1% to 10%: Gastrointestinal: Diarrhea, nausea, abdominal pain, cramping, vomiting (especially with high single-dose regimens)

<1%: Agitation, allergic reaction, anemia, anorexia, candidiasis, chest pain, conjunctivitis, dermatitis (fungal), dizziness, dyspepsia, eczema, enteritis, facial edema, fatigue, flatulence, gastritis, headache, hyperkinesia, increased cough, insomnia, jaundice, leukopenia, malaise, nervousness, pain, pharyngitis, pleural effusion, pruritus, rash, rhinitis, urticaria

Postmarketing and/or case reports: Acute renal failure, aggressive behavior, anaphylaxis, angioedema, anxiety, arrhythmia (including ventricular tachycardia), arthralgia, cholestatic jaundice, deafness, edema, erythema multiforme (rare), hearing loss, hepatic necrosis (rare), hepatitis, hypertrophic pyloric stenosis, hypotension, interstitial nephritis, pancreatitis, paresthesia, pseudomembranous colitis, QTc prolongation (rare), seizure, somnolence, Stevens-Johnson syndrome (rare), syncope, taste abnormality, thrombocytopenia, tinnitus, tongue discoloration (rare), torsade de pointes (rare), vertigo, weakness

Decreased peak serum levels: Aluminum- and magnesium-containing antacids by 24% but not total absorption

Increased effect/toxicity: Azithromycin may increase levels of tacrolimus, phenytoin, ergot alkaloids, alfentanil, bromocriptine, carbamazepine, cyclosporine, digoxin, disopyramide, and triazolam; azithromycin did not affect the response to warfarin or theophylline although caution is advised when administered together; nelfinavir may increase azithromycin serum levels (monitor for adverse effects)

Avoid use with pimozide due to significant risk of cardiotoxicity

Injection: Store intact vials of injection at room temperature. Reconstitute the 500 mg vial with 4.8 mL of sterile water for injection and shake until all of the drug is dissolved. Each mL contains 100 mg azithromycin. Reconstituted solution is stable for 24 hours when stored below 30°C/86°F.

The initial solution should be further diluted to a concentration of 1 mg/mL (500 mL) to 2 mg/mL (250 mL) in 0.9% sodium chloride, 5% dextrose in water, or lactated Ringer's. The diluted solution is stable for 24 hours at or below room temperature (30°C or 86°F) and for 7 days if stored under refrigeration (5°C or 41°F).

Other medications should not be infused simultaneously through the same I.V. line.

Suspension: Store dry powder below 30°C (86°F); following reconstitution, store suspension at 5°C to 30°C (41°F to 86°F).

Tablets: Store between 15°C to 30°C (59°F to 86°F).

Absorption: Rapid

Distribution: Extensive tissue; distributes well into skin, lungs, sputum, tonsils, and cervix; penetration into CSF is poor

Protein binding (concentration dependent): 7% to 50%

Metabolism: Hepatic

Bioavailability: 37%; variable effect with food (increased with oral suspension, unchanged with tablet)

Half-life elimination: Terminal: 68 hours

Time to peak, serum: 2.3-4 hours

Excretion: Feces (50% as unchanged drug); urine (~5% to 12%)

Oral:

Children 6 months:

Community-acquired pneumonia: 10 mg/kg on day 1 (maximum: 500 mg/day) followed by 5 mg/kg/day once daily on days 2-5 (maximum: 250 mg/day)

Bacterial sinusitis: 10 mg/kg once daily for 3 days (maximum: 500 mg/day)

Otitis media:

1-day regimen: 30 mg/kg as a single dose (maximum dose: 1500 mg)

3-day regimen: 10 mg/kg once daily for 3 days (maximum: 500 mg/day)

5-day regimen: 10 mg/kg on day 1 (maximum: 500 mg/day) followed by 5 mg/kg/day once daily on days 2-5 (maximum: 250 mg/day)

Children 2 years: Pharyngitis, tonsillitis: 12 mg/kg/day once daily for 5 days (maximum: 500 mg/day)

Children:

M. avium-infected patients with acquired immunodeficiency syndrome (unlabeled use): 5 mg/kg/day once daily (maximum dose: 250 mg/day) or 20 mg/kg (maximum dose: 1200 mg) once weekly given alone or in combination with rifabutin

