FDA Safety Labeling Changes: May 17, 2004

May 17, 2004

Yael Waknine

May 17, 2004 ( updated May 18, 2004) — The U.S. Food and Drug Administration (FDA) has approved revisions to safety labeling for ethambutol hydrochloride, atazanavir sulfate, zafirlukast, ciprofloxacin hydrochloride, and bone cements and bone void fillers.

Ethambutol (Myambutol) Associated with Decreases in Visual Acuity

The FDA approved revisions on March 24 to the contraindications, precautions, and adverse reactions portions of the safety labeling for ethambutol hydrochloride (Myambutol, made by Wyeth).

Ethambutol may produce decreases in visual acuity, including irreversible blindness that may appear to be due to optic neuritis. Symptoms of optic neuropathy include decreased visual acuity, scotoma, color blindness, and/or visual defect. These events have also been reported in the absence of a diagnosis of optic or retrobulbar neuritis.

Ethambutol hydrochloride is contraindicated in patients with optic neuritis unless clinical judgment determines that it may be used. It is also contraindicated in patients who are unable to appreciate and report visual adverse effects or changes in vision, such as young children or unconscious patients.

Other adverse reactions include hypersensitivity, anaphylactic reactions, neutropenia, hypersensitivity syndrome, and pulmonary infiltrates with or without eosinophilia. Ethambutol is also contraindicated in patients who are known to be hypersensitive to this drug.

Precautions include use of ethambutol in pediatric patients aged 13 years and younger, and in nursing mothers due to drug excretion in breast milk. It should not be administered within four hours of aluminum hydroxide–containing antacids, which reduce ethambutol's mean serum concentration and urinary excretion rate.

Atazanavir (Reyataz) Interacts With Phosphodiesterase-5 Inhibitors

On March 16, the FDA approved revisions to the warnings and precautions sections of labeling for atazanavir sulfate capsules (Reyataz, made by Bristol-Myers Squibb), describing a drug interaction with phosphodiesterase-5 (PDE5) inhibitors prescribed for erectile dysfunction.

The FDA warns that concurrent administration of PDE5 inhibitors (sildenafil, tadalafil, or vardenafil) in patients receiving protease inhibitors such as atazanavir sulfate is expected to substantially increase PDE5 inhibitor concentration and may result in PDE5 inhibitor–mediated effects such as hypotension, visual changes, and priapism.

Zafirlukast (Accolate) Associated With Hepatotoxicity

The FDA approved a revision on March 26 to the warnings and precautions sections of labeling for zafirlukast (Accolate, made by AstraZeneca) describing the associated risk of hepatotoxicity.

Cases of life-threatening hepatic failure have been reported to the FDA. Patients should be advised to be alert for signs and symptoms of liver dysfunction such as right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia. Patients should contact their physician immediately if these occur, the FDA advised.

Ciprofloxacin (Cipro) Associated With Tendon Ruptures, Pseudomembranous Colitis

The FDA approved revisions on March 25 to the precautions and adverse reactions sections of labeling for ciprofloxacin hydrochloride tablets and oral suspension (Cipro, made by Bayer), describing the associated risk of Achilles and other tendon ruptures.

Reports have been received by the FDA of tendon ruptures resulting in prolonged disability or requiring surgical repair in patients receiving ciprofloxacin and other quinolones. The risk may be increased in patients concomitantly receiving corticosteroids, especially in the elderly. The FDA recommends that ciprofloxacin be discontinuedif the patient experiences pain, inflammation, or rupture of a tendon.

Ciprofloxacin is also associated with the risk of pseudomembranous colitis. Discontinuation resolves most mild cases. Treatment of moderate to severe cases should involve consideration of fluids and electrolyte management, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis. Drugs that inhibit peristalsis should be avoided, the FDA advised.

FDA Expands Warning to Include More Bone Cements and Bone Void Fillers

On May 7, the FDA expanded its Oct. 31, 2002, advisory to the healthcare community to include all bone cements (polymethylmethacrylate and calcium phosphate) and bone void fillers that are not specifically cleared and labeled for vertebroplasty or kyphoplasty, warning that there have been serious complications from the use of acrylic bone cements in treating compression fractures of the spine.

The FDA advises physicians to follow the labeling when using bone cement cleared by FDA for vertebroplasty or kyphoplasty. Those considering the use of bone cements and bone void fillers not cleared by FDA for this purpose should be especially attentive to patient selection, treatment techniques, potential complications, and patient monitoring. Physicians should also be aware of the literature in this area, as well as recommendations from professional organizations.

The FDA points out that a bone cement (KyphX HV-R, made by Kyphon) was approved in April for the treatment of pathological vertebral fractures due to osteoporosis using a kyphoplasty procedure, and that other products may be cleared for this purpose in the future.

Bone cements and bone void fillers that have been cleared for use in vertebroplasty and kyphoplasty are listed at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm. Enter product code NDN. The database is updated as new products are cleared.

Reviewed by Gary D. Vogin, MD

Yael Waknine is a freelance writer for Medscape.