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Azithromycin

Class: Other Macrolides
- Antimycobacterial Agents
VA Class: AM200
Chemical Name: [2R-(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)]-13-[2,6,Dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6,trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyloxy]-1-oxa-6-azacyclopentadecan-15-one
CAS Number: 83905-01-5
Brands: Zithromax, Zithromax Tri-Paks, Zithromax Z-Pak, Zmax

Medically reviewed by Drugs.com. Last updated on Jul 28, 2020.

Warning

Special Alerts:

COVID-19

For information on the use of this drug in patients with coronavirus disease 2019 (COVID-19), see the document “Assessment of the Evidence for COVID-19-Related Treatments” on ASHP's COVID-19 Resource Center. To view this document, please click here: [Web]

[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.

Uses for Azithromycin

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.

Not a drug of first choice; considered an alternative for patients with type I penicillin hypersensitivity. 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.

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. 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.

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

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. (See Selection and Use of Anti-infectives under Cautions),

GI Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni. Recommended by CDC, NIH, IDSA, AAP, and others as a drug of choice for empiric treatment.

Treatment of cryptosporidiosis in HIV-infected adults, adolescents, or children. Anti-infectives may suppress the infection, but none found to reliably eradicate Cryptosporidium. 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.

Treatment of shigellosis caused by susceptible strains of Shigella dysenteriae, S. boydii, S. flexneri, or S. sonnei. Usual drugs of choice are fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin); alternatives are azithromycin, ampicillin, ceftriaxone, or co-trimoxazole. Because of increasing resistance, select anti-infective based on susceptibility patterns of locally circulating Shigella.

Treatment of travelers’ diarrhea. Generally self-limited and may resolve within 3–4 days without anti-infective treatment; 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. Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually recommended. 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.

Treatment of severe diarrhea caused by enterotoxigenic Escherichia coli (ETEC). ETEC diarrhea generally is of moderate severity and self-limited, but may be severe. 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.

Treatment of dysentery caused by enteroinvasive E. coli (EIEC). 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.

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

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.

Respiratory Tract Infections

Treatment of acute bacterial sinusitis caused by susceptible Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

Treatment of mild to moderate acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) caused by H. influenzae, M. catarrhalis, or S. pneumoniae.

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.

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.

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). Do not use a macrolide alone for empiric treatment of CAP in hospitalized patients.

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. 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.

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. 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).

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.

Treatment of infections caused by L. pneumophila (Legionnaires’ disease). Drugs of choice are macrolides (usually azithromycin) or fluoroquinolones with or without rifampin.

Treatment and postexposure prophylaxis of pertussis caused by Bordetella pertussis. (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).

Babesiosis

Treatment of babesiosis caused by Babesia microti.

Regimens of choice for babesiosis are atovaquone in conjunction with azithromycin or quinine in conjunction with clindamycin. The clindamycin and quinine regimen may be preferred for severe babesiosis; 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. Also consider exchange transfusions in severely ill patients with high levels of parasitemia (>10%), substantial hemolysis, or compromised renal, hepatic, or pulmonary function.

Bartonella Infections

Treatment of infections caused by B. henselae (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis). 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. Anti-infectives also indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome. Optimum regimens have not been identified; some clinicians recommend azithromycin, ciprofloxacin, erythromycin, doxycycline, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.

Treatment of bacteremia caused by Bartonella quintana; used in conjunction with ceftriaxone. Optimum anti-infective regimens have not been identified.

Chancroid

Treatment of chancroid (genital ulcers caused by Haemophilus ducreyi).

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin for treatment of chancroid.

Safety and efficacy of azithromycin established in men (not women), but has been effective for and is recommended by CDC for treatment of chancroid in women.

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

Chlamydial Infections

Treatment of uncomplicated urethritis or cervicitis caused by C. trachomatis. CDC and others recommend azithromycin or doxycycline as drug of choice for nongonococcal urethritis (NGU) or cervicitis. 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.

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

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

Treatment of ocular trachoma caused by C. trachomatis. A drug of choice; recommended for use in mass treatment programs.

Treatment of chlamydial pneumonia in infants or chlamydial conjunctivitis in neonates (ophthalmia neonatorum caused by C. trachomatis).

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

Treatment of lymphogranuloma venereum caused by C. trachomatis. 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.

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; efficacy not proven to date.

