AZITHROMYCIN (Generic for ZITHROMAX)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral Solid Formulations
-May be taken with or without food; however, increased tolerability has been observed when the tablets are taken with food.

Oral Liquid Formulations
Oral suspension (immediate-release, bottles for reconstitution):
-Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution may vary from manufacturer to manufacturer.
-Tap the bottle to loosen the powder. Add water in 2 portions and shake well after each portion.
-Azithromycin for oral suspension (100 mg/5 mL or 200 mg/5 mL strengths) may be taken with or without food.
-Measure dosage with a calibrated spoon, cup, or oral syringe.
-Storage after reconstitution: Store at 5 to 30 degrees C (41 to 86 degrees F). Discard any unused portion per manufacturer recommendations.

Oral suspension (1 gram single-dose packet):
-Do not use for administration of doses other than 1 gram.
-Zithromax for oral suspension (1-g single-dose packet) may be taken with or without food; however, administration with food may increase tolerability.
-Mix the entire contents of the packet in 60 mL (approximately 2 ounces) of water. Administer the entire contents immediately, then add an additional 60 mL of water, mix and administer to assure complete administration of the dosage.

Oral suspension (extended-release, bottles for reconstitution):
-Extended-release oral suspension (2 grams azithromycin) should be taken as a single dose at least 1 hour before or 2 hours after a meal.
-If a patient vomits within 5 minutes of the dose, the manufacturer recommends additional antibiotic treatment due to minimal absorption of the azithromycin dose. If a patient vomits between 5 to 60 minutes following the dose, consider alternate therapy. In patients with normal gastric emptying, if vomiting occurs 60 minutes or later after the dose, no additional antibiotic therapy is warranted. In patients with delayed gastric emptying, consider alternative therapy.
-Constitute with 60 mL of water, replace cap, and shake bottle well.
-Storage after reconstitution: Do not refrigerate. Use within 12 hours.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution:
-Add 4.8 mL of Sterile Water Injection to a concentration of 100 mg/mL.
-Because the vial is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of sterile water is dispensed.
-Shake until all of the drug is dissolved.
-Further dilution is required.
-Storage: The reconstituted solution is stable for 24 hours when stored below 30 degrees C (86 degrees F).

Dilution:
-Dilute by transferring 5 mL of the reconstituted solution into a compatible diluent; use 500 mL of diluent for a concentration of 1 mg/mL and 250 mL of diluent for a concentration of 2 mg/mL.
-Compatible diluents include: 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and 0.45% Sodium Chloride Injection with 20 mEq KCl, 5% Dextrose and Lactated Ringer's Injection, 5% Dextrose and 0.3% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, Normosol-M and 5% Dextrose Injection, and Normosol-R and 5% Dextrose Injection.
-Storage: Diluted solutions are stable for 24 hours at or below room temperature (30 degrees C or 86 degrees F) or for 7 days if stored under refrigeration (5 degrees C or 41 degrees F).

Intravenous infusion:
-Do not administer intramuscularly or via IV bolus.
-Other intravenous substances, additives, or medications should not be added to azithromycin or infused simultaneously through the same IV line.
-Infuse over at least 1 hour. For patients receiving the adult dose at a concentration of 1 mg/mL (i.e., 500 mg in 500 mL of diluent), infuse over 3 hours.



Ophthalmic Administration
-For ophthalmic use only. Apply topically only to the eye.
-Instruct patient on proper instillation of eye solution.
-Avoid contamination of the eye solution; do not touch the tip of the eye dropper to the eye, fingertips, or other surface.
-Due to the difficulty of administering eye drops to pediatric patients, consider a 2 person administration approach to ensure proper installation of the drops (1 person to hold the eyelids open and 1 person to administer the drops).
-To avoid contamination, do not share an opened bottle among patients.

The most common adverse reactions in pediatric patients receiving systemic azithromycin are gastrointestinal-related and are typically more frequent with higher doses. In clinical trials, some of the most commonly reported gastrointestinal adverse reactions were diarrhea/loose stools (1.8% to 10%), nausea (0.4% to 4%), vomiting (1.1% to 14%), abdominal pain (1.2% to 4%), and anorexia (2% or less). Adverse GI reactions occurring in 1% or less of pediatric patients included constipation, dyspepsia, flatulence, enteritis, and gastritis. In adult clinical trials, melena, oral moniliasis, and mucositis were also reported in up to 1%; stomatitis was reported by 1.9% of patients. Postmarketing adverse reactions have also included pancreatitis and rare reports of tongue discoloration.

In clinical trials, elevated hepatic enzymes (ALT, AST) occurred in less than 1% of pediatric patients receiving oral azithromycin therapy. Cholestasis with jaundice has been reported in 1% or less of patients. Hyperbilirubinemia was noted in up to 3% of adult patients. Postmarketing reports indicate that systemic azithromycin has been associated with abnormal liver function, including cholestatic jaundice, hepatitis, as well as rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with azithromycin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other infections reported during treatment with systemic azithromycin therapy during clinical trials include vaginitis (up to 2.8%), fungal superinfection (less than 1%), and fungal dermatitis (less than 1%). Cases of oral candidiasis (thrush) and vaginitis have also been noted during postmarketing use of the drug.

Hematologic adverse reactions have been reported with systemic azithromycin therapy. In children, anemia and leukopenia have occurred in 1% or less of patients. Decreased lymphocytes (lymphopenia), alterations in neutrophils, and eosinophilia have been reported in 1% or more of patients. Decreased platelet counts, elevated monocytes, and elevated basophils have been reported in less than 1% of adults. Thrombocytopenia and mild neutropenia have been reported during postmarketing surveillance.

