Drug Interactions between betiatide and Symfi Lo

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

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.