As with erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), dermatologic reactions including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) (rarely fatal), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Some of these reactions with Zynomax 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.
Since liver is the principal route of elimination for Zynomax, the use of Zynomax should be undertaken with caution in patients with significant hepatic disease.
In patients receiving ergot derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and Zynomax. However, because of the theoretical possibility of ergotism, Zynomax and ergot derivatives should not be coadministered.
As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zynomax, 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.
In patients with severe renal impairment (GFR <10 ml/min) a 33% increase in systemic exposure to Zynomax was observed.
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including Zynomax. Prescribers should consider the risk of QT prolongation, which can be fatal, when weighing the risks and benefits of Zynomax for at-risk groups including: Patients with congenital or documented QT prolongation.
Patients currently receiving treatment with other active substances known to prolong QT interval, such as antiarrhythmics of Classes IA and III, antipsychotic agents, antidepressants, and fluoroquinolones.
Patients with electrolyte disturbance, particularly in cases of hypokalemia 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.
Infantile hypertrophic pyloric stenosis (IHPS) has been reported following the use of azithromycin in infants (treatment up to 42 days of life). Parents and caregivers should be informed to contact their physician if vomiting and/ or irritability with feeding occurs.
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCARs) [e.g. Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) & acute generalised exanthematous pustulosis (AGEP)], Zynomax should be discontinued immediately and appropriate treatment should be urgently initiated.
Effects on Ability to Drive and Use Machines: There is no evidence to suggest that Zynomax may have an effect on the patient's ability to drive or operate machinery.