Drug Interactions between aspirin / omeprazole and betiatide

MONITOR: Coadministration of the radiopharmaceutical technetium (Tc99m) mertiatide with another drug that is also eliminated by active tubular secretion may result in increased plasma concentrations of one or both drugs. The exact mechanism has not been fully described but may involve competition in binding to organic anion transporter 1 (OAT1) in the proximal tubule of the kidney, which is involved in moving some drugs from the blood into the urine. The risk and significance of this interaction may vary. Some sources state that the risk is expected with diuretics like hydrochlorothiazide, but only theoretical with others (e.g., nonsteroidal anti-inflammatory drugs). Delayed excretion of Tc99m mertiatide may affect the efficacy of the diagnostic procedure. However, clinical data are limited. One crossover study conducted in 12 healthy male volunteers (22-25 years old), reviewed the differences in scans using Tc99m mertiatide injection alone to those obtained when subjects received either a selective OAT1 substrate (10% sodium p-aminohippurate (PAH) given via intravenous infusion at 120 mg/min 10 minutes prior to and during the scan) or a potent OAT1 inhibitor (probenecid 750 mg 1 hour prior to the scan). PAH appeared to have a greater impact than probenecid, increasing the late phase (30-60 minutes post radiopharmaceutical injection) plasma clearance half-life of Tc99m mertiatide from approximately 27.7 minutes to 54.9 minutes. However, in some circumstances, the administration of an NSAID or other medication that affects the secretion of Tc99m mertiatide may be clinically indicated. For example, there are some protocols that utilize aspirin to enhance Tc99m mertiatide renography for the investigation/diagnosis of renal artery stenosis.

MANAGEMENT: Caution is recommended with the concomitant administration of technetium (Tc99m) mertiatide with drugs that are secreted in the proximal tubule due to the potential to affect the efficacy of the diagnostic procedure. Likewise, since Tc99m mertiatide may also delay the excretion of other drugs eliminated via this route, monitoring for excessive pharmacologic effects of both drugs should be considered. Current clinical guidelines and/or manufacturer's labeling should be consulted for more specific information and guidance. Dehydration and acidosis can also impact kidney function and prolong renal drug elimination. Refer to the product labeling or local protocols for guidelines on patient hydration prior to testing with Tc99m mertiatide.

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.