Azithromycin Dihydrate (Monograph)

Brand names: Zithromax, Zithromax Tri-Paks, Zithromax Z-Pak, Zmax
Drug class: Other Macrolides
- Antimycobacterial Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Warning

[Posted 08/03/2018]

AUDIENCE: Patient, Health Professional, Oncology

ISSUE: The antibiotic azithromycin (Zithromax, Zmax) should not be given long-term to prevent a certain inflammatory lung condition in patients with cancers of the blood or lymph nodes who undergo a donor stem cell transplant. Results of a clinical trial found an increased rate of relapse in cancers affecting the blood and lymph nodes, including death, in these patients. We are reviewing additional data and will communicate our conclusions and recommendations when our review is complete.

BACKGROUND: The serious lung condition for which long-term azithromycin was being studied called bronchiolitis obliterans syndrome is caused by inflammation and scarring in the airways of the lungs, resulting in severe shortness of breath and dry cough. Cancer patients who undergo stem cell transplants from donors are at risk for bronchiolitis obliterans syndrome. The manufacturer of brand name azithromycin is providing a Dear Healthcare Provider letter on this safety issue to health care professionals who care for patients undergoing donor stem cell transplants.

Azithromycin is not approved for preventing bronchiolitis obliterans syndrome. It is an FDA-approved antibiotic used to treat many types of infections affecting the lungs, sinuses, skin, and other parts of the body. The drug has been used for more than 26 years. It is sold under the brand names Zithromax and Zmax and as generics by many different drug companies. It works by stopping the growth of bacteria that can cause infections.

RECOMMENDATION: Health care professionals should not prescribe long-term azithromycin for prophylaxis of bronchiolitis obliterans syndrome to patients who undergo donor stem cell transplants because of the increased potential for cancer relapse and death.

Patients who have had a stem cell transplant should not stop taking azithromycin without first consulting with your health care professional. Doing so could be harmful without your health care professional's direct supervision. Talk with them if you have any questions or concerns about taking this medicine.

For more information visit the FDA website at: [Web] and [Web].

Introduction

Antibacterial; an azalide, a subclass of macrolide antibiotics.¹ ³ ¹⁰ ¹⁶³ ¹⁹⁶ ²¹⁰ ²¹¹ ³⁰²

Uses for Azithromycin Dihydrate

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Acute Otitis Media (AOM)

Treatment of AOM caused by H. influenzae, M. catarrhalis, or S. pneumoniae.¹ ⁹⁴ ¹⁰⁶ ¹³⁹ ¹⁷⁴ ¹⁷⁵ ¹⁷⁶ ¹⁷⁷ ¹⁷⁹ ²⁰³ ²¹¹ ²⁹⁴

Not a drug of first choice; considered an alternative for patients with type I penicillin hypersensitivity.²⁰³ ²⁹⁴ S. pneumoniae resistant to amoxicillin may also be resistant to azithromycin and the drug may not be effective for AOM that fails to respond to amoxicillin.²⁸²

Pharyngitis and Tonsillitis

Treatment of pharyngitis or tonsillitis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci) when first-line therapy cannot be used.¹ ¹⁵ ²⁹ ²⁰³ ²¹¹ Often effective in eradicating susceptible S. pyogenes from the nasopharynx, but efficacy in the prevention of subsequent rheumatic fever has not been established to date.¹

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;¹ ⁶ ¹⁵ ¹³⁶ ¹³⁷ ²⁰³ oral cephalosporins and oral macrolides are considered alternatives.⁶ ¹⁵ ¹³⁶ ¹³⁷ ²⁰³ Amoxicillin sometimes used instead of penicillin V, especially for young children.¹³⁶ ²⁰³

Consider that strains of S. pyogenes resistant to macrolides are common is some areas of the world (e.g., Japan, Finland) and azithromycin-resistant strains have been reported in the US.¹ ²⁰² ²⁰³ ³⁰⁹ (See Selection and Use of Anti-infectives under Cautions),

GI Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni ^{† [off-label]}.³⁰⁸ Recommended by CDC, NIH,³⁰⁸ IDSA,³⁰⁸ AAP, and others as a drug of choice for empiric treatment.¹⁵ ¹⁴² ²⁰³ ³⁰⁸

Treatment of cryptosporidiosis^{† [off-label]} in HIV-infected adults, adolescents, or children.²⁵⁶ ³⁰⁷ ³⁰⁸ Anti-infectives may suppress the infection, but none found to reliably eradicate Cryptosporidium.²⁰³ ²⁹⁰ ³⁰⁷ ³⁰⁸ CDC, NIH, IDSA, and others state the most appropriate treatment for cryptosporidiosis in HIV-infected individuals is use of potent antiretroviral agents (to restore immune function) and symptomatic treatment of diarrhea.²⁹⁰ ³⁰⁷ ³⁰⁸

Treatment of shigellosis^{† [off-label]} caused by susceptible strains of Shigella dysenteriae, S. boydii, S. flexneri, or S. sonnei.¹⁵ ¹⁴² ²⁰³ ³⁰⁷ ³¹⁶ ³¹⁷ ³¹⁸ Usual drugs of choice are fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin); alternatives are azithromycin, ampicillin, ceftriaxone, or co-trimoxazole.¹⁵ ¹⁴² ²⁰³ ³⁰⁷ Because of increasing resistance, select anti-infective based on susceptibility patterns of locally circulating Shigella.²⁰³ ³¹⁷

Treatment of travelers’ diarrhea^{† [off-label]}.³¹⁹ ³²⁰ ³⁵⁹ ³⁶⁰ ³⁷² Generally self-limited and may resolve within 3–4 days without anti-infective treatment;³¹⁹ ³²⁰ ³³⁶ if diarrhea is moderate or severe, persists >3 days, or is associated with fever or bloody stools, short-term anti-infective therapy (1–3 days) may be indicated.²⁰³ ³¹⁹ ³³⁶ ³⁷² Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually recommended.³¹⁹ ³²⁰ ³³⁶ ³⁷² Azithromycin is an alternative for those who should not receive fluoroquinolones (children, pregnant women) and may be drug of choice for travelers in areas with high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, Nepal) or those who have not responded after 48 hours of fluoroquinolone therapy.²⁰³ ³¹⁹ ³²⁰ ³⁵⁹ ³⁶⁰ ³⁷²

Treatment of severe diarrhea caused by enterotoxigenic Escherichia coli ^{† [off-label]} (ETEC).²⁰³ ³⁵⁶ ETEC diarrhea generally is of moderate severity and self-limited, but may be severe.¹⁸⁷ ²⁰³ ³⁵⁶ Anti-infectives not usually indicated, but AAP, CDC, and others suggest an anti-infective (e.g., azithromycin, co-trimoxazole, a fluoroquinolone, rifamycin) can be considered in addition to supportive care if diarrhea is severe or intractable and causative organism is susceptible.¹⁸⁷ ²⁰³ ³⁵⁶

Treatment of dysentery caused by enteroinvasive E. coli ^† (EIEC).²⁰³ AAP suggests that an oral anti-infective (e.g., azithromycin, ciprofloxacin, co-trimoxazole) can be used; whenever possible, select anti-infective based on in vitro susceptibility testing.²⁰³

Treatment of diarrhea associated with enteroaggregative E. coli ^† (EAEC).³³¹ A drug of choice, especially in children with severe or persistent illness.³³¹

Role of anti-infectives in treatment of hemorrhagic colitis caused by shiga toxin-producing E. coli ^† (STEC; formerly known as enterohemorrhagic E. coli [EHEC] or verotoxin-producing E. coli) unclear; most experts do not recommend use of anti-infectives in the treatment of enteritis caused by E. coli 0157:H7 since there is no evidence of benefit from such therapy.¹⁴² ¹⁸⁷ ²⁰³

Respiratory Tract Infections

Treatment of acute bacterial sinusitis caused by susceptible Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.¹ ³ ¹⁰³ ¹⁷⁹ ²¹⁰ ²¹¹ ³⁰²

Treatment of mild to moderate acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) caused by H. influenzae, M. catarrhalis, or S. pneumoniae.¹ ³ ¹⁵ ⁹⁶ ⁹⁷ ⁹⁸ ¹⁷⁹ ²¹⁰ ²¹¹

Treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) when oral therapy is indicated.¹ ³ ¹⁵ ²⁹ ⁹¹ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁵⁹ ¹⁷⁹ ²⁰³ ²¹⁰ ²¹¹ ³⁰² ³²⁹

Treatment of CAP caused by susceptible C. pneumoniae, H. influenzae, M. catarrhalis, Legionella pneumophila, M. pneumoniae, Staphylococcus aureus, or S. pneumoniae when initial IV therapy is indicated.¹⁹⁶

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).³²⁹ Do not use a macrolide alone for empiric treatment of CAP in hospitalized patients.³²⁹

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.³²⁹ If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.³²⁹

For empiric inpatient treatment of CAP when treatment in an intensive care unit (ICU) is not necessary, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, or moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.³²⁹ For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) S. aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).³²⁹

For empiric treatment of CAP in adults with risk factors for Ps. aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (cefepime, imipenem, meropenem, fixed combination of piperacillin and tazobactam) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.³²⁹

Treatment of infections caused by L. pneumophila (Legionnaires’ disease).¹⁵ ¹³⁰ ¹⁶⁸ ¹⁹⁶ ²⁰³ ²³² ²⁵⁰ ³¹¹ ³¹² ³¹⁴ ³²⁹ ³³⁰ Drugs of choice are macrolides (usually azithromycin) or fluoroquinolones with or without rifampin.¹⁵ ²⁰³ ²³² ³¹¹ ³¹² ³²⁹ ³³⁰

Treatment and postexposure prophylaxis of pertussis^† caused by Bordetella pertussis.¹⁵ ²⁸ ¹³⁸ ²⁰³ ³²⁴ ³²⁵ ³²⁶ ³²⁹ ³³³ ³³⁴ (See Pertussis under Uses.)