Treatment and secondary prevention of disseminated MAC (unlabeled use): 5 mg/kg/day once daily (maximum dose: 250 mg/day) in combination with ethambutol, with or without rifabutin

Prophylaxis for bacterial endocarditis (unlabeled use): 15 mg/kg 1 hour before procedure

Uncomplicated chlamydial urethritis or cervicitis (unlabeled use): Children 45 kg: 1 g as a single dose

Adolescents 16 years and Adults:

Respiratory tract, skin and soft tissue infections: 500 mg on day 1 followed by 250 mg/day on days 2-5 (maximum: 500 mg/day)

Alternative regimen: Bacterial exacerbation of COPD: 500 mg/day for a total of 3 days

Bacterial sinusitis: 500 mg/day for a total of 3 days

Urethritis/cervicitis:

Due to C. trachomatis: 1 g as a single dose

Due to N. gonorrhoeae: 2 g as a single dose

Chancroid due to H. ducreyi: 1 g as a single dose

Prophylaxis of disseminated M. avium complex disease in patient with advanced HIV infection (unlabeled use): 1200 mg once weekly (may be combined with rifabutin)

Treatment of disseminated M. avium complex disease in patient with advanced HIV infection (unlabeled use): 600 mg daily (in combination with ethambutol 15 mg/kg)

Prophylaxis for bacterial endocarditis (unlabeled use): 500 mg 1 hour prior to the procedure

I.V.: Adults:

Community-acquired pneumonia: 500 mg as a single dose for at least 2 days, follow I.V. therapy by the oral route with a single daily dose of 500 mg to complete a 7-10 day course of therapy

Pelvic inflammatory disease (PID): 500 mg as a single dose for 1-2 days, follow I.V. therapy by the oral route with a single daily dose of 250 mg to complete a 7-day course of therapy

Dosage adjustment in renal impairment: Use caution in patients with Clcr<10 mL/minute

Dosage adjustment in hepatic impairment: Use with caution due to potential for hepatotoxicity (rare). Specific guidelines for dosing in hepatic impairment have not been established.

I.V.: Infusate concentration and rate of infusion for azithromycin for injection should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour. Other medications should not be infused simultaneously through the same I.V. line.

Oral: Suspension and tablet may be taken without regard to food.

Powder for oral suspension may be administered with or without food.

Tablet may be administered with food to decrease GI effects.

Sodium content:

Injection: 114 mg (4.96 mEq) per vial

Powder: 3.7 mg per 100 mg/5 mL of constituted solution; 7.4 mg per 200 mg/5 mL of constituted solution; 37 mg per 1 g single-dose packet

Tablet: 0.9 mg/250 mg tablet; 1.8 mg/500 mg tablet; 2.1 mg/600 mg tablet

Injection, powder for reconstitution, as dihydrate: 500 mg

Powder for oral suspension, as dihydrate: 100 mg/5 mL (15 mL); 200 mg/5 mL (15 mL, 22.5 mL, 30 mL) [cherry creme de vanilla and banana flavor]; 1 g [single-dose packet; cherry creme de vanilla and banana flavor]

Tablet, as dihydrate: 250 mg, 500 mg, 600 mg

Zithromax® TRI-PAK™ [unit-dose pack]: 500 mg (3s)

Zithromax® Z-PAK® [unit-dose pack]: 250 mg (6s)

"1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus. USPHS/IDSA Prevention of Opportunistic Working Group,"MMWR Recomm Rep, 1997, 46(RR-12):1-46.

American Thoracic Society, "Guidelines for the Initial Management of Adults With Community-Acquired Pneumonia: Diagnosis, Assessment of Severity, and Initial Antimicrobial Therapy,"Am Rev Respir Dis, 1993, 148(5):1418-26.

Amsden GW, "Erythromycin, Clarithromycin, and Azithromycin: Are the Differences Real?"Clin Ther, 1996, 18(1):56-72.

Bahal N and Nahata MC, "The New Macrolide Antibiotics: Azithromycin, Clarithromycin, Dirithromycin, and Roxithromycin,"Ann Pharmacother, 1992, 26(1):46-55.

