Azithromycin: uses, appearance and warnings

Azithromycin for oral suspension 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 ( 1.1 ) Acute bacterial sinusitis in adults ( 1.1 ) Uncomplicated skin and skin structure infections in adults ( 1.1 ) Urethritis and cervicitis in adults ( 1.1 ) Genital ulcer disease in men ( 1.1 ) Acute otitis media in pediatric patients (6 months of age and older) ( 1.2 ) Community-acquired pneumonia in adults and pediatric patients (6 months of age and older) ( 1.1 , 1.2 ) Pharyngitis/tonsillitis in adults and pediatric patients (2 years of age and older) ( 1.1 , 1.2 ) Limitation of Use: Azithromycin for oral suspension 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. ( 1.3 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin for oral suspension and other antibacterial drugs, azithromycin for oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.4 ) 1.1 Indications in Adult Patients Azithromycin for oral suspension is indicated in adult patients for the treatment of mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below: Acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae , Moraxella catarrhalis, or Streptococcus pneumoniae . Acute bacterial sinusitis due to Haemophilus influenzae , Moraxella catarrhalis. or Streptococcus pneumoniae . Community-acquired pneumonia due to Chlamydophila pneumoniae , Haemophilus influenzae , Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy. Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. Uncomplicated skin and skin structure infections due to Staphylococcus aureus , Streptococcus pyogenes , or Streptococcus agalactiae . Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae . Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established. 1.2 Indications in Pediatric Patients Azithromycin for oral suspension is indicated in pediatric patients for the treatment of mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below: [see Use in Specific Populations (8.4) and Clinical Studies (14.2) ] . Acute otitis media caused by Haemophilus influenzae , Moraxella catarrhalis, or Streptococcus pneumoniae , in pediatric patients 6 months of age and older. Community-acquired pneumonia due to Chlamydophila pneumoniae , Haemophilus influenzae , Mycoplasma pneumoniae , or Streptococcus pneumoniae in pediatric patients 6 months of age and older appropriate for oral therapy. Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy in pediatric patients 2 years of age and older. …

Azithromycin for oral suspension USP after constitution contains a pale to dark pink flavored suspension. Azithromycin for oral suspension USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles. Azithromycin for oral suspension USP 100 mg/5 mL and 200 mg/5 mL ( 3 )

How Supplied Azithromycin for oral suspension USP after constitution contains a pale to dark pink flavored suspension. Azithromycin for oral suspension USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows: 100 mg/5 mL 15 mL Bottle (300 mg) NDC 59651-007-15 200 mg/5 mL 15 mL Bottle (600 mg) NDC 59651-008-15 22.5 mL Bottle (900 mg) NDC 59651-008-23 30 mL Bottle (1200 mg) NDC 59651-008-30 Constitution instructions are described for each bottle type elsewhere in the prescribing information [see Dosage and Administration (2) ]. Storage and Handling Store dry powder at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Store constituted suspension between 5° to 30°C (41° to 86°F) and discard when full dosing is completed [see Dosage and Administration (2) ].

Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug. ( 4.1 ) Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin. ( 4.2 ) 4.1 Hypersensitivity Azithromycin for oral suspension is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug. 4.2 Hepatic Dysfunction Azithromycin for oral suspension is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Serious (including fatal) allergic and skin reactions: Discontinue azithromycin if reaction occurs. (5.1) Hepatotoxicity: Severe, and sometimes fatal, hepatotoxicity has been reported. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. (5.2) 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. (5.3) 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. (5.4) Cardiovascular Death: Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. Consider balancing this potential risk with treatment benefits when prescribing azithromycin. ( 5.5 ) Clostridioides difficile -Associated Diarrhea: Evaluate patients if diarrhea occurs. ( 5.6 ) Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis. ( 5.7 ) 5.1 Hypersensitivity Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy. [see Contraindications (4.1) ] Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued. 5.2 Hepatotoxicity Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. 5.3 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. 5.4 QT Prolongation Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including: patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure patients on drugs known to prolong the QT interval patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval. 5.5 Cardiovascular Death Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use. Consider balancing this potential risk with treatment benefits when prescribing azithromycin. 5.6 Clostridioides difficile- Associated Diarrhea Clostridioides 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 antibacterial 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. …

The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Infantile Hypertrophic Pyloric Stenosis (IHPS) [see Warnings and Precautions (5.3) ] QT Prolongation [see Warnings and Precautions (5.4) ] Cardiovascular Death [see Warnings and Precautions (5.5) ] Clostridioides difficile- Associated Diarrhea (CDAD) [see Warnings and Precautions (5.6) ] Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.7) ] Most common adverse reactions are diarrhea (5 to 14%), nausea (3 to 18%), abdominal pain (3 to 7%), or vomiting (2 to 7%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. ( 7.1 ) Warfarin: Use with azithromycin may increase coagulation times; monitor prothrombin time. ( 7.2 ) 7.1 Nelfinavir Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. …