WASHINGTON — Patients who develop neuropathy while taking the antibiotic Zyvox (linezolid) do so after prolonged overuse of the drug, a scientist with the Food and Drug Administration's division of anti-infective drugs reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
Once the drug is discontinued, the neuropathy seems to resolve in only a minority of the affected patients, Olga Belen, M.D., said in presenting findings from a search of the FDA's adverse event report system from April 2000, when the drug was approved, to November 2003. Zyvox, an oxazolidinone, is made by Pfizer.
Dr. Belen found 55 reports of neuropathy: 41 cases of peripheral neuropathy, 4 of optic neuropathy, and 10 with both optic and other areas affected.
Fifty-two of the patients received 600 mg twice daily. The mean age was 51 years, with a range of 12-80 years. There were 24 male patients and 28 female, and 32 reports from the United States and 28 from overseas.
Neuropathies had not been observed in preclinical or clinical studies, but they began to appear in the postmarketing period. Pfizer added language to Zyvox's label in December 2002 saying that neuropathies had been reported, but usually in patients treated for longer than the recommended maximum treatment period of 28 days.
The recommended duration of Zyvox treatment for complicated and uncomplicated skin and skin structure infections and community-acquired pneumonia is 10-14 days. For the indication of vancomycin-resistant Enterococcus faecium infections, the recommended treatment is 600 mg intravenously or orally twice daily, for 14-28 days.
But the median duration of treatment for patients who had neuropathies was 127 days—well beyond the recommended treatment period. The majority of patients with neuropathies had been taking Zyvox for 90-180 days, Dr. Belen said at the conference, sponsored by the American Society for Microbiology.
Of the 55, nine patients recovered, nine had a partial recovery, and 15 had not recovered at the last reported follow-up. There were no outcomes reported for 22 patients.
Dr. Belen said she could not draw a conclusion that Zyvox was responsible for the neuropathies reported, since the adverse event report database is just a passive collector of information. The case series “provides a temporal association with neuropathy,” she said.
When asked why there had been such long duration of use in the reports, Dr. Belen said it seemed that much of the use was for joint and lung infections, which may have prompted physicians to prescribe for longer periods.