Differential effect of cimetidine on serum concentrations of carbamazepine and phenytoin

Levine, Marc; Jones, Michael W.; Sheppard, Ian

doi:10.1212/wnl.35.4.562

Cited by 28 publications

(20 citation statements)

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“…It is also an inhibitor of cytochrome P450 isoenzymes CYP2C19, CYP2D6 (9), and CYP3A4 (114), and is capable of prolonging the half-lives of those AEDs that would normally be metabolised by these isoenzymes (e.g., PHT and CBZ) (115)(116)(117)(118). The inhibitory effect of cimetidine on CYP3A4 is not substantial, and the interaction with CBZ is of modest clinical significance (118,119). PB and PRM also are metabolised by CYP2C19 and may be affected by coadministration with cimetidine.…”

Section: Antiulcer Drugsmentioning

confidence: 99%

The Importance of Drug Interactions in Epilepsy Therapy

et al. 2002

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Summary: Long-term antiepileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to control seizures effectively, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. The fact that over-the-counter drugs and nutritional supplements are increasingly being self-administered by patients also must be considered. Therefore the probability of patients with epilepsy experiencing drug interactions is high, particularly with the traditional AEDs, which are highly prone to drug interactions. Physicians prescribing AEDs to patients with epilepsy must, therefore, be aware of the potential for drug interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur both during combination therapy and on drug discontinuation. Although pharmacokinetic interactions are numerous and well described, pharmacodynamic interactions are few and usually concluded by default. Perhaps the most clinically significant pharmacodynamic interaction is that of lamotrigine (LTG) and valproic acid (VPA); these drugs exhibit synergistic efficacy when coadministered in patients with refractory partial and generalised seizures. Hepatic metabolism is often the target for pharmacokinetic drug interactions, and enzyme-inducing drugs such as phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) will readily enhance the metabolism of other AEDs [e.g., LTG, topiramate (TPM), and tiagabine (TGB)].The enzyme-inducing AEDs also enhance the metabolism of many other drugs (e.g., oral contraceptives, antidepressants, and warfarin) so that therapeutic efficacy of coadministered drugs is lost unless the dosage is increased. VPA inhibits the metabolism of PB and LTG, resulting in an elevation in the plasma concentrations of the inhibited drugs and consequently an increased risk of toxicity. The inhibition of the metabolism of CBZ by VPA results in an elevation of the metabolite CBZepoxide, which also increases the risk of toxicity. Other examples include the inhibition of PHT and CBZ metabolism by cimetidine and CBZ metabolism by erythromycin. In recent years, a more rational approach has been taken with regard to metabolic drug interactions because of our enhanced understanding of the cytochrome P450 system that is responsible for the metabolism of many drugs, including AEDs. The review briefly discusses the mechanisms of drug interactions and then proceeds to highlight some of the more clinically relevant drug interactions between AEDs and between AEDs and non-AEDs. Understanding the fundamental principles that contribute to a drug interaction may help the physician to better anticipate a drug interaction and allow a graded and planned therapeutic response and, therefore, help to enhance the management of patients with epilepsy who may require treatment with polytherapy regimens.

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Section: Antiulcer Drugsmentioning

confidence: 99%

The Importance of Drug Interactions in Epilepsy Therapy

et al. 2002

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“…The administration of cimetidine 1000 mgj day to 7 epileptic patients receiving long term carhamazepine monotherapy had no effect on the steady-state plasma concentrations of either carhamazepine or its 10,II-epoxide metabolite (Sonne et al 1983). Similarly, mean serum carbamazepine concentrations in 11 epileptic patients were unaltered by cimetidine coadministration (Levine et al 1985). Limited data are available on the pharmacokinetic-dynamic effects of the cimetidine-carbamazepine interaction.…”

Section: Anticonvulsantsmentioning

confidence: 95%

“…The literature contains only limited data describing the effects of cimetidine on the disposition of phenytoin in epileptic patients, but these published studies confirm that cimetidine increases the plasma concentration of phenytoin (Hetzel et al 1981;Levine et al 1985). However, in one ofthese studies patients were also receiving carbamazepine, and this may have influenced the results (Levine et al 1985).…”

Section: Anticonvulsantsmentioning

confidence: 99%

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Clinical Relevance of Cimetidine Drug Interactions

Shinn

1992

Drug Safety

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The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

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“…Thus, the enzyme sys tem becomes saturated and phenytoin metab olism is inhibited. Cimetidine caused an in crease in the plasma concentration of carba mazepine resulting neurological toxicity in an elderly woman who had been successfully treated with carbamazepine 600 mg daily for 20 years for trigeminal neuralgia [141,142],…”

Section: H Histamine Receptor Blockersmentioning

confidence: 99%

Psychotropic and Medical Drug Interactions

Ananth

Johnson

1992

Psychother Psychosom

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In a number of situations, drugs used to treat psychiatric and physical illnesses are coadministered to patients suffering primarily from a psychiatric illness. Hence, coadministration of medical and psychiatric drugs is not uncommon. With increasing use of multiple drugs, our ability to treat a number of disorders has increased, but simultaneously, the problem of drug interactions has also assumed importance. A number of factors contribute to such drug interactions in psychiatric patients. All these interactions are both pharmacologically and genetically determined. Genetic susceptibility is not practical to determine. It is therefore essential for the physician to employ drug combinations only when necessary, be aware of the known clinically significant interactions, anticipate and watch for them, avoid dangerous combinations, and monitor the patients receiving combination of drugs with vigilance.

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Differential effect of cimetidine on serum concentrations of carbamazepine and phenytoin

Cited by 28 publications

References 0 publications

The Importance of Drug Interactions in Epilepsy Therapy

The Importance of Drug Interactions in Epilepsy Therapy

Clinical Relevance of Cimetidine Drug Interactions

Psychotropic and Medical Drug Interactions

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