first-order
to saturation kinetics at therapeutic dosage. Accordingly, at higher levels a moderate increment