Generic Name: Azithromycin (multiple manufacturers)
Common Brand Name: Zithromax (Pfizer — U.S.)
Popularity: 11th most commonly prescribed drug between 2002 — 2007 (U.S.)
Class: Macrolide antibiotic
Treatment Uses — For treatment of bacterial infections. Azithromycin has distinct advantages over earlier macrolides such as erythromycin that include better tolerance, better tissue penetration and more favorable pharmacokinetics. Because azithromycin can be dosed once daily, it improves patient compliance — a leading cause of antibiotic failures. Macrolides act primarily against streptococci and staphylococci, and are often used to treat these bugs in patients intolerant of penicillins. The therapeutic uses for azithromycin are broad and continually changing. They range from infective exacerbations of COPD and bacterial conjunctivitis to pelvic inflammatory disease. A single 1 gram dose of azithromycin is equally effective against Chlamydia trachomatis as 100 milligrams of doxycycline taken twice daily for seven days.
Despite the higher cost of azithromycin, there remains a niche for first line use of azithromycin when patient compliance is highly suspect. Azithromycin also garners a first line recommendation in chancroid and non-gonococcal urethritis infections. It has become favored for treating uncomplicated community acquired pneumonia (CAP) as well as suspected bacterially caused acute sinus infections. The main advantage (despite the higher costs for azithromycin) is significantly lessened GI side effects coupled with once daily dosing for a much shorter period than erythromycin or clarithromycin. Many prescribers now opt to use five days of azithromycin as prophylaxis for pertussis exposures (versus 14 days of four times daily erythromycin). Short treatment durations, once daily dosing, and acceptable taste make azithromycin attractive for pediatric infections. Azithromycin has been successfully used for respiratory tract infections, uncomplicated skin infections, typhoid fever, acne, traveler’s diarrhea, legionella, Mediterranean spotted fever, and shigellosis. Azithromycin is not recommended for cystic fibrosis (to improve lung function), malaria prophylaxis, H-pylori or salmonella GI infections, or syphilis and is not recommended as a first line agent for otitis media, granuloma inguinale, or Lyme disease.
Antibiotic prescribing is one of the most difficult tasks in medicine. Customizing antibiotic use to the specific organism(s) causing an infection is the gold standard, a task not easily accomplished. Preliminary laboratory identification of an organism can take up to 24 hours and often requires an additional 24 hours to determine the particular antibiotics the organism is sensitive to. While some “on the spot” diagnostic tests are available, their sensitivity and specificity vary considerably. Most antibiotic prescribing is empiric — meaning based on patient symptoms coupled with some knowledge of the current pathogens in a community and the local antibiotic resistance patterns. This frequently requires initial antibiotic therapy cover all likely infective organisms using broad-spectrum antibiotics. This sort of shotgun approach can lead to development of antibiotic resistance in patients and across communities.
Dosing and Administration — Azithromycin dosing varies both by the condition and severity being treated. Usual adult dosing for most indications is 500 milligrams orally on the first day as a single dose, followed by 250 milligrams once daily thereafter. CAP dosing in adults is usually 500 milligrams daily for seven to 10 days. Acute bacterial sinusitis recommended dosing is 500 milligrams once daily for three days. A single 1 gram oral dose is recommended for both chlamydia and chancroid infections. Patients allergic to amoxicillin who require endocarditis prophylaxis for invasive procedures like dental work can alternatively take 500 milligrams of azithromycin 30 to 60 minutes before the procedure. A variety of other dosing schemes have been studied and are in use.
Oral dosing for children 6 months and older ranges from 5 to 30 milligrams per kilogram of patient weight depending on the indication and intended duration of therapy. Calculated pediatric doses should not exceed doses recommended for adults.
Intravenous azithromycin is available and is dosed comparably to oral therapy, no faster than over 60 minutes. It should not be given as a bolus or intramuscular injection.
