Azithromycin

ZITHROMAX is a macrolide antibacterial drug indicated for treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below: • Acute bacterial exacerbations of chronic bronchitis in adults. • Acute bacterial sinusitis in adults. • Uncomplicated skin and skin structure infections in adults. • Urethritis and cervicitis in adults. • Genital ulcer disease in men. • Acute otitis media in pediatric patients (6 months of age and older). • Community-acquired pneumonia in adults and pediatric patients (6 months of age and older). • Pharyngitis/tonsillitis in adults and pediatric patients (2 years of age and older). Limitation of Use: ZITHROMAX is not recommended in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors.

Azithromycin is a macrolide antibacterial drug. Mechanism of Action Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit. Resistance Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B (MLS B phenotype). Antimicrobial Activity Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections.

Recommended Dosage for Adult Patients. Infection Recommended Dose/Duration of Therapy Community-acquired pneumonia (mild severity) Pharyngitis/tonsillitis (second-line therapy) Skin/skin structure (uncomplicated) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5. Acute bacterial exacerbations of chronic bronchitis (mild to moderate) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 or 500 mg once daily for 3 days. Acute bacterial sinusitis 500 mg once daily for 3 days. Genital ulcer disease (chancroid) Non-gonococcal urethritis and cervicitis One single 1 gram dose. Gonococcal urethritis and cervicitis One single 2 gram dose. Recommended Dosage for Pediatric Patients.

• Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug. • Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

• Serious (including fatal) allergic and skin reactions: Discontinue ZITHROMAX if reaction occurs. • Hepatotoxicity: Severe, and sometimes fatal, hepatotoxicity has been reported. Discontinue ZITHROMAX immediately if signs and symptoms of hepatitis occur. • Infantile Hypertrophic Pyloric Stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs. • Prolongation of QT interval and cases of torsades de pointes have been reported. This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval.

The following clinically significant adverse reactions are described elsewhere in labeling: • Hypersensitivity • Hepatotoxicity • Infantile Hypertrophic Pyloric Stenosis (IHPS) • QT Prolongation • Cardiovascular Death • Clostridioides difficile- Associated Diarrhea (CDAD) • Exacerbation of Myasthenia Gravis Most common adverse reactions are diarrhea (5 to 14%), nausea (3 to 18%), abdominal pain (3 to 7%), or vomiting (2 to 7%).

• Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. • Warfarin: Use with azithromycin may increase coagulation times, monitor prothrombin time.

Store ZITHROMAX tablets between 15° to 30°C (59° to 86°F). Storage and Handling Store dry powder below 30°C (86°F). Store constituted suspension between 5° to 30°C (41° to 86°F) and discard when full dosing is completed.