Drug Interactions between ampicillin / probenecid 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.

MONITOR: The administration of an organic anion transporter 1 (OAT1) inhibitor just prior to or concurrently with the radiopharmaceutical, technetium (Tc99m) mertiatide, may reduce its renal uptake and excretion as it is a substrate of this transporter. Delayed clearance could result in a misinterpretation of diagnostic study results. Clinical data is limited. One crossover study conducted in 12 healthy male volunteers (22-25 years old), compared the results of Tc99m mertiatide injection alone to those obtained after the subjects received a potent OAT1 inhibitor (probenecid 750 mg) 1 hour prior to the radiopharmaceutical injection. Probenecid administration prolonged the plasma clearance half-life of Tc99m mertiatide in the late phase (30-60 minutes post injection), from 24.4 +/- 9.9 minutes to 33.1 +/- 12.9 minutes. Similarly, the volunteer's Tc99m mertiatide blood concentrations were higher after treatment with probenecid, suggesting that renal excretion of the radiopharmaceutical was inhibited by the OAT1 inhibitor.

MANAGEMENT: Administration of an organic anion transporter 1 (OAT1) inhibitor just prior to or concurrently with technetium (Tc99m) mertiatide should be done with caution as it may delay excretion of the radiopharmaceutical and affect the efficacy of the diagnostic procedure. Dehydration and acidosis can also lead to prolonged elimination of Tc99m mertiatide, further impacting the efficacy of the diagnostic test. Refer to the product labeling or local protocols for guidelines on patient hydration.

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.