Respiratory adverse reactions that have been reported in 1% or less of pediatric patients receiving azithromycin include asthma, bronchitis, cough, dyspnea, pharyngitis, pleural effusion, and rhinitis. Nasal congestion and sinusitis have been reported in less than 1% of patients receiving the ophthalmic preparation of azithromycin.

Injection site reaction may occur with intravenous azithromycin. Reactions may include injection site pain, local inflammation or erythema, and application site reactions.

Fatigue, malaise, and pain (unspecified) have been reported in 1% or less of pediatric patients receiving systemic azithromycin. Fever was noted in 2% or less of patients. Chills and flu-like syndrome were reported in less than 1% of pediatric patients in trials. Paresthesias and asthenia were noted in postmarketing reports.

Central nervous system adverse reactions reported in 1% or less of pediatric patients receiving systemic azithromycin include agitation, dizziness, drowsiness, headache, hyperkinesis, insomnia, nervousness, and vertigo. In pediatric patients receiving the extended-release suspension, less than 1% of patients experienced emotional lability, hostility, hyperkinesia, insomnia, and irritability. Postmarketing CNS reactions have also included convulsions (seizures), hyperactivity, and syncope. Postmarketing psychiatric adverse reactions include aggression and anxiety.

Cardiovascular adverse reactions associated with systemic azithromycin therapy reported in up to 1% of patients include chest pain (unspecified) and palpitations. Although uncommon, these are potentially serious adverse reactions. In postmarketing experience, there have been reports of arrhythmias including ventricular tachycardia, hypotension, QT prolongation, and torsade de pointes. Acute cardiovascular death has been noted in postmarketing reports in adults.

Conjunctivitis and uveitis (adults) were reported in 1% or less of patients receiving systemic azithromycin. Taste perversion (dysgeusia) was reported in 1% or less of patients receiving systemic azithromycin and in less than 1% of patients using the ophthalmic preparation. Postmarketing reports for azithromycin have included cases of dysosmia (smell perversion) and/or anosmia (loss of smell), and hearing disturbances including hearing loss, deafness, and/or tinnitus.

Dermatological or hypersensitivity-related adverse reactions have been reported with azithromycin therapy. Rash has been reported in 5% or less of pediatric patients receiving oral therapy and in less than 1% of patients receiving ophthalmic therapy. Other adverse reactions that have been reported in 1% or less of pediatric patients include maculopapular rash, pruritus, photosensitivity, urticaria, bronchospasm, angioedema, diaphoresis, and vesicular rash. Eczema was reported in 1% or less of pediatric patients, while dermatitis was noted in 2% of pediatric patients. Postmarketing reports of arthralgia and edema have been noted. Serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported. Discontinue azithromycin therapy if there are signs and symptoms of an allergic reaction. Some patients have a recurrence of allergic symptoms once symptomatic treatment is withdrawn, even though azithromycin therapy is not reinstated. Correlation between the long tissue half-life of azithromycin and the duration of allergic symptoms has not yet been determined. Anaphylaxis (anaphylactoid reactions, anaphylactic shock) has been reported, including fatal cases. Other adverse reactions reported in less than 1% of patients using the ophthalmic azithromycin solution include contact dermatitis, hives, and periocular swelling.

Azithromycin (systemic therapy) has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly and is associated with fever above 38 degrees C. Drugs are the main cause of AGEP. A period of 2 to 3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days.

Ocular irritation was the most frequently reported adverse reaction after ophthalmic administration of azithromycin and occurred in approximately 1% to 2% of patients. Other reported adverse reactions occurring in less than 1% of patients included blurred vision, corneal erosion, ocular discharge, ocular pain (burning, stinging, and irritation upon instillation), ocular pruritus, punctate keratitis, visual impairment (i.e., visual acuity reduction), and xerophthalmia.

The exacerbation of myasthenia gravis symptoms as well as the new onset of myasthenic syndrome have been reported with systemic azithromycin therapy. While rare, this side effect has been reported with other macrolide antibacterial agents.

Laboratory abnormalities that have been noted with systemic azithromycin use in pediatric patients include hyperkalemia (1% or more), hypokalemia (less than 1%), and alterations in sodium and glucose (less than 1%). In adult patients, other laboratory abnormalities include decreased bicarbonate (up to 1%), increased bicarbonate (less than 1%), hyponatremia (less than 1%), hyperglycemia and hypoglycemia (up to 1%), elevated phosphokinase (1% to 2%), elevated serum alkaline phosphatase (less than 1%), elevated LDH (up to 3%), and elevated phosphate (less than 1%).

Azithromycin has been associated with infantile hypertrophic pyloric stenosis (IHPS), particularly in newborns younger than 2 weeks of age. In a retrospective study of 148 infants given azithromycin during the first 14 days of life, IHPS developed in 3 patients (2%) for an odds ratio (OR) of 8.26 (95% CI: 2.62 to 26; p less than 0.001). Of 729 infants aged 15 to 42 days at the time of azithromycin exposure, 5 patients developed IHPS for an OR of 2.98 (95% CI: 1.24 to 7.2; p = 0.015). No infants aged 43 to 90 days at the time of azithromycin exposure developed IHPS. A male predominance was also observed, as all 8 infants who developed IHPS were boys. IHPS was also reported in 2 former 32-week premature infants (2 out of 3 triplets) who received 5 days of azithromycin after hospitalization at 7 weeks of age. The infants were diagnosed with IHPS at 89 and 94 days of age, respectively, and both infants underwent surgical pyloromyotomies. Closely monitor infants, particularly males who receive azithromycin within the first few weeks of life, for signs and symptoms of IHPS for 6 weeks after azithromycin treatment. Pyloric stenosis rarely affects infants older than 3 months. Pyloric stenosis has been noted in postmarketing reports.

