Database/Interactions/fenytoin/cimetidin

fenytoin - cimetidin

Klassificering


Klassificering fenytoin cimetidin
D4 Enteral eller Parenteral Enteral eller Parenteral

Medicinsk konsekvens

Plasmakoncentrationen av fenytoin ökar vid samtidig administrering av cimetidin. Toxiska plasmanivåer kan uppkomma på grund av fenytoins icke-linjära farmakokinetik.

Rekommendation

Kombinationen av cimetidin och fenytoin bör undvikas såvida ej plasmakoncentrationsmätningar av fenytoin kan göras. Famotidin eller ranitidin interagerar ej med fenytoin och kan vara alternativ till cimetidin.

Mechanism

Cimetidine inhibits the drug metabolising enzyme CYP2C19, which is involved in the biotransformation of phenytoin.

Background

Increased serum concentrations of phenytoin (by 13-57 %) have been observed both in patients and healthy volunteers at concomitant administration of cimetidine, both orally and intravenously (1-3). Hence, the mechanism of interaction between cimetidine and phenytoin is most likely due to enzyme inhibition (4). However, no significant changes in serum concentrations or pharmacokinetic parameters were observed in nine epileptic patients given 200 mg bid of cimetidine for 2 weeks together with phenytoin. Since five of the patients were also taking carabamazepine, a known inducer of cytochrome P450s, a counteractive effect might have influenced the result. Furthermore, the daily doses of cimetidine were probably too low (400 mg/day compared to other studies with at least 1000 mg/day) to have any substantial impact (1-3, 5). Since phenytoin exhibits non-linear pharmacokinetics, its serum levels are difficult to predict and therapeutic drug monitoring should be performed if cimetidine is administered concomitantly (1-2).

Referenser

  1. Hetzel DJ, Bochner F, Hallpike JF, Shearman DJ, Hann CS. Cimetidine interaction with phenytoin. Br Med J (Clin Res Ed). 1981;282:1512.  PubMed
  2. Levine M, Jones MW, Sheppard I. Differential effect of cimetidine on serum concentrations of carbamazepine and phenytoin. Neurology. 1985;35:562-5.  PubMed
  3. Neuvonen PJ, Tokola RA, Kaste M. Cimetidine-phenytoin interaction: effect on serum phenytoin concentration and antipyrine test. Eur J Clin Pharmacol. 1981;21:215-20.  PubMed
  4. Frigo GM, Lecchini S, Caravaggi M, Gatti G, Tonini M, D'Angelo L et al. Reduction of phenytoin clearance caused by cimetidine. Eur J Clin Pharmacol. 1983;25:135-7.  PubMed
  5. Rafi JA, Frazier LM, Driscoll-Bannister SM, O'Hara KA, Garnett WR, Pugh CB. Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures. Ann Pharmacother. 1999 Jul-Aug;33:769-74.  PubMed

Kommentera»


SFINX - interaktionsdatabas sammanställd av avdelning för klinisk farmakologi vid Karolinska Institutet, Läkemedelscentrum inom SLL och medbase Ltd, Finland.

« Tillbaka