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus, S. pyogenes, or S. agalactiae (group B streptococci).¹ ³ ²¹⁰ ²¹¹

Babesiosis

Treatment of babesiosis^† caused by Babesia microti.¹²⁵ ²⁰³ ²⁸⁸ ³³⁷

Regimens of choice for babesiosis are atovaquone in conjunction with azithromycin or quinine in conjunction with clindamycin.¹²⁵ ²⁸⁸ ³³⁷ The clindamycin and quinine regimen may be preferred for severe babesiosis;²⁸⁸ in those with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the quinine and clindamycin regimen.¹²⁵ ³³⁷ Also consider exchange transfusions in severely ill patients with high levels of parasitemia (>10%), substantial hemolysis, or compromised renal, hepatic, or pulmonary function.¹²⁵ ²⁰³ ²⁸⁸

Bartonella Infections

Treatment of infections caused by B. henselae ^† (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis).¹⁵ ²⁰³ ²⁶¹ ³¹⁰ Cat scratch disease generally self-limited in immunocompetent individuals and may resolve spontaneously in 2–4 months; some clinicians suggest that anti-infectives be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and such therapy probably is indicated in immunocompromised patients.²⁰³ ²⁶¹ ³¹⁰ Anti-infectives also indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome.²⁰³ Optimum regimens have not been identified; some clinicians recommend azithromycin, ciprofloxacin, erythromycin, doxycycline, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.¹⁵ ²⁰³ ²⁶¹ ³¹⁰

Treatment of bacteremia caused by Bartonella quintana ^†;¹⁵ ²⁵⁷ ²⁶¹ used in conjunction with ceftriaxone.²⁵⁷ ²⁶¹ ³⁰⁷ Optimum anti-infective regimens have not been identified.²⁵⁷ ²⁵⁹ ²⁶⁰ ³⁰⁷ ³¹⁰

Chancroid

Treatment of chancroid (genital ulcers caused by Haemophilus ducreyi).¹ ⁸ ¹⁰ ¹⁵ ¹⁵⁷ ¹⁵⁹ ¹⁸¹ ²⁰³ ²⁴²

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin for treatment of chancroid.⁸ ¹⁵ ¹⁵⁹ ¹⁸¹ ²⁰³ ²⁴²

Safety and efficacy of azithromycin established in men (not women),¹ but has been effective for and is recommended by CDC for treatment of chancroid in women^†.⁸ ¹⁵⁷ ¹⁵⁹ ¹⁸¹ ²⁰³ ²⁶²

HIV-infected patients and uncircumcised males may not respond to treatment as well as those who are HIV-negative or circumcised.²⁴² CDC recommends that single-dose azithromycin or ceftriaxone regimens be used in HIV patients only if follow-up can be ensured.²⁴²

Chlamydial Infections

Treatment of uncomplicated urethritis or cervicitis caused by C. trachomatis.¹ ⁷ ⁸ ¹⁰ ¹⁵ ⁹² ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹¹² ¹¹⁴ ¹⁷⁹ ¹⁸⁴ ¹⁸⁵ ²⁰³ ²¹¹ ²⁴² CDC and others recommend azithromycin or doxycycline as drug of choice for nongonococcal urethritis (NGU) or cervicitis.⁸ ²⁴² For recurrent or persistent urethritis in patients with NGU who have already been treated with a recommended regimen, CDC recommends metronidazole or tinidazole used in conjunction with azithromycin.²⁴²

A drug of choice for presumptive treatment of coexisting chlamydial infection in patients being treated for gonorrhea.⁸ ²⁴²

A drug of choice for treatment of urogenital chlamydial infections in pregnant women.⁸ ²⁰³ ²⁴²

Treatment of ocular trachoma^† caused by C. trachomatis.¹⁵ ²⁹ ¹¹² ¹¹⁴ ¹⁸⁹ ²⁰³ ²¹⁷ ³⁰¹ ³⁵⁴ ³⁷⁰ ³⁷³ ³⁷⁴ ³⁷⁵ ³⁷⁶ A drug of choice;¹⁵ ³⁵³ ³⁵⁴ ³⁷⁰ ³⁷⁶ recommended for use in mass treatment programs.³⁵⁴ ³⁷⁰ ³⁷⁵ ³⁷⁶

Treatment of chlamydial pneumonia in infants²⁰³ or chlamydial conjunctivitis in neonates (ophthalmia neonatorum caused by C. trachomatis).⁸ ²⁰³ ²⁴²

Alternative to tetracyclines for treatment of psittacosis^† caused by Chlamydophila psittaci (formerly Chlamydia psittaci),¹⁵ ²⁰³ ³²⁹ especially in children <8 years of age who should not receive tetracyclines.²⁰³

Treatment of lymphogranuloma venereum caused by C. trachomatis.²⁰³ ²⁴² CDC recommends doxycycline as drug of choice and erythromycin as an alternative; some experts suggest that azithromycin may be effective, but clinical data are lacking.²⁰³ ²⁴²

Has been used to treat adults with CAD who have elevated anti-C. pneumoniae antibody titers^† (a possible risk factor for MI or CAD) in an attempt to reduce recurrent ischemic events;²³¹ ²⁹⁷ ²⁹⁸ efficacy not proven to date.²⁹⁷ ²⁹⁸

Cholera

Treatment of cholera^† caused by Vibrio cholerae 01 or 0139.³⁵⁰ ³⁵¹ ³⁵²

A tetracycline or, alternatively, a fluoroquinolone or co-trimoxazole generally used for treatment of cholera in conjunction with fluid and electrolyte replacement therapy.¹⁵ ¹⁴² ²⁰³ Although further study is needed, azithromycin may be an alternative, especially for treatment of cholera in children or infections caused by V. cholerae resistant to tetracyclines and fluoroquinolones.³⁵⁰ ³⁵¹ ³⁵²

Gonorrhea

Treatment of uncomplicated urethritis or cervicitis caused by susceptible Neisseria gonorrhoeae.¹ ¹⁷⁹ ¹⁸² ¹⁸³ ¹⁹⁰ ¹⁹¹ ²⁴² ³⁰³ ³⁰⁵

Not recommended for routine treatment of gonorrhea.¹⁷⁹ ¹⁸² ¹⁸³ ²⁴² ²⁵⁰ CDC and others state azithromycin can be used as an alternative for treatment of uncomplicated gonorrhea when preferred drugs cannot be used (e.g., in patients hypersensitive to cephalosporins when spectinomycin is unavailable and desensitization to cephalosporins is not an option).³⁰³ ³⁰⁶ ³⁷¹ Although azithromycin is effective, CDC recommends the drug be used only when necessary because of concerns related to emerging resistance to macrolides.³⁷¹

Granuloma Inguinale (Donovanosis)

Alternative for treatment of granuloma inguinale^† (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis).²²¹ ²⁴² CDC recommends doxycycline as the drug of choice and azithromycin, ciprofloxacin, erythromycin, or co-trimoxazole as alternatives.²⁴²

Leptospirosis

Alternative for treatment of leptospirosis caused by Leptospira^†.³⁶³ ³⁶⁵ Penicillin G is drug of choice for severe infections; tetracyclines (usually doxycycline) or ceftriaxone are recommended as alternatives for less severe infections.¹⁵ ²⁰³ Azithromycin also has been effective.³⁶³ ³⁶⁵

Lyme Disease

Alternative for treatment of early disseminated Lyme disease^† associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block, when first-line agents cannot be used.¹⁵ ¹²⁴ ¹⁷⁹ ²¹¹ ²²⁶ ²²⁷ ²⁸⁸ IDSA, AAP, and others recommend oral doxycycline, oral amoxicillin, or oral cefuroxime as first-line therapy for treatment of early localized or early disseminated Lyme disease when oral therapy is appropriate;¹⁵ ²⁰³ ²⁸⁹ ²²⁶ ²⁸⁸ macrolides generally have been less effective than first-line agents.²⁰³ ²²⁶ ²⁸⁸ ²⁸⁹

Malaria

Although further study is needed, has been used in conjunction with an antimalarial (e.g., chloroquine, quinine, artesunate [not commercially available in the US]) for treatment of uncomplicated malaria^† caused by Plasmodium falciparum, including multidrug-resistant strains.³⁴¹ ³⁴² ³⁴³ Should not be used alone as monotherapy for treatment of malaria.³⁴¹ ³⁴²

Although further study is needed, has been used for treatment or prevention of P. vivax malaria^†.³⁴⁴ ³⁴⁵ When used for treatment, the rate of resolution of parasitemia reported for azithromycin was considerably slower than that reported for chloroquine.³⁴⁵

Mycobacterium avium Complex (MAC) Infections

Primary prevention (primary prophylaxis) of disseminated MAC infection in adults, adolescents, and children^† with advanced HIV infection.¹⁰ ¹² ²⁰³ ²³⁴ Recommended as a drug of choice for primary prevention of MAC in HIV-infected patients;²³⁴ usually used alone but has been used in conjunction with rifabutin.¹⁰ ²³⁴

Treatment of disseminated MAC disease, including in HIV-infected adults, adolescents, and children.¹⁰ ¹¹⁷ ²⁰³ ²³³ ²³⁴ ³⁰⁷ ³⁰⁸ ATS, IDSA, CDC, NIH, and others recommend a regimen of clarithromycin (or azithromycin) and ethambutol with or without rifabutin.²³³ ²³⁴ ³⁰⁷ ³⁰⁸ Clarithromycin usually the preferred macrolide for initial treatment; azithromycin can be substituted if clarithromycin cannot be used because of drug interactions or intolerance and is preferred in pregnant women.²³³ ³⁰⁷ ³⁰⁸

Prevention of recurrence (secondary prophylaxis) of disseminated MAC infection in HIV-infected adults, adolescents, and children^†.¹⁰ ¹¹⁷ ²⁰³ ²³³ ²³⁴ ATS, CDC, NIH, and IDSA recommend a macrolide (clarithromycin or azithromycin) given with ethambutol (with or without rifabutin).²³³ ²³⁴ ³⁰⁷ ³⁰⁸

Treatment of pulmonary MAC infections^† in conjunction with other antimycobacterials.²³³ ³¹³ ³¹⁵ For initial treatment of nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a 3-times-weekly regimen of clarithromycin (or azithromycin), ethambutol, and rifampin in most patients.²³³ For initial treatment of fibrocavitary or severe nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a daily regimen of clarithromycin (or azithromycin), ethambutol, and rifampin (or rifabutin) and state that consideration can be given to adding amikacin or streptomycin during the first 2–3 months of treatment for extensive (especially fibrocavitary) disease or when previous therapy has failed.²³³ Although a 2-drug regimen of clarithromycin (or azithromycin) and ethambutol may be adequate for treatment of nodular/bronchiectatic MAC disease in some patients, such regimens should not be used in fibrocavitary disease because of the risk of emergence of macrolide resistance.²³³

Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.²³³

Mycobacterium abscessus, M. kansasii, and M. marinum Infections

Treatment of infections caused by M. abscessus^†.²³³ For serious skin, soft tissue, and bone infections, ATS and IDSA recommend a multiple-drug regimen of clarithromycin (or azithromycin) used in conjunction with a parenteral anti-infective (e.g., amikacin, cefoxitin, imipenem);²³³ surgery usually indicated for extensive disease, abscess formation, and when drug therapy is difficult.²³³ This multiple-drug regimen also has been used in the treatment of M. abscessus lung disease; anti-infectives may control symptoms and disease progression, but generally cannot produce long-term sputum conversion.²³³ Curative therapy may be possible in those with focal infections and limited lung disease if surgical resection is used in conjunction with a multiple-drug treatment regimen.²³³

