Azithromycin (Zithromax®)

Azithromycin in Brief
  • Generic name: Azithromycin
  • Brand names: Zithromax®, Sumamed®, TRI-PAK®, Z-PAK®, Zmax®
  • Therapeutic class: Antibiotic
  • Pharmacologic class: Macrolide, Azalide group
  • Pregnancy Category: B
  • FDA Approved: November, 1991
  • Originally discovered: 1981, Pliva, Croatia Croatia

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch


Azithromycin is the first macrolide antibiotic belonging to the azalide group. This azalide is derived from erythromycin by adding a nitrogen atom into the lactone ring of erythromycin A. Azithromycin is sold under the brand names Zithromax® and Sumamed®, and is one of the world's best-selling antibiotics.



Since the 1970s, PLIVA's (Croatian pharmaceutical company, based in Zagreb, Croatia) research team, led by Dr Slobodan Dokic, had been working in the area of macrolide antibiotics1. In 1981, his team of researchers, Gabrijela Kobrehel, Zrinka Tamburasev and Gorjana Radobolja-Lazarevski, synthesised a novel antibiotic named azithromycin, the first member of a new class of macrolide antibiotics, termed azalides. Azithromycin dihydrate was obtained from the erythromycin molecule and demonstrated superior properties.

It was patented in 1981, and was later found by Pfizer's scientists while going through patent documents. In 1986 Pliva and Pfizer signed a licensing agreement which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva brought their azithromycin on the market in Central and Eastern Europe under the brand name of Sumamed in 1988, and Pfizer under the brand name Zithromax in 1991.

Because of its exceptional therapeutic properties azithromycin became one of the most successful drugs worldwide. From its early trials, it proved to be an extremely efficient antibiotic with expanded and enhanced antibacterial activity (particularly against gram-negative pathogens), prolonged and higher tissue concentration and a low incidence of gastrointestinal side effects compared to other similar antibiotics.

FDA approved uses

Azithromycin is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms:

  • Upper respiratory tract infections: pharyngitis/tonsillitis, sinusitis, otitis media
  • Lower respiratory tract infections: bronchitis, acute exacerbation of chronic bronchitis, community acquired pneumonia of mild severity.
  • Sexually transmitted diseases: uncomplicated urethritis, uncomplicated cervicitis due to Neisseria gonorrhoeae or Chlamydia trachomatis.
  • Chancroid (genital ulcer disease in men).
  • Skin and soft tissue infections: erysipelas, impetigo, secondary pyoderma, erythema migrans.
  • Mycobacterial Infections.

Off-label & Investigational uses

Off-label and investigational uses of Azithromycin include:

Infectious diseases:

  • Pelvic inflammatory disease (PID)
    PID is an inflammatory and infectious disorder of the upper female genital tract (endometrium, fallopian tubes, ovaries, and pelvic peritoneum), and may represent any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis are the major pathogens causing PID. Azithromycin provides a short simple treatment option for PID 3.
  • Traveler's Diarrhea
    Acute diarrhea is the most common illness among travelers. Azithromycin has the broadest activity against the bacteria causing traveler's diarrhea13.(including Salmonella and Shigella species, as well as other diarrheal pathogens such as Yersinia and Campylobacter). It is a good choice for pregnant women, children, and for other patients who cannot take or tolerate fluoroquinolones 4. Azithromycin is also recommended in areas with quinolone-resistant Campylobacter (e.g., Thailand and surrounding areas of Southeast Asia).
    Azithromycin 500 mg per day for 1 - 3 days appears to be effective in most cases of traveler's diarrhea.
  • Dental infections
    Azithromycin is given to people allergic to penicillins and those who have abscesses and other dental infections, especially those extending into the sinuses, gums and bone, and for whom other antibiotics have proved ineffective.
  • Periodontal therapy
    Azithromycin seems to have a triple role in the treatment and resolution of periodontal diseases: suppressing periodontal pathogens, anti-inflammatory activity, and healing through persistence at low levels in macrophages and fibroblasts in periodontal tissues15.
    However, recent data suggests that azithromycin provides no additional benefit over nonsurgical periodontal treatment in patients with generalized aggressive periodontitis16.
  • Acne
    Acne vulgaris is a common inflammatory disorder of the skin. Azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side effects and good compliance, even in adolescents.
    In 2004, researchers studied azithromycin in patients with moderate to severe papulopustular acne vulgaris 6. The researchers found that 83% of patients showed at least a 60% improvement in only 4 weeks and the majority achieved 80% clearance in 12 weeks.
  • Pertussis
    Azithromycin is as effective as and better tolerated than erythromycin for the treatment of pertussis (whooping cough)7.
  • Prostatitis
    Azithromycin is used in the treatment of chronic prostatitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae.
  • Syphilis
    Azithromycin has been successfully used as a multidose treatment in persons who have early syphilis8. However, CDC cautions against use of azithromycin for treating syphilis among men who have sex with men (MSM).
  • Mediterranean spotted fever (Rickettsiosis)
    Mediterranean spotted fever, also known as boutonneuse fever, is transmitted by the dog tick Rhipicephalus sanguineus and has a characteristic rash and a distinct mark, a tache noire (black spot) at the site of the tick bite. Azithromycin is effective treatment in children and can be used as alternatives to doxycycline in adults9.
  • Endocarditis
    Azithromycin is used for prophylaxis of bacterial endocarditis in persons who are allergic to penicillin and undergoing surgical or dental procedures10.
  • Non-cystic fibrosis bronchiectasis 14
  • Posterior blepharitis21