Cholera

Treatment of cholera caused by Vibrio cholerae 01 or 0139.

A tetracycline or, alternatively, a fluoroquinolone or co-trimoxazole generally used for treatment of cholera in conjunction with fluid and electrolyte replacement therapy. 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.

Gonorrhea

Treatment of uncomplicated urethritis or cervicitis caused by susceptible Neisseria gonorrhoeae.

Not recommended for routine treatment of gonorrhea. 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). Although azithromycin is effective, CDC recommends the drug be used only when necessary because of concerns related to emerging resistance to macrolides.

Granuloma Inguinale (Donovanosis)

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

Leptospirosis

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

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. 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; macrolides generally have been less effective than first-line agents.

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. Should not be used alone as monotherapy for treatment of malaria.

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

Mycobacterium avium Complex (MAC) Infections

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

Treatment of disseminated MAC disease, including in HIV-infected adults, adolescents, and children. ATS, IDSA, CDC, NIH, and others recommend a regimen of clarithromycin (or azithromycin) and ethambutol with or without rifabutin. 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.

Prevention of recurrence (secondary prophylaxis) of disseminated MAC infection in HIV-infected adults, adolescents, and children. ATS, CDC, NIH, and IDSA recommend a macrolide (clarithromycin or azithromycin) given with ethambutol (with or without rifabutin).

Treatment of pulmonary MAC infections in conjunction with other antimycobacterials. 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. 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. 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.

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.

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

Treatment of infections caused by M. abscessus. 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); surgery usually indicated for extensive disease, abscess formation, and when drug therapy is difficult. 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. 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.

Treatment of rifampin-resistant M. kansasii infections in conjunction with other antimycobacterials. 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.

Treatment of M. marinum infections. 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.

Neisseria meningitidis Infections

Elimination of nasopharyngeal carriage of N. meningitidis.

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. Although further study is needed, CDC suggests azithromycin can be used as an alternative in areas where ciprofloxacin-resistant N. meningitidis have been reported (e.g., Minnesota, North Dakota).

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. If anaerobic bacteria are suspected, an anti-infective active against anaerobes should be used in conjunction with azithromycin. Although azithromycin is not included in CDC’s recommended or alternative regimens for treatment of PID, CDC states a regimen of amoxicillin and clavulanic acid, azithromycin, and metronidazole has demonstrated short-term clinical cure when used in outpatients.

Pertussis

Treatment of pertussis caused by Bordetella pertussis and postexposure prophylaxis of pertussis in household and other close contacts of an individual with pertussis.

Macrolides (azithromycin, clarithromycin, erythromycin) are the drugs of choice. Although erythromycin traditionally has been considered the drug of choice for treatment and postexposure prophylaxis of pertussis, 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.

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; co-trimoxazole is an alternative for those ≥2 months of age when a macrolide cannot be used. 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.

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. 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.

All household and other close contacts of an individual with suspected pertussis should receive anti-infective postexposure prophylaxis, regardless of age or vaccination status. 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). In addition, all close contacts who are unvaccinated or incompletely vaccinated against pertussis should receive age-appropriate vaccination with a preparation containing pertussis antigens.

Scrub Typhus

Alternative for treatment of scrub typhus caused by Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi). Drug of choice usually is doxycycline; alternatives are chloramphenicol or a fluoroquinolone. 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).

Syphilis

Alternative for treatment of primary, secondary, or early latent syphilis in nonpregnant adults and adolescents hypersensitive to penicillin.

Penicillin G is drug of choice for treatment of all stages of syphilis, 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.

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

Toxoplasmosis

Treatment of infections caused by Toxoplasma gondii, including toxoplasmic encephalitis in HIV-infected patients and ocular toxoplasmosis; usually used in conjunction with pyrimethamine.

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). 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; this regimen has not been evaluated in children.

Typhoid Fever and Other Salmonella Infections

Treatment of uncomplicated typhoid fever caused by susceptible Salmonella. 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.

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).

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.

Prophylaxis in Sexual Assault Victims

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

Azithromycin Dosage and Administration

Administration

Administer orally or by IV infusion. Do not administer IM or by rapid IV injection.

Oral Administration

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

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

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

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

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). 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. 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. 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. If patient with normal gastric emptying vomits ≥60 minutes after taking the 2-g dose, additional azithromycin doses or alternative treatment not required.