Treatment of rifampin-resistant M. kansasii^† infections in conjunction with other antimycobacterials.²³³ ATS and IDSA recommend a 3-drug regimen based on results of in vitro susceptibility testing, including clarithromycin (or azithromycin), moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.²³³

Treatment of M. marinum^† infections.²³³ A regimen of clarithromycin and ethambutol has been used; based on experience in other mycobacterial infections, a regimen of azithromycin and ethambutol may be an alternative.²³³

Neisseria meningitidis Infections

Elimination of nasopharyngeal carriage of N. meningitidis ^†.³⁴⁶ ³⁴⁷ ³⁴⁹

CDC and AAP consider rifampin, ceftriaxone, or ciprofloxacin the drugs of choice to eliminate nasopharyngeal carriage of N. meningitidis and for postexposure prophylaxis in household or other close contacts of patients with invasive meningococcal disease.²⁰³ ³⁴⁹ Although further study is needed,³⁴⁹ CDC suggests azithromycin can be used as an alternative in areas where ciprofloxacin-resistant N. meningitidis have been reported (e.g., Minnesota, North Dakota).³⁴⁷

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease (PID) caused by C. trachomatis, Mycoplasma hominis, or N. gonorrhoeae when initial IV therapy is considered necessary.¹⁹⁶ ¹⁹⁷ If anaerobic bacteria are suspected, an anti-infective active against anaerobes should be used in conjunction with azithromycin.¹⁹⁶ Although azithromycin is not included in CDC’s recommended or alternative regimens for treatment of PID,²⁴² ³⁷¹ CDC states a regimen of amoxicillin and clavulanic acid, azithromycin, and metronidazole has demonstrated short-term clinical cure when used in outpatients.³⁷¹

Pertussis

Treatment of pertussis^† caused by Bordetella pertussis and postexposure prophylaxis of pertussis^† in household and other close contacts of an individual with pertussis.¹⁵ ²⁸ ¹³⁸ ²⁰³ ³²⁴ ³²⁵ ³²⁶ ³³³ ³³⁴

Macrolides (azithromycin, clarithromycin, erythromycin) are the drugs of choice.¹⁵ ¹³⁸ ²⁰³ ³²⁶ ³³³ ³³⁴ Although erythromycin traditionally has been considered the drug of choice for treatment and postexposure prophylaxis of pertussis,¹⁵ ¹³⁸ ²⁰³ ³²⁶ ³³³ ³³⁴ azithromycin and clarithromycin appear to be as effective and may be associated with better compliance because shorter regimens are required and the drugs are better tolerated.²⁰³ ³²⁴ ³³³ ³³⁴

For treatment and postexposure prophylaxis of pertussis in adults and children ≥1 month of age, CDC and AAP recommend azithromycin, clarithromycin, or erythromycin as drug of choice;²⁰³ ³³⁴ co-trimoxazole is an alternative for those ≥2 months of age when a macrolide cannot be used.²⁰³ ³³⁴ AAP and CDC state azithromycin is the preferred macrolide for treatment of pertussis in infants <1 month of age; however, safety and efficacy not established in this age group and only limited data are available.²⁰³ ³³⁴

If given during the catarrhal stage of pertussis (approximately 1–2 weeks of nasal congestion, runny nose, mild sore throat, nonproductive cough, minimal or no fever), anti-infectives may reduce the duration and severity of symptoms and lessen the period of communicability.²⁰³ ³³⁴ After paroxysmal cough is established, anti-infectives may not affect the course of illness but are recommended to limit spread of the disease to others.²⁰³

All household and other close contacts of an individual with suspected pertussis should receive anti-infective postexposure prophylaxis, regardless of age or vaccination status.¹⁹⁸ ²⁰³ Prophylaxis should be initiated within 21 days of exposure; if >21 days have elapsed since onset of cough in the index patient, prophylaxis has limited value but should be considered for those in households with high-risk contacts (e.g., young infants, pregnant women, individuals with contact with infants).²⁰³ In addition, all close contacts who are unvaccinated or incompletely vaccinated against pertussis should receive age-appropriate vaccination with a preparation containing pertussis antigens.¹⁹⁸ ²⁰³

Scrub Typhus

Alternative for treatment of scrub typhus caused by Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi).³⁶² ³⁶³ ³⁶⁴ Drug of choice usually is doxycycline;¹⁵ ³⁶² ³⁶³ ³⁶⁴ alternatives are chloramphenicol or a fluoroquinolone.¹⁵ ³⁶² ³⁶⁴ Azithromycin may be a preferred alternative for treatment of scrub typhus in children or pregnant women or when scrub typhus was acquired in areas where doxycycline-resistant O. tsutsugamushi have been reported (e.g., South Korea, Thailand).³⁶² ³⁶³ ³⁶⁴

Syphilis

Alternative for treatment of primary, secondary, or early latent syphilis in nonpregnant adults and adolescents hypersensitive to penicillin^†.²⁴² ²⁹² ²⁹³ ³⁵⁸

Penicillin G is drug of choice for treatment of all stages of syphilis,⁸ ²⁰³ ²⁴² but CDC, NIH, and IDSA state azithromycin can be considered for treatment of primary, secondary, or early latent syphilis^† in nonpregnant adults and adolescents hypersensitive to penicillin if close follow-up can be ensured.²⁰³ ²⁴² ²⁹³ ³⁰⁷

Use with caution and with close follow-up; efficacy not well documented (especially in HIV-infected individuals) and resistance and treatment failures reported.⁸ ²⁴² ²⁹³ ³⁰⁷ ³²⁷ ³²⁸

Toxoplasmosis

Treatment of infections caused by Toxoplasma gondii, including toxoplasmic encephalitis^† in HIV-infected patients¹²⁷ ¹²⁸ ¹²⁹ ²⁹⁶ ³⁰⁷ and ocular toxoplasmosis^†;²⁹⁵ usually used in conjunction with pyrimethamine.²⁹⁵ ²⁹⁶

CDC, NIH, IDSA, and others usually recommend pyrimethamine in conjunction with sulfadiazine and leucovorin for treatment of toxoplasmosis in adults and children, especially immunocompromised patients (e.g., HIV-infected individuals).¹²⁵ ³⁰⁷ ³⁰⁸ Azithromycin in conjunction with pyrimethamine and leucovorin is one of several alternative regimens that can be considered in adults and adolescents when the regimen of choice cannot be used;³⁰⁷ this regimen has not been evaluated in children.³⁰⁸

Typhoid Fever and Other Salmonella Infections

Treatment of uncomplicated typhoid fever^† caused by susceptible Salmonella.¹⁵ ³²¹ ³²² ³²³ ³³² ³⁶¹ Drugs of choice are fluoroquinolones (e.g., ciprofloxacin, ofloxacin), especially in areas with multidrug-resistant S. typhi (strains resistant to ampicillin, amoxicillin, chloramphenicol, co-trimoxazole); alternatives are azithromycin and third generation cephalosporins (cefotaxime, ceftriaxone, cefixime), especially for fluoroquinolone-resistant strains.¹⁵ ²⁰³ ³³² ³⁶¹

Prevention of Bacterial Endocarditis

Alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis^† in penicillin-allergic individuals with certain cardiac conditions who are undergoing certain dental procedures (i.e., procedures that involve manipulation of gingival tissue, the periapical region of teeth, or perforation of oral mucosa) or certain invasive respiratory tract procedures (i.e., procedures involving incision or biopsy of respiratory mucosa).²⁰¹

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with the highest risk of adverse outcome from endocarditis and specific recommendations regarding use of prophylaxis to prevent endocarditis in these patients.²⁰¹

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims^†;⁸ ²⁴² used in conjunction with IM ceftriaxone and oral metronidazole.²⁴²

Azithromycin Dihydrate Dosage and Administration

Administration

Administer orally¹ ¹⁰ ³⁰² or by IV infusion.¹⁹⁶ Do not administer IM or by rapid IV injection.¹⁹⁶

Oral Administration

Available as conventional film-coated tablets,¹ conventional powder for oral suspension,¹ and extended-release microspheres for oral suspension.³⁰²

Extended-release oral suspension is not bioequivalent to and is not interchangeable with conventional oral suspension or tablets.³⁰²

Conventional tablets: Administer orally without regard to meals;¹ ¹⁰ administering tablets with food may increase tolerability.⁸ ¹⁰ Two 250-mg tablets are bioequivalent to one 500-mg tablet.¹

Reconstituted conventional oral suspension: Administer orally without regard to meals.¹ ¹⁰ The safety of repeating a dose in children who vomit after receiving 30 mg/kg as a single dose has not been established.¹ The single-dose 1-g packets should not be used to administer doses other than 1 g and are not for pediatric use.¹⁰

Reconstituted extended-release oral suspension: Administer as a single dose on an empty stomach (at least 1 hour before or 2 hours after a meal).³⁰² Single-dose 2-g extended-release oral suspension is used only for the treatment of acute bacterial sinusitis and CAP in adults and is not for pediatric use.³⁰² If patient vomits within 5 minutes of taking the 2-g dose, consider additional anti-infective treatment since only minimal drug absorption would have occurred.³⁰² If patient vomits within 5–60 minutes after taking the dose, consider alternative anti-infective since insufficient data available regarding drug absorption under these circumstances.³⁰² If patient with normal gastric emptying vomits ≥60 minutes after taking the 2-g dose, additional azithromycin doses or alternative treatment not required.³⁰²

Reconstitution

Conventional oral suspension: Reconstitute 1-g single-dose packet for oral suspension with 60 mL of water.¹⁰ The entire contents should be ingested immediately and an additional 60 mL of water should be added, mixed, and ingested to ensure complete consumption of the dose.¹⁰

Conventional oral suspension: Reconstitute multiple-dose bottles for oral suspension at time of dispensing.¹ Add 9 mL of water to bottle containing 300 mg of azithromycin to provide a suspension of 100 g/5 mL.¹ Add 9, 12, or 15 mL of water to bottles containing 600 mg, 900 mg, or 1.2 g of azithromycin, respectively, to provide suspensions with 200 mg/5 mL.¹ Shake suspension well prior to administration of each dose.¹

Extended-release oral suspension: Reconstitute at time of dispensing.³⁰² Add 60 mL of water to bottle containing 2 g of azithromycin.³⁰² Shake suspension well at time of dispensing and immediately prior to consumption.³⁰² Entire bottle contents should be consumed as a single dose.³⁰²

IV Infusion

Administer by IV infusion.¹⁹⁶

Azithromycin for IV infusion must be reconstituted and then further diluted prior to administration.¹⁹⁶

Other IV substances, additives, or other drugs should not be added to azithromycin IV infusions and should not be infused simultaneously through the same IV line.¹⁹⁶

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute vial containing 500 mg of azithromycin by adding 4.8 mL of sterile water for injection and shaking the vial until the drug is dissolved.¹⁹⁶ Since the vial contains a vacuum, a standard (non-automated) 5-mL syringe should be used to ensure that exact amount of diluent is added during reconstitution.¹⁹⁶

Reconstituted solution contains 100 mg/mL.¹⁹⁶

Dilution

Dilute to a concentration of 1 or 2 mg/mL by adding reconstituted azithromycin solution to 250 or 500 mL of a compatible IV solution.¹⁹⁶ (See Solution Compatibility under Stability.)

