Interaksi Midazolam dan Ranitidin

Cytochrome P450-3A4 Inhibitors Concomitant administration with drugs that are known to inhibit the P450-3A4 enzyme system, such as cimetidine (not ranitidine), erythromycin, diltiazem, verapamil, ketoconazole and itraconazole, may result in prolonged sedation due to a decrease in plasma clearance of midazolam.

The effect of single oral doses of 800 mg cimetidine and 300 mg ranitidine on steady-state concentrations of midazolam was examined in a randomized crossover study (n=8).

Ranitidine increased the mean steady-state concentration to 62 ng/mL.

No change in choice reaction time or sedation index was detected after dosing with the H2 receptor antagonists.

This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib).

Midazolam Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily.

However, in another interaction study in 8 volunteers receiving IV midazolam, a 300 mg oral dose of ranitidine increased midazolam exposure by about 9%.

Monitor patients for excessive or prolonged sedation when ranitidine is coadministered with oral midazolam.