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Azithromycin (Systemic)

Medically reviewed on Sep 10, 2018

Pronunciation

(az ith roe MYE sin)

Index Terms

  • Azithromycin Dihydrate
  • Azithromycin Monohydrate
  • Z-Pak
  • Zithromax TRI-PAK
  • Zithromax Z-PAK

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Packet, Oral:

Zithromax: 1 g (3 ea, 10 ea) [cherry-banana flavor]

Generic: 1 g (3 ea, 10 ea)

Solution Reconstituted, Intravenous:

Zithromax: 500 mg (1 ea)

Generic: 500 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 500 mg (1 ea)

Suspension Reconstituted, Oral:

Zithromax: 100 mg/5 mL (15 mL) [cherry-vanilla-banana flavor]

Zithromax: 200 mg/5 mL (15 mL, 22.5 mL, 30 mL) [cherry flavor]

Zmax: 2 g (1 ea [DSC]) [cherry-banana flavor]

Generic: 100 mg/5 mL (15 mL); 200 mg/5 mL (15 mL, 22.5 mL, 30 mL)

Tablet, Oral:

Zithromax: 250 mg, 500 mg, 600 mg

Zithromax Tri-Pak: 500 mg

Zithromax Z-Pak: 250 mg

Generic: 250 mg, 500 mg, 600 mg

Brand Names: U.S.

  • Zithromax
  • Zithromax Tri-Pak
  • Zithromax Z-Pak
  • Zmax [DSC]

Pharmacologic Category

  • Antibiotic, Macrolide

Pharmacology

Inhibits RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation

Absorption

Oral: Rapid from the GI tract

Distribution

Extensive tissue; distributes well into skin, lungs, sputum, tonsils, and cervix; penetration into CSF is poor; Vd: 31 to 33 L/kg

Metabolism

Hepatic to inactive metabolites

Excretion

Oral, IV: Biliary (major route 50%, unchanged); urine (6% to 14% unchanged)

Time to Peak

Oral: Serum: Immediate release: ~2 to 3 hours; Extended release: 3 to 5 hours

Half-Life Elimination

Terminal: Oral, IV: Infants and Children 4 months to 15 years: 54.5 hours; Adults: Immediate release: 68 to 72 hours; Extended release: 59 hours

Protein Binding

Concentration dependent and dependent on alpha1-acid glycoprotein concentrations: Oral, IV: 7% to 51%

Special Populations: Renal Function Impairment

Cmax and AUC increased 61% and 35%, respectively, in subjects with severe renal impairment.

Special Populations: Elderly

In elderly women, a higher Cmax was observed but there was no change in drug accumulation.

Use: Labeled Indications

Oral, IV:

Chancroid: Treatment of genital ulcer disease (in men) due to Haemophilus ducreyi (chancroid)

Chronic obstructive pulmonary disease, bacterial exacerbations: Treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae

Mycobacterium avium complex: Prevention of Mycobacterium avium complex(MAC) (alone or in combination with rifabutin) in patients with advanced HIV infection; treatment of disseminated MAC (in combination with ethambutol) in patients with advanced HIV infection

Otitis media, acute: Treatment of acute otitis media due to H. influenzae, M. catarrhalis, or S. pneumoniae

Pneumonia, community-acquired: Treatment of community-acquired pneumonia (CAP) due to Chlamydophila pneumoniae, H. influenzae, Legionella pneumophila, M. catarrhalis, Mycoplasma pneumoniae, or S. pneumoniae

Skin and skin structure infection, uncomplicated: Treatment of uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae

Streptococcal pharyngitis (group A): Treatment of pharyngitis/tonsillitis due to S. pyogenes as an alternative to first-line therapy

Urethritis/cervicitis: Treatment of urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae

Off Label Uses

Acne vulgaris

Data from controlled trials support the use of azithromycin in the treatment of acne vulgaris in adults with moderate to severe acne.

Based on the American Academy of Dermatology guidelines of care for the management of acne vulgaris, azithromycin, in combination with topical therapy, may be considered as a treatment option for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments. However, its use should be limited to patients who cannot receive a tetracycline (ie, pregnant women or children <8 years of age). Concomitant topical therapy with benzoyl peroxide or a retinoid should be administered with systemic antibiotic therapy (eg, azithromycin) and continued for maintenance after the antibiotic course is completed.

Babesiosis

Data from a prospective, nonblinded, randomized trial in patients with non-life-threatening babesiosis, support the use of azithromycin (in combination with atovaquone) for the treatment of this condition [Krause 2000]. Clinical experience also suggests the utility of azithromycin (in combination with atovaquone) for the treatment of immunocompetent patients with mild to moderate babesiosis [Vannier 2012].

Based on the Infectious Diseases Society of America (IDSA) guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, azithromycin (in combination with atovaquone) is effective and recommended for the treatment of babesiosis.

Bronchiectasis (non-cystic fibrosis), prevention of pulmonary exacerbations

Data from a randomized, double-blind, placebo-controlled trial in patients with a diagnosis of bronchiectasis defined by high-resolution CT who had at least one pulmonary exacerbation requiring antibiotic treatment in the prior year support the use of azithromycin for the prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis [Wong 2012].

Bronchiolitis obliterans syndrome

Data from 2 retrospective observational studies, a prospective observational study, and several case series found that 30% to 83% of lung transplant patients with bronchiolitis obliterans syndrome (BOS) had improved lung function (increase in FEV1 of ≥10%) after receiving azithromycin treatment; however, in some studies, nonresponders experienced lung function decline [Gottlieb 2008], [Jain 2010], [Meyer 2014], [Vos 2010]. Two of the observational studies found that lower mortality was seen in select patients (ie, early posttransplant or BOS stage 1) who received azithromycin treatment [Jain 2010], [Vos 2010].

