Pfizer's Zithromax (azithromycin) has FDA's okay for use as a single-dose treatment for Chlamydia trachomatis infections in men and women. Individuals with non-gonococcal urethritis or cervicitis will be able to receive a single 1 gram dose of Zithromax instead of the standard twice-daily dose of doxycycline over seven days. The single dose therapy should enhance compliance significantly. The approved labeling notes, however, that the single dose may not be appropriate to treat gonorrhea or syphilis. "Antimicrobial agents used in high doses for short periods of time to treat non- gonococcal urethritis may mask or delay the symptoms of incubating gonorrhea or syphilis," labeling cautions. Physicians are urged to perform serologic tests for syphilis and appropriate cultures for gonorrhea at the time of diagnosis of a sexually transmitted urethritis or cervicitis. Susceptibility testing to azithromycin is recommended. In several studies presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), azithromycin eradicated chlamydial infections at a rate similar to that of doxycycline, from 91%-100% ("The Pink Sheet" Oct. 7, T&G- 4). Meanwhile, in another study, presented at the meeting by Hunter Handsfield, MD, University of Washington, the 1 gram dose of azithromycin cured uncomplicated gonorrhea in 75% of patients. When the researcher raised the dose to 2 grams, the gastrointestinal side effects increased. At the ICAAC meeting, Handsfield commented that if azithromycin is priced to compete with respiratory and cutaneous anti-infectives, the drug may be too costly for common use in sexually transmitted disease clinics. Pfizer has not announced a price for azithromycin; the company says that it will be priced "competitively." It is additionally approved for uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae. Pfizer received all of the indications recommended by FDA's Anti-Infective Drugs Advisory Committee at its July 18 meeting ("The Pink Sheet" July 22, p. 10). Azithromycin received a second-line indication as a treatment of streptococcal pharyngitis/tonsillitis (strep throat). Labeling notes that Zithromax should only be used "as an alternative to first line therapy of acute pharyngitis/tonsillitis due to Streptococcus pyogenes occurring in individuals who cannot use first line therapy." Penicillin is the drug of choice in the treatment of S. pyogenes and for prophylaxis of rheumatic fever, labeling states. "Zithromax is often effective in the eradication of susceptibile strains of S. pyogenes from the nasopharynx," labeling notes; however, "because some strains are resistant to Zithromax, susceptibility tests should be performed." In those penicillin intolerant patients, azithromycin would be given in a once-daily 250 mg dose over five days, compared to the standard 10-14 day treatment with other antibiotics. In its Nov. 1 approval letter to Pfizer, FDA warns the company against promoting Zithromax as a first-line therapy for strep throat. Such advertising would be misleading "if it presents suggestions or representations regarding the use of azithromycin as a general, first-line therapy for the treatment of streptococcal pharyngitis/tonsillitis or otherwise represents the drug for use not consistent with the approved labeling," FDA said in the letter to Pfizer. Another macrolide, Abbott's Biaxin (clarithromycin) Filmtabs, approved one day earlier, received an indication for strep throat without any caveats ("The Pink Sheet" Nov. 4, p. 8). An indication of Abbott's positioning for its product is provided by a recent newsletter, Infectious Disease Quarterly (Volume 1, Number 1) produced under a grant from the firm. The newsletter says that reports from the 17th International Congress of Chemotherapy "suggest the new macrolides such as clarithromycin, roxithromycin [RU-965, Hoechst] and rokitamycin have increased the intrinsic antimicrobial activity of erythromycin, improved on its stability in the stomach and prolonged its dosing interval by improvements to its pharmacokinetic profile." Further portraying Biaxin as a replacement for erythromycin, the newsletter quotes Gail Cassell, PhD, microbiology department chairman at the University of Alabama: "When the advanced macrolides, like clarithromycin, with enhanced microbiologic activity, become available, they may replace erythromycin as an agent of choice." Another article in the newsletter maintains that "clarithromycin may also prove useful in the treatment of resistant pathogens." The article contends that some strains of "common bacterial pathogens including S. pneumonia and H. influenzae are reportedly showing increasing resistance to beta- lactam antibiotics." Although indicated for slightly different infections -- clarithromycin is not indicated for chlamydia -- the Abbott and Pfizer macrolides are likely to be viewed as competitors. Pfizer said that it will ship the product "as soon as possible" and a launch is expected by early 1992. According to the Zithromax approval letter, Pfizer must conduct four Phase IV studies and submit the results within a year. The studies are intended to provide information on pharmacokinetic mass balance, the pharmacokinetics of azithromycin in hepatically-impaired and renally-impaired patients, the interaction between azithromycin and terfenadine; and additional information on dissolution conditions. The major adverse reactions to azithromycin were gastrointestinal side effects. Patients receiving the multiple- dose (250 mg) regimen of azithromycin experienced diarrhea/loose stools (5%), nausea (3%), and abdominal pain (3%). With the single one gram dose the adverse reactions increased and, in addition, patients experienced vomiting (2%) and vaginitis (2%). Pfizer is further investigating the use of azithromycin in AIDS patients with cerebral toxoplasmosis or Mycobacterium avium complex (MAC). A small uncontrolled Phase I study published in the Nov. 2 issue of Lancet reports that azithromycin safely reduced M. avium complex bacteremia and associated symptoms, such as fever and night sweats, in 75% of the AIDS patients treated for at least 20 days. The principal author of the study was Lowell Young, MD, of the Kuzzell Institute for Arthritis and Infectious Disease in San Francisco. Clarithromycin has also shown efficacy against MAC infections in AIDS patients in early clinical trials.
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