Lamotrigine metabolism

In addition to phenytoin, carbamazepine, and lamotrigine, metabolically optimized analogs of these drugs, such as fosphenytoin and oxcarbazepine, show clinical promise. Other anticonvulsants that block sodium channels, among several mechanisms of action, include zonisamide, felbamate, topiramate, and valproate (Fig. 5). 

If lamotrigine is added to patients taking valproate, remember that valproate inhibits lamotrigine metabolism and therefore titration rate and ultimate dose of lamotrigine should be reduced by 50% to reduce the risk of rash... 

Oxcarbazepine Lamotrigine Interaction less marked than that caused by carbamazepine Induction of lamotrigine metabolism... 

Valproate Lamotrigine Risk of toxicity therapeutic synergism possible Inhibition of lamotrigine metabolism and pharmacodynamic interaction... 

Rifampicin markedly increased the clearance of lamotrigine in a pharmacokinetic study. A case report has described a similar finding, and also included some limited evidence suggesting that isoniazid may inhibit lamotrigine metabolism. 

Rifampicin increases the loss of lamotrigine from the body, probably by inducing glucuronidation via UDP-glucuronyl transferases. It was suggested that isoniazid may have inhibited lamotrigine metabolism. ... 

Phenytoin is a known hepatic enzyme inducer, which increases lamotrigine metabolism. The recommended starting dose and long-term maintenance dose of lamotrigine in patients already taking phenytoin is twice that of patients receiving lamotrigine monotherapy. 

Yuen AWC, Land G, Weatherley BC, Peck AW. Sodium valproate acutely inhibits lamotrigine metabolism, BrJ Clin Pharmacol (1992) 33,511-13. 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

Valproic acid is an enzyme inhibitor that increases serum concentrations of concurrently administered phenobarbital and may increase concentrations of carbamazepine 10,11-epoxide without affecting concentrations of the parent drug. It also inhibits the metabolism of lamotrigine. 

Metabolism/Excretion - Lamotrigine is approximately 55% bound to human plasma proteins. Following multiple administrations to healthy volunteers taking no other medications, lamotrigine induced its own metabolism resulting in a 25% decrease in half-life and a 37% increase in plasma clearance. 

Special risk Caution is advised when using lamotrigine in patients with diseases or conditions that could affect metabolism or elimination of the drug, such as renal or hepatic function impairment (see Warnings) or cardiac function impairment. Caution is advised when using lamotrigine in patients with diseases or conditions that could affect metabolism or elimination of the drug, such as renal, hepatic, or cardiac functional impairment. 

Lamotrigine is metabolized by glucuronidation, possibly by the UGT 1A4 system. As such, it is vulnerable to other UGT inducers—oral contraceptives, phenytoin, carbamazepine, phenobarbital and primidone, and to a UGT inhibitor, valproate (Hachad et ah, 2002). 

Lamotrigine is almost completely absorbed after oral administration and metabolized completely in liver. 

BARBITURATES 1. CARBAMAZEPINE 2. LAMOTRIGINE 3. TIAGABINE 4. VALPROATE 5. ZONISAMIDE L levels of these antiepileptics Induction of metabolism Watch for poor response to these antiepileptics... 

LAMOTRIGINE 1. ANTIBIOTICS -rifampicin 2. OESTROGENS 3. PROGESTOGENS 1 lamotrigine levels t metabolism Monitor levels... 

RIFAMPICIN LAMOTRIGINE l lamotrigine levels t metabolism Monitor levels... 

Lamotrigine dose should be reduced by perhaps 50% if used with valproate, as valproate inhibits metabolism of lamotrigine and raises lamotrigine plasma levels, theoretically increasing the risk of rash... 

Sodium valproate is extensively metabolised in the liver and has a t / of 13 h. It is 90% bound to plasma albumin. Sodium valproate is a nonspecific inhibitor of metabolism, and indeed inhibits its own metabolism, and that of lamotrigine, phenobarbitone, phenytoin and carbamazepine. Sodium valproate does not induce drug metabolising enzymes but its metabolism is enhanced by induction due to other drugs, including antiepileptics. 

Metabolic inhibition by valproate prolongs the action of co-administered antiepilepsy drugs (see above). The effect is significant and the dose of lamotrigine, for example, should be halved in patients who are also taking sodium valproate. 

Valproate Carbamazepine epoxide Diazepam Felbamate Lamotrigine Phenobarbital Risk of toxicity, particularly with phenobarbital including primidone-derived phenobarbital and lamotrigine Inhibition of metabolism of the affected drug. Valproate also displaces diazepam from protein binding sites, affecting relation between total diazepam concentration and effect... 

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