The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society (ISHLT/ATS/ERS) clinical practice guidelines for the diagnosis and management of BOS suggest a trial of azithromycin (continuous treatment for a minimum of 3 months) for lung transplant patients who experience a decline in FEV1 consistent with the onset of BOS.

Campylobacter infection

Data from a randomized, double-blind trial of patients with infectious diarrhea (64% with Campylobacter) suggest that azithromycin may be beneficial for the treatment of travelers' diarrhea caused by Campylobacter [Tribble 2007].

Based on the American College of Gastroenterology (ACG) guideline for the diagnosis, treatment, and prevention of acute diarrheal infections in adults, the IDSA practice guidelines for the diagnosis and management of infectious diarrhea, and the US Department of Health and Human Services (HHS) guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, azithromycin is an effective and recommended treatment for patients with Campylobacter infection. Due to increased levels of resistance to fluoroquinolones, azithromycin may be a recommended first-line treatment, especially in regions with a high prevalence of Campylobacter (eg, Southeast Asia, India) or in geographical areas with suspected fluoroquinolone-resistant pathogens.

Cat scratch disease

Data from a prospective, randomized, double-blind, placebo-controlled trial in patients (children and adults) with cat scratch disease caused by Bartonella henselae support the use of azithromycin for the treatment of this condition [Bass 1998].

Based on the IDSA guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), azithromycin is an effective and recommended treatment for cat scratch disease.

Cesarean delivery (intrapartum or after rupture of membranes), preoperative prophylaxis

Data from a prospective, randomized, double-blind, placebo-controlled trial in patients undergoing nonelective cesarean delivery support the use of a single preoperative dose of azithromycin IV, in conjunction with standard preoperative antibiotics, to reduce the postpartum maternal infection rate [Tita 2016].

Chlamydia trachomatis conjunctivitis (infants)

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin is an effective and recommended alternative agent in the treatment of conjunctivitis due to C. trachomatis in infants when erythromycin (base or ethylsuccinate) is not appropriate.

Chlamydia trachomatis infection of the pharynx

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin is an effective and recommended agent in the treatment of Chlamydia trachomatis infection of the cervix, urethra, or pharynx.

Chlamydia trachomatis infection, expedited partner therapy

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin is an effective and recommended treatment of chlamydia in heterosexual partners of infected patients, unless prohibited by law.

Cholera

Data from a prospective, double-blind, randomized trial support the use of azithromycin for the treatment of severe cholera in adults [Saha 2006].

Chronic obstructive pulmonary disease, prevention of exacerbations

Data from randomized, placebo-controlled trials support the use of azithromycin for prevention of chronic obstructive pulmonary disease (COPD) exacerbations [Albert 2011], [Uzun 2014].

Based on the European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines for prevention of COPD exacerbations and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, azithromycin is an effective and recommended agent to prevent COPD exacerbations.

Cystic fibrosis, anti-inflammatory

Data from 3 randomized, double-blind trials support the use of azithromycin as an anti-inflammatory agent for patients with cystic fibrosis [Equi 2002], [Saiman 2003], [Wolter 2002].

Based on the Cystic Fibrosis Foundation cystic fibrosis pulmonary guidelines on chronic medications for maintenance of lung heath, azithromycin is an effective and recommended agent to improve lung function and reduce exacerbations.

Endocarditis prophylaxis (dental or invasive respiratory tract procedure)

Based on the American Heart Association (AHA) guidelines for the prevention of infective endocarditis, azithromycin is an effective and recommended alternative for prophylaxis against infective endocarditis associated with dental procedures in patients with certain cardiac conditions who are allergic to penicillins or ampicillin.

Gonococcal infection, disseminated (arthritis, arthritis-dermatitis syndrome, meningitis, endocarditis)

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin in combination with ceftriaxone is an effective and recommended treatment for patients with disseminated gonococcal infections including arthritis, arthritis-dermatitis syndrome, meningitis, and endocarditis.

Gonococcal infection, expedited partner therapy

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin in combination with cefixime is an effective and recommended treatment of gonorrhea in heterosexual partners of infected patients, unless prohibited by law.

Gonococcal infection, uncomplicated (infection of the rectum or pharynx; conjunctivitis)

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin in combination with ceftriaxone is an effective and recommended treatment for patients with uncomplicated gonococcal infections of the rectum or pharynx, or conjunctivitis.

Granuloma inguinale (donovanosis)

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin is an effective and recommended agent in the treatment of granuloma inguinale.

Lyme disease

Based on the IDSA guidelines for the clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, azithromycin is an effective and recommended alternative agent for the treatment of early localized or disseminated Lyme disease (erythema migrans or borrelial lymphocytoma) in patients who are unable to take or who are intolerant of tetracyclines, penicillins, or cephalosporins.

Mycobacterium abscessus infection

Based on the ATS/IDSA guideline on the diagnosis, treatment, and prevention of nontuberculosis mycobacterial disease, the British Thoracic Society (BTS) guidelines for the management of nontuberculous mycobacterial pulmonary disease, and the US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of nontuberculous mycobacteria in individuals with cystic fibrosis, azithromycin (in combination with other antimicrobials) is effective and recommended for the treatment of Mycobacterium abscessus pulmonary, skin, soft tissue, and bone infections.

Mycoplasma genitalium

A meta-analysis of controlled trials and observational studies supports the use of azithromycin in the management of Mycoplasma genitalium but notes that overall susceptibility to the drug appears to be decreasing, with cure rates of less than 70% reported since 2009 [Lau 2015].

CDC guidelines for treatment of sexually transmitted diseases state that azithromycin is more effective and preferred over doxycycline for the treatment of M. genitalium. The extended 5-day regimen may be slightly more effective than single-dose therapy and be less likely to select for macrolide resistance of M. genitalium.

Pertussis

Based on the CDC guidelines on recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis, azithromycin is effective and recommended for the treatment of pertussis.

