Zithromax Special Precautions

Hypersensitivity: As with erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), and dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (rarely fatal), have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Hepatotoxicity: Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in deaths. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
In patients with mild (class A) to moderate (class B) hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to those with normal hepatic function. In these patients, urinary recovery of azithromycin appears to increase, perhaps to compensate for reduced hepatic clearance. Hence, no dose adjustment is recommended for patients with mild to moderate hepatic impairment.
Ergot Derivatives: 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 antibiotic preparation, observation for signs of superinfection with nonsusceptible organisms, including fungi is recommended.
Clostridium difficile-Associated Diarrhea: 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.
C. difficile 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 two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility test should be performed when patients are treated with Zithromax. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available. If an allergic reaction occurs, Zithromax should be discontinued and appropriate therapy should be instituted. The physician should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for outpatient oral therapy because of moderate to severe illness or risk factors eg, any of the following: Patients with nosocomially acquired infections; patients with known or suspected bacteremia; patients requiring hospitalization; elderly or debilitated patients; or patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).
In patients with severe renal impairment (GFR <10 mL/min), a 33% increase in the systemic exposure to azithromycin was observed (see Pharmacokinetics under Actions).
Diabetic Patients: 5 mL of reconstituted suspension contain sucrose 3.87 g. Due to sucrose content (3.87 g/5 mL of reconstituted suspension), Zithromax is not indicated for persons with fructose intolerance (hereditary fructose intolerance), glucose-galactose malabsorption or saccharase-isomaltase deficiency.
No dose adjustment is needed in patients with mild renal impairment (creatinine clearance >40 mL/min) but there are no data regarding azithromycin usage in patients with more severe renal impairment; thus, caution should be exercised before prescribing Zithromax in these patients.
Prolongation of the QT Interval: Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and Torsade de pointes, have been seen in treatment with other macrolides, including azithromycin (see Adverse Reactions), therefore caution is required when treating: Patients with congenital or documented QT prolongation, patients currently receiving treatment with other active substances known to prolong QT interval eg, antiarrhythmics of classes IA and III; antipsychotic agents; antidepressants; and fluoroquinolones, patients with electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesemia, patients with clinically relevant bradycardia, cardiac arrhythmia or cardiac insufficiency, elderly patients: elderly patients may be more susceptible to drug-associated effects on the QT interval.
IV Administration: Zithromax IV should be reconstituted and diluted as directed and administered as an IV infusion over not less than 60 min. Do not administer as an IV bolus or IM injection (see Dosage & Administration and Cautions for Usage).
Effects on the Ability to Drive or Operate Machinery: There is no evidence to suggest that azithromycin may have an effect on a patient's ability to drive or operate machinery.
Use in pregnancy & lactation: Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the fetus due to azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.
Azithromycin has been reported to be secreted into human breast milk, but there are no adequate and well-controlled clinical studies in nursing women that have characterized the pharmacokinetics of azithromycin excretion into human breast milk.
In fertility studies conducted in rat, reduced pregnancy rates were noted following administration of azithromycin. The relevance of this finding to humans is unknown.