Reconstitution

Conventional oral suspension: Reconstitute 1-g single-dose packet for oral suspension with 60 mL of water. 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.

Conventional oral suspension: Reconstitute multiple-dose bottles for oral suspension at time of dispensing. Add 9 mL of water to bottle containing 300 mg of azithromycin to provide a suspension of 100 g/5 mL. 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. Shake suspension well prior to administration of each dose.

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

IV Infusion

Administer by IV infusion.

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

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.

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. 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.

Reconstituted solution contains 100 mg/mL.

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. (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. Do not give 500-mg doses by IV infusion over a period <1 hour.

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.

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. Alternatively, 10 mg/kg as a single dose on day 1, followed by 5 mg/kg once daily on days 2–5.

Pharyngitis and Tonsillitis
Oral

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

GI Infections†
Mild to Moderate Campylobacter jejuni Infections†
Oral

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

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.

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.

Optimum duration of treatment unknown; no anti-infective reliably eradicates Cryptosporidium.

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.

Adolescents: 500 mg on day 1 followed by 250 mg once daily on days 2–5.

Treatment of Travelers’ Diarrhea†
Oral

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

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.

Respiratory Tract Infections
Acute Bacterial Sinusitis
Oral

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

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. Efficacy of shorter regimens (e.g., 1–3 days) for treatment of CAP in children has not been established.

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).

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).

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.

Bartonella Infections in HIV-infected Individuals†
Oral

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

Chancroid†
Oral

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

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

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.

Chlamydial Infections
Uncomplicated Chlamydial Urethritis or Cervicitis†
Oral

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

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

Ocular Trachoma†
Oral

20 mg/kg (up to 1 g) as a single dose. Alternatively, 20 mg/kg once weekly for 3 weeks or 20 mg/kg once every 4 weeks for a total of 6 doses.

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

Chlamydial Pneumonia in Infants†
Oral

20 mg/kg once daily for 3 days.

Chlamydial Conjunctivitis in Neonates†
Oral

20 mg/kg once daily for 3 days.

Legionella Infections†
IV

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

Leptospirosis†
Oral

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

Lyme Disease†
Early Localized or Early Disseminated Lyme Disease†
Oral

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

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.

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.

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.

Primary Prevention of MAC in Adolescents with Advanced HIV Infection
Oral

1.2 g once weekly given alone.

Initiate primary prophylaxis if CD4+ T-cell count is <50/mm3. 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. Reinitiate prophylaxis if CD4+ T-cell count decreases to <50–100/mm3.

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.

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.

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).

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

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.

Secondary prophylaxis to prevent MAC recurrence usually continued for life in HIV-infected adolescents. 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.

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. 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.

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.

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

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

Toxoplasmosis†
Oral

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

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

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. Dosage of 10 mg/kg (up to 500 mg) once daily for 7 days also has been used.

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.

Prophylaxis in Sexual Assault Victims†
Oral

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

Adults

Pharyngitis and Tonsillitis
Oral

500 mg as a single dose on day 1, followed by 250 mg once daily on days 2–5.

GI Infections†
Mild to Moderate Campylobacter jejuni Infections†
Oral

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

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).

Shigella Infections†
Oral

500 mg on day 1 followed by 250 mg once daily on days 2–5. If bacteremia is present, continue for 14 days depending on the severity of infection.

Treatment of Travelers’ Diarrhea†
Oral

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

Respiratory Tract Infections
Acute Bacterial Sinusitis
Oral

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

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

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.

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.

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

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; then switch to an oral regimen of 500 mg once daily to complete 7–10 days of treatment.

Legionnaires’ Disease†
Oral

500 mg once daily. 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.

IV

500 mg once daily. 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.

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.

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). Higher azithromycin dosage (0.6–1 g daily) may be used in immunocompromised patients.

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

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.

Bartonella Infections in HIV-infected Patients
Oral

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

Chancroid
Oral

1 g as a single dose.

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.

Chlamydial Infections
Uncomplicated Chlamydial Urethritis or Cervicitis
Oral

1 g as a single dose.

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.

Ocular Trachoma†
Oral

20 mg/kg (up to 1 g) as a single dose. Alternatively, 1 g once weekly for 3 weeks.

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

Lymphogranuloma Venereum†
Oral

1 g once weekly for 3 weeks may be effective.

