Dose and serum concentration relationships in cimetidine-associated mental confusion

A patient with severe liver disease and mildly abnormal but stable renal function was given cimetidine on two occasions for gastrointestinal hemorrhage. In each course, dosing was initiated at half the recommended dosage of 600 mg daily, and mental status deteriorated shortly after dosing began. A further dosage decrease to 300 mg daily allowed continuation of cimetidine therapy in absence of mental status alterations. In this patient, mental status changes occurred at lower serum concentrations than we have previously reported. This discrepancy was explained by analysis of cimetidine CSF concentrations, as this patient had abnormally high cimetidine blood to CSF permeability. Although the cause of increased CSF concentrations is unclear, cimetidine-associated mental confusion was dose related and completely reversible upon a decrease in dosage. Patients who develop cimetidine-associated mental status changes and who cannot have treatment stopped may be safely treated by individualizing the dosing rate.