Sexually transmitted infections, prophylaxis following sexual assault

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin in combination with ceftriaxone (plus metronidazole or tinidazole), is a recommended regimen for prophylaxis against sexually transmitted infections following sexual assault in adolescents and adults.

Shigella infection

Based on the World Health Organization (WHO) guidelines for the control of shigellosis and the IDSA practice guidelines for the diagnosis and management of infectious diarrhea, azithromycin, as an alternative to ciprofloxacin, may be used to treat this condition although there are limited data on efficacy.

Syphilis, primary and secondary

Based on the CDC sexually transmitted diseases treatment guidelines, azithromycin is a recommended alternative treatment for primary and secondary syphilis in patients who are unable to receive penicillin or doxycycline. Note: Azithromycin should be used with caution, and should not be used to treat syphilis in patients with HIV, pregnant women, or in the men who have sex with men (MSM) population.

Travelers' diarrhea, empiric treatment

Data from a randomized, double-blind trial of patients with infectious diarrhea suggest that azithromycin may be beneficial for the treatment of travelers' diarrhea caused by Campylobacter [Tribble 2007].

Based on the CDC Yellow Book, the ACG guideline for the diagnosis, treatment, and prevention of acute diarrheal infections in adults, and the IDSA practice guidelines for the diagnosis and management of infectious diarrhea, azithromycin is effective and recommended treatment for patients with travelers' diarrhea. Due to increased levels of resistance to fluoroquinolones, azithromycin may be a recommended first-line treatment, especially in regions with a high prevalence of Campylobacter (eg, Southeast Asia, India) or in geographical areas with suspected fluoroquinolone-resistant pathogens or enterotoxigenic Escherichia coli.

Contraindications

Hypersensitivity to azithromycin, erythromycin, other macrolide (eg, azalide or ketolide) antibiotics, or any component of the formulation; history of cholestatic jaundice/hepatic dysfunction associated with prior azithromycin use

Note: The manufacturer does not list concurrent use of pimozide as a contraindication; however, azithromycin is listed as a contraindication in the manufacturer’s labeling for pimozide.

Dosing: Adult

Note: Extended-release suspension (Zmax) is not interchangeable with immediate-release formulations. Use should be limited to approved indications. All doses are expressed as immediate-release azithromycin unless otherwise specified.

Acne vulgaris, inflammatory (moderate to severe) (off-label use): Note: Use as an adjunct to topical acne therapy (AAD [Zaenglein 2016]). Oral: Dosing regimens used in clinical trials have varied greatly. All trials used pulse-dosing regimens; regimens included: 500 mg once daily for 4 consecutive days per month for 3 consecutive months (Babaeinejad 2011; Parsad 2001) or 500 mg once daily for 3 days in the first week, followed by 500 mg once weekly until week 10 (Maleszka 2011) or 500 mg once daily for 3 consecutive days each week in month 1, followed by 500 mg once daily for 2 consecutive days each week in month 2, then 500 mg once daily for 1 day each week in month 3 (Kus 2005). The shortest possible duration should be used to minimize development of bacterial resistance; reevaluate at 3 to 4 months (AAD [Zaenglein 2016]).

Babesiosis (off-label use):

Mild to moderate disease: Oral: 500 mg on day 1, followed by 250 mg once daily in combination with atovaquone for 7 to 10 days in immunocompetent patients (IDSA [Wormser 2006]; Krause 2000; Vannier 2012); higher doses of azithromycin may be used in immunocompromised patients (600 to 1,000 mg daily) (IDSA [Wormser 2006]; Weiss 2001; Wormser 2010).

Severe disease: IV: 500 mg daily in combination with atovaquone for 7 to 10 days (Kletsova 2017; Sanchez 2016); a longer duration may be needed for those at high risk for relapse (Krause 2008; Sanchez 2016; Vannier 2012). Note: May switch to oral azithromycin (at the same dose) following improvement on IV therapy (Sanchez 2016); when switching to oral treatment in immunocompromised patients, a higher dose (600 to 1,000 mg daily) has been used (IDSA [Wormser 2006]; Sanchez 2016; Weiss 2001).

Bronchiectasis (non-cystic fibrosis), prevention of pulmonary exacerbations (off-label use): Oral: 500 mg 3 times weekly (Wong 2012) or 250 mg once daily (Altenburg 2013). Note: Recommended for patients with ≥2 (Barker 2018) or ≥3 (ERS [Polverino 2017]) exacerbations per year; for those who do not have Pseudomonas aeruginosa infection, have P. aeruginosa but cannot take an inhaled antibiotic, or continue to have exacerbations despite an inhaled antibiotic. Patients should be screened for nontuberculous mycobacterial infection prior to treatment and azithromycin should not be given if present (ERS [Polverino 2017]).

Bronchiolitis obliterans syndrome (off-label use): Oral: 250 mg daily for 5 days, followed by 250 mg 3 times weekly for at least a 3-month trial (ISHLT/ATS/ERS [Meyer 2014]); some experts continue indefinitely, regardless of response to therapy (Pilewski 2018).

Cat scratch disease (lymphadenitis) (off-label use): Oral: 500 mg as a single dose, then 250 mg once daily for 4 additional days (Bass 1998; IDSA [Stevens 2014]; Psarros 2012)

Cesarean delivery (intrapartum or after rupture of membranes), preoperative prophylaxis (off-label use): IV: 500 mg as a single dose 1 hour prior to surgical incision; use in combination with standard preoperative antibiotics (Tita 2016)

Chronic obstructive pulmonary disease (COPD):

Bacterial exacerbation, treatment: Oral: 500 mg in a single loading dose on day 1, followed by 250 mg once daily on days 2 to 5 (Castaldo 2003) or 500 mg once daily for 3 days (Swanson 2005).