Rate of Administration

Administer final solutions containing 1 mg/mL by IV infusion over 3 hours and those containing 2 mg/mL by IV infusion over 1 hour.¹⁹⁶ Do not give 500-mg doses by IV infusion over a period <1 hour.¹⁹⁶

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as azithromycin dihydrate; dosage expressed in terms of anhydrous azithromycin.¹ ¹⁰ ¹⁹⁶ ³⁰²

Pediatric Patients

Acute Otitis Media (AOM)

Oral

Children ≥6 months of age: 30 mg/kg as a single dose or 10 mg/kg once daily for 3 days.¹ Alternatively, 10 mg/kg as a single dose on day 1, followed by 5 mg/kg once daily on days 2–5.¹ ²⁹⁴

Pharyngitis and Tonsillitis

Oral

Children ≥2 years of age: 12 mg/kg (up to 500 mg) once daily for 5 days.¹ ⁹³

GI Infections†

Mild to Moderate Campylobacter jejuni Infections†

Oral

Adolescents: 500 mg once daily for 7 days recommended by CDC, NIH, and IDSA.³⁰⁸ If bacteremia is present, continue treatment for ≥2 weeks and consider use of a second anti-infective (e.g., an aminoglycoside).³⁰⁸

Cryptosporidiosis†

Oral

HIV-infected infants or children: 10 mg/kg as a single dose on day 1 followed by 5 mg/kg once daily (up to 600 mg daily) on days 2–10.³⁰⁷

HIV-infected adolescents: 10 mg/kg as a single dose on day 1 followed by 5 mg/kg once daily (up to 600 mg daily) on days 2–10.³⁰⁸

Optimum duration of treatment unknown;³⁰⁸ no anti-infective reliably eradicates Cryptosporidium.²⁰³ ²⁹⁰ ³⁰⁷ ³⁰⁸

Shigella Infections†

Oral

Children: 12 mg/kg (up to 500 mg) on day 1 followed by 6 mg/kg orally once daily (up to 250 mg daily) on days 2–5 has been used.³⁰⁸ ³¹⁸

Adolescents: 500 mg on day 1 followed by 250 mg once daily on days 2–5.³⁰⁸

Treatment of Travelers’ Diarrhea†

Oral

Empiric treatment in children: 10 mg/kg once daily for 3 days.³¹⁹ ³⁷²

Severe Diarrhea Caused by Enterotoxigenic Escherichia coli (ETEC)†

Oral

Children with severe or intractable diarrhea caused by susceptible strains: 10 mg/kg once daily for 2 days if use of an anti-infective is considered necessary.³⁵⁶

Respiratory Tract Infections

Acute Bacterial Sinusitis

Oral

Children ≥6 months of age: 10 mg/kg once daily for 3 days.¹

Community-acquired Pneumonia

Oral

Children ≥6 months of age: 10 mg/kg as a single dose on day 1, followed by 5 mg/kg once daily on days 2–5.¹ ²⁰³ Efficacy of shorter regimens (e.g., 1–3 days) for treatment of CAP in children has not been established.¹

Babesiosis†

Oral

10 mg/kg (up to 500 mg) once on day 1, then 5 mg/kg (up to 250 mg) once daily for total of 7–10 days recommended by IDSA; used in conjunction with atovaquone (20 mg/kg [up to 750 mg] twice daily for 7–10 days).²⁸⁸

Others suggest 12 mg/kg once daily for 7–10 days in conjunction with atovaquone (20 mg/kg daily in 2 divided doses for 7–10 days).¹²⁵

Bartonella Infections†

Cat Scratch Disease Caused by Bartonella henselae†

Oral

10 mg/kg on day 1 followed by 5 mg/kg once daily on days 2–5.³¹⁰

Bartonella Infections in HIV-infected Individuals†

Oral

Adolescents: 600 mg once daily for ≥3 months recommended by CDC, NIH, and IDSA.³⁰⁷ If relapse occurs, consider life-long secondary prophylaxis (chronic maintenance therapy) with erythromycin or doxycycline.³⁰⁷

Chancroid†

Oral

Children weighing <45 kg: 20 mg/kg (maximum 1 g) as a single dose.²⁰³

Children weighing ≥45 kg: 1 g as a single dose.²⁰³

Only limited data on efficacy of single-dose azithromycin regimen for treatment of chancroid in HIV-infected patients; use only if follow-up can be ensured.²⁴²

Chlamydial Infections

Uncomplicated Chlamydial Urethritis or Cervicitis†

Oral

Children <8 years of age weighing ≥45 kg: 1 g as a single dose.²⁰³ ²⁴²

Children ≥8 years of age: 1 g as a single dose.²⁰³ ²⁴²

Ocular Trachoma†

Oral

20 mg/kg (up to 1 g) as a single dose.²¹⁷ ³⁵³ ³⁵⁴ ³⁷⁰ ³⁷³ ³⁷⁵ Alternatively, 20 mg/kg once weekly for 3 weeks²⁰³ ²¹⁷ ³⁰¹ or 20 mg/kg once every 4 weeks for a total of 6 doses.²¹⁷

Single-dose regimen has been used in mass treatment programs,³⁷⁰ ³⁷³ ³⁷⁵ but multiple doses (e.g., once yearly for 3 years) may be necessary to minimize reservoirs of infection in high-prevalence areas.³⁵⁴ ³⁷⁰ ³⁷⁴ ³⁷⁵

Chlamydial Pneumonia in Infants†

Oral

20 mg/kg once daily for 3 days.⁸ ²⁰³

Chlamydial Conjunctivitis in Neonates†

Oral

20 mg/kg once daily for 3 days.⁸ ²⁴²

Legionella Infections†

IV

10 mg/kg (up to 500 mg) once daily for 5–10 days.²⁰³ If patient is improving, parenteral therapy may be switched to oral therapy.²⁰³

Leptospirosis†

Oral

Children 5–18 years of age: 15 mg/kg daily in 2 divided doses for 7 days has been used.³⁶⁵

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

10 mg/kg (up to 500 mg) once daily for 7–10 days.²⁸⁸ Macrolides generally less effective than first-line agents; monitor closely to ensure resolution of clinical manifestations.²⁸⁸

Mycobacterium avium Complex (MAC) Infections†

Primary Prevention of MAC in Children <13 Years of Age with Advanced HIV Infection

Oral

20 mg/kg (up to 1.2 g) once weekly or 5 mg/kg (up to 250 mg) once daily.²³⁴

Initiate primary prophylaxis if CD4⁺ T-cell count is <750/mm³ in those <1 year, <500/mm³ in those 1–2 years, <75/mm³ in those 2–6 years, or <50/mm³ in those ≥6 years of age.²³⁴

Safety of discontinuing primary MAC prophylaxis in children whose CD4⁺ T-cell counts have increased as a result of highly active antiretroviral therapy has not been studied to date.²³⁴

Primary Prevention of MAC in Adolescents with Advanced HIV Infection

Oral

1.2 g once weekly given alone.²³⁴

Initiate primary prophylaxis if CD4⁺ T-cell count is <50/mm³.²³⁴ May be discontinued if there is immune recovery in response to antiretroviral therapy with an increase in CD4⁺ T-cell count to >100/mm³ sustained for ≥3 months.²³⁴ Reinitiate prophylaxis if CD4⁺ T-cell count decreases to <50–100/mm³.²³⁴

Treatment of Disseminated MAC in HIV-infected Infants and Children†

Oral

10–12 mg/kg once daily (up to 500 mg daily) in conjunction with ethambutol (15–25 mg/kg once daily [up to 1 g daily]) with or without rifabutin (10–20 mg/kg once daily [up to 300 mg daily]) recommended by CDC, NIH, and IDSA.³⁰⁷

Treatment of Disseminated MAC in HIV-infected Adolescents†

Oral

500–600 mg once daily in conjunction with ethambutol (15 mg/kg once daily) with or without rifabutin (300–450 mg once daily) recommended by ATS, CDC, IDSA, and NIH.³⁰⁸

Prevention of MAC Recurrence in HIV-infected Children <13 Years of Age†

Oral

5 mg/kg (maximum 250 mg) once daily, given in conjunction with ethambutol (with or without rifabutin).²³⁴

Secondary prophylaxis to prevent MAC recurrence in HIV-infected children usually continued for life.²³⁴ The safety of discontinuing secondary MAC prophylaxis in children whose CD4⁺ T-cell count increases in response to antiretroviral therapy has not been studied.²³⁴

Prevention of MAC Recurrence in HIV-infected Adolescents†

Oral

500–600 mg once daily in conjunction with ethambutol (15 mg/kg once daily) with or without rifabutin (300 mg once daily) recommended by CDC, NIH, and IDSA.²³⁴ ³⁰⁸

Secondary prophylaxis to prevent MAC recurrence usually continued for life in HIV-infected adolescents.²³⁴ Consideration can be given to discontinuing such prophylaxis after ≥12 months in those who remain asymptomatic with respect to MAC and have an increase in CD4⁺ T-cell count to >100/mm³ sustained for ≥6 months.²³⁴

Pertussis†

Treatment or Postexposure Prophylaxis of Pertussis†

Oral

Infants <6 months of age^†: 10 mg/kg once daily for 5 days recommended by AAP and CDC.²⁰³ ³³⁴ Although only limited data available in infants <1 month of age, CDC states this dosage can be used when necessary for treatment or prophylaxis of pertussis in this age group.³³⁴

Children and infants ≥6 months of age: 10 mg/kg (up to 500 mg) once on day 1, followed by 5 mg/kg (up to 250 mg) once daily on days 2–5 recommended by CDC, AAP, and others.²⁰³ ³²⁴ ³²⁵ ³³⁴

