Lamotrigine Cimetidine

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

Drugs that may affect valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

Ebert U, Thong NQ, Oertel R, et al. Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. Eur J Clin Pharmacol 2000 56(4) 299-304. 

The effect of cimetidine on the pharmacokinetics of lamotrigine has been studied in 10 healthy men (73). Cimetidine had no effect on the pharmacokinetics of lamotrigine. 

Phenobarbital, phenytoin, and valproic acid may increase the metabolism of carbamazepine by inducing CYP3A4 carbamazepine may enhance the biotransformation of phenytoin. Concurrent administration of carbamazepine may lower concentrations of valproic acid, lamotrigine, tiagabine, and topiramate. Carbamazepine reduces both the plasma concentration and therapeutic effect of haloperidol. The metabolism of carbamazepine may be inhibited by propoxyphene, erythromycin, cimetidine, fluoxetine, and isoniazid. 

Therefore, plasma concentrations for drugs metabolized by these isoforms will be affected (see Chapter 10). Thus, the addition of phenytoin to an AED regimen can reduce their plasma levels by inducing their CYP3A4 metabolism for carbamazepine, felbamate, lamotrigine, oxcarbazepine, tiagabine, valproate, and zonisamide. Other drugs for which metabolism is induced by phenytoin include methadone, theophylline, warfarin, and oral contraceptives. On the other hand, plasma phenytoin levels are increased by carbamazepine, felbamate, cimetidine, warfarin, chloramphenicol, isoniazid, and disulfiram. Plasma phenytoin levels are decreased by rifampin, antacids, and valproate (free phenytoin levels remain the same). 

Because of its inducing effect on hepatic enzymes, phenobarbitai has many drug interactions, decreasing plasma levels of CBZ, valproate, lamotrigine, tiagabine, zonisamide, warfarin, theophylline, cimetidine, and those of other CYP3A4 substrates. Serum concentrations of phenobarbitai are increased by valproate. 

Cimetidine 400 mg twice daily for 5 days had no effect on the pharmacokinetics of a single 25-mg dose of lamotrigine in 10 healthy subjects. No change in lamotrigine dose appears to be needed during concurrent use. ... 

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