Prevention of exacerbations (off-label use): Oral: 250 to 500 mg 3 times weekly (Berkhof 2013; Uzun 2014) or 250 mg once daily (Albert 2011)

Cystic fibrosis, anti-inflammatory (off-label use): Oral: 250 mg (<40 kg) or 500 mg (≥40 kg) 3 times weekly (Equi 2002; Saiman 2003) or 250 mg once daily (Wolter 2002). Note: Patients should be screened for nontuberculous mycobacterial infection prior to treatment and azithromycin should not be given if present (Mogayzel 2013; Saiman 2003).

Diarrhea, infectious (off-label use):

Campylobacter infection: Oral: 1 g as a single dose or 500 mg once daily for 3 days (ACG [Riddle 2016]; Tribble 2007). If symptoms have not resolved after 24 hours following single-dose therapy, continue with 500 mg once daily for 2 more days (ACG [Riddle 2016]). For HIV-infected patients, 500 mg once daily for 5 days is recommended (HHS [OI adult] 2018). Note: Increased nausea may occur with the 1 g single-dose regimen (Tribble 2007), which may be reduced by administering azithromycin as 2 divided doses on the same day (CDC 2018; Riddle 2017).

Cholera (alternative agent): Oral: 1 g as a single dose (Saha 2006)

Shigella infection: Note: Confirm susceptibility if possible (Agha 2018; HHS [OI adult] 2018; WHO 2005). Oral: 500 mg once daily for 3 days (ACG [Riddle 2016]); 5 days of therapy should be given for Shigella dysenteriae type 1 infection or for patients with HIV coinfection (Agha 2018; HHS [OI adult] 2018).

Travelers' diarrhea, empiric treatment: Oral: 1 g as a single dose or 500 mg once daily for 3 days (ACG [Riddle 2016]; CDC 2018; Riddle 2017; Tribble 2007). If symptoms have not resolved after 24 hours following single-dose therapy, continue with 500 mg once daily for 2 more days. A 3-day course of 500 mg once daily is the preferred regimen for dysentery or febrile diarrhea (ACG [Riddle 2016]). Note: Most cases are self-limited and may not warrant antimicrobial therapy. Increased nausea may occur with the 1 g single-dose regimen (Tribble 2007), which may be reduced by administering azithromycin as 2 divided doses on the same day (CDC 2018; Riddle 2017).

Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative agent for penicillin-allergic patients) (off-label use): Oral: 500 mg 30 to 60 minutes prior to procedure. Note: Only recommended for patients with cardiac conditions associated with the highest risk of an adverse outcome from endocarditis and who are undergoing a procedure likely to result in bacteremia with an organism that has the potential to cause endocarditis. (AHA [Wilson 2007]).

Lyme disease (erythema migrans or borrelial lymphocytoma) (alternative agent) (off-label use): Oral: 500 mg once daily for 7 to 10 days. Note: Use with caution and only when recommended agents cannot be used (due to decreased efficacy compared to other agents) (IDSA [Wormser 2006]).

Mycobacterial (nontuberculous) infection:

Mycobacterium avium complex (MAC) infection:

Disseminated disease in HIV-infected patients (HHS [OI adult] 2018):

Treatment: Oral: 500 to 600 mg daily as part of a combination therapy regimen

Primary prophylaxis (patients with CD4 count <50 cells/mm3): Oral: 1,200 mg once weekly (preferred) or 600 mg twice weekly; may discontinue prophylaxis when CD4 count >100 cells/mm3 for ≥3 months in response to antiretroviral therapy (ART). Note: If effective ART is initiated immediately and viral suppression is achieved, some experts do not recommend routine initiation of MAC primary prophylaxis, regardless of initial CD4 count (IAS-USA [Gunthard 2016]).

Secondary prophylaxis: Oral: 500 to 600 mg daily as part of an appropriate combination regimen; may discontinue when patient has completed ≥12 months of therapy, has no signs/symptoms of MAC disease, and has sustained (>6 months) CD4 count >100 cells/mm3 in response to ART

Pulmonary disease (nodular/bronchiectatic disease) (off-label use): Oral: 500 to 600 mg 3 times weekly as part of an appropriate combination regimen; continue treatment until patient is culture negative on therapy for ≥1 year (ATS/IDSA [Griffith 2007]); some experts prefer 500 mg 3 times weekly due to improved tolerability (BTS [Haworth 2017])

Pulmonary disease (severe nodular/bronchiectatic or cavitary disease) (off-label use): Oral: 250 to 500 mg once daily as part of an appropriate combination regimen (ATS/IDSA [Griffith 2007]; BTS [Haworth 2017]; Deshpande 2016; van Ingen 2012); continue treatment until patient is culture negative on therapy for ≥1 year (ATS/IDSA [Griffith 2007]; BTS [Haworth 2017]). Preliminary data suggest a relationship between peak concentration and clinical outcome among patients receiving daily therapy for pulmonary MAC (Jeong 2016); as such, some experts recommend checking levels and/or using higher doses of azithromycin (Kasperbauer 2018).

Pulmonary disease in patients with cystic fibrosis (off-label use): Oral: 250 to 500 mg once daily as part of an appropriate combination regimen; continue treatment until patient is culture negative on therapy for ≥1 year. Note: Intermittent dosing (3 times weekly) is not recommended for patients with cystic fibrosis (CFF/ECFS [Floto 2016]).

Mycobacterium abscessus infection (off-label use):

Note: Presence of inducible erm gene can result in decreased susceptibility even with a “susceptible” MIC result; perform susceptibility testing before and after ≥14 days of clarithromycin incubation to evaluate for the presence of an active erm gene, which may preclude use of azithromycin (CFF/ECFS [Floto 2016]; Griffith 2018).