Adolescents: 500 mg once on day 1, then 250 mg once daily on days 2–5 recommended by CDC and AAP.²⁰³ ³³⁴

Postexposure prophylaxis regimen is the same as the treatment regimen.²⁰³ ³³⁴ When used for postexposure prophylaxis, initiate within 3 weeks of exposure or onset of cough in the index patient.²⁰³ ³³⁴

Toxoplasmosis†

Oral

Adolescents: 900–1200 mg once daily in conjunction with pyrimethamine and leucovorin recommended by CDC, NIH, and IDSA.³⁰⁸

Continue acute treatment for ≥6 weeks;³⁰⁸ longer duration may be appropriate if disease is extensive or response incomplete at 6 weeks.³⁰⁸

Typhoid Fever and Other Salmonella Infections†

Oral

Children 3–17 years of age: 20 mg/kg (up to 1 g) once daily for 5–7 days.³²¹ ³²² Dosage of 10 mg/kg (up to 500 mg) once daily for 7 days also has been used.³⁶¹

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental or Respiratory Tract Procedures

Oral

15 mg/kg (up to 500 mg) as a single dose given 30–60 minutes prior to the procedure.²⁰¹

Prophylaxis in Sexual Assault Victims†

Oral

Adolescents: 1 g as a single dose in conjunction with IM ceftriaxone and oral metronidazole.²⁴²

Adults

Pharyngitis and Tonsillitis

Oral

500 mg as a single dose on day 1, followed by 250 mg once daily on days 2–5.¹

GI Infections†

Mild to Moderate Campylobacter jejuni Infections†

Oral

500 mg once daily for 7 days recommended by CDC, NIH, and IDSA.³⁰⁸ If bacteremia is present, continue treatment for ≥2 weeks and consider use of a second anti-infective (e.g., an aminoglycoside).³⁰⁸

Cryptosporidiosis†

Oral

HIV-infected adults: 600 mg once daily for 4 weeks; has been given in conjunction with paromomycin (1 g twice daily for 12 weeks).²⁵⁶

Shigella Infections†

Oral

500 mg on day 1 followed by 250 mg once daily on days 2–5.³⁰⁸ ³¹⁶ If bacteremia is present, continue for 14 days depending on the severity of infection.³⁰⁸

Treatment of Travelers’ Diarrhea†

Oral

Empiric treatment: 1 g as a single dose.³¹⁹ ³⁵⁹ ³⁶⁰ ³⁷² Alternatively, 500 mg once daily for 3 days.³¹⁹ ³⁵⁹ ³⁶⁰ ³⁷²

Respiratory Tract Infections

Acute Bacterial Sinusitis

Oral

Conventional tablets or oral suspension: 500 mg once daily for 3 days.¹

Extended-release oral suspension: 2 g given as a single dose.³⁰²

Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease

Oral

500 mg once daily for 3 days or, alternatively, 500 mg as a single dose on day 1, followed by 250 mg once daily on days 2–5.¹ ⁹⁶ ⁹⁷ ⁹⁸ ⁹⁹

Mild to Moderate Community-acquired Pneumonia

Oral

Conventional tablets or oral suspension: 500 mg as a single dose on day 1, followed by 250 mg once daily on days 2–5.¹ ³ ⁹⁶ ⁹⁷ ⁹⁸ ⁹⁹ ²¹¹

Extended-release oral suspension: 2 g given as a single dose.³⁰²

Moderate to Severe Community-acquired Pneumonia When IV therapy is Necessary

IV, then Oral

Initiate treatment with an IV regimen of 500 mg once daily given for ≥2 days;¹⁹⁶ ¹⁹⁷ then switch to an oral regimen of 500 mg once daily to complete 7–10 days of treatment.¹⁹⁶ ²⁵¹

Legionnaires’ Disease†

Oral

500 mg once daily.³¹¹ ³¹² ³¹⁴ Usual duration is 3–5 days for mild to moderate infections in immunocompetent patients; longer duration of treatment (at least 7–10 days or 3 weeks) may be necessary to prevent relapse in those with more severe infections or with underlying comorbidity or immunodeficiency.³¹¹ ³¹²

Skin and Skin Structure Infections

Oral

500 mg as a single dose on day 1, followed by 250 mg once daily on days 2–5.¹ ¹⁰ ¹⁰⁷ ¹⁰⁸

Babesiosis†

Oral

0.5–1 g once on day 1, then 250 mg once daily for total of 7–10 days recommended by IDSA; used in conjunction with atovaquone (750 mg twice daily for 7–10 days).²⁸⁸ Higher azithromycin dosage (0.6–1 g daily) may be used in immunocompromised patients.²⁸⁸

Others suggest 600 mg once daily for 7–10 days in conjunction with atovaquone (750 mg twice daily for 7–10 days).¹²⁵

Bartonella Infections†

Cat Scratch Disease Caused by Bartonella henselae†

Oral

500 mg on day 1 followed by 250 mg once daily on days 2–5.³¹⁰

Bartonella Infections in HIV-infected Patients

Oral

600 mg once daily for ≥3 months recommended by CDC, NIH, and IDSA.³⁰⁸ If relapse occurs, consider life-long secondary prophylaxis (chronic maintenance therapy) with erythromycin or doxycycline.³⁰⁸

Chancroid

Oral

1 g as a single dose.¹ ⁸ ²⁴²

Only limited data on efficacy of single-dose azithromycin regimen for treatment of chancroid in HIV-infected patients; use only if follow-up can be ensured.²⁴²

Chlamydial Infections

Uncomplicated Chlamydial Urethritis or Cervicitis

Oral

1 g as a single dose.¹ ⁷ ⁸ ¹⁰ ¹⁰⁹ ¹¹² ¹¹⁴ ¹⁸⁴ ¹⁸⁵ ²⁴²

Recurrent or Persistent Urethritis

Oral

CDC recommends a single 1-g dose in conjunction with a single 2-g dose of oral metronidazole or tinidazole.²⁴²

Ocular Trachoma†

Oral

20 mg/kg (up to 1 g) as a single dose.¹¹² ¹¹⁴ ¹⁸⁹ ³⁵³ ³⁵⁴ ³⁷⁰ Alternatively, 1 g once weekly for 3 weeks.³⁰¹

Lymphogranuloma Venereum†

Oral

1 g once weekly for 3 weeks may be effective.²⁴²

Cholera†

Oral

A single dose of 1 g has been used for treatment of cholera caused by V. cholerae O1 or O139.³⁵⁰

Gonorrhea

Uncomplicated Gonorrhea

Oral

2 g as a single dose.¹ ¹⁸² ¹⁸³ ¹⁹¹ ²⁴² ³⁷¹ Because of concerns regarding rapid emergence of macrolide resistance, do not use lower dosage and use only when necessary.²⁴² ³⁷¹ (See Gonorrhea under Uses).

Granuloma Inguinale (Donovanosis)†

Oral

1 g once weekly for at least 3 weeks or until all lesions have healed completely;²²¹ ²⁴² consider adding IV aminoglycoside (e.g., 1 mg/kg of gentamicin IV every 8 hours) in HIV-infected individuals or if improvement is not evident within the first few days of treatment.²⁴² Despite effective anti-infective therapy, relapse may occur 6–18 months later.²⁴²

Leptospirosis†

Oral

1 g as a single dose on day 1 followed by 500 mg once daily for 2 days.³⁶³ Alternatively, 15 mg/kg daily in 2 divided doses for 7 days has been used.³⁶⁵

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

500 mg once daily for 7–10 days.²⁸⁸ Macrolides generally less effective than first-line agents; monitor closely to ensure resolution of clinical manifestations.²⁸⁸

Mycobacterium avium Complex (MAC) Infections

Primary Prevention of MAC in Adults with Advanced HIV Infection

Oral

1.2 g once weekly.¹⁰ ²³³ ²³⁴ Usually given alone, but has been given in conjunction with rifabutin.¹⁰ ²³³ ²³⁴

ATS, IDSA, and others recommend initiating primary prophylaxis if CD4⁺ T-cell count is <50/mm³.²³³ ²³⁴ May be discontinued if there is immune recovery in response to antiretroviral therapy with an increase in CD4⁺ T-cell count to >100/mm³ sustained for ≥3 months.²³³ ²³⁴ Reinitiate prophylaxis if CD4⁺ T-cell count decreases to <50–100/mm³.²³³ ²³⁴

Treatment of Disseminated MAC in HIV-infected Adults

Oral

Manufacturer recommends 600 mg once daily in conjunction with ethambutol (15 mg/kg daily), with or without an additional antimycobacterial.¹⁰

ATS, CDC, NIH, and IDSA recommend 500–600 mg once daily in conjunction with ethambutol (15 mg/kg once daily) with or without rifabutin (300 mg once daily).²³³ ³⁰⁸

Prevention of MAC Recurrence in HIV-infected Adults†

Oral

500–600 mg once daily in conjunction with ethambutol (15 mg/kg once daily) with or without rifabutin (300 mg once daily) recommended by CDC, NIH, and IDSA.²³⁴ ³⁰⁸

Secondary prophylaxis to prevent MAC recurrence usually continued for life in HIV-infected adults.²³³ ²³⁴ Consideration can be given to discontinuing such prophylaxis after ≥12 months in those who remain asymptomatic with respect to MAC and have an increase in CD4⁺ T-cell count to >100/mm³ sustained for ≥6 months.²³³ ²³⁴ Reinitiate prophylaxis if CD4⁺ T-cell count decreases to <100/mm³.²³³

Initial Treatment of Pulmonary MAC Infections (Nodular/bronchiectatic Disease) Caused by Macrolide-susceptible Strains†

Oral

500–600 mg 3 times weekly in conjunction with ethambutol (25 mg/kg 3 times weekly) and rifampin (600 mg 3 times weekly) recommended by ATS and IDSA.²³³ Continue until patient has been culture negative on treatment for 1 year.²³³

Intermittent (3-times-weekly) regimen is not recommended for those with cavitary or moderate or severe disease or those who have been previously treated.²³³

Initial Treatment of Pulmonary MAC Infections (Fibrocavitary or Severe Nodular/bronchiectatic Disease) Caused by Macrolide-susceptible Strains†

Oral

250–300 mg once daily in conjunction with ethambutol (15 mg/kg once daily) and either rifampin (450–600 mg once daily) or rifabutin (150–300 mg once daily) recommended by ATS and IDSA.²³³ Continue until patient has been culture negative on treatment for 1 year.²³³ Consideration can be given to including amikacin or streptomycin 3 times weekly during the first 2–3 months of treatment for extensive disease, especially fibrocavitary disease, or when previous therapy has failed.²³³

