FDA Safety Changes: Prevpac, Arava, Treanda

Yael Waknine

July 01, 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 1, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of an interaction between amoxicillin and certain urine glucose tests, and to include patient information regarding the risk for the development of Clostridium difficile–associated diarrhea more than 2 months after completion of treatment with a prepackaged regimen of lansoprazole, amoxicillin, and clarithromycin tablets. The agency has also approved safety labeling revisions to advise of the need for tuberculosis screening before initiation of leflunomide therapy and the potential for dermatologic reactions in patients receiving treatment with bendamustine HCl.

Antibiotic Components of Prepackaged Regimen (Prevpac) Linked to Risk for CDAD

On April 6, the FDA approved revisions to the safety labeling for a prepackaged regimen of lansoprazole, amoxicillin, and clarithromycin tablets (Prevpac; TAP Pharmaceutical Products Inc) to warn of a laboratory test interaction with amoxicillin and to provide patient information regarding the risk for diarrhea during and after completion of treatment.

According to the agency, high urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using Clinitest (Bayer Diagnostics), Benedict's solution, or Fehling's solution. Use of glucose tests based on enzymatic glucose oxidase reactions (eg, Clinistix; Bayer Diagnostics) is therefore recommended.

The agency also warned that amoxicillin, clarithromycin, and other antibiotics have been linked to a risk for Clostridium difficile–associated diarrhea (CDAD) that may range in severity from mild diarrhea to fatal colitis and occur more than 2 months after treatment is completed. Because hypertoxin-producing strains of C difficile can be refractory to antimicrobial therapy, they are associated with increased morbidity and mortality rates and may require colectomy.

Patients should be advised that diarrhea is a common problem caused by antibiotics that usually ends on discontinuation of therapy and to contact their clinician if watery and bloody stools occur (with or without stomach cramps and fever) within a few months of antibiotic therapy.

The FDA notes that current antibiotic therapy for the primary infection may need to be discontinued in patients with known or suspected CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic therapy for C difficile, and surgical evaluation also may be required.

Lansoprazole, amoxicillin, and clarithromycin combination therapy is indicated for Helicobacter pylori eradication to reduce the risk for duodenal ulcer recurrence.

Tuberculosis Screening Advised Before Initiating Leflunomide (Arava) Therapy

On April 3, the FDA approved safety labeling revisions for leflunomide tablets (Arava; sanofi-aventis US, Inc) to advise of the need for tuberculosis screening before initiation of therapy.

Medications with immunosuppressive potential, such as leflunomide, may increase patient susceptibility to opportunistic infections, particularly tuberculosis (including extrapulmonary disease), Pneumocystis jiroveci pneumonia, and aspergillosis.

The FDA notes that leflunomide has not been studied in patients with a positive tuberculin screen result, and the safety of leflunomide in those with latent infection remains unknown. Patients with a positive test result should be treated by standard medical practice before starting leflunomide therapy.

Leflunomide is indicated to reduce signs and symptoms of disease, inhibit structural damage, and improve physical function in patients with active rheumatoid arthritis.

Bendamustine HCl (Treanda) May Be Linked to Potentially Severe Skin Reactions

On May 1, the FDA approved safety labeling revisions for bendamustine HCl intravenous infusion (Treanda; Cephalon, Inc) to warn of the potential for skin reactions.

Skin reactions reported in clinical trials and postmarketing experience have included rash, toxic skin reactions, and bullous exanthema. Because some of these events occurred with concomitant use of other anticancer agents, their relationship to bendamustine remains unclear.

In a study of bendamustine (90 mg/m2) administered with rituximab, 1 case of toxic epidermal necrolysis (TEN) occurred; however, TEN has also been reported in connection with rituximab. Cases of Stevens-Johnson syndrome and TEN, some fatal, were also reported when bendamustine was administered concomitantly with allopurinol and other agents known to cause these syndromes.

The FDA warns that patients with skin reactions should be monitored closely. Bendamustine therapy should be withheld or discontinued for conditions that are severe or progressive.

Bendamustine is an alkylating drug indicated for the treatment of patients with chronic lymphocytic leukemia, and indolent B-cell non-Hodgkin's lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

FDA Safety Information

Treanda Prescribing Information

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