Pulmonary, skin, soft tissue, or bone infection: Oral: 250 to 500 mg once daily as part of an appropriate combination regimen and continued for ≥6 to 12 months for pulmonary and bone infections, and ≥4 months for skin/soft tissue infections (ATS/IDSA [Griffith 2007]; CFF/ECFS [Floto 2016]; Griffith 2018). Note: Patients should be under the care of a clinician with expertise in managing mycobacterial infection.

Pertussis (off-label use): Oral: 500 mg on day 1, followed by 250 mg once daily on days 2 to 5 (CDC [Tiwari 2005])

Pneumonia, community-acquired: Note: For empiric therapy, may need to use in combination with other appropriate agents (depending on disease severity and/or risk factors for drug-resistant pathogens, particularly Streptococcus pneumoniae). Duration of therapy varies based on disease severity and response to therapy. Patients should be afebrile for 48 to 72 hours and clinically stable prior to discontinuation (IDSA/ATS [Mandell 2007]).

Outpatient: Oral: 500 mg on day 1, followed by 250 mg once daily for 4 days or 500 mg once daily for 3 days (Amsden 1999; IDSA/ATS [Mandell 2007]; Schönwald 1991)

ER suspension (Zmax): 2 g as a single dose

Inpatient: Oral, IV: 500 mg once daily for a minimum of 3 days (File 2018; IDSA/ATS [Mandell 2007])

Sexually transmitted infections:

Cervicitis, empiric therapy: Oral: 1 g as a single dose, preferably under direct observation; give in combination with ceftriaxone if the patient is at high risk for gonorrhea, if follow-up is a concern, or if the local prevalence of gonorrhea is high (eg, >5%) (CDC [Workowski 2015]; Marrazzo 2018)

Chancroid (due to Haemophilus ducreyi): Oral: 1 g as a single dose. Note: Data are limited concerning efficacy in HIV infected patients (CDC [Workowski 2015]).

Chlamydia trachomatis infection of the cervix, urethra, or pharynx(off-label use [pharynx]): Oral: 1 g as a single dose, preferably under direct observation (CDC [Workowski 2015])

Chlamydia trachomatis infection, expedited partner therapy (off-label use): Oral: 1 g as a single dose, preferably under direct observation. Note: Clinical evaluation and presumptive treatment is preferred for sexual partners of patients with chlamydia. Alternatively, expedited partner therapy for chlamydia can be used for heterosexual partners if the provider is concerned that the partner will otherwise not be promptly evaluated and treated; state laws regarding expedited partner therapy vary (CDC [Workowski 2015]).

Gonococcal infection, disseminated (arthritis, arthritis-dermatitis, meningitis, endocarditis) (off-label use): Oral: 1 g as a single dose in combination with ceftriaxone, preferably under direct observation (CDC [Workowski 2015])

Gonococcal infection, expedited partner therapy (off-label use): Oral: 1 g as a single dose in combination with cefixime. Note: Clinical evaluation and presumptive treatment is preferred for sexual partners of patients with gonorrhea. Alternatively, expedited partner therapy for gonorrhea can be used for heterosexual partners if the provider is concerned that the partner will otherwise not be promptly evaluated and treated; state laws regarding expedited partner therapy vary (CDC [Workowski 2015]).

Gonococcal infection, uncomplicated (infection of the cervix, urethra, rectum, or pharynx; conjunctivitis): Oral:

Dual-therapy regimen (off-label): 1 g as a single dose in combination with ceftriaxone (CDC [Workowski 2015])

Patients with severe cephalosporin allergy (off-label): 2 g as a single dose in combination with gemifloxacin (not available in the US) or gentamicin IM (CDC [Workowski 2015]). Note: Patients with pharyngeal infection treated with an alternative regimen should have a 14-day test-of-cure performed. Consult an infectious diseases specialist when treatment failure is suspected and report failures to the CDC through state and local health departments within 24 hours of diagnosis (CDC [Workowski 2015]).

Granuloma inguinale (donovanosis) (off-label use): Oral: 1 g once weekly or 500 mg once daily for ≥3 weeks and until lesions have healed. Note: If symptoms do not improve within the first few days of therapy, the addition of gentamicin may be considered (CDC [Workowski 2015]).

Mycoplasma genitalium (off-label use) (CDC [Workowski 2015]; Falk 2015): Oral:

Note: Azithromycin resistance is rapidly emerging; consider alternative therapy.

Single-dose regimen: 1 g as a single dose

Extended-dose regimen: 500 mg on day 1, followed by 250 mg once daily on days 2 through 5

Prophylaxis against sexually transmitted infections following sexual assault (off-label use): Oral: 1 g as a single dose in combination with ceftriaxone (plus metronidazole or tinidazole) (CDC [Workowski 2015])

Syphilis, primary and secondary (alternative agent for penicillin-allergic patients) (off-label use): Oral: 2 g as a single dose. Note: Limited data support the use of alternatives to penicillin; close serologic and clinical follow-up is warranted. Use only if no other options are available due to the potential for rapid emergence of macrolide resistance in Treponema pallidum and treatment failure; do not use to treat syphilis in patients with HIV, pregnant women, or the men who have sex with men (MSM) population (CDC [Workowski 2015]).

Urethritis, empiric therapy: Oral: 1 g as a single dose, preferably under direct observation; give in combination with ceftriaxone if there is microscopic evidence of gonococcal urethritis or if there is high clinical suspicion for gonococcal infection (Bachmann 2018; CDC [Workowski 2015])

Streptococcal pharyngitis (group A) (alternative agent for severely penicillin-allergic patients): Oral: 500 mg on day 1, followed by 250 mg once daily on days 2 through 5 (IDSA [Shulman 2012]) or 500 mg once daily for 3 days (Casey 2005)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Extended release suspension (Zmax) is not interchangeable with immediate release formulations. Use should be limited to approved indications. All doses are expressed as immediate release azithromycin unless otherwise specified.

