Interactions between cimetidine and Dilantin infatabs (phenytoin)
cimetidine and phenytoin (Major Drug-Drug)
GENERALLY AVOID: Coadministration with cimetidine may significantly increase the plasma concentrations of phenytoin. The proposed mechanism is cimetidine inhibition of CYP450 2C9 and 2C19, the isoenzymes responsible for the metabolic clearance of phenytoin. In pharmacokinetic studies, cimetidine administered at dosages of 1000 to 1200 mg/day has consistently been found to increase phenytoin plasma levels, with wide intersubject variability ranging from a 13% to almost 300% increase and phenytoin toxicity developing in some. There have also been rare reports of severe and life-threatening thrombocytopenia, agranulocytosis, and cutaneous reactions including toxic epidermal necrolysis in patients receiving phenytoin and cimetidine, with or without glucocorticoids. Whether these events are related to a pharmacokinetic or pharmacodynamic interaction is unknown. Cimetidine at a dosage of 400 mg/day for two weeks did not significantly affect phenytoin serum levels or seizure frequency in a study of nine patients on long-term phenytoin therapy.
MANAGEMENT: The use of cimetidine should generally be avoided in patients treated with phenytoin because safer alternatives exist, such as other H2-receptor antagonists or proton pump inhibitors. These agents (except omeprazole) have demonstrated a lack of interaction with phenytoin in pharmacokinetic studies, and only rare cases of suspected interaction have been reported, if any.