Azithromycin oral tablets can be taken with or without food; tolerability improves when taken with food or milk. Variations in peak concentrations of azithromycin were observed when taken with food or high fat meals, but were not clinically significant. Food does significantly impair absorption of azithromycin capsules; these should be taken one hour before or two hours after eating (most oral azithromycin is manufactured in tablet form, not capsules). Extended release liquid (suspension) forms of azithromycin should be taken on an empty stomach (one hour before or two hours after meals). Additional antibiotic should be considered if vomiting occurs within 60 minutes of ingesting extended release suspension. As with all antibiotics, effectiveness depends on a fixed dosing schedule. Azithromycin dosed daily should be taken at the same time each day; twice daily doses should be spaced at 12 hour intervals.
Dose adjustments of azithromycin do not appear necessary in patients with mild to moderate renal or liver dysfunction, or the geriatric population. Prescribers are warned to use the drug cautiously in patients with renal or liver failure. Azithromycin is not removed by hemodialysis.
Overdoses typically manifest side effects mentioned with higher dosing regimens. Treatment is supportive. As mentioned above, hemodialysis is not helpful.
Pharmacology/Pharmacokinetics/Stability — Following oral administration, azithromycin reaches peak bloodstream concentrations in 2.2 to 3.2 hours. Within 48 hours, most patients with pneumonias will be afebrile. The liver is responsible for most metabolism of azithromycin.
Antibiotics fall into three major classes according to their mechanism of action: cell walls, protein synthesis, or nucleic acid synthesis. Cell wall agents attack bacterial cell walls. Protein synthesis and nucleic acid agents inhibit the ability of bacteria to synthesize these important components. Azithromycin is a protein synthesis inhibitor.
Bile is the major route for eliminating azithromycin (more than 50 percent). Urine accounts for up to 6 percent. There have been no controlled studies evaluating the fetal effects of azithromycin in pregnant women. Studies in animals have not shown fetal damage. Azithromycin is found in the breast milk of nursing mothers in quantities small enough to be considered clinically insignificant to infants.
Azithromycin comes in 250, 500 and 600 milligram tablets as well as an oral suspension and a powder for intravenous reconstitution. Capsules only come in 250 milligram strength. The color, size and shape vary by manufacturer. Azithromycin is sold in bottles for pharmacy repackaging as well as in blister cards of six tablets each, often called a “Z Pack.” Tablets and capsules should be stored at room temperature between 59 and 86 F. A 1 percent azithromycin ophthalmic solution is available which needs to be stored under refrigeration.
Cautions and Warnings — Azithromycin should not be used by patients with a history of hypersensitivity or allergy to macrolide antibiotics. Oral azithromycin should not be used in patients with moderate to severe illness, significant underlying health problems or other risk factors that would compromise their immune system ability to respond to illness. Caution is advised in patients with impaired liver function. Macrolide antibiotics can produce QT prolongation and while azithromycin has not been known to produce torsades, both erythromycin and clarithromycin have, so caution is advised in patients with prolonged QT intervals.
Important Side Effects and Interactions — GI symptoms (nausea, vomiting, abdominal pain, and diarrhea) are the most frequent side effects associated with azithromycin, occurring in 3 to 5 percent of patients at usual doses and up to 80 percent of patients treated with higher doses. In comparison, these same side effects may be five or more times greater with erythromycin. Other rare side effects reported include palpitations and arrhythmias, headache and dizziness, elevated liver enzymes, wheezing, rash, photosensitivity, and hearing loss.
Thirty-one drugs are reported to interact with azithromycin, of which five have significance for EMS providers. Combining azithromycin with antacids or any drugs containing aluminum, calcium, or magnesium may significantly decrease serum antibiotic concentrations with loss of therapeutic effectiveness. Combination with amiodarone may lengthen QT intervals with proarrhythmic effects. Use in digitalized patients may result in digoxin toxicity. Azithromycin decreases clearance of fentanyl and may prolong its effects. Warfarin metabolism is decreased by azithromycin which can prolong clotting times leading to an increased risk of bleeding.
Average Costs — U.S.*
• 250 mg and 600 mg tablets (azthromycin generic)
Patient cost: $ 2.48 and 4.11 each
Large Hospital cost: $1.90 and 3.15 each
• Z-Pak (6 tablets 250 mg each — generic)
Patient cost: $ 28.00 pack
Large Hospital cost: $13.20 pack
*(Wal Mart® and Target don’t include this med in their $4/month programs)
References:
1. MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed November, 2008).
2. Albany Medical Center Pharmacy, Albany, New York.
