FDA Safety Changes: Rocephin, Amaryl, Prandin

Yael Waknine

July 29, 2009

This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.

July 29, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn of the potential for cephalosporin-associated hemolytic anemia, drug interactions that may potentiate the hypoglycemic effects of glimepiride, and repaglinide drug interactions with fenofibrate and cyclosporine.

Ceftriaxone Sodium Linked to Risk for Cephalosporin-Associated Anemia

The FDA approved class safety labeling revisions for ceftriaxone sodium injection to warn of the risk for immune-mediated hemolytic anemia in patients receiving cephalosporin antibacterials. In June, the label for Rocephin (Roche Pharmaceuticals, Inc) was updated.

Severe cases of hemolytic anemia, including fatalities, have been reported in both adults and children, the agency noted. The diagnosis of cephalosporin-associated anemia should be considered in patients in whom anemia develops during treatment, and ceftriaxone should be stopped until the cause of the anemia is determined.

Ceftriaxone injection is indicated for the treatment of infections caused by susceptible microorganisms. Specific uses include lower respiratory tract infections, acute bacterial otitis media, skin/skin structure infections, urinary tract infections, uncomplicated gonorrhea, pelvic inflammatory disease, bacterial septicemia, bone and joint infections, intra-abdominal infections, and meningitis.

Ceftriaxone injection may also be used to reduce the risk for postoperative infection in patients undergoing contaminated or potentially contaminated surgical procedures.

Glimepiride (Amaryl) Drug Interactions May Cause Hypoglycemia

On June 4, the FDA approved revisions to the safety labeling for glimepiride tablets (Amaryl; sanofi-aventis US, Inc) to warn of drug interactions.

The hypoglycemic action of sulfonylureas, including glimepiride, may be potentiated by certain drugs. Agents previously listed by the FDA have included nonsteroidal anti-inflammatory drugs; clarithromycin; and other drugs that are highly protein bound, such as salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors, and β-adrenergic blocking agents.

The agency now warns that disopyramide, fluoxetine, and quinolones also potentiate the effects of sulfonylureas. Patients receiving these drugs in conjunction with glimepiride should be closely observed for signs of hypoglycemia and for loss of glycemic control when the drugs are withdrawn.

Glimepiride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Repaglinide (Prandin) Coadministration With Gemfibrozil Contraindicated

On June 10, the FDA approved safety labeling revisions for repaglinide tablets (Prandin; Novo Nordisk, Inc) to warn of drug interactions.

Repaglinide is metabolized in part by the hepatic cytochrome P 450 isoenzyme 2C8 (CYP 2C8); concomitant administration of CYP 2C8 inhibitors may decrease its metabolism and increase the risk for exposure-related adverse events.

In a pharmacokinetic study of healthy volunteers, coadministration of 100 mg of gemfibrozil (a CYP 2C8 inhibitor), yielded an 8.1-fold increase in total exposure to a single 0.25-mg dose of repaglinide and prolonged its half-life from 1.3 hours to 3.7 hours. Coadministration of repaglinide and gemfibrozil is therefore contraindicated.

According to the FDA, repaglinide also appears to be a substrate for the hepatic uptake transporter organic anion-transporting protein (OATP1B1). Drugs that inhibit OATP1B1, such as cyclosporine, may therefore also increase plasma concentrations of repaglinide and the potential for exposure-related adverse events.

In a pharmacokinetic study of healthy volunteers, coadministration of 100 mg of cyclosporine increased the maximal exposure and total exposure to a single dose of 0.25 mg of repaglinide by 1.8-fold and 2.5-fold, respectively.

Repaglinide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

FDA Safety Information

Amaryl Prescribing Information

Prandin Prescribing Information


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