An increased relapse rate of cancers of the blood or lymph nodes (i.e. leukemia, lymphoma), including death, has been observed in allogeneic stem cell transplant patients who were receiving azithromycin as prophylaxis for bronchiolitis obliterans syndrome (BOS). In a clinical trial (n = 480) evaluating the effectiveness of long-term azithromycin to prevent BOS in patients who undergo donor stem cell transplants for cancers of the blood or lymph nodes, cancer relapse was observed in 32.9% of azithromycin-treated patients vs. 20.8% of patients who were given placebo. The 2-year survival rate was 56.6% in azithromycin-treated patients vs. 70.1% in those given placebo.

The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe.

Renal adverse reactions reported in pediatric patients receiving systemic azithromycin include dysuria (less than 1%), elevated BUN (azotemia; 1% or more), and elevated creatinine (less than 1%) with elevated creatinine reported in 4% to 6% of adult patients receiving IV therapy. In adult clinical trials, nephritis was also reported in up to 1% of patients. Postmarketing adverse genitourinary reactions have also included acute renal failure (unspecified) and interstitial nephritis.

Azithromycin is contraindicated in patients with a known azithromycin or macrolide hypersensitivity. Azithromycin has a rare risk of serious hypersensitivity reactions or anaphylaxis, including angioedema and severe dermatologic reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis. Fatalities associated with these severe reactions have been reported. There is a risk of cross sensitivity with other macrolide antibiotics. Some patients have a recurrence of allergic symptoms once symptomatic treatment is withdrawn, even though azithromycin therapy is not reinstated.

Systemic azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with the prior use of azithromycin.

Use caution when administering azithromycin extended-release suspension to patients with renal failure (GFR less than 10 mL/minute), due to a higher incidence of gastrointestinal adverse events (8 of 19 subjects) observed in a limited number of subjects with GFR less than 10 mL/minute.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including azithromycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Macrolides are associated with QT prolongation; cases of cardiac arrhythmias and torsade de pointes (TdP) have been reported during postmarketing surveillance. Caution is warranted when using the drug in high-risk pediatric patients, including those with known prolongation of the QT interval or a history of TdP. Use azithromycin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. In patients taking azithromycin with another drug that prolongs the QT interval (see Therapeutic Drug Monitoring for recommendations specific to using azithromycin with chloroquine or hydroxychloroquine in the treatment of COVID-19), obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device. Obtain baseline electrolytes, including calcium, magnesium, and potassium. Determine if the patient is currently on any QT-prolonging medications that can be discontinued. Document high-risk cardiovascular and comorbid conditions. If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then again at 48 and 96 hours after treatment initiation. If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpuberal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. Some parenteral formulations of azithromycin contain sodium. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure.

An approximately 2-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterials has been noted in observational studies. The 5-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. The potential risk was noted to be greater during the first 5 days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. These data 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.

Advise patients to avoid wearing contact lenses if they have signs or symptoms of bacterial conjunctivitis and until completing the prescribed course of azithromycin ophthalmic solution.

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 systemic azithromycin therapy.

Do not use azithromycin for long-term prophylaxis of bronchiolitis obliterans syndrome (BOS) in patients with cancers of the blood or lymph nodes (i.e. leukemia, lymphoma) who undergo an allogeneic stem cell transplant because of the increased risk for cancer relapse or death.

While azithromycin may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. Azithromycin, at the recommended dose, should not be relied upon to treat syphilis.

Use azithromycin with caution and with proper monitoring in young infants and neonates; there have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in young infants after azithromycin therapy. Because azithromycin is sometimes used for the treatment of conditions that are associated with significant mortality or morbidity (e.g., pertussis), weigh the benefit of azithromycin therapy against the potential risk of developing IHPS. Inform parents and other caregivers to contact their physician if vomiting or irritability with feeding occurs. In a retrospective study of 148 infants given azithromycin during the first 14 days of life, IHPS developed in 3 patients (2%) for an odds ratio of 8.26 (95% CI: 2.62 to 26; p less than 0.001). Of 729 infants aged 15 to 42 days at the time of azithromycin exposure, 5 patients developed IHPS for an OR of 2.98 (95% CI: 1.24 to 7.2; p = 0.015). A male predominance was also observed, as all 8 infants who developed IHPS were boys. No infants aged 43 to 90 days at the time of azithromycin exposure developed IHPS; however, there have been 2 case reports of older infants developing IHPS (89 and 94 days old at diagnosis, respectively).

