Azithromycin is a macrolide antibacterial drug indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. Recommended dosages and durations of therapy in adult and pediatric patient populations vary in these indications. [see Dosage and Administration ( 2 )] Azithromycin is a macrolide antibacterial drug indicated for mild to moderate infections caused by designated, susceptible bacteria:
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 ( 1.2 )
Community-acquired pneumonia in adults and pediatric patients ( 1.1 , 1.2 )
Pharyngitis/tonsillitis in adults and pediatric patients ( 1.1 , 1.2 ) Limitation of Use : Azithromycin should not be used 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 infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.4 )
1.1Adult
Patients
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.
Patients [see Use in Specific Populations ( 8.4 ) and Clinical Studies ( 14.2 )]
Acute otitis media ( >6 months of age) c aused by Haemophilus influenzae , Moraxella catarrhalis, or Streptococcus pneumoniae
Community-acquired pneumonia ( >6 months of age) due to Chlamydophila pneumoniae , Haemophilus influenzae , Mycoplasma pneumonia , or Streptococcus pneumoniae in patients appropriate for oral therapy.
Pharyngitis/tonsillitis ( > 2 years of age ) caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.
1.3Limitations of Use
Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:
patients with cystic fibrosis,
patients with nosocomial 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).
1.4Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Contraindications
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 )
4.1Hypersensitivity Azithromycin
for oral suspension is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug.
4.2Hepatic Dysfunction Azithromycin
for oral suspension is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.
Warnings and precautions
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 )
Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis. ( 5.6 )
5.1Hypersensitivity
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.
5.2Hepatotoxicity
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.
5.3Infantile 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.
5.4QT 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 Clostridium difficile-Associated Diarrhea (CDAD) Clostridium difficile -associated diarrhea 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.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
5.6Exacerbation of Myasthenia Gravis Exacerbation
of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
5.7 Use in Sexually Transmitted Infections Azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.
5.8Development of Drug-Resistant Bacteria
Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Interactions
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 )
7.1Nelfinavir 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. [see Adverse Reactions ( 6 )]
7.2Warfarin
Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.
7.3Potential Drug-Drug Interactions with Macrolides Interactions
with digoxin or phenytoin have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interactions. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin or phenytoin are used concomitantly with azithromycin careful monitoring of patients is advised.
Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic dose concentrations (i.e., 200 mg/kg/day). These daily doses in rats and mice, based on body surface area, are estimated to be 4 and 2 times, respectively, an adult daily dose of 500 mg. In the animal 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.
Adverse reactions
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 Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported.
Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related adverse reactions was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse reactions was approximately 1%.
Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see Clinical Studies ( 14.2 )] Adults Multiple-dose regimens: Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (4 to 5%), nausea (3%), and abdominal pain (2 to 3%) being the most frequently reported.
No other adverse reactions occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following: Cardiovascular: Palpitations, chest pain. Gastrointestinal: Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice. Genitourinary: Monilia, vaginitis, and nephritis. Nervous System: Dizziness, headache, vertigo, and somnolence.
General: Fatigue. Allergic: Rash, pruritus, photosensitivity, and angioedema. Single 1-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen. Adverse reactions that occurred in patients on the single 1-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).
Single 2-gram dose regimen: Overall, the most common adverse reactions in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Adverse reactions that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). The majority of these complaints were mild in nature.
Pediatric Patients Single and Multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients. Acute Otitis Media: For the recommended total dosage regimen of 30 mg/kg, the most frequent adverse reactions (≥1%) attributed to treatment were diarrhea, abdominal pain, vomiting, nausea, and rash. [see Dosage and Administration ( 2 ) and Clinical Studies ( 14.2 )] The incidence, based on dosing regimen, is described in the table below: Dosage Regimen Diarrhea % Abdominal Pain % Vomiting % Nausea % Rash % 1-day 4.3% 1.4% 4.9% 1% 1% 3-day 2.6% 1.7% 2.3% 0.4% 0.6% 5-day 1.8% 1.2% 1.1% 0.5% 0.4% Community-Acquired Pneumonia: For the recommended dosage regimen of 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5, the most frequent adverse reactions attributed to treatment were diarrhea/loose stools, abdominal pain, vomiting, nausea, and rash.
The incidence is described in the table below: Dosage Regimen Diarrhea/Loose stools % Abdominal Pain % Vomiting % Nausea % Rash % 5-day 5.8% 1.9% 1.9% 1.9% 1.6% Pharyngitis/Tonsillitis: For the recommended dosage regimen of 12 mg/kg on Days 1 to 5, the most frequent adverse reactions attributed to treatment were diarrhea, vomiting, abdominal pain, nausea, and headache. The incidence is described in the table below: Dosage Regimen Diarrhea % Abdominal Pain % Vomiting % Nausea % Rash % Headache % 5-day 5.4% 3.4% 5.6% 1.8% 0.7% 1.1% With any of the treatment regimens, no other adverse reactions occurred in pediatric patients treated with azithromycin with a frequency greater than 1%.
Adverse reactions that occurred with a frequency of 1% or less included the following: Cardiovascular: Chest pain. Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, and oral moniliasis. Hematologic and Lymphatic: Anemia and leukopenia. Nervous System: Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness, and insomnia. General: Fever, face edema, fatigue, fungal infection, malaise, and pain.
Allergic: Rash and allergic reaction. Respiratory: Cough, pharyngitis, pleural effusion, and rhinitis. Skin and Appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria, and vesiculobullous rash. Special Senses: Conjunctivitis.
6.2Postmarketing Experience
The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include: Allergic: Arthralgia, edema, urticaria, and angioedema.
Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation and torsades de pointes . Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration. General: Asthenia, paresthesia, fatigue, malaise, and anaphylaxis Genitourinary: Interstitial nephritis and acute renal failure and vaginitis.
Hematopoietic: Thrombocytopenia. Liver/Biliary: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [see Warnings and Precautions ( 5.2 )] Nervous System: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation, and syncope. Psychiatric: Aggressive reaction and anxiety. Skin/Appendages: Pruritus serious skin reactions including erythema multiforme, AGEP, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS.
Special Senses: Hearing disturbances including hearing loss, deafness and/or tinnitus, and reports of taste/smell perversion and/or loss.
6.3Laboratory Abnormalities Adults:
Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin, hematocrit, lymphocytes, neutrophils, and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils, and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium, potassium, platelet count, ele
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
AZITHROMYCIN EQ 100MG BASE/5ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