Acne vulgaris (off-label use): Adolescents ≥13 years: Oral: Dosing regimens used in clinical trials have varied greatly. All trials used pulse-dosing regimens; regimens include: 500 mg once daily for 4 consecutive days per month for 3 consecutive months (Babaeinejad 2011) or 500 mg once daily for 3 days in the first week, followed by 500 mg once weekly until week 10 (Maleszka 2011). The shortest possible duration should be used to minimize development of bacterial resistance; re-evaluate at 3 to 4 months (AAD [Zaenglein 2016]).

Bacterial sinusitis: Children ≥6 months: Oral: 10 mg/kg once daily for 3 days (maximum: 500 mg daily)

Cat scratch disease (off-label use) (Bass 1998; Stevens 2014): Oral:

<45.5 kg: 10 mg/kg as a single dose, then 5 mg/kg once daily for 4 additional days

≥45.5 kg: Refer to adult dosing.

Chlamydia trachomatis infection: Oral:

Cervicitis, urethritis (off-label): Children and Adolescents ≥45 kg: 1 g as a single dose (CDC [Workowski 2015])

Conjunctivitis (off-label use; alternative agent): Infants: 20 mg/kg once daily for 3 days (CDC [Workowski 2015]; WHO [Chlamydia 2016])

Community-acquired pneumonia (CAP) (IDSA/PIDS 2011): Infants >3 months and Children: Note: A beta-lactam antibiotic should be added if typical bacterial pneumonia cannot be ruled out.

Presumed mild infection or step-down therapy, atypical (M. pneumoniae, Chlamydophila [also known as Chlamydia] pneumoniae, C. trachomatis) (preferred): Oral: 10 mg/kg (maximum dose: 500 mg) as a single dose on the first day, followed by 5 mg/kg/day (maximum dose: 250 mg) on days 2 through 5

Presumed moderate to severe infection, atypical (M. pneumoniae, Chlamydophila [also known as Chlamydia] pneumoniae, C. trachomatis): IV: 10 mg/kg/day on days 1 and 2, then switch to oral azithromycin therapy if possible to finish the 5-day course

Alternative regimens for community-acquired pneumonia: Oral: 10 mg/kg (maximum dose: 500 mg) once daily for 3 days (Kogan 2003)

Extended release suspension (Zmax): Infants ≥6 months and Children: Oral:

<75 lbs (34 kg): 60 mg/kg as a single dose

≥75 lbs (34 kg): Refer to adult dosing

Disseminated M. avium complex disease in patients with advanced HIV infection (off-label use) (DHHS 2013): Oral:

Treatment: 10 to 12 mg/kg/day (maximum: 500 mg) in combination with ethambutol; patients with severe disease should also receive rifabutin

Primary prophylaxis: 20 mg/kg (maximum: 1,200 mg) once weekly (preferred) or alternatively, 5 mg/kg/day once daily (maximum: 250 mg daily)

Secondary prophylaxis: 5 mg/kg/day once daily (maximum: 250 mg daily) in combination with ethambutol, with or without rifabutin

Gonococcal infection, conjunctivitis (off-label use): Adolescents: Refer to adult dosing.

Gonococcal infection, disseminated (arthritis, arthritis-dermatitis, meningitis, endocarditis) (off-label use): Adolescents: Refer to adult dosing.

Gonococcal infection, uncomplicated (cervix, rectum [off-label use], urethra) (off-label regimen): Adolescents: Refer to adult dosing.

Gonococcal infection, uncomplicated (pharynx) (off-label use): Adolescents: Refer to adult dosing.

Group A streptococcal infection; treatment of streptococcal tonsillopharyngitis:

Manufacturer's labeling and AHA recommendations: Infants, Children, and Adolescents: Oral: 12 mg/kg/dose once daily for 5 days; maximum dose: 500 mg/dose (AHA [Gerber 2009])

Alternate dosing:

IDSA recommendations: Note: Recommended as an alternative agent for group A streptococcal pharyngitis in penicillin-allergic patients. Infants, Children, and Adolescents: Oral: 12 mg/kg (maximum: 500 mg/dose) on day 1 followed by 6 mg/kg/dose (maximum: 250 mg/dose) once daily on days 2 through 5 (IDSA [Shulman 2012]).

Three-day regimen: Limited data available: Children and Adolescents: Oral: 20 mg/kg/dose once daily for 3 days; maximum dose: 1,000 mg/dose (Cohen 2004, O'Doherty 1996)

Otitis media: Children ≥6 months: Oral:

1-day regimen: 30 mg/kg as a single dose (maximum dose: 1,500 mg)

3-day regimen: 10 mg/kg once daily for 3 days (maximum: 500 mg daily)

5-day regimen: 10 mg/kg on day 1 (maximum: 500 mg daily) followed by 5 mg/kg/day once daily on days 2 to 5 (maximum: 250 mg daily)

Pertussis (off-label use) (CDC 2005): Oral:

Children <6 months: 10 mg/kg/day for 5 days

Children ≥6 months: 10 mg/kg on day 1 (maximum: 500 mg daily) followed by 5 mg/kg/day once daily on days 2 to 5 (maximum: 250 mg daily)

Prophylaxis against infective endocarditis (off-label use): Oral: 15 mg/kg 30 to 60 minutes before procedure. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Adolescents: Refer to adult dosing.

Shigella dysentery type 1 (off-label use): Oral: 6 to 20 mg/kg/day for 1 to 5 days (WHO 2005)

Dosing: Renal Impairment

Use with caution in patients with GFR <10 mL/minute (AUC increased by 35% compared to patients with normal renal function); however, no dosage adjustment is provided in the manufacturer's labeling.

No supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD) (Aronoff 2007; Heintz 2009).

Dosing: Hepatic Impairment

Azithromycin is predominantly hepatically eliminated; however, there is no dosage adjustment provided in the manufacturer's labeling, Use with caution due to potential for hepatotoxicity (rare); discontinue immediately for signs or symptoms of hepatitis.