Description: Azithromycin is a semisynthetic antibiotic belonging to the macrolide subgroup of azalides and is similar in structure to erythromycin. Azithromycin offers the advantage that it can be dosed once daily and produces less GI intolerance than does erythromycin. Azithromycin has a wider spectrum of activity than erythromycin against M. avium complex (MAC), H. influenzae, nontuberculous mycobacteria, and C. trachomatis. Another apparent advantage over erythromycin is that azithromycin reaches higher intracellular concentrations, thus increasing its efficacy and duration of action. These advantages are demonstrated in studies that show that single doses of azithromycin are effective for the treatment of acute otitis media and sexually transmitted diseases (STDs) due to chlamydia and gonorrhea. Azithromycin is better tolerated and offers shorter treatment durations compared with clarithromycin. Azithromycin is used for the treatment of a variety of respiratory infections, including otitis media, pharyngitis/tonsillitis, pertussis, community-acquired pneumonia, and sinusitis. However, macrolides are not recommended for empiric monotherapy of acute bacterial sinusitis due to high rates of S. pneumoniae resistance (approximately 30%). Azithromycin is also used for the treatment of STDs due to chlamydia and gonorrhea, and for the prophylaxis and treatment of M. avium complex (MAC) disease. An ophthalmic preparation is used for the treatment of bacterial conjunctivitis. Long-term azithromycin is used off-label to improve lung function and decrease pulmonary exacerbation in cystic fibrosis patients 6 years and older who have sputum cultures persistently positive for P. aeruginosa. While azithromycin has been studied in regimens for H. pylori eradication and some studies show efficacy, the azithromycin-containing regimens have not been as effective as regimens containing clarithromycin in terms of eradication rates. Macrolide cross-resistance is also an issue. The oral formulations of azithromycin (excluding 600-mg tablets and 1-g suspension) are FDA approved for use in children 6 months of age and older; the intravenous formulation is FDA approved for use in adolescents 16 years of age and older. An ophthalmic formulation is FDA approved for use in children 1 year of age and older.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Bacteroides bivius, Bordetella pertussis, Borrelia burgdorferi, Campylobacter jejuni, CDC coryneform group G, Chlamydia trachomatis, Chlamydophila pneumoniae, Clostridium perfringens, Haemophilus ducreyi, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Legionella pneumophila, Moraxella catarrhalis, Mycobacterium avium, Mycobacterium intracellulare, Mycoplasma hominis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Peptostreptococcus sp., Prevotella bivia, Staphylococcus aureus (MSSA), Streptococcus agalactiae (group B streptococci), Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Streptococcus sp., Treponema pallidum, Ureaplasma urealyticum, Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Babesia microti, Campylobacter sp., Klebsiella granulomatis, Salmonella enterica serotype Typhi , Shigella sp., Vibrio cholerae
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of community-acquired pneumonia (CAP):
Oral dosage (immediate-release):
Neonates*: 10 mg/kg/dose PO once daily. Guidelines in older pediatric patients generally recommend a 5-day treatment course. Azithromycin is recommended as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.
Infants 1 to 5 months*: 10 mg/kg/dose PO for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days. Guidelines in older pediatric patients recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.
Infants and Children 6 months to 12 years: 10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized persons living with HIV.
Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for persons living with HIV.
Oral dosage (extended-release):
Infants, Children, and Adolescents 6 months to 17 years: 60 mg/kg/dose (Max: 2 g/dose) PO as a single dose. This dosage form is not recommended for patients with moderate or severe illness or those with other underlying risk factors for which oral therapy is inappropriate.
Intravenous dosage:
Neonates*: 10 mg/kg/dose IV once daily. Guidelines in older pediatric patients generally recommend IV therapy for 2 days, followed by oral step-down therapy to complete a 5-day treatment course. Azithromycin is recommended as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.
Infants 1 to 3 months*: 10 mg/kg/dose IV once daily. Guidelines in older pediatric patients generally recommend IV therapy for 2 days, followed by oral step-down therapy to complete a 5-day treatment course. Azithromycin is recommended as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.
Infants, Children, and Adolescents 4 months to 15 years*: 10 mg/kg/dose (Max: 500 mg/dose) IV once daily for 2 days, followed by oral therapy to complete a 5-day treatment course. Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected.
Adolescents 16 to 17 years: 500 mg IV once daily for at least 2 days, followed by oral therapy to complete a 5-day treatment course. Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including persons living with HIV, when atypical pathogens are suspected. FDA-approved labeling recommends IV therapy for at least 2 days then step-down to oral therapy to complete a 7- to 10-day treatment course. The switch to oral therapy should be done at the discretion of the physician and based on the clinical response of the patient.

For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
Oral dosage (immediate-release):
Infants* and Children 1 year*: 12 mg/kg/dose PO once daily for 5 days as an alternative in patients allergic to penicillin.
Children and Adolescents 2 to 17 years: 12 mg/kg/dose (Max: 500 mg/dose) PO once daily for 5 days as an alternative in patients allergic to penicillin.

For the treatment of acute bacterial sinusitis:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 6 months to 17 years: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days. Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.

For the treatment of acute otitis media:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 6 months to 17 years: 30 mg/kg/dose (Max: 1,500 mg/dose) PO as a single dose, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Because macrolides have limited efficacy against both H. influenzae and S. pneumoniae, these agents are not included in guidelines.

For the treatment of bacterial conjunctivitis:
Ophthalmic dosage:
Children and Adolescents: 1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for 2 days, then 1 drop in the affected eye(s) once daily for 5 days.

For the treatment of pelvic inflammatory disease (PID):
Intravenous dosage:
Adolescents 13 to 15 years*: 500 mg IV once daily for 1 to 2 days, followed by oral therapy for a total of 7 days in combination with metronidazole as an alternative.
Adolescents 16 to 17 years: 500 mg IV once daily for 1 to 2 days, followed by oral therapy for a total of 7 days in combination with metronidazole as an alternative.
Oral dosage (immediate-release):
Adolescents 13 to 15 years*: 250 mg PO once daily to complete a total of 7 days after IV therapy in combination with metronidazole as an alternative.
Adolescents 16 to 17 years: 250 mg PO once daily to complete a total of 7 days after IV therapy in combination with metronidazole as an alternative.

For the treatment of uncomplicated gonorrhea*, including cervicitis*, urethritis*, and proctitis*:
Oral dosage (immediate-release):
Children weighing more than 45 kg and Adolescents: 2 g PO as a single dose plus gentamicin as an alternative in patients with a cephalosporin allergy or when ceftriaxone is not available.

For the treatment of chancroid*:
Oral dosage (immediate-release):
Infants and Children: 20 mg/kg/dose (Max: 1 g/dose) PO as a single dose. Data are limited in HIV-infected patients.
Adolescents: 1 g PO as a single dose. Data are limited in HIV-infected patients.