Non-infectious diseases:

Gastroparesis (delayed gastric emptying)12
Azithromycin has been shown to increase gastrointestinal motility.

Azithromycin appears to reduce the risk of Chlamydia pneumoniae-induced atherosclerosis11.

Cystic fibrosis
According to the studies2, azithromycin significantly improves quality of life, reduces the number of respiratory exacerbations, and reduces the rate of decline in lung function in persons with cystic fibrosis. Azithromycin is considered an appropriate choice for patients with chronic P. aeruginosa infection, in whom maintaining respiratory condition has been difficult17.
While the exact mechanisms are unknown, anti-inflammatory rather than antimicrobial properties of macrolides seem to be responsible for the beneficial effects.


Azithromycin "pros" and "cons"


  • Excellent efficacy. Many scientific studies have shown that azithromycin is better or equally effective compared to other antibiotics.
  • Low potential for drug interactions. Azithromycin, unlike the majority of macrolides, does not bind to cytochrome P-450 in the liver, resulting in low potential for drug to drug interaction.
  • Low rate of side effects. Side effects with azithromycin are mild to moderate, mostly gastrointestinal.
  • Sustained antimicrobial activity. Azithromycin reaches high and sustained tissue concentrations that results in sustained antimicrobial activity.
  • Active against intracellular bacteria (Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp.). Since azithromycin is a weak base, it easily penetrates the cell membrane and stays within the cell.
  • Targeted activity at the site of infection. Because of the transport with white blood cells, azithromycin possesses a unique property - targeted activity at the site of infection. In infected tissues, azithromycin achieves high and sustained therapeutic concentrations that last five to seven days after the last dose.
  • Suitable choice for empirical therapy. Since azithromycin has a good activity against the most common pathogens it is used as a choice for empirical therapy.
  • Good compliance: short once daily dosing regimen. Azithromycin's short dosing regimen is convenient and improves patient compliance. For the majority of infections, azithromycin is administered once daily for three days. In the treatment of sexually transmitted diseases, azithromycin is administered as a single dose.
  • Active against most respiratory tract infections. Betalactams lack activity against atypical pathogens. Among macrolides, azithromycin shows the best activity against H. influenzae.
  • Azithromycin has anti-rhinoviral activity and may have a role in prevention of exacerbations of COPD21.


  • Food reduces absorption rate of azithromycin capsules. Capsules should not be mixed with or taken with food, however tablets may be taken without regard to food.
  • In 2013, the U.S. FDA sent out a communication18 stating that azithromycin may cause irregular heartbeats. However, in the study19 (published in the New England Journal of Medicine on May 2013) azithromycin use was not linked with an increased risk of death from cardiovascular (heart) causes in a general population of young and middle-aged adults.

Mode of action

Azithromycin acts by interfering with bacterial protein synthesis. Although this mechanism is considered bacteriostatic, concentrations several times higher than minimum inhibitory concentrations (MIC) contribute to the bactericidal activity of azithromycin.

Rapid distribution of azithromycin into tissues and high concentration within cells result in very high tissues concentrations, that are greater than plasma concentration.

Azithromycin accumulates in macrophages, neutrophils, and fibroblasts.

Non-antibiotic properties: immunomodulating effect

There is evidence that macrolides have immunomodulatory activities: in vitro and ex vivo studies clearly show that macrolides can influence cytokine production by several cell types; furthermore, macrolides can alter polymorphonuclear cell functions in vitro and ex vivo. Although immunomodulation may serve as one explanation for the beneficial effects of macrolides in patients with chronic pulmonary inflammation, the effect of low-dose macrolide therapy on biofilm-formation may provide additional clarification for the positive effects of long-term low-dose macrolide therapy.

