Zithromax®

azithromycin · oral tablet

Antibiotic

Approved uses

Systemic bacterial infection, this label's only approved uses: acute bacterial exacerbation of chronic bronchitis, acute bacterial sinusitis, community-acquired pneumonia, second-line pharyngitis or tonsillitis, uncomplicated skin and skin structure infection, urethritis and cervicitis, genital ulcer disease in men, and pediatric acute otitis media

500 mg on day 1 then 250 mg once daily on days 2 through 5, or 500 mg once daily for 3 days; one single 1 gram dose for non-gonococcal urethritis or cervicitis, one single 2 gram dose for the gonococcal form

OFF-LABELNot in the FDA label for this product

Trachoma, individual treatment and community mass drug administration

Single oral dose of 20 mg/kg

RCT · n=64 · Cochrane moderate

In a randomized controlled trial of 64 patients with active trachoma, a single 20 mg/kg oral dose resolved disease in 63.3% versus 65.4% treated with 6 weeks of topical tetracycline ointment, with no significant difference between groups and no adverse events noted. A 2019 Cochrane review found moderate-certainty evidence for mass treatment: one low risk of bias cluster-randomized study in high-prevalence communities showed reduced active trachoma 12 months after a single dose (RR 0.58, 95% CI 0.52 to 0.65), and two pooled studies showed reduced ocular infection at 12 months (RR 0.36, 95% CI 0.31 to 0.43), against high-certainty evidence of roughly five-fold increased resistance of Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli at 12 months.

Tabbara KF, Abu-el-Asrar A, al-Omar O, Choudhury AH, al-Faisal Z. Single-dose azithromycin in the treatment of trachoma. A randomized, controlled study. Ophthalmology. 1996;103(5):842-846; Evans JR, Solomon AW, Kumar R, et al. Antibiotics for trachoma. Cochrane Database Syst Rev. 2019;9:CD001860 (10.1002/14651858.CD001860.pub4)

Posterior blepharitis and meibomian gland dysfunction

500 mg on day 1 then 250 mg once daily on days 2 through 5, repeated for three cycles separated by 5-day intervals

RCT · n=30 · oral subgroup NS

A randomized comparative trial of 30 patients, 15 per arm, found this oral course and topical azithromycin 1.5% both improved Ocular Surface Disease Index, lissamine green staining and Schirmer scores, while the topical arm held cytologic improvement at least 5 weeks and produced longer tear break-up time. A 2020 systematic review and meta-analysis of 18 studies found pooled symptom scores improved with azithromycin overall (SMD 1.54, 95% CI 1.15 to 1.92), but the oral subgroup alone did not reach significance for tear break-up time (P=0.08) or corneal staining (P=0.14); the pooled adverse event rate was 7% for oral and 25% for topical.

Yildiz E, Yenerel NM, Turan-Yardimci A, Erkan M, Gunes P. Comparison of the Clinical Efficacy of Topical and Systemic Azithromycin Treatment for Posterior Blepharitis. J Ocul Pharmacol Ther. 2018;34(4):365-372; Tao T, Tao L. Systematic review and meta-analysis of treating meibomian gland dysfunction with azithromycin. Eye (Lond). 2020;34(10):1797-1808 (10.1038/s41433-020-0876-2)

Contraindications

Known hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide drug
History of cholestatic jaundice or hepatic dysfunction on prior exposure to this drug

Available Forms

250 mg tablets, supplied as a 6-tablet blister card that is the standard 5-day course; 500 mg tablets, including a 3-tablet card

Mechanism of Action

Macrolide that binds the 23S rRNA of the 50S ribosomal subunit, inhibiting bacterial protein synthesis and impeding assembly of the 50S subunit. Active against Chlamydia trachomatis, the organism of trachoma and inclusion conjunctivitis, and cross-resistant with erythromycin.

Warnings & Precautions

Hypersensitivity: Angioedema, anaphylaxis, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome and toxic epidermal necrolysis reported, with fatalities. Allergic symptoms have recurred after symptomatic treatment was stopped without further drug exposure, so prolonged observation may be needed.
Hepatotoxicity: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure, some resulting in death; discontinue immediately if signs or symptoms of hepatitis appear.
QT prolongation: Torsades de pointes reported in postmarketing surveillance; weigh the risk in patients with known QT prolongation, prior torsades, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, or on Class IA or Class III antiarrhythmics. Elderly patients may be more susceptible.
Cardiovascular death: Observational studies show roughly a two-fold increase in short-term risk of acute cardiovascular death versus other antibacterials including amoxicillin, at 20 to 400 deaths per million treatment courses, greatest in the first five days and not limited to patients with preexisting cardiovascular disease. The data are insufficient to establish or exclude causation.
Infantile hypertrophic pyloric stenosis: Reported after use in neonates treated up to 42 days of life, presenting as vomiting or irritability with feeding.
Clostridium difficile diarrhea: Ranges from mild diarrhea to fatal colitis and has been reported more than two months after the antibacterial was taken.
Myasthenia gravis exacerbation: Symptom exacerbation and new onset of myasthenic syndrome reported during therapy.
Syphilis masking: At the recommended dose this drug should not be relied on to treat syphilis, and agents used for non-gonococcal urethritis can mask or delay incubating syphilis; serologic testing at diagnosis and follow-up testing are needed.

Common Side Effects

Ocular: Conjunctivitis, reported at 1% or less in pediatric trials.
Special senses, postmarketing: Hearing disturbance including hearing loss, deafness and tinnitus, and taste or smell perversion or loss.
Systemic: Diarrhea 5 to 14%, nausea 3 to 18%, abdominal pain 3 to 7%, vomiting 2 to 7%; the top of each range comes from the single 2 gram regimen, which produced nausea 18%, diarrhea 14%, vomiting 7% and abdominal pain 7%.
Single 1 gram regimen: Diarrhea 7%, nausea 5%, abdominal pain 5%, vomiting 2%, dyspepsia 1%, vaginitis 1%.
Multiple-dose regimens in adults: Diarrhea or loose stools 4 to 5%, nausea 3%, abdominal pain 2 to 3%, with nothing else above 1%.
Hepatic: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure, some fatal.
Cardiac, postmarketing: QT prolongation, torsades de pointes, ventricular tachycardia, hypotension and cardiovascular death.
Skin, postmarketing: Erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS.

Pregnancy & Lactation

Pregnancy: Published data and postmarketing experience over several decades have not identified drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes; animal studies showed no drug-induced fetal malformations at up to 4 times (rats) and 2 times (mice and rabbits) an adult 500 mg daily dose by body surface area.

Lactation: Present in human milk and still detectable up to 4 weeks after a single 2 gram dose given during labor; non-serious reactions have been reported in breastfed infants, so monitor for diarrhea, vomiting or rash.

Pediatric Use

Established from 6 months of age; the pharyngitis and tonsillitis indication starts at 2 years.