Azithromycin tablets USP
Azithromycin tablets USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38H72N2O12, and its molecular weight is 749.00.
Azithromycin, as the dihydrate, is a white or almost white powder with a molecular formula of C38H72N2O12•2H2O and a molecular weight of 785.0.
Azithromycin is supplied as tablets containing azithromycin dihydrate USP equivalent to either 250 mg or 500 mg azithromycin and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, hypromellose, lactose monohydrate, pregelatinized starch (maize), magnesium stearate, sodium lauryl sulfate, titanium dioxide and triacetin.
INDICATIONS AND USAGE
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
- 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:
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.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin tablets and other antibacterial drugs, azithromycin tablets should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.
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.
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 (MLSB phenotype).
DOSAGE AND ADMINISTRATION
|Infection||Recommended Dose/Duration of Therapy|
|Acute otitis media (6 months of age and older)||30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5.|
|Acute bacterial sinusitis (6 months of age and older)||10 mg/kg once daily for 3 days.|
|Community-acquired pneumonia (6 months of age and older)||10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5.|
|Pharyngitis/tonsillitis (2 years of age and older)¨C10C||12 mg/kg once daily for 5 days.|
|Infection*||Recommended Dose/Duration of Therapy|
|Community-acquired pneumonia 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 obstructive pulmonary disease||500 mg once daily for 3 days|
500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5
|Acute bacterial sinusitis||500 mg once daily for 3 days|
|Genital ulcer disease (chancroid)||One single 1 gram dose|
|Non-gonococcal urethritis and cervicitis||One single 1 gram dose|
|Gonococcal urethritis and cervicitis||One single 2 gram dose|
Azithromycin tablets can be taken with or without food.
- 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.
WARNINGS AND PRECAUTIONS
Serious (including fatal) allergic and skin reactions: Discontinue azithromycin if reaction occurs. 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.
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.
Hepatotoxicity: Severe, and sometimes fatal, hepatotoxicity has been reported. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. 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.
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.
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.
Clostridioides difficile Associated Diarrhea: Evaluate patients if diarrhea occurs. 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
Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis:Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
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.
Development 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.
Nelfinavir: Close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. 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.
Warfarin: Use with azithromycin may increase coagulation times; monitor prothrombin time. 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.
Potential Drug-Drug Interaction with Macrolides: Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interaction. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.
USE IN SPECIFIC POPULATIONS
Pediatric use: Safety and effectiveness in the treatment of patients under 6 months of age have not been established. Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled trials in adults.
Geriatric use: Elderly patients may be more susceptible to development of torsades de pointes arrhythmias.
Pregnancy: Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Lactation: Azithromycin is present in human milk. Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Clinical Considerations). There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.
Adverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required.
Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections.
- Staphylococcus aureus
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Haemophilus ducreyi
- Haemophilus influenzae
- Moraxella catarrhalis
- Neisseria gonorrhoeae
- Chlamydophila pneumoniae
- Chlamydia trachomatis
- Mycoplasma pneumoniae
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.