For the treatment of non-gonococcal urethritis (NGU)* and cervicitis* and chlamydia infection*, including urethritis*, cervicitis*, trachoma*, and chlamydial conjunctivitis*:
-for the treatment of urethritis and cervicitis due to C. trachomatis*:
Oral dosage (immediate-release):
Children weighing 45 kg or more and Adolescents: 1 g PO as a single dose as an alternative.
-for the treatment of nonspecified non-gonococcal urethritis (NGU)*:
Oral dosage (immediate-release):
Children weighing 45 kg or more and Adolescents: 1 g PO as a single dose or 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days as an alternative. For recurrent or persistent urethritis due to noncompliance or reexposure, may consider retreatment with the initial regimen.
-for the treatment of recurrent or persistent non-gonococcal urethritis (NGU) due to M. genitalium*:
Oral dosage (immediate-release):
Children weighing 45 kg or more and Adolescents: 1 g PO on day 1, followed by 500 mg PO once daily for 3 days (2.5 g total), following initial treatment with doxycycline in persons with macrolide-sensitive M. genitalium or as an alternative when resistance testing is not possible and moxifloxacin cannot be used.
-for the treatment of pneumonia caused by C. trachomatis in neonates and infants*:
Oral dosage (immediate-release):
Neonates: 20 mg/kg/dose PO once daily for 3 days as an alternative.
Infants: 20 mg/kg/dose PO once daily for 3 days as an alternative.
-for the treatment of trachoma*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) PO as a single dose.
-for the treatment of chlamydial conjunctivitis*:
Oral dosage (immediate-release):
Adolescents: 1 g PO as a single dose.

For the treatment of lymphogranuloma venereum* caused by C. trachomatis:
Oral dosage (immediate-release):
Adolescents: 1 g PO once weekly for 3 weeks as an alternative.

For the treatment of granuloma inguinale* (Donovanosis):
Oral dosage (immediate-release):
Children weighing 45 kg or more: 1 g PO once weekly or 500 mg PO once daily for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.
Adolescents: 1 g PO once weekly or 500 mg PO once daily for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

For the treatment of Mycobacterium avium complex infection* (MAC) in HIV-infected patients:
Oral dosage (immediate-release):
Infants and Children: 10 to 12 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.
Adolescents: 500 to 600 mg PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.

For Mycobacterium avium complex (MAC) prophylaxis* in HIV-infected patients:
-for primary Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients:
Oral dosage (immediate-release):
Infants: 20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in infants with a CD4 count less than 750 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.
Children 1 year: 20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 1 to 2 years with a CD4 count less than 500 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.
Children 2 to 5 years: 20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 2 to 5 years with a CD4 count less than 75 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 200 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.
Children 6 to 12 years: 20 mg/kg/dose (Max: 1,200 mg/dose) PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose (Max: 250 mg/dose) PO once daily. Primary prophylaxis is recommended in children 6 years and older with a CD4 count less than 50 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 100 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.
Adolescents: 1,200 mg PO once weekly or 600 mg PO twice weekly as preferred therapy. Primary prophylaxis is only recommended for patients not on fully suppressive antiretroviral therapy (ART) with CD4 counts less than 50 cells/mm3 after ruling out disseminated MAC. Discontinue primary prophylaxis upon initiation of effective ART. Restart primary prophylaxis if the CD4 count decreases to less than 50 cells/mm3 and not on fully suppressive ART.
-for secondary Mycobacterium avium complex (MAC) prophylaxis (long-term suppressive therapy)* in HIV-infected patients:
Oral dosage (immediate-release formulations):
Infants and Children 1 year: 5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Do not discontinue secondary prophylaxis for children younger than 2 years.
Children 2 to 5 years: 5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in children who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 200 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.
Children 6 to 12 years: 5 mg/kg/dose (Max: 250 mg/dose) PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in patients who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.
Adolescents: 500 to 600 mg PO once daily as part of combination therapy and preferred therapy. Consider discontinuing secondary prophylaxis in patients who have completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for more than 6 months in response to antiretroviral therapy (ART). Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.

For the treatment of bartonellosis*, including cat scratch disease*, neuroretinitis*, bacillary angiomatosis*, bacillary peliosis* (peliosis hepatis*), bacteremia*, osteomyelitis*, and chronic verruga peruana*:
-for the treatment of typical cat scratch disease in immunocompetent patients*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.
-for the treatment of atypical hepatosplenic or bony cat scratch disease in immunocompetent patients*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 to 6 weeks plus rifampin as first-line therapy.
Intravenous dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) IV on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) IV once daily for 4 to 6 weeks plus rifampin as first-line therapy.
-for the treatment of Bartonella-related neuroretinitis in immunocompetent patients*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily plus rifampin for 4 to 6 weeks with or without corticosteroids as first-line therapy.
-for the treatment of Bartonella infections, including cat scratch disease, bacillary angiomatosis, bacillary peliosis (peliosis hepatis), bacteremia, and osteomyelitis, in immunocompromised patients*:
Oral dosage (immediate-release):
Infants and Children: 10 mg/kg/dose (Max: 500 mg/dose) PO on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for at least 3 months as an alternative.
Adolescents: 500 mg PO once daily for at least 3 months as an alternative.
-for the treatment of severe Bartonella infections, including multifocal disease or with clinical decompensation, in immunocompromised patients*:
Oral dosage (immediate-release):
Adolescents: 500 mg PO once daily for at least 3 months plus rifampin as an alternative.
-for the treatment of chronic verruga peruana*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 7 to 14 days.