Bendayan R, Georgis W, and Rafi-Tari S, "Interaction of 3'-Azido-d'-Deoxythymidine With the Organic Base Transporter in a Cultured Renal Epithelium,"Pharmacotherapy, 1995, 15(3):338-44.

Clauzel AM, Visier S, and Michel FB, "Efficacy and Safety of Azithromycin in Lower Respiratory Tract Infections,"Eur Respir J, 1990, 3(Suppl 10):89.

Coates P, Daniel R, Houston AC, et al, "An Open Study to Compare the Pharmacokinetics, Safety, and Tolerability of a Multiple-Dose Regimen of Azithromycin in Young and Elderly Volunteers,"Eur J Clin Microbiol Infect Dis, 1991, 10(10):850-2.

Dajani AS, Taubert KA, Wilson W, et al, "Prevention of Bacterial Endocarditis Recommendations by the American Heart Association,"JAMA, 1997, 277(22):1794-801.

Drew RH and Gallis HA, "Azithromycin - Spectrum of Activity, Pharmacokinetics, and Clinical Applications,"Pharmacotherapy, 1992, 12(3):161-73.

Feldman RJ, Alcid DV, and Boruchoff SE, "Failure of Prolonged Azithromycin Therapy in Early Lyme Disease,"Infect Dis Clin Pract, 1995, 4(3):230-2.

Foulds G, Shepard RM, and Johnson RB, "The Pharmacokinetics of Azithromycin in Human Serum and Tissues,"J Antimicrob Chemother, 1990, 25(Suppl A):73-82.

Goldman MP and Longworth DL, "The Role of Azithromycin and Clarithromycin in Clinical Practice,"Cleve Clin J Med, 1993, 60(5):359-64.

Guay DR, "Pharmacokinetics of the New Macrolides,"Infect Med, 1992, 9:9-13.

Hammerschlag MR, Golden NH, Oh MK, et al, "Single Dose of Azithromycin for the Treatment of Genital Chlamydial Infections in Adolescents,"J Pediatr, 1993, 122(6):961-5.

Hoffler D, Koeppe P, and Paeske B, "Pharmacokinetics of Azithromycin in Normal and Impaired Renal Function,"Infection, 1995, 23(6):356-61.

Ljutic D and Rumboldt Z, "Possible Interaction Between Azithromycin and Cyclosporin: A Case Report,"Nephron , 1995, 70(1):130.

Nahata MC, Koranyi KI, Gadgil SD, et al, "Pharmacokinetics of Azithromycin After Oral Administration of Multiple Doses of Suspension,"Antimicrob Agents Chemother, 1993, 37(2):314-16.

Neu HC, "New Macrolide Antibiotics: Azithromycin and Clarithromycin,"Ann Intern Med, 1992, 116(6):517-9.

Peters DH, Friedel HA, and McTavish D, "Azithromycin: A Review of Its Antimicrobial Activity, Pharmacokinetic Properties and Clinical Efficacy,"Drugs, 1992, 44(5):750-99.

Rapeport WG, Dewland PM, Muirhead DC, et al, "Lack of Interaction Between Azithromycin and Carbamazepine,"Br J Clin Pharmacol, 1992, 30:551P.

Starke JR and Correa AG, "Management of Mycobacterial Infection and Disease in Children,"Pediatr Infect Dis J, 1995, 14(6):455-69.

Steingrimsson O, Olafsson JH, Thorarinsson H, et al, "Azithromycin in the Treatment of Sexually Transmitted Disease,"J Antimicrob Chemother, 1990, 25(Suppl A):109-14.

Tartaglione TA, "Therapeutic Options for the Management and Prevention of Mycobacterium avium Complex Infection in Patients With the Acquired Immunodeficiency Syndrome,"Pharmacotherapy, 1996, 16(2):171-82.

Wahlstrom E, Zamora JU, and Teichman S, "Improvement in Cyclosporin-Associated Gingival Hyperplasia With Azithromycin Therapy,"N Engl J Med, 1995, 332(11):753-4.

Wynn RL, "New Erythromycins,"Gen Dent, 1996, 44(4):304-7.

Zuckerman JM and Kaye KM, "The Newer Macrolides. Azithromycin and Clarithromycin,"Infect Dis Clin North Am, 1995, 9(3):731-45.