Seizure prophylaxis in epilepsy.
Epilepsy is classified by seizure type which, in turn, guides
antiepileptic drug choice. Lamotrigine is an option for first-line
monotherapy or add-on therapy in focal seizures (with or without secondary generalisation), generalised tonic–clonic seizures and absence seizures.
The mechanism of action of lamotrigine is incompletely understood.
Like carbamazepine and phenytoin, it binds to voltage-sensitive neuronal Na+ channels, interfering with Na+
influx into the neuron. This impedes repetitive neuronal firing, which
is a characteristic of seizure activity.
Additionally, it appears to
have effects on synaptic function, including inhibition of a
post-synaptic glutamate receptor (the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid [AMPA] receptor).
These effects, and others, may contribute to its
antiepileptic action.
The mechanism by which it reduces depressive
symptoms in bipolar disorder is uncertain.
Important adverse effects
The most common adverse effects are headache, drowsiness, irritability, blurred vision, dizziness and gastrointestinal symptoms.
A minority of patients develop a skin rash
within a few weeks of starting lamotrigine. This is usually mild, but
requires urgent review and possibly discontinuation of the drug. This is
because it may be the first sign of a severe hypersensitivity reaction; although rare, this may be life threatening, and early discontinuation of the drug is of paramount importance (see Carbamazepine).
Warnings
Lamotrigine should be avoided if possible in patients who have a prior history of hypersensitivity to other antiepileptic drugs,
due to the risk of cross-reactivity.
Lamotrigine is metabolised by
hepatic glucuronidation, so dosage reduction may be necessary in
patients with moderate or severe hepatic impairment.
In general, there is no evidence that lamotrigine exposure in pregnancy
increases the overall risk of congenital malformations, so it is a
reasonable choice in women of child-bearing age.
During pregnancy, due
to changes in lamotrigine metabolism, plasma concentration measurement
should be considered to guide dosage adjustment.
Important interactions
Lamotrigine has many interactions arising from its metabolism by glucuronidation. These are of sufficient importance to necessitate pre-emptive dosage modification.
Drugs that induce glucuronidation include carbamazepine, phenytoin, oestrogens, rifampicin and protease inhibitors. These can cause the lamotrigine
concentration to fall, potentially leading to treatment failure.
Glucuronidation is inhibited by valproate,
causing the lamotrigine concentration to rise, increasing the risk of
toxicity.
Severe hypersensitivity reactions are also more common when
lamotrigine is co-administered with valproate.
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