Mycobacterium abscessus Infections†

Oral

250 mg daily in conjunction with parenteral amikacin, cefoxitin, or imipenem.²³³ Duration of therapy should be at least 4 months for serious infections; a duration of 6 months is recommended for bone infections.²³³

Neisseria meningitidis Infections†

Elimination of Nasopharyngeal Carrier State†

Oral

500 mg as a single dose.³⁴⁶ ³⁴⁹

Pelvic Inflammatory Disease

IV, then Oral

500 mg IV once daily for 1–2 days, followed by 250 mg orally once daily to complete 7 days of therapy.¹⁹⁶ If anaerobic bacteria are suspected, an anti-infective active against anaerobes should also be used.¹⁹⁶

Pertussis†

Treatment or Postexposure Prophylaxis of Pertussis†

Oral

500 mg once on day 1, then 250 mg once daily on days 2–5 recommended by CDC and AAP.²⁰³ ³³⁴

Scrub Typhus†

Oral

500 mg as a single dose.³⁶² ³⁶⁴ Alternatively, 1 g as a single dose on day 1, then 500 mg once daily for 2 days.³⁶³

Syphilis†

Treatment of Primary or Secondary Syphilis in Penicillin-allergic Patients†

Oral

2 g as a single dose;²⁴² ²⁹³ ³⁰⁸ close follow-up is essential since efficacy not well documented.⁸ ²⁴² ²⁹³ ³⁰⁸

Toxoplasmosis†

Oral

900–1200 mg once daily in conjunction with pyrimethamine and leucovorin recommended by CDC, NIH, and IDSA.³⁰⁸

Continue acute treatment for ≥6 weeks;³⁰⁸ longer duration may be appropriate if disease is extensive or response incomplete at 6 weeks.³⁰⁸

Typhoid Fever and Other Salmonella Infections†

Oral

1 g once daily for 5 days.³²³ Alternatively, 8–10 mg/kg (up to 500 mg) once daily for 7 days.³³² ³⁶¹

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental or Respiratory Tract Procedures†

Oral

500 mg as a single dose given 30–60 minutes prior to the procedure.²⁰¹

Prophylaxis in Sexual Assault Victims†

Oral

1 g as a single dose in conjunction with IM ceftriaxone and oral metronidazole.²⁴²

Special Populations

Hepatic Impairment

Manufacturer states dosage recommendations not available.¹ ¹⁰ ¹⁹⁶ ³⁰² Some clinicians state dosage adjustments not necessary in patients with class A or B liver cirrhosis.¹⁷³

Use caution;¹ ³ ¹⁰ ¹⁹⁶ ²¹⁰ ²¹¹ pharmacokinetics in hepatic impairment not completely established.¹ ¹⁰ ¹⁹⁶

Renal Impairment

Dosage adjustment not necessary.¹ ¹⁰ ¹⁹⁶ ³⁰²

Use caution in severe renal impairment (GFR <10 mL/minute) because of limited data.¹ ¹⁰ ¹⁹⁶ ³⁰²

Geriatric Patients

Dosage adjustments not usually necessary in geriatric patients with normal renal and hepatic function receiving conventional or extended-release formulations.¹ ¹⁰ ⁷⁰ ²⁰² ³⁰²

Cautions for Azithromycin Dihydrate

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Known hypersensitivity to azithromycin, erythromycin, any macrolide, or any ketolide.¹ ¹⁰ ¹⁹⁶ ³⁰²

Warnings/Precautions

Warnings

Severe Pneumonia

Should not be used orally for treatment of moderate to severe pneumonia or when there are risk factors that make oral therapy inappropriate (e.g., cystic fibrosis, nosocomial infection, known or suspected bacteremia, illness requiring hospitalization, geriatric or debilitated status, immunodeficiency or functional asplenia or other underlying conditions that may compromise ability to respond to treatment).¹ ¹⁰

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹ ¹⁰ ¹⁹⁶ ³⁰² Institute appropriate therapy if superinfection occurs.¹ ¹⁰ ¹⁹⁶

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.¹ ¹⁰ ¹⁹⁶ ³⁰² C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including azithromycin, and may range in severity from mild diarrhea to fatal colitis.¹ ¹⁰ ¹⁹⁶ ³⁰² Hyper toxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹ ¹⁰ ¹⁹⁶ ³⁰²

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.¹ ¹⁰ ¹⁹⁶ ³⁰² Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.¹ ¹⁰ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁶⁷ ³⁰²

If CDAD is suspected or confirmed, azithromycin may need to be discontinued.¹ ¹⁰ ¹⁹⁶ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁶⁷ ³⁰² Some mild cases may respond to discontinuance alone.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁶⁷ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.¹ ¹⁰ ¹⁹⁶ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁶⁷ ³⁰²

Sensitivity Reactions

Hypersensitivity and Dermatologic Reactions

Serious allergic and dermatologic reactions (e.g., angioedema, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have occurred.¹ ¹⁰ ¹⁹⁶ ³⁰² Fatalities reported.¹ ¹⁰ ¹⁹⁶ ³⁰²

If a hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).¹ ¹⁰ ¹⁹⁶ ³⁰²

Despite initially successful symptomatic management of allergic reactions, symptoms have recurred soon after symptomatic treatment was discontinued; the relationship between these episodes and the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown.¹ ¹⁰ ¹⁹⁶ ³⁰²

General Precautions

Cardiac Effects

Prolonged cardiac repolarization and QT interval with risk of cardiac arrhythmia and torsades de pointes reported with some macrolides.¹ ¹⁰ ¹⁹⁶ ³⁰² Possibility of such effects with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarization.¹ ¹⁰ ¹⁹⁶ ³⁰²

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of azithromycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹ ¹⁰ ¹⁹⁶ ³⁰²

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ ¹⁰ ¹⁹⁶ ³⁰² In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹ ¹⁰ ¹⁹⁶ ³⁰²

Because S. pyogenes (group A β-hemolytic streptococci) resistant to azithromycin have been reported, in vitro susceptibility tests should be performed when the drug is used for treatment of pharyngitis and tonsillitis.¹

Sodium Content

Conventional tablets: Each 250- or 500-mg tablet contains 0.9 or 1.8 mg of sodium, respectively,¹ and each 600 mg tablet contains 2.1 mg of sodium.¹⁰

Conventional oral suspension: Each 5 mL containing 100 or 200 mg of azithromycin contains 3.7 or 7.4 mg of sodium, respectively.¹ The single-dose 1-g oral suspension contains 37 mg of sodium per package.¹⁰

Extended-release oral suspension: 2-g dose contains 148 mg (6.43 mEq) of sodium.³⁰²

IV infusion: Each vial contains 114 mg (4.96 mEq) of sodium.¹⁹⁶ (See Geriatric Use under Cautions.)

Specific Populations

Pregnancy

Category B.¹ ¹⁰ ¹⁹⁶ ³⁰²

Lactation

Distributed into milk; ¹⁴⁴ use with caution.¹ ¹⁰ ¹⁹⁶ ³⁰²

Pediatric Use

Conventional tablets and oral suspension: Safety and efficacy not established for treatment of pharyngitis and tonsillitis in children <2 years of age¹ or for treatment of AOM in children <6 months of age.¹

Conventional tablets and oral suspension: Safety and efficacy of oral azithromycin not established for treatment of acute maxillary sinusitis in children <6 months of age.¹ Use for sinusitis in those ≥6 months of age is supported by evidence from adequate and well-controlled studies in adults, similar pathophysiology of acute sinusitis in adults and pediatric patients, and studies of AOM in pediatric patients.¹

Conventional tablets and oral suspension: Safety and efficacy of oral azithromycin not established for treatment of acute community-acquired pneumonia in children <6 months of age.¹ Safety and efficacy for pneumonia caused by C. pneumoniae or M. pneumoniae were documented in pediatric trials; although safety and efficacy for pneumonia caused by H. influenzae or S. pneumoniae were not documented in pediatric trials, use for infections caused by these bacteria is supported by evidence from adequate and well-controlled studies in adults.¹

Extended-release oral suspension: Safety and efficacy not established in pediatric patients.³⁰²

IV azithromycin: Safety and efficacy not established in children or adolescents <16 years of age.¹⁹⁶

Manufacturer states that safety and efficacy of azithromycin not established for prevention or treatment of MAC infection in HIV-infected pediatric patients,¹⁰ but some experts recommend use of the drug for HIV-infected infants and children.²³⁴

Adverse effects reported in pediatric patients are similar to those reported in adults and generally involve the GI tract.¹ ¹⁰ Treatment-related reversible hearing impairment reported in some HIV-infected children receiving the drug for treatment of opportunistic infections.¹⁰

Geriatric Use

No overall differences in safety and efficacy of oral azithromycin in those ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.¹ ¹⁰ ³⁰²

When used in a dosage >300 mg daily for a mean of 207 days for the treatment of various opportunistic infections (including MAC) in adults 65–94 years of age, adverse effect profile generally was similar to that in younger adults, except for a higher incidence of adverse GI effects and reversible hearing impairment.¹⁰

No overall differences in safety of IV azithromycin in those ≥65 years of age compared with younger adults; similar decreases in clinical response were noted with increasing age in both azithromycin- and comparator-treated patients.¹⁹⁶

Azithromycin preparations contain sodium.¹ ¹⁰ ¹⁹⁶ ³⁰² (See Sodium Content under Cautions.) Patients receiving the usual IV dosage will receive 114 mg (4.96 mEq) of sodium per dose.¹⁹⁶ Geriatric patients may respond to salt loading with blunted natriuresis,¹⁹⁶ and the total sodium content from dietary and nondietary sources may be clinically important with regard to such diseases as congestive heart failure.¹⁹⁶

Hepatic Impairment

Use caution.¹ ¹⁰ ¹⁹⁶ ³⁰²

Pharmacokinetics not studied in hepatic impairment, but the drug is principally eliminated by the liver.¹ ¹⁰ ¹⁹⁶

Renal Impairment

Because of limited data, use caution if GFR <10 mL/minute.¹ ¹⁰ ¹⁹⁶ ³⁰²

Clearance is decreased in severe renal impairment.¹ ¹⁰ ¹⁹⁶ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Adverse GI effects, including diarrhea/loose stools, nausea, vomiting, abdominal pain.¹ ³ ¹⁰ ¹⁰⁸ ¹¹⁰ ¹³² ¹⁵⁵ ¹⁹⁶ ²¹⁰ ²¹¹ ³⁰² Adverse GI effects occur more frequently with single-dose regimens (1 or 2 g) than multiple-dose regimens.¹ ¹⁰

Adverse effects reported with long-term azithromycin used for prevention of MAC infection are similar to those reported with short-term dosage regimens but also included reversible hearing impairment.¹⁰