Time for Azithromycin to leave the system

The half-life of Azithromycin is about 68 hours. So it takes about 16-17 days to clear out of the system.

Azithromycin and Alcohol

There are no known interactions between Azithromycin and alcohol. Alcohol does not affect how azithromycin works and does not lessen its effectiveness.

Animal study demonstrated that alcohol doesn’t alter the pharmacokinetics of azithromycin and doesn’t reduce its antibacterial effects 20.

Further reading


  • 1. SUMAMED - success story, from
  • 2. Wolter J, Seeney S, Bell S, Bowler S, Masel P, McCormack J. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax. 2002 Mar;57(3):212-6.
  • 3. Bevan CD, Ridgway GL, Rothermel CD. Efficacy and safety of azithromycin compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res. 2003 Jan-Feb;31(1):45-54. PubMed
  • 4. Casburn-Jones AC, Farthing MJ. Management of infectious diarrhoea. Gut. 2004 Feb;53(2):296-305.
  • 5. Khan WA, Seas C, Dhar U, Salam MA, Bennish ML. Treatment of shigellosis. Ann Intern Med. 1997 May 1;126(9):697-703. PubMed
  • 6. Kapadia N, Talib A. Acne treated successfully with azithromycin. Int J Dermatol. 2004 Oct;43(10):766-7. PubMed
  • 7. Langley JM, Halperin SA, Boucher FD, Smith B; Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC). Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis. Pediatrics. 2004 Jul;114(1):e96-101. PubMed
  • 8. Gruber F, Kastelan M, Cabrijan L, Simonić E, Brajac I. Treatment of early syphilis with azithromycin. J Chemother. 2000 Jun;12(3):240-3.
  • 9. Dzelalija B, Petrovec M, Avsic-Zupanc T, Strugar J, Milic' TA. Randomized trial of azithromycin in the prophylaxis of Mediterranean spotted fever. Acta Med Croatica. 2002;56(2):45-7. PubMed
  • 10. Rouse MS, Steckelberg JM, Brandt CM, Patel R, Miro JM, Wilson WR. Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis. Antimicrob Agents Chemother. 1997 Aug;41(8):1673-6.
  • 11. Bouwman JJ, Visseren FL, Bevers LM, van der Vlist WE, Bouter KP, Diepersloot RJ. Azithromycin reduces Chlamydia pneumoniae-induced attenuation of eNOS and cGMP production by endothelial cells. Eur J Clin Invest. 2005 Sep;35(9):573-82. PubMed
  • 12. Potter TG, Snider KR. Azithromycin for the treatment of gastroparesis. Ann Pharmacother. 2013 Mar;47(3):411-5. PubMed
  • 13. DuPont HL. Azithromycin for the self-treatment of traveler's diarrhea. Clin Infect Dis. 2007 Feb 1;44(3):347-9.4.
  • 14. Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, van der Werf TS, Boersma WG. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9. PubMed
  • 15. Hirsch R, Deng H, Laohachai MN. Azithromycin in periodontal treatment: more than an antibiotic. J Periodontal Res. 2012 Apr;47(2):137-48
  • 16. Emingil G, Han B, Ozdemir G, Tervahartiala T, Vural C, Atilla G, Baylas H, Sorsa T. Effect of azithromycin, as an adjunct to nonsurgical periodontal treatment, on microbiological parameters and gingival crevicular fluid biomarkers in generalized aggressive periodontitis. J Periodontal Res. 2012 Dec;47(6):729-39.
  • 17. Saiman L, Marshall BC, Mayer-Hamblett N, et. al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003 Oct 1;290(13):1749-56.
  • 18. Azithromycin (Zithromax or Zmax): Drug Safety Communication - Risk of Potentially Fatal Heart Rhythms FDA
  • 19. Svanström H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. N Engl J Med. 2013 May 2;368(18):1704-12.
  • 20. Preheim LC1, Olsen KM, Yue M, Snitily MU, Gentry MJ. Ethanol feeding does not affect the efficacy or pharmacokinetics of azithromycin ... in a rat model of pneumococcal pneumonia. Alcohol Clin Exp Res. 1999 May;23(5):842-9. PubMed
  • 21. Igami TZ, Holzchuh R, Osaki TH, Santo RM, Kara-Jose N, Hida RY. Oral azithromycin for treatment of posterior blepharitis. Cornea. 2011 Oct;30(10):1145-9. PubMed
  • 22. Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016 Jun 28;6:28698. PubMed

Published: March 31, 2008
Last updated: July 20, 2017


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