Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.
Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral ranitidine at a dose exceeding 300 mg per day.
There have been reports of altered prothrombin time among patients on concomitant warfarin and ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.
Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. 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). Appropriate clinical monitoring is recommended.
Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.
Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H2-receptor antagonists with delavirdine is not recommended.
Gefitinib exposure was reduced by 44% with the coadministration of ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.
In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral ranitidine. Use appropriate clinical monitoring when initiating or discontinuing ranitidine.
Oral ketoconazole exposure was reduced by up to 95% when oral ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of ranitidine (150 mg twice daily) is unknown.
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.
Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.