azithromycin
Zithromax

Available forms
Available by prescription only
Injection: 500 mg
Powder for oral suspension: 100 mg/5 ml, 200 mg/ 5 ml; 300 mg ◆, 600 mg ◆, 900 mg ◆, 1,000 mg/ packet
Tablets: 250 mg, 500 mg, 600 mg

Indications and dosages
 Acute bacterial exacerbations of COPD caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae; uncomplicated skin and skin-structure infections caused by Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae; and second-line therapy of pharyngitis or tonsillitis caused by Streptococcus pyogenes. Adults and adolescents age 16 and older: Initially, 500 mg P.O. as a single dose on day 1, followed by 250 mg daily on days 2 through 5. Total cumulative dose is 1.5 g. Alternatively for COPD exacerbations, 500 mg P.O. once daily for 3 days.
 Community-acquired pneumonia caused by Chlamydia pneumoniae, H. influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae; I.V. form can be used for above infections and those caused by Legionella pneumophila, Moraxella catarrhalis, and Staphylococcus aureus. Adults and adolescents age 16 and older: 500 mg P.O. as a single dose on day 1, followed by 250 mg P.O. daily on days 2 to 5. Total dose is 1.5 g. For those who require initial I.V. therapy, 500 mg I.V. as a single daily dose for 2 days, followed by 500 mg P.O. as a single daily dose to complete a 7- to 10-day course of therapy. The timing of the change from I.V. to P.O. therapy should be based on patient’s clinical response.
 Nongonococcal urethritis or cervicitis caused by Chlamydia trachomatis. Adults and adolescents age 16 and older: 1 g P.O. as a single dose.
 Pelvic inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma hominis in patients requiring initial I.V. therapy. Adults: 500 mg I.V. as a single daily dose for 1 to 2 days, followed by 250 mg P.O. daily to complete a 7-day course of therapy. The timing of the change from I.V. to P.O. therapy should be based on patient’s clinical response.
 Otitis media. Children older than age 6 months: 30 mg/kg P.O. as a single dose. Or 10 mg/kg P.O. once daily for 3 days. Or 10 mg/kg P.O. on day 1, then 5 mg/kg once daily on days 2 to 5.
 Tonsillitis. Children older than age 2: 12 mg/kg P.O. daily for 5 days.
Adults: 1 g P.O. as a single dose.
Infants and children: 20 mg/kg (maximum of 1 g) as a single oral dose.
 Prevention of disseminated Mycobacterium avium complex (MAC) in patients with advanced infection with HIV. Adults: 1.2 g P.O. once weekly alone or with rifabutin.
Children: 20 mg/kg P.O. (maximum of 1.2 g) weekly or 5 mg/kg (maximum of 250 mg) can be given P.O. daily.
 Prophylaxis of bacterial endocarditis in penicillin-allergic adults at moderate to high risk. Adults: 500 mg 1 hour before procedure.
 Chlamydial ophthalmia neonatorum. Infants: 20 mg/kg once daily P.O. for 3 days.

Pharmacodynamics
Antibiotic action: Azithromycin, a derivative of erythromycin, binds to the 50S subunit of bacterial ribosomes, blocking protein synthesis. It is bacteriostatic or bactericidal, depending on concentration. Azithromycin is effective against many gram-positive and gram-negative aerobic and anaerobic bacteria in addition to Borrelia burgdorferi, C. pneumoniae, C. trachomatis, M. pneumoniae, and MAC.

Pharmacokinetics
Absorption: Rapidly absorbed from the GI tract; food decreases both maximum plasma levels and amount of drug absorbed.
Distribution: Rapidly distributed throughout the body and readily penetrates cells; it doesn’t readily enter the CNS. It concentrates in fibroblasts and phagocytes. Significantly higher levels of drug are reached in the tissues as compared with the plasma. Uptake and release of drug from tissues contribute to the long half-life. With a loading dose, peak and trough blood levels are stable within 48 hours. Without a loading dose, 5 to 7 days are required before steady state is reached.
Metabolism: Not metabolized.
Excretion: Excreted mostly in the feces after excretion into the bile. Less than 10% is excreted in the urine. Terminal elimination half-life is 68 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to erythromycin or other macrolides. Use cautiously in patients with impaired hepatic function.

