Zmax or Zithromax (Azithromycin)


Azithromycin belongs to macrolides and exerts antibacterial activity through inhibition of microbial protein synthesis by binding to the 50S ribosomal subunit of susceptible pathogens. Azithromycin has oral immediate release or intravenous formulations as Zithromax®. Zmax® is a novel extended-release oral formulation of azithromycin, and allows for single-dose administration. Zmax® is pharmacokinetically bioequivalent to and interchangeable with the immediate-release oral Zithromax®. Zmax® achieves higher intracellular concentrations in mononuclear and polymorphonuclear leukocyte and alveolar cells, and higher tissue/fluid concentrations in lung serum, tissue and epithelial lining fluid than in serum. Additionally, azithromycin concentrations of Zmax® in these compartments are generally higher than those achieved with the immediate-release oral Zithromax®.


Zmax® is FDA approved for 1) mild to moderate acute bacterial sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae, and 2) community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in adults and pediatrics aged 6 months and over deemed appropriate for oral therapy.


Zithromax® is indicated in adults for infection of 1) lower respiratory tract (acute bacterial exacerbations of chronic obstructive pulmonary disease and community-acquired pneumonia of mild severity in patients appropriate for outpatient oral therapy); 2) upper respiratory tract (streptococcal pharyngitis/tonsillitis); 3) uncomplicated skin and skin structure infections; 4) sexually transmitted diseases (urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae; genital ulcer disease in men due to Haemophilus ducreyi); 5) prophylaxis and treatment of disseminated Mycobacterium avium complex (MAC) Disease. For pediatric patients, Zithromax® is indicated for acute otitis media and community-acquired pneumonia in patients appropriate for outpatient oral therapy.


Bacteria acquire resistance to azithromycin via efflux of the drug from the cell (mutations in the mefA gene) or alterations in the drug target site (mutations in the ermB gene). Generally, bacteria that are resistant to erythromycin are cross-resistant to azithromycin. In various US surveillance studies, S. pneumonia azithromycin resistance rates were 27.5%-31%, similar to that of erythromycin and clarithromycin. Compared with other macrolides, azithromycin does not interact with drugs metabolized by CYP3A4, and this applies to both Zmax® and Zithromax®. The most frequent adverse events are diarrhea or loose stools.


Clinical Trials

A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. Dolecek C, Tran TP, Nguyen NR, Le TP, Ha V, Phung QT, Doan CD, Nguyen TB, Duong TL, Luong BH, Nguyen TB, Nguyen TA, Pham ND, Mai NL, Phan VB, Vo AH, Nguyen VM, Tran TT, Tran TC, Schultsz C, Dunstan SJ, Stepniewska K, Campbell JI, To SD, Basnyat B, Nguyen VV, Nguyen VS, Nguyen TC, Tran TH, Farrar J. PLoS ONE. 2008 May 21;3(5):e2188.

This trial enrolled 358 children and adult and 80% of them were culture confirmed cases. Both azithromycin and gatifolxacin had equivalent safety and efficacy in terms of resolution of fever and overall treatment success (90.7% vs. 91%) while the cost of azithromycin was higher in Vietnam.

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study. Tamm M, Todisco T, Feldman C, Garbino J, Blasi F, Hogan P, de Caprariis PJ, Hoepelman IM. Clin Microbiol Infect. 2007 Feb;13(2):162-71.

This prospective, randomized and open-label multicentre clinical trial demonstrated that an intravenous-to-oral regimen of ceftriaxone/azithromycin had equivalent efficacy and safety as the comparator regimen did. The mean length of hospital stay was shorter for patients receiving ceftriaxone/azithromycin if the identified pathogens were atypical or atypical and conventional.

An observational cohort study of Chlamydia trachomatis treatment in pregnancy. Rahangdale L, Guerry S, Bauer HM, Packel L, Rhew M, Baxter R, Chow J, Bolan G. Sex Transm Dis. 2006 Feb;33(2):106-10.

In this a retrospective cohort study of pregnant women with genital chlamydial infection, rates of test-of-cure was significantly higher in those treated with azithromycin than erythromycin, and no difference existed in complications for women or infants between azithromycin and other regimens.

Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis. Langley JM, Halperin SA, Boucher FD, Smith B; Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC). Pediatrics. 2004 Jul;114(1):e96-101.

In this large, randomized, controlled trial, patients in azithromycin arm had equivalent eradication rate and no bacterial recurrence as those in erythromycin group did, but had less nausea, vomiting, and diarrhea.

Review Articles

Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Giamarellos-Bourboulis EJ. Int J Antimicrob Agents. 2008 Jan;31(1):12-20. Epub 2007 Nov 1.

This article summarized the anti-inflammatory modes of actions of macrolies and reviewed experimental studies and clinical trials that evaluated the effects of macrolides on chronic inflammatory disorders of the lower respiratory tract, such as cystic fibrosis, and acute inflammatory conditions.

Azithromycin extended release: a review of its use in the treatment of acute bacterial sinusitis and community-acquired pneumonia in the US. Swainston Harrison T, Keam SJ. Drugs. 2007;67(5):773-92.

The article comprehensively reviewed the pharmacodynamic and pharmacokinetic profiles, clinical trials and indications, and tolerability of azithromycin extended release formulation. Its role in treatment of acute bacterial sinusitis and community-acquired pneumonia in the US was also discussed.

Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever). Effa EE, Bukirwa H. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006083. Review.

In this review, compared with fluoroquinolones, azithromycin significantly reduced clinical failure and duration of hospital stay in patients with uncomplicated enteric fever, including those with multiple-drug-resistant or nalidixic acid-of resistant strains of S. Typhi or S. Paratyphi. Compared with ceftriaxon, azithromycin significantly reduced relapse.

Pertussis: review of epidemiology, diagnosis, management and prevention. Wood N, McIntyre P. Paediatr Respir Rev. 2008 Sep;9(3):201-11.w.

This review described recent changes in the burden of pertussis, its different clinical presentations in infants and adolescents, performance of diagnostic tools, and prophylaxis and treatment. Azithromycin and clarithromycin, instead of erythromycin, were recommended as first-line treatment due to equivalent efficacy and better tolerance with improved compliance.

Prevention and treatment of sexually transmitted diseases: an update. Van Vranken M. Am Fam Physician. 2007 Dec 15;76(12):1827-32. Review.

This article summarized the recent changes in The Centers for Disease Control and Prevention revised guidelines for the prevention and treatment of sexually transmitted diseases. Currently, azithromycin (Zithromax) is recommended as a first-line treatment for Chlamydia trachomatis infection during pregnancy and close follow-up is required if azithromycin is used as an alternative treatment in the management of primary or secondary syphilis due to increasing resistance.

Adverse Drug Reactions and Warnings


FDA Information

Zmax®, Zithromax®

Manufacturer/Distributor Product Information