Reconstitution

Injection (Zithromax): Prepare initial solution by adding 4.8 mL of sterile water for injection to the 500 mg vial (resulting concentration: 100 mg/mL). Use of a standard syringe is recommended due to the vacuum in the vial (which may draw additional solution through an automated syringe).

The initial solution should be further diluted to a concentration of 1 mg/mL (500 mL) to 2 mg/mL (250 mL) in NS, D5W, or LR.

Administration

IV: Infuse over 1 hour (2 mg/ml infusion) or over 3 hours (1 mg/ml infusion). Not for IM or IV bolus administration.

Oral: Immediate release suspension and tablet may be taken without regard to food; extended release suspension should be taken on an empty stomach (at least 1 hour before or 2 hours following a meal), within 12 hours of reconstitution.

Dietary Considerations

Some products may contain sodium and/or sucrose.

Oral suspension, immediate release, may be administered with or without food.

Oral suspension, extended release, should be taken on an empty stomach (at least 1 hour before or 2 hours following a meal).

Tablet may be administered with food to decrease GI effects.

Storage

Injection (Zithromax): Store intact vials of injection at room temperature. Reconstituted solution is stable for 24 hours when stored below 30°C (86°F). The diluted solution D5W, D5LR, D51/4NS, D51/3NS, D51/2NS (with or without 20 mEq/L KCl), Normosol-M in D5, Normosol-R in D5, LR, NS, or 1/2NS is stable for 24 hours at or below room temperature (30°C [86°F]) and for 7 days if stored under refrigeration (5°C [41°F]).

Suspension, immediate release (Zithromax): Store dry powder below 30°C (86°F). Store reconstituted suspension at 5°C to 30°C (41°F to 86°F) and use within 10 days.

Suspension, extended release (Zmax): Store dry powder ≤30°C (86°F). Following reconstitution, store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not refrigerate or freeze. Should be consumed within 12 hours following reconstitution.

Tablet (Zithromax): Store between 15°C to 30°C (59°F to 86°F).

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Amiodarone: Azithromycin (Systemic) may enhance the QTc-prolonging effect of Amiodarone. Management: The concomitant use of amiodarone, which has a high risk for QTc prolongation, with azithromycin, which may also prolong the QT interval, should be avoided. Avoid combination

AtorvaSTATin: Azithromycin (Systemic) may enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Cardiac Glycosides: Macrolide Antibiotics may increase the serum concentration of Cardiac Glycosides. Monitor therapy

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Cisapride: Macrolide Antibiotics may enhance the QTc-prolonging effect of Cisapride. Macrolide Antibiotics may decrease the metabolism of Cisapride. Avoid combination

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification

CycloSPORINE (Systemic): Azithromycin (Systemic) may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Ivermectin (Systemic): Azithromycin (Systemic) may increase the serum concentration of Ivermectin (Systemic). Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lovastatin: Azithromycin (Systemic) may enhance the myopathic (rhabdomyolysis) effect of Lovastatin. Monitor therapy

Macimorelin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Mizolastine: Macrolide Antibiotics may increase the serum concentration of Mizolastine. Avoid combination

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Nelfinavir: May increase the serum concentration of Azithromycin (Systemic). Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy

Pimozide: Macrolide Antibiotics may enhance the QTc-prolonging effect of Pimozide. Macrolide Antibiotics may decrease the metabolism of Pimozide. This mechanism may not apply to azithromycin. Avoid combination

Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

QuiNINE: Macrolide Antibiotics may increase the serum concentration of QuiNINE. Avoid combination

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Simvastatin: Azithromycin (Systemic) may enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tacrolimus (Systemic): Azithromycin (Systemic) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tacrolimus (Topical): Macrolide Antibiotics may increase the serum concentration of Tacrolimus (Topical). Monitor therapy

Terfenadine: Macrolide Antibiotics may enhance the QTc-prolonging effect of Terfenadine. Macrolide Antibiotics may increase the serum concentration of Terfenadine. Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vinflunine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Adverse Reactions

>10%: Gastrointestinal: Loose stools (≤14%; single-dose regimens tend to be associated with increased incidence), vomiting (children, single-dose regimens tend to be associated with increased incidence: 1% to 14%; adults: ≤2%; adults, single 2 g dose: 1% to 7%), diarrhea (2% to 9%; single-dose regimens 4% to 14%), nausea (≤7%; high single-dose regimens 4% to 18%)

1% to 10%:

Cardiovascular: Chest pain (≤1%), palpitations (≤1%)

Central nervous system: Dizziness (≤1%), drowsiness (≤1%), fatigue (≤1%), headache (≤1%), vertigo (≤1%)

Dermatologic: Skin rash (≤5%; single-dose regimens tend to be associated with increased incidence), dermatitis (children: ≤2%), pruritus (≤2%), skin photosensitivity (≤1%)

Endocrine & metabolic: Increased lactate dehydrogenase (1% to 3%), increased gamma-glutamyl transferase (1% to 2%), increased serum potassium (1% to 2%), decreased serum bicarbonate (adults: ≥1%), decreased serum glucose (adults: >1%)

Gastrointestinal: Abdominal pain (1% to 7%; single-dose regimens tend to be associated with increased incidence), anorexia (≤2%), dysgeusia (≤1%), dyspepsia (≤1%), flatulence (≤1%), gastritis (≤1%), melena (adults, multiple-dose regimens: ≤1%), mucositis (≤1%), oral candidiasis (≤1%)

Genitourinary: Vaginitis (≤3%), genital candidiasis (adults, multiple-dose regimens: ≤1%)

Hematologic & oncologic: Decrease in absolute neutrophil count (children: 15% to 16%; 500 to 1,500 cells/mm3), decreased hematocrit (adults: >1%), decreased hemoglobin (adults: >1%), increased neutrophils (adults: >1%), thrombocythemia (adults: >1%), change in neutrophil count (children: ≥1%), eosinophilia (≥1%), lymphocytopenia (≥1%)