Interactions
Drug-drug. Antacids containing aluminum and magnesium: May reduce peak plasma levels of azithromycin. Separate administration times by at least 2 hours.
Dihydroergotamine, ergotamine: Acute ergot toxicity has been reported when macrolides have been administered with ergotamine or dihydroergotamine. Use together cautiously.
Drugs metabolized by the hepatic cytochrome P-450 system (such as barbiturates, carbamazepine, cyclosporine, and phenytoin): May result in impaired metabolism of these agents and increased risk of toxicity. Monitor patient for signs of drug toxicity.
Theophylline: Macrolides may increase plasma theophylline levels by decreasing theophylline clearance. Monitor theophylline levels carefully.
Triazolam: May decrease clearance of triazolam, increasing risk of triazolam toxicity. Monitor patient for signs of drug toxicity.
Warfarin: Other macrolides may increase PT and INR; effect of azithromycin is unknown. Monitor PT and INR carefully.

Adverse reactions
CNS: dizziness, vertigo, headache, fatigue, somnolence.
CV: palpitations, chest pain.
GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia, flatulence, melena, cholestatic jaundice, pseudomembranous colitis.
GU: candidiasis, vaginitis, nephritis.
Skin: rash, photosensitivity.
Other: angioedema.

Effects on lab test results
None reported.

Overdose and treatment
No information available. Treat symptomatically.

Special considerations
• Azithromycin has been used investigationally in Helicobacter pylori regimens, infections caused by Bartonella, Lyme disease caused by Borrelia burgdorferi, Toxoplasma gondii encephalitis, babesiosis, granuloma inguinale, and AIDS-related cryptosporidiosis.
• Obtain culture and sensitivity tests before giving first dose. Therapy can begin before results are obtained.
• Reconstitute 500-mg vial with 4.8 ml of sterile water for injection. Shake well until drug is dissolved (yields 100 mg/ml). Dilute solution further in at least 250 ml of normal saline solution, half-normal saline solution, D₅W, or lactated Ringer’s solution to yield 1 to 2 mg/ml.
 ALERT Infuse 500-mg dose of azithromycin I.V. over 1 hour or longer. Don’t give as a bolus or I.M. injection.
• Oral form shouldn’t be used for moderate to severe pneumonia or when complicating risk factors exist.
• Monitor liver enzyme levels, especially in patients with impaired renal function.
• Obtain serologic tests for syphilis and cultures for gonorrhea in patients diagnosed with sexually transmitted urethritis or cervicitis. Drug shouldn’t be used to treat gonorrhea or syphilis.
• Drug may cause overgrowth of nonsusceptible bacteria or fungi. Watch for signs and symptoms of superinfection.
Pregnant patients
• Preliminary studies have shown drug to be safe for the treatment of chlamydial infection in pregnant women, but there are insufficient data for routine use.
Breast-feeding patients
• It’s unknown if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy haven’t been established in children age 16 and younger for I.V. administration and 6 months and younger for P.O. administration.
Geriatric patients
• Clinical trials of patients ages 65 to 85 with normal hepatic and renal function, in using the 5-day dosage regimen, yielded no significant pharmacokinetic differences.

Patient education
• Tell patient to take all of drug prescribed, even if he’s feeling better.
• Remind patient to take oral suspension on an empty stomach because food and antacids decrease absorption. Patient should take oral suspension 1 hour before or 2 hours after a meal and shouldn’t take antacids. Tablets and single-dose products can be taken with or without food or milk; GI distress may be reduced by taking drug with food or milk.
• Instruct patient to promptly report adverse reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use