For secondary bartonellosis prophylaxis* (i.e., long-term suppressive therapy*) in persons living with HIV:
Oral dosage (immediate-release):
Adolescents: 500 mg PO once daily if a relapse occurs after at least 3 months of treatment. Discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.

For the treatment of infectious diarrhea* and gastroenteritis*, including campylobacteriosis*, cholera*, salmonellosis*, shigellosis*, and traveler's diarrhea*:
-for the empiric treatment of infectious diarrhea*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days or 30 mg/kg/dose (Max: 1,000 mg/dose) as a single dose. Routine use is not recommended.
-for the treatment of campylobacteriosis* in persons without HIV:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days or 30 mg/kg/dose (Max: 1,000 mg/dose) as a single dose as first-line therapy.
-for the treatment of campylobacteriosis* in persons living with HIV:
Oral dosage (immediate-release):
Adolescents: 500 mg PO once daily for 5 days as first-line therapy. Azithromycin is not recommended for Campylobacter bacteremia.
-for the treatment of cholera*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1,000 mg/dose) PO as a single dose as an alternative.
-for the treatment of salmonellosis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 48 to 72 hours or the patient becomes afebrile; treat for 7 to 14 days if concurrent bacteremia. Routine use is not recommended; reserve for patients at high risk for invasive infection.
-for the treatment of shigellosis* in persons without HIV:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days.
-for the treatment of shigellosis* in persons living with HIV:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 500 mg PO once daily for 5 days as an alternative. Treat for up to 6 weeks for recurrent infections. Azithromycin is not recommended for Shigella bacteremia.
-for the treatment of traveler's diarrhea*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

For the treatment of typhoid fever*:
-for the treatment of multidrug-resistant uncomplicated typhoid fever* or quinolone-resistant uncomplicated typhoid fever*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 7 days.
-for the treatment of extensively drug-resistant typhoid fever*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 1 day, followed by 8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 10 days. Use as a single agent for uncomplicated disease or in combination with a carbapenem for complicated disease.

For the treatment of early Lyme disease* (erythema migrans*), including solitary and multiple erythema migrans* as second line therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/day (Max: 500 mg/day) PO once daily for 7 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.

For the treatment of babesiosis*:
-for the treatment of babesiosis* in immunocompetent ambulatory patients with mild to moderate disease in combination with atovaquone:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 7 to 10 days.
-for the treatment of babesiosis* in immunocompromised ambulatory patients with mild to moderate disease in combination with atovaquone:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for at least 7 to 10 days; duration may need to be extended in these patients.
-for the initial treatment of babesiosis* in immunocompetent hospitalized patients with acute, severe disease in combination with atovaquone:
Intravenous dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) IV every once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of 7 to 10 days.
-for the initial treatment of babesiosis* in immunocompromised hospitalized patients with acute, severe disease in combination with atovaquone:
Intravenous dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.
-for oral stepdown treatment of babesiosis* in immunocompetent hospitalized patients in combination with atovaquone after initial IV therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of 7 to 10 days.
-for oral stepdown treatment of babesiosis* in immunocompromised hospitalized patients in combination with atovaquone after initial IV therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.
-for the initial treatment of babesiosis* in highly immunocompromised patients in combination with atovaquone:
Intravenous dosage:
Infants and Children: 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.
Adolescents: 10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.
-for oral stepdown treatment of babesiosis* in highly immunocompromised patients in combination with atovaquone after initial IV therapy:
Oral dosage (immediate-release):
Infants and Children: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.
Adolescents: 10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.
-for the initial treatment of refractory or relapsed babesiosis* as part of combination therapy:
Intravenous dosage:
Infants and Children: 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.
Adolescents: 10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.
-for oral stepdown treatment of refractory or relapsed babesiosis* as part of combination therapy after initial IV therapy:
Oral dosage (immediate-release):
Infants and Children: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.
Adolescents: 10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

For bacterial endocarditis prophylaxis*:
Oral dosage (immediate-release):
Children and Adolescents: 15 mg/kg/dose (Max: 500 mg/dose) PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

For the treatment of cystic fibrosis* to improve pulmonary function and reduce exacerbations:
Oral dosage (immediate-release):
Infants, Children, and Adolescents weighing less than 40 kg: 10 mg/kg/dose (Max: 250 mg/dose) PO 3 times weekly. Consider an initial 6-month trial.
Children and Adolescents weighing 40 kg or more: 500 mg PO 3 times weekly. Consider an initial 6-month trial.

For the treatment of pertussis (whooping cough)*:
Oral dosage (immediate-release):
Neonates: 10 mg/kg/dose PO once daily for 5 days.
Infants 1 to 5 months: 10 mg/kg/dose PO once daily for 5 days.
Infants, Children, and Adolescents 6 months to 17 years: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

For the adjunctive treatment of diphtheria*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 14 days as an adjunct to diphtheria antitoxin.

For postexposure pertussis prophylaxis*:
Oral dosage (immediate-release):
Neonates: 10 mg/kg/dose PO once daily for 5 days. Administer to close contacts within 3 weeks of exposure.
Infants 1 to 5 months: 10 mg/kg/dose PO once daily for 5 days. Administer to close contacts within 3 weeks of exposure.
Infants, Children, and Adolescents 6 months to 17 years: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. Administer to close contacts within 3 weeks of exposure.

For the post-exposure diphtheria prophylaxis* of close contacts of persons with diphtheria:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 7 days.

For post-exposure meningococcal infection prophylaxis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO as a single dose. Not recommended for first-line use; use in the rare circumstance of sustained ciprofloxacin-resistance in a community. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

For the treatment of leptospirosis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, then 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 2 days as alternative therapy for mild or moderate disease.