Local reactions (pain, inflammation) with IV administration.¹⁹⁶

Drug Interactions

Does not appear to have an effect on CYP isoenzymes.⁶⁵ ⁶⁷ ¹⁶² ²¹¹

Many drug interactions reported with other macrolides (e.g., erythromycin, clarithromycin) have not been reported to date with azithromycin.¹ ¹⁰ ¹³² ¹⁶² ¹⁹⁶ ²¹¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Although pharmacokinetic interactions with substrates, inhibitors, or inducers of CYP isoenzymes have been reported with other macrolides (e.g., clarithromycin), they have not been reported to date with azithromycin.¹ ¹⁰ ⁶⁵ ⁶⁷ ¹⁶² ¹⁹⁶ ²¹¹ Azithromycin appears to have no effect on the CYP isoenzyme system and interactions mediated by this enzyme system would not be expected to occur.¹⁶² ²¹¹ However, the possibility that such drug interactions may occur cannot be ruled out.¹ ¹⁰ ¹⁹⁶ ²¹¹

Specific Drugs

Drug	Interaction	Comments
Albendazole	Increased peak plasma concentration and AUC of azithromycin when azithromycin, albendazole, and ivermectin given concomitantly³⁵⁵	Effect on azithromycin not considered clinically important³⁵⁵
Antacids (aluminum- and magnesium-containing)	Conventional tablets or oral suspension: Decreased azithromycin plasma concentrations; AUC unaffected¹ ¹⁰ ¹⁴⁶ Extended-release oral suspension: Rate and extent of azithromycin absorption not affected³⁰²	Conventional tablets or oral suspension: Simultaneous administration with aluminum- or magnesium-containing antacids not recommended¹ ¹⁰ Extended-release oral suspension: May be taken without regard to aluminum- or magnesium-containing antacids³⁰²
Anticoagulants, oral	Does not appear to affect PT response to a single warfarin dose;¹ ¹⁰ ¹⁹⁶ increased anticoagulant effects reported rarely with azithromycin¹⁹² and also reported with other macrolides¹ ¹⁰ ¹⁹⁶	Monitor PT carefully when used with warfarin¹ ¹⁰ ¹⁹⁶ ³⁰²
Antimycobacterials, rifamycins (rifabutin)	Modest effect on rifabutin pharmacokinetics¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Atazanavir	Clinically important pharmacokinetic interactions not expected²⁹⁹
Benzodiazepines (midazolam, triazolam)	Modest effect on pharmacokinetics of midazolam or triazolam;¹ ¹⁹⁶ decreased clearance of triazolam and increased pharmacologic effect reported with other macrolides¹⁰	No dosage adjustment recommended¹ ¹⁰ ¹⁹⁶ ³⁰²
Carbamazepine	Modest effect on pharmacokinetics of carbamazepine;¹ ¹⁹⁶ ¹⁴⁷ ¹⁴⁸ increased carbamazepine concentrations reported with other macrolides¹⁰	No dosage adjustment recommended;¹ ¹⁹⁶ ³⁰² monitor closely¹⁰
Cetirizine	Modest effect on pharmacokinetics of cetirizine¹ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Chloroquine	No clinically important pharmacokinetic interactions between chloroquine and azithromycin³³⁸ In vitro evidence of additive to synergistic effects against P. falciparum, including multidrug-resistant strains³³⁹ ³⁵⁷
Cimetidine	No effect on azithromycin absorption if cimetidine given 2 hours prior to azithromycin ¹ ¹⁰ ¹⁴⁶
Co-trimoxazole	Modest effect on pharmacokinetics of co-trimoxazole;¹ ¹⁰ no clinically important effect on pharmacokinetics of azithromycin	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Cyclosporine	No interaction studies with azithromycin; ¹ ¹⁰ ¹⁹⁶ increased cyclosporine concentrations reported with other macrolides ¹ ¹⁰ ¹⁹⁶	Monitor carefully¹ ¹⁰ ¹⁹⁶
Didanosine	Modest or no effect on pharmacokinetics of didanosine¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Digoxin	No interaction studies with azithromycin; ¹ ¹⁰ ¹⁹⁶ increased digoxin concentrations reported with other macrolides¹ ¹⁰ ¹⁹⁶	Monitor carefully¹ ¹⁰ ¹⁹⁶
Efavirenz	Modest or no effect on efavirenz and azithromycin pharmacokinetics¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Ergot alkaloids (ergotamine, dihydroergotamine)	No interaction studies with azithromycin;¹ ¹⁰ ¹⁹⁶ acute ergot toxicity (severe peripheral vasospasm and dysesthesia)reported with other macrolides¹ ¹⁰ ¹⁹⁶	Monitor carefully¹ ¹⁰ ¹⁹⁶
Fluconazole	Modest or no effect on pharmacokinetics of azithromycin and fluconazole ¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Hexobarbital	No interaction studies with azithromycin; ¹⁰ ¹⁹⁶ increased hexobarbital concentrations reported with other macrolides ¹⁰ ¹⁹⁶	Monitor carefully¹⁰ ¹⁹⁶
HMG-CoA reductase inhibitors (atorvastatin)	Modest effect on pharmacokinetics of atorvastatin¹ ¹⁹⁶ Rhabdomyolysis reported with lovastatin²²⁹	No dosage adjustment recommended;¹ ¹⁹⁶ ³⁰² monitor closely²²⁹
Indinavir	Modest or no effect on pharmacokinetics of indinavir¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Ivermectin	Increased peak plasma concentrations and AUC of azithromycin and ivermectin when azithromycin, ivermectin, and albendazole given concomitantly³⁵⁵	Effect on azithromycin not considered clinically important; additional study needed regarding effect on pharmacokinetics of ivermectin³⁵⁵
Lopinavir	Clinically important pharmacokinetic interactions not expected³⁰⁰
Nelfinavir	Decreased AUC of nelfinavir and its M8 metabolite; increased plasma concentrations and AUC of azithromycin¹⁰ ¹⁹⁶	No dosage adjustment recommended;¹⁰ ¹⁹⁶ ³⁰² closely monitor for adverse effects of azithromycin (e.g., liver enzyme abnormalities, hearing impairment)¹⁰ ¹⁹⁶ ³⁰²
Phenytoin	No interaction studies with azithromycin;¹ ¹⁰ ¹⁹⁶ increased phenytoin concentrations reported with other macrolides¹ ¹⁰ ¹⁹⁶	Monitor carefully¹ ¹⁰ ¹⁹⁶
Pimozide	Potential increased pimozide plasma concentrations and risk of prolonged QT interval and serious cardiac arrhythmias reported with other macrolides²⁴³ ²⁴⁴ ²⁴⁵	Manufacturer of pimozide states concomitant use contraindicated²⁴⁵
Quinine	In vitro evidence of additive to synergistic effects against P. falciparum, including multidrug-resistant strains³³⁹ ³⁴⁰ ³⁵⁷
Sildenafil	Modest effect on sildenafil pharmacokinetics¹ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁹⁶ ³⁰²
Theophylline	Modest or no effect on theophylline pharmacokinetics;¹ ¹⁰ ¹⁹⁶ increased theophylline concentrations have been reported with other macrolides¹⁰	No dosage adjustment recommended;¹ ¹⁹⁶ ³⁰² closely monitor theophylline concentrations¹⁰
Zidovudine	Modest effect on zidovudine pharmacokinetics¹ ¹⁰ ¹⁹⁶	No dosage adjustment recommended¹ ¹⁰ ¹⁹⁶ ³⁰²

Azithromycin Dihydrate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract.¹ ⁶⁵ ⁶⁶ ⁶⁷ ⁶⁸ ²¹¹

Conventional tablets or oral suspension: Absolute oral bioavailability is 34–52%.¹⁰ ⁶⁶ ⁶⁷ ⁶⁸ ¹³¹ ¹⁶³ ¹⁷⁰ ¹⁹⁶ ²⁰⁰ Peak serum concentrations attained about 2 hours after an oral dose.¹

Extended-release oral suspension: Bioavailability is approximately 83% of that reported with conventional oral suspension.³⁰² Peak serum concentrations attained a median of 5 hours (range: 2–8 hours) after an oral dose (about 2.5 hours later than that reported with conventional oral suspension).³⁰²

Extended-release oral suspension not bioequivalent to conventional oral suspension or tablets.³⁰²

A single 500-mg conventional tablet is bioequivalent to two 250-mg conventional tablets.¹

Food

Conventional tablets or oral suspension: Food may increase peak plasma concentrations and rate of absorption, but does not change extent of absorption (AUC).¹ ¹⁰ ¹⁷⁰

Extended-release oral suspension: Administration with high-fat or standard meal increases mean peak concentrations by 115 or 119%, respectively, and increases AUC by 23 or 12%, respectively, compared with administration in the fasted state.³⁰²

Distribution

Extent

Distributed into most tissues and fluids following oral or IV administration, including skin, lungs, sputum, tonsils, and cervix.¹ ¹⁰ ⁶⁵ ⁶⁶ ⁶⁷ ⁶⁸ ⁷¹ ¹³¹ ¹⁶³ ¹⁶⁴ ¹⁹⁶ Tissue concentrations generally exceed plasma concentrations by at least 10- to 100-fold.¹ ¹⁰ ⁶⁵ ⁶⁶ ⁶⁷ ⁸⁴ ¹⁶³ ¹⁶⁴

Only low concentrations detected in CSF in the presence of noninflamed meninges.¹ ¹⁰ ¹⁹⁶

Crosses the placenta and is distributed into cord blood and amniotic fluid.³⁶⁸ ³⁶⁹

Distributed into milk.¹⁴⁴

Plasma Protein Binding

51% at plasma azithromycin concentration of 0.02 mcg/mL; 7% at concentration of 2 mcg/mL.¹ ¹⁰ ⁶⁵ ⁶⁶ ⁶⁷ ¹³¹ ¹⁶³ ¹⁹⁶

Elimination

Metabolism

At least 10 microbiologically inactive metabolites identified.⁶⁵ ⁶⁶ ⁶⁷ ²¹⁰ ²¹¹

Elimination Route

Biliary excretion as unchanged drug is a major route of elimination.¹ ¹⁰ ¹⁹⁶ Excreted in feces principally as unchanged drug.⁶⁵ ⁶⁶ ⁶⁷ ⁶⁸ ¹⁶³ ²¹⁰ ²¹¹

Only a small portion (approximately 6%) of a dose excreted in urine as unchanged drug.¹ ¹⁰ ⁶⁶ ⁶⁷ ¹³¹ ¹⁶³ ¹⁹⁶ ²¹¹ ²⁵¹

