Lamotrigine

CLINICAL USE

Monotherapy and adjunctive treatment of partial seizures, and primary and secondary generalised tonic-clonic seizuresTrigeminal neuralgia (unlicensed)

DOSE IN NORMAL RENAL FUNCTION

25–200 mg daily in 1–2 divided doses, according to clinical indication. Maximum 500 mg daily; 700 mg with enzyme-inducing drugs

PHARMACOKINETICS

Molecular weight :256.1

%Protein binding :55

%Excreted unchanged in urine :

<10 :

Volume of distribution (L/kg) :0.92–1.22

half-life – normal/ESRD (hrs) :24–35/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Caution. Start with low doses and monitor closely

10 to 20 : Caution. Start with low doses and monitor closely

<10 : Caution. Start with low doses and monitor closely

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely dialysability. Dose as in GFR <10 mL/min.

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: concentration reduced by rifampicin

Antidepressants: antagonism of anticonvulsant effect

Antimalarials: mefloquine antagonises anticonvulsant effect; chloroquine and hydroxychloroquine occasionally reduce seizure thresholdOestrogens and progestogens: concentration of lamotrigine reduced and the dose may need to be increased by as much as 2-fold

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

There is no experience of treatment with lamotrigine in patients with renal failure. Pharmacokinetic studies using single doses in subjects with renal failure indicate that lamotrigine pharmacokinetics are little affected, but plasma concentrations of the major glucuronide metabolite increase almost 8-fold due to reduced renal clearanceThe 2-N-glucuronide is inactive and accounts for 75–90% of the metabolised drug present in the urine. Although the metabolite is inactive the consequences of accumulation are unknown; hence the company advise caution with the use of lamotrigine in renal impairmentThe half-life of lamotrigine is affected by other drugs; reduced to 14 hours when given with enzyme-inducing drugs, e.g. carbamazepine and phenytoin, and is increased to approximately 70 hours when co-administered with sodium valproate alone.

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