Cimetidine interaction with phenytoin.

Hetzel, David J.; Bochner, Felix; Hallpike, J. F.; Shearman, D. J. C.; Hann, C S

doi:10.1136/bmj.282.6275.1512

Cited by 98 publications

(26 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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).…”

Section: Antiulcer Drugsmentioning

confidence: 99%

The Importance of Drug Interactions in Epilepsy Therapy

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Section: Antiulcer Drugsmentioning

confidence: 99%

The Importance of Drug Interactions in Epilepsy Therapy

et al. 2002

View full text Add to dashboard Cite

show abstract

Section: Lack Of Interaction Between Ranitidine and Phenytoinmentioning

confidence: 51%

“…Adverse effects resulting from the interaction of cimetidine with warfarin (Hetzel et al, 1979;Serlin et al, 1979) and phenytoin (Hetzel et al, 1981) have been reported. Ranitidine, a newer histamine H2-receptor antagonist, has a different chemical structure from cimetidine; the imidazole ring of cimetidine has been replaced by a furan ring and the side chain has been modified.…”

Section: Lack Of Interaction Between Ranitidine and Phenytoinmentioning

confidence: 99%

Lack of interaction between ranitidine and phenytoin [letter]

Watts¹,

Hetzel²,

Bochner³

et al. 1983

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

“…(1981) following 3 weeks' cimetidine. This is a greater effect than the 13-33% increase in mean plasma phenytoin concentrations that we found after 6 days' cimetidine treatment of a different group of patients (Hetzel et al, 1981).The clinical importance of the interaction is illustrated by patient 4 who developed symptoms, signs and plasma concentrations consistent with phenytoin intoxication after 14 days of cimetidine treatment. No adverse effects were seen during ranitidine treatment.…”

mentioning

confidence: 76%

The interaction of cimetidine with metoprolol, atenolol, propranolol, pindolol and penbutolol [letter]

Spahn¹,

Kirch²,

Mutschler³

1983

Brit J Clinical Pharma

View full text Add to dashboard Cite

LETTERS TO THE EDITORSBr. J. cin. Pharmac. (1983), 15 centrations continued to increase (week 6 mean-week 5 mean, t23 = 4.6, P < 0.001) followed by a significant fall when the drug was withdrawn (week 7 mean, t23 = 2.6, P < 0.02 ,Imol/l) in contrast to a peak of 59 umol/l found during the second week of ranitidine administration when no adverse effects had been noted.These results show that standard therapeutic doses of ranitidine, unlike cimetidine, produced no change in plasma phenytoin concentrations in these four patients. The extent of the increase during cimetidine administration varied considerably from patient to patient with a mean increase in phenytoin concentrations of 70% (range from 22% to 280%) similar to that reported by Neuvonen etal. (1981) following 3 weeks' cimetidine. This is a greater effect than the 13-33% increase in mean plasma phenytoin concentrations that we found after 6 days' cimetidine treatment of a different group of patients (Hetzel et al., 1981).The clinical importance of the interaction is illustrated by patient 4 who developed symptoms, signs and plasma concentrations consistent with phenytoin intoxication after 14 days of cimetidine treatment. No adverse effects were seen during ranitidine treatment. Caution is necessary when adding cimetidine to phenytoin treatment, while ranitidine in these standard doses produced no significant increase in plasma phenytoin concentrations.Ranitidine may be a more suitable histamine H2-receptor antagonist when this treatment is necessary for epileptic patients receiving phenytoin.

show abstract

Cimetidine interaction with phenytoin.

Cited by 98 publications

References 5 publications

The Importance of Drug Interactions in Epilepsy Therapy

The Importance of Drug Interactions in Epilepsy Therapy

Lack of interaction between ranitidine and phenytoin [letter]

The interaction of cimetidine with metoprolol, atenolol, propranolol, pindolol and penbutolol [letter]

Contact Info

Product

Resources

About