Half-life

Conventional tablets or oral suspension: Terminal serum half-life averages 68–72 hours.¹ ¹⁰ ¹³¹ ¹⁶³ ¹⁹⁶ ¹⁹⁸

Extended-release oral suspension: Terminal serum half-life averages 59 hours.³⁰²

The prolonged terminal half-life apparently occurs because of extensive uptake and subsequent release from tissues.¹

Tissue half-life averages 1–4 days;⁶⁵ ⁶⁶ ⁶⁷ ¹³¹ half-life in peripheral leukocytes averages 34–57 hours.¹⁰

Special Populations

Pharmacokinetics of conventional oral preparations in men 65–85 years of age similar to that in younger adults.¹ ¹⁰ ⁷⁰ Peak plasma concentrations of conventional oral preparations may be 30–50% higher in geriatric women compared with younger adults, but clinically important accumulation does not occur.¹ ¹⁰ Pharmacokinetics of extended-release oral suspension not evaluated in geriatric patients.³⁰²

Pharmacokinetics in hepatic impairment not fully established.¹ ¹⁹⁶ ³⁰² In patients with moderate hepatic impairment, mean residence time prolonged, but other pharmacokinetic parameters (clearance, volume of distribution, AUC) similar to those in healthy individuals.¹⁶³ ¹⁷³ ²¹¹

Compared with adults with normal renal function, peak plasma concentrations and AUC are increased by 5.1 and 4.2%, respectively, in adults with GFR 10–80 mL/minute and by 61 and 35%, respectively, in adults with severe renal impairment (GFR <10 mL/minute).¹ ¹⁰ ¹⁹⁶

Stability

Storage

Oral

Conventional Powder For Suspension

Single-dose packets: 5–30°C.¹⁰ Use oral solution immediately after reconstitution.¹⁰

Multiple-dose bottles: <30°C.¹ Following reconstitution, 5–30°C and use within 10 days; discard when full dosing is completed.¹

Conventional Tablets

15–30°C.¹ ¹⁰

Extended-release Microspheres For Suspension

Single-dose bottle: ≤30°C.³⁰² Following reconstitution, store in original bottle at 25°C (may be exposed to 15–30°C) and consume within 12 hours.³⁰² Do not refrigerate or freeze reconstituted suspension.³⁰²

Parenteral

Powder for Infusion

Following reconstitution and dilution, store at room temperature (≤30°C) for 24 hours or refrigerate at 5°C for 7 days.¹⁹⁶

Compatibility

Parenteral

Solution Compatibility

For dilution of reconstituted azithromycin injection:

Compatible
Dextrose 5% in Ringer’s injection, lactated¹⁹⁶ ^HID
Dextrose 5% in sodium chloride 0.3¹⁹⁶ or 0.45%¹⁹⁶ ^HID
Dextrose 5% in sodium chloride 0.45% with 20 mEq KCl¹⁹⁶
Dextrose 5% in water¹⁹⁶ ^HID
Normosol M in dextrose 5%¹⁹⁶ ^HID
Normosol R in dextrose 5%¹⁹⁶ ^HID
Ringer’s injection, lactated¹⁹⁶ ^HID
Sodium chloride 0.45 or 0.9%¹⁹⁶ ^HID

Drug Compatibility

Admixture CompatibilityHID
Incompatible
Ciprofloxacin

Y-Site CompatibilityHID
Compatible
Bivalirudin
Caspofungin acetate
Ceftaroline fosamil
Dexmedetomidine HCl
Diphenhydramine HCl
Dolasetron mesylate
Doripenem
Droperidol
Hetastarch in lactated electrolyte injection (Hextend)
Ondansetron HCl
Telavancin HCl
Tigecycline
Incompatible
Amikacin sulfate
Aztreonam
Cefotaxime sodium
Ceftazidime
Ceftriaxone sodium
Cefuroxime sodium
Ciprofloxacin
Clindamycin phosphate
Famotidine
Fentanyl citrate
Furosemide
Gentamicin sulfate
Imipenem-cilastatin sodium
Ketorolac tromethamine
Levofloxacin
Morphine sulfate
Piperacillin sodium-tazobactam sodium
Potassium chloride
Ticarcillin disodium-clavulanate potassium
Tobramycin sulfate

Actions and Spectrum

An azalide macrolide with a broader spectrum of activity than other macrolides (erythromycin, clarithromycin).³ ⁶⁵ ¹⁶³ ¹⁹⁸ ²⁰⁴ ²⁰⁷ ²⁰⁹ ²¹⁰ ²¹¹ ²¹²
Usually bacteriostatic, but may be bactericidal against some organisms at high concentrations.³ ¹⁸ ²⁹ ¹⁶³ ²¹¹ ²¹² ²¹⁶
Like other macrolide antibacterials, inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits.¹ ³ ¹⁰ ²⁹ ¹⁶³ ¹⁶⁴ ¹⁶⁷ ¹⁹⁶ ²¹¹ ²¹⁶
Spectrum of activity includes many gram-positive and -negative aerobic and anaerobic bacteria and some other organisms (e.g., Mycobacterium, Chlamydia, Mycoplasma avium complex [MAC]).¹ ³ ⁵ ¹⁰ ²⁹ ³³ ³⁴ ³⁹ ⁴⁰ ⁴¹ ⁸⁹ ¹⁶³ ¹⁶⁴ ¹⁶⁶ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹ ¹⁹⁶ ²⁰⁶ ²¹⁰ ²¹¹ ²¹⁴
More active than erythromycin or clarithromycin against gram-negative bacteria; activity comparable to erythromycin against gram-positive bacteria.³ ²⁹ ¹⁶³ ¹⁶⁴ ²⁰⁴ ²⁰⁷ ²¹⁰ ²⁵⁰
Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus aureus,¹ ¹⁰ ¹⁹⁶ S. pneumoniae,¹ ¹⁰ ¹⁹⁶ S. pyogenes (group A β-hemolytic streptococci),¹ ¹⁰ and S. agalactiae (group B streptococci).¹ ¹⁰ Also active in vitro against some other streptococci (e.g., groups C, F, and G streptococci, viridans streptococci).¹ Enterococci (e.g., Enterococcus faecalis) and oxacillin-resistant (methicillin-resistant) staphylococci are resistant.¹ ¹⁰
Gram-negative aerobes: Active in vitro and in clinical infections against Haemophilus influenzae,¹ ¹⁰ ¹⁹⁶ H. ducreyi,¹ Moraxella catarrhalis,¹ ¹⁰ ¹⁹⁶ and Neisseria gonorrhoeae.¹ ¹⁹⁶ Also active in vitro against N. meningitidis³⁴⁶ ³⁴⁸ and some strains of Bordetella pertussis¹ and Legionella pneumophila.¹ ¹⁹⁶
Other organisms: Active in vitro and in clinical infections against C. pneumoniae,¹ ¹⁹⁶ C. trachomatis,¹ ¹⁰ ¹⁹⁶ M. pneumoniae,¹ ¹⁹⁶ and M. hominis.¹⁹⁶ Also active against MAC,³ ⁵ ¹⁰ ¹¹ ³⁹ ⁴⁰ ⁴¹ ⁸⁹ ¹¹¹ ¹⁶⁵ ¹⁶⁶ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹ Borrelia burgdorferi,³ ¹⁰ ²⁶ ⁴⁶ ⁴⁷ ⁸⁸ ²¹⁰ ²¹¹ Toxoplasma gondii,⁴⁸ ⁴⁹ ⁵⁰ ⁵¹ ⁵² ²¹² Plasmodium falciparum,³⁴⁰ ³⁵⁷ Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi),³⁶⁶ Rickettsia conorii,³⁶⁷ R. typhi,³⁶⁷ and Coxiella burnettii.³⁶⁷
Streptococci and staphylococci resistant to erythromycin usually are cross-resistant to azithromycin.¹ ¹⁰ ²⁹ ¹⁶³ ¹⁹⁶ ²⁰⁷ ²¹⁰ ²¹² ²¹³
Complete cross-resistance occurs between azithromycin and clarithromycin in MAC.¹⁰

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Advise patients that antibacterials (including azithromycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹ ¹⁰ ¹⁹⁶ ³⁰²
Importance of completing full course of therapy, even if feeling better after a few days.¹ ¹⁰ ¹⁹⁶ ³⁰²
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with azithromycin or other antibacterials in the future.¹ ¹⁰ ¹⁹⁶ ³⁰²
Conventional tablets or oral suspension can be taken without regard to meals.¹ ¹⁰ Extended-release oral suspension should be taken on an empty stomach (at least 1 hour before or 2 hours after a meal).³⁰²
Importance of not taking aluminum- or magnesium-containing antacids at the same time as conventional tablets or oral suspension.¹ ¹⁰ Extended-release oral suspension can be taken without regard to aluminum- or magnesium-containing antacids.³⁰²
Advise patients taking the extended-release oral suspension about the importance of contacting their clinician for additional treatment if they vomit within the first hour after taking the dose.³⁰²
Importance of discontinuing azithromycin and informing clinician if an allergic reaction occurs.¹ ¹⁰ ¹⁹⁶ ³⁰²
Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ ¹⁰ ¹⁹⁶ ³⁰² Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹ ¹⁰ ¹⁹⁶ ³⁰²
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.¹⁰
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹⁰
Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Azithromycin Dihydrate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	For suspension	100 mg (of anhydrous azithromycin) per 5 mL*	Azithromycin for Suspension
			Zithromax	Pfizer
		200 mg (of anhydrous azithromycin) per 5 mL*	Azithromycin for Suspension
			Zithromax	Pfizer
		1 g (of anhydrous azithromycin) per packet*	Azithromycin for Suspension
			Zithromax Single Dose Packets	Pfizer
	For suspension, extended-release	2 g (of anhydrous azithromycin)	Zmax	Pfizer
	Tablets, film-coated	250 mg (of anhydrous azithromycin)*	Azithromycin Tablets
			Azithromycin Tablets (available as a 5-day mnemonic pack of 6 tablets)
			Zithromax	Pfizer
			Zithromax Z-Paks (available as a 5-day mnemonic pack of 6 tablets)	Pfizer
		500 mg (of anhydrous azithromycin)*	Azithromycin Tablets
			Azithromycin Tablets (available as a 3-day mnemonic pack of 3 tablets)
			Zithromax	Pfizer
			Zithromax Tri-Paks (available as a 3-day mnemonic pack of 3 tablets)	Pfizer
		600 mg (of anhydrous azithromycin)*	Azithromycin Tablets
			Zithromax	Pfizer
Parenteral	For injection, for IV infusion only	500 mg (of anhydrous azithromycin)*	Azithromycin for Injection
			Zithromax	Pfizer
		2.5 g (of anhydrous azithromycin)*	Azithromycin for Injection

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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