Hepatic: Increased serum ALT (≤6%), increased serum AST (≤6%), increased serum bilirubin (≤3%), cholestatic jaundice (≤1%)

Local (adults with IV administration): Pain at injection site (7%), local inflammation (3%)

Neuromuscular & skeletal: Increased creatine phosphokinase (1% to 2%)

Renal: Increased serum creatinine (≤6%), increased blood urea nitrogen (≤1%), nephritis (adults, multiple-dose regimens: ≤1%)

Respiratory: Bronchospasm (≤1%)

Miscellaneous: Fever (children: (≤2%)

<1%, postmarketing, and/or case reports: Abnormal stools, acute generalized exanthematous pustulosis, acute renal failure, ageusia, aggressive behavior, agitation, alteration in sodium, altered sense of smell, altered serum glucose, anaphylaxis, anemia, angioedema, anosmia, anxiety, arthralgia, asthma, basophilia, bronchitis, cardiac arrhythmia, chills, Clostridium difficile associated diarrhea, conjunctivitis (children), constipation, convulsions, cough, deafness, decreased serum potassium (children), decreased serum sodium, diaphoresis, DRESS syndrome, dyspnea, dysuria, eczema, edema, emotional lability, enteritis, erythema multiforme, exacerbation of myasthenia gravis, facial edema, flu-like symptoms, fungal dermatitis, fungal infection, gastrointestinal disease, hearing loss, hepatic failure, hepatic insufficiency, hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014), hostility, hyperactivity, hyperkinesia, hypersensitivity reaction, hypotension, increased monocytes, increased serum alkaline phosphatase, increased serum bicarbonate, increased serum glucose, increased serum phosphate, interstitial nephritis, insomnia, irritability, jaundice, Lambert-Eaton syndrome, leukopenia, maculopapular rash, malaise, nervousness, neutropenia , otitis media, pain, pancreatitis, paresthesia, pharyngitis, pleural effusion, prolonged Q-T interval on ECG , pseudomembranous colitis, pyloric stenosis, pyloric stenosis (infantile hypertrophic), rhinitis, seizure, Stevens-Johnson syndrome, syncope, thrombocytopenia, tinnitus, tongue discoloration, torsades de pointes toxic epidermal necrolysis, urticaria, ventricular tachycardia, vesiculobullous dermatitis, weakness

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Allergic reactions (eg, angioedema, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported (rare), including fatalities; reappearance of allergic reaction may occur shortly after discontinuation of symptomatic treatment without further azithromycin exposure.

• Altered cardiac conduction: Macrolides (especially erythromycin) have been associated with rare QTc prolongation and ventricular arrhythmias, including torsades de pointes; consider avoiding use in patients with prolonged QT interval, congenital long QT syndrome, history of torsades de pointes, bradyarrhythmias, uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, uncompensated heart failure, or concurrent use of Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents or other drugs known to prolong the QT interval.

• Cardiac risk: A retrospective cohort study done in Tennessee Medicaid patients demonstrated an increased cardiac risk with azithromycin relative to amoxicillin or ciprofloxacin, and similar risk compared to levofloxacin; notably, increased cardiac mortality (an estimated 47 additional deaths per 1 million 5-day courses of treatment compared to amoxicillin) was associated with higher baseline cardiovascular risk (Ray 2012); however, these data may not be generalizable to the population as a whole (Ray 1989). In another retrospective population study of US veterans, azithromycin was shown to significantly increase the risk of mortality and arrhythmia on days 1 to 5, but not on days 6 to 10 after dispensing the prescription (Rao 2014). In contrast, 2 additional large retrospective cohort studies did not demonstrate an increased risk of cardiovascular events, including all-cause mortality or cardiovascular death (Svanstrom 2013, Mortensen 2014). The implications of these data have yet to be determined.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD); CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Gonorrhea/syphilis: May mask or delay symptoms of incubating gonorrhea or syphilis, so appropriate culture and susceptibility tests should be performed prior to initiating a treatment regimen.

• Hepatic impairment: Use with caution in patients with preexisting liver disease; hepatocellular and/or cholestatic hepatitis, with or without jaundice, hepatic necrosis, failure, and death have occurred. Discontinue immediately if symptoms of hepatitis occur (malaise, nausea, vomiting, abdominal colic, fever).

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation and new onset of symptoms have occurred.

• Renal impairment: Use with caution in patients with severe renal impairment (GFR <10 mL/minute); increased gastrointestinal adverse effects may occur.

Special populations:

• Infants: Use of azithromycin in neonates and infants (treatment up to 42 days of life) has been associated with infantile hypertrophic pyloric stenosis (IHPS); observe for non-bilious vomiting or irritability with feeding (Eberly 2015).

Dosage form specific issues:

• Oral suspensions: Immediate release and extended release suspensions are not interchangeable.

Monitoring Parameters

Liver function tests, CBC with differential

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Azithromycin crosses the placenta (Ramsey 2003). The maternal serum half-life of azithromycin is unchanged in early pregnancy and decreased at term; however, high concentrations of azithromycin are sustained in the myometrium and adipose tissue (Fischer 2012; Ramsey 2003). Azithromycin is recommended for the treatment of several infections, including chlamydia, gonococcal infections, and Mycobacterium avium complex (MAC) in pregnant patients (consult current guidelines) (CDC [Workowski 2015]; HHS [opportunistic; adult] 2015).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal pain, diarrhea, headache, nausea, vomiting, itching, or lack of appetite. Have patient report immediately to prescriber tachycardia, abnormal heartbeat, hearing impairment, angina, muscle pain, joint pain, tinnitus, seizures, severe dizziness, passing out, difficulty swallowing, difficulty speaking, enlarged lymph nodes, vaginitis, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.