For the treatment of psittacosis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily on day 1, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

For the treatment of bronchiectasis* to reduce exacerbations in patients with high exacerbation rates:
Oral dosage (immediate-release):
Children and Adolescents: 30 mg/kg PO once weekly has been studied.

For the prevention of ophthalmia neonatorum (i.e., ophthalmia neonatorum prophylaxis*) as an alternative therapy:
Ophthalmic dosage:
Neonates: 1 to 2 drops placed in each conjunctival sac immediately after birth (i.e., within 1 hour) as an alternative if erythromycin ointment is unavailable.

Therapeutic Drug Monitoring:
The following recommendations are for baseline and continuous monitoring when using azithromycin with hydroxychloroquine or chloroquine:
-Obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device.
-Obtain baseline electrolytes, including calcium, magnesium, and potassium; correct abnormalities.
-Determine if the patient is currently on any QT-prolonging medications that can be discontinued.
-Document high-risk cardiovascular and comorbid conditions. Assess and adjust for hepatic and renal dysfunction.

Inpatient Use
-Place telemetry prior to initiation, if possible.
-Monitor and optimize serum electrolytes daily.
-If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Some experts recommend withholding treatment for patients with a baseline QTc of 500 msec or more (or more than 530 to 550 msec in patients with a QRS interval more than 120 msec) or in those with congenital long QT syndrome.
-If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc daily (or 48 and 96 hours after treatment initiation).
-If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpubertal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc daily (or 48 and 96 hours after treatment initiation).
-Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then daily (some recommend 48 and 96 hours after treatment initiation).
-Discontinue azithromycin and/or reduce the antimalarial dose if the subsequent QTc is prolonged or significantly increased above the specified parameters. If the QTc remains prolonged or significantly increased, reevaluate the risk/benefit of therapy, consider consultation with an electrophysiologist, and consider hydroxychloroquine/chloroquine discontinuation.

Outpatient Use
-Do not initiate outpatient therapy in the setting of acute renal or hepatic failure.
-If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Some experts recommend withholding treatment in patients with a baseline QTc of 480 msec or more (or more than 510 to 530 msec in patients with a QRS interval more than 120 msec), congenital long QT syndrome, or a Tisdale risk score of 11 or more.
-Consider no further ECG/telemetry assessment for patients with a Tisdale risk score of 6 or less, if resource or quarantine constraints are prohibitive of monitoring. Otherwise, repeat the ECT 2 to 3 hours after dosing on day 3 of therapy. If the QTc exceeds 500 msec (or 530 to 550 msec if QRS is more than 120 msec) or increases by more than 30 to 60 msec, consider discontinuing therapy.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.
-Infants
1 to 2 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.
3 to 5 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO or 10 mg/kg/day IV have been used off-label.
6 to 11 months: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.
-Children
1 year: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.
2 to 12 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.
-Adolescents
13 to 15 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) or 1,200 mg/day are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.
16 to 17 years: 500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.

Patients with Hepatic Impairment Dosing
No dosage adjustment recommendations can be made; azithromycin has not been studied in patients with impaired hepatic function.

Patients with Renal Impairment Dosing
Data in pediatric patients with renal impairment are not available. No dosage adjustment is recommended in patients with a CrCl less than 80 mL/minute; however, in patients with CrCl less than 10 mL/minute, FDA-approved labeling recommends caution as mean AUC is increased by approximately 35% in adult patients with severe renal impairment.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Azithromycin inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms. Azithromycin is more active against gram-negative organisms but has less activity against streptococci and staphylococci than does erythromycin; erythromycin-resistant gram-positive isolates demonstrate cross-resistance to azithromycin. Azithromycin concentrates in phagocytes and fibroblasts leading to high intracellular concentrations. Drug distribution to inflamed tissues is thought to occur from the concentration in phagocytes.

The susceptibility interpretive criteria for azithromycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, S. viridans group, and S. pneumoniae as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for S. enterica ser. Typhi as susceptible at 16 mcg/mL or less and resistant at 32 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, and Kingella sp. as susceptible at 4 mcg/mL or less. The MICs are defined for N. meningitidis as susceptible at 2 mcg/mL or less, which may be only appropriate for prophylaxis of meningococcal case contacts and does not apply to treatment of invasive disease. The MICs are defined for N. gonorrhoeae as susceptible at 1 mcg/mL or less, presuming use of a 1 g single dose regimen that includes an additional antimicrobial agent. The MICs are defined for M. catarrhalis as susceptible at 0.25 mcg/mL or less. The MICs are defined for V. cholerae as susceptible at 2 mcg/mL or less. The MICs are defined for Pasteurella sp. as susceptible at 1 mcg/mL or less. Erythromycin-susceptible Campylobacter jejuni/coli may be considered susceptible to azithromycin.

Macrolides have reported immunomodulatory properties in pulmonary inflammatory disorders. They may downregulate inflammatory responses and reduce the excessive cytokine production associated with respiratory viral infections; however, their direct effects on viral clearance are uncertain. Immunomodulatory mechanisms may include reducing chemotaxis of neutrophils (PMNs) to the lungs by inhibiting cytokines (i.e., IL-8), inhibition of mucus hypersecretion, decreased bacterial adhesion to the epithelium, decreased production of reactive oxygen species, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors.

