Drug Interactions between aspirin / omeprazole and tipranavir

MONITOR CLOSELY: Theoretically, tipranavir may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, high supplemental dosages of vitamin E, or agents that commonly cause thrombocytopenia. Tipranavir has been shown to inhibit human platelet aggregation in vitro at levels consistent with exposures observed in patients receiving tipranavir/ritonavir. Cases of intracranial hemorrhage, some fatal, have been reported during postmarketing use. However, many of these patients had other medical conditions or were receiving concomitant medications that may have caused or contributed to these events. No pattern of abnormal coagulation parameters has been observed in patients in general, or preceding the development of intracranial hemorrhage.

MANAGEMENT: Caution is advised if tipranavir/ritonavir is used in combination with other drugs that affect hemostasis. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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ADJUST DOSE: The concomitant administration of tipranavir-ritonavir with omeprazole or esomeprazole may significantly decrease systemic exposure to the proton pump inhibitors. The proposed mechanism is induction of CYP450 2C19 metabolism by tipranavir-ritonavir. In clinical studies, concurrent administration of tipranavir-ritonavir reduced the steady state AUC and Cmax of omeprazole by 71% and 73%, respectively. Esomeprazole, the S-enantiomer of omeprazole, was similarly affected.

MANAGEMENT: If this combination is given concurrently, patients should be monitored for altered clinical efficacy of the proton pump inhibitor. Dose adjustments may be necessary; however, specific dosage recommendations are not available.

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Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates.

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