Zithrolide Special Precautions

As with erythromycin and other macrolides, rare serious allergic reactions including angioedema and anaphylaxis (rarely fatal), have been reported. Some of these reactions with Zithrolide have resulted in recurrent symptoms, and required a longer period of observation and treatment. Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic diseases. In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered. As with any antibiotics preparation, observation for signs of superinfection with nonsusceptible organisms, including fungi is recommended. Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents including azithromycin and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. It produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. In patients with severe renal impairment (GFR <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed. Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrythmia and Torsade de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation.
Use in pregnancy & lactation: Animal reproduction studies have demonstrated that azithromycin crosses the placenta, but have revealed no evidence of harm to the foetus. There are no adequate and well controlled studies in pregnant women. Since animal studies are not always predictive of human response, Zithrolide should be used during pregnancy only if adequate alternatives are not available.
No data on secretion of azithromycin in breast milk are available, so that Zithrolide should only be used in lactating women where adequate alternatives are not available.