Pharmacokinetics: Azithromycin is administered orally, intravenously, and topically to the eye. It is widely distributed after systemic administration to body tissues and fluids, including bone, prostate, ovary, uterus, stomach, liver, middle ear, lung, tonsils and adenoids, and sputum. Azithromycin exhibits significant intracellular penetration and concentrates within fibroblasts and phagocytes. As a result, tissue concentrations are significantly higher than are plasma concentrations. Azithromycin is distributed widely into brain tissue but not into cerebrospinal fluid or the aqueous humor of the eye. Protein binding varies with plasma concentration; 51% of the drug is bound at low concentrations (0.02 mcg/mL), and this binding decreases to 7% at higher concentrations (2 mcg/mL). Azithromycin has a long half-life in children (32 to 64 hours), which is partially explained by its extensive tissue uptake and slow release. Elimination is largely in the feces, after excretion into the bile, with less than 14% excreted in the urine.

Affected cytochrome P450 isoenzymes and drug transporters: none


-Route-Specific Pharmacokinetics
Oral Route
Immediate-release suspension
Peak concentrations of azithromycin occur approximately 2 hours after administration. Food increases the Cmax by approximately 56%, but the extent of absorption is unaltered.

Single-dose (1 g) immediate-release suspension
Administration with food increased the Cmax by 46% and the AUC by 14%.

250 mg and 500 mg immediate-release tablets
The absolute bioavailability is approximately 38%. The Cmax for a 5-day regimen of 250 mg PO ranged from 0.24 to 0.43 mcg/mL and the AUC was 14.9 mcg x hour/mL. The Cmax for 3-day regimen of 500 mg PO ranged from 0.44 to 0.54 mcg/mL and the AUC was 17.4 mcg x hour/mL. Food increases the Cmax by approximately 23%, but the extent of absorption is unaltered.

600 mg immediate-release tablets
The absolute bioavailability is 34%. For a 1,200 mg dose, the Cmax is 0.33 mcg/mL, the Tmax is 2.5 hours, and the AUC is 6.8 mcg x hour/mL. Administration with food increased the Cmax by 31%; however, the AUC was unchanged.

Extended-release suspension
The bioavailability of the extended-release suspension compared to the immediate-release suspension is 83%. Food increases absorption. Administration with a high-fat meal increased the Cmax by 115% and the AUC by 23% compared to the fasted state. Administration with a standard meal increased the Cmax by 119% and the AUC by 12%. Peak concentrations occur approximately 3 hours (range 2 to 8 hours) after administration. Extended-release suspension and immediate-release formulations are not bioequivalent and cannot be interchanged.

Intravenous Route
Azithromycin doses of 500 mg IV daily administered over 1 hour for 2 to 5 days resulted in a mean Cmax +/- SD of 3.63 +/- 1.60 mcg/mL, a 24-hour trough of 0.20 +/- 0.15 mcg/mL, and an AUC24 of 9.60 +/- 4.80 mcg x hour/mL. Doses of 500 mg IV administered over 3 hours resulted in a mean Cmax of 1.14 +/- 0.14 mcg/mL, a 24-hour trough of 0.18 +/- 0.02 mcg/mL, and an AUC24 of 8.03 +/- 0.86 mcg x hour/mL. Similar pharmacokinetic values were obtained in patients that received the same 3-hour IV infusion regimen for 2 to 5 days. A comparison of the pharmacokinetics after the first and fifth daily doses showed an increase in AUC24 of 61%, reflecting a 3-fold rise in trough concentrations. Cmax increased by 8%.


-Special Populations
Ophthalmic Route
The systemic concentration of azithromycin after ocular administration is estimated to be below quantifiable limits (10 ng/mL or less).
Pediatrics
Immediate-release oral formulations:
Infants and Children 6 months to 5 years
Maximum plasma concentrations (Cmax) and area under the curve (AUC) have been reported to be lower, and clearance has been reported to be higher for younger pediatric patients compared with older patients. In a pharmacokinetic study in pediatric patients 6 months to 5 years who received azithromycin 10 mg/kg orally on day 1, followed by 5 mg/kg orally on days 2 to 5, mean Cmax, AUC, and clearance were 0.224 mcg/mL, 1.841 mcg x hour/mL, and 2.27 L/kg/hour, respectively. Mean elimination half-life was 32 hours.

Children and Adolescents 6 to 15 years

In a pharmacokinetic study in pediatric patients 6 to 15 years who received 10 mg/kg azithromycin orally on day 1, followed by 5 mg/kg orally on days 2 to 5, mean Cmax, AUC, and clearance were 0.383 mcg/mL, 3.109 mcg x hour/mL, and 4.27 L/kg/hour, respectively.

Extended-release suspension:
Infants, Children, and Adolescents 3 months to 16 years
The pharmacokinetics of azithromycin were characterized after a single 60 mg/kg dose in pediatric patients 3 months to 16 years. Although there was high inter-patient variability in systemic exposure (AUC and Cmax) across the age groups studied, individual azithromycin AUC and Cmax values in pediatric patients were comparable to or higher than those after administration of 2 g extended-release suspension in adults.

Intravenous formulation:
Infants, Children, and Adolescents 6 months to 15 years
In a pharmacokinetic study in pediatric patients (6 months to 15 years), after a single azithromycin IV dose of 10 mg/kg (Max: 500 mg/dose), mean peak concentration was 2.4 mcg/mL, clearance was 15.3 mL/minute/kg, and elimination half-life was 65 hours. Peak concentrations occurred 1 hour after administration. No differences in pharmacokinetic parameters were noted among different age groups.

Hepatic Impairment
The pharmacokinetics of azithromycin in pediatric patients with hepatic impairment have not been evaluated. Azithromycin is not appreciably metabolized.

Renal Impairment
The pharmacokinetics of azithromycin in pediatric patients with renal impairment have not been evaluated. However, in adult patients with severe renal impairment (CrCl less than 10 mL/minute), mean Cmax and AUC were 61% and 35% higher, respectively. In patients with a CrCl of 10 to 80 mL/minute, mean Cmax and AUC were not altered significantly.