Cholera†
Oral

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

Gonorrhea
Uncomplicated Gonorrhea
Oral

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

Granuloma Inguinale (Donovanosis)†
Oral

1 g once weekly for at least 3 weeks or until all lesions have healed completely; 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. Despite effective anti-infective therapy, relapse may occur 6–18 months later.

Leptospirosis†
Oral

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

Lyme Disease†
Early Localized or Early Disseminated Lyme Disease†
Oral

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

Mycobacterium avium Complex (MAC) Infections
Primary Prevention of MAC in Adults with Advanced HIV Infection
Oral

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

ATS, IDSA, and others recommend initiating primary prophylaxis if CD4+ T-cell count is <50/mm3. 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. Reinitiate prophylaxis if CD4+ T-cell count decreases to <50–100/mm3.

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.

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).

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.

Secondary prophylaxis to prevent MAC recurrence usually continued for life in HIV-infected adults. 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. Reinitiate prophylaxis if CD4+ T-cell count decreases to <100/mm3.

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. Continue until patient has been culture negative on treatment for 1 year.

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

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. Continue until patient has been culture negative on treatment for 1 year. 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.

Mycobacterium abscessus Infections†
Oral

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

Neisseria meningitidis Infections†
Elimination of Nasopharyngeal Carrier State†
Oral

500 mg as a single dose.

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. If anaerobic bacteria are suspected, an anti-infective active against anaerobes should also be used.

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.

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

Scrub Typhus†
Oral

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

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

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

Toxoplasmosis†
Oral

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

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

Typhoid Fever and Other Salmonella Infections†
Oral

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

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.

Prophylaxis in Sexual Assault Victims†
Oral

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

Special Populations

Hepatic Impairment

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

Use caution; pharmacokinetics in hepatic impairment not completely established.

Renal Impairment

Dosage adjustment not necessary.

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

Geriatric Patients

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

Cautions for Azithromycin

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.

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).

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

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

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. 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. 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.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. 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.

If CDAD is suspected or confirmed, azithromycin may need to be discontinued. Some mild cases may respond to discontinuance alone. 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.

Sensitivity Reactions

Hypersensitivity and Dermatologic Reactions

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

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

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.

General Precautions

Cardiac Effects

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

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.

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

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.

Sodium Content

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

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

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

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

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk; use with caution.

Pediatric Use

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

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. 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.

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. 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.

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

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

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

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

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.

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.

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.

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

Hepatic Impairment

Use caution.

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

Renal Impairment

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

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

Common Adverse Effects

Adverse GI effects, including diarrhea/loose stools, nausea, vomiting, abdominal pain. Adverse GI effects occur more frequently with single-dose regimens (1 or 2 g) than multiple-dose regimens.

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.

Local reactions (pain, inflammation) with IV administration.

Interactions for Azithromycin

Does not appear to have an effect on CYP isoenzymes.

Many drug interactions reported with other macrolides (e.g., erythromycin, clarithromycin) have not been reported to date with azithromycin.

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. Azithromycin appears to have no effect on the CYP isoenzyme system and interactions mediated by this enzyme system would not be expected to occur. However, the possibility that such drug interactions may occur cannot be ruled out.

Specific Drugs

Drug

Interaction

Comments

Albendazole

Increased peak plasma concentration and AUC of azithromycin when azithromycin, albendazole, and ivermectin given concomitantly

Effect on azithromycin not considered clinically important

Antacids (aluminum- and magnesium-containing)

Conventional tablets or oral suspension: Decreased azithromycin plasma concentrations; AUC unaffected

Extended-release oral suspension: Rate and extent of azithromycin absorption not affected

Conventional tablets or oral suspension: Simultaneous administration with aluminum- or magnesium-containing antacids not recommended

Extended-release oral suspension: May be taken without regard to aluminum- or magnesium-containing antacids

Anticoagulants, oral

Does not appear to affect PT response to a single warfarin dose; increased anticoagulant effects reported rarely with azithromycin and also reported with other macrolides

Monitor PT carefully when used with warfarin

Antimycobacterials, rifamycins (rifabutin)

Modest effect on rifabutin pharmacokinetics

No dosage adjustment recommended

Atazanavir

Clinically important pharmacokinetic interactions not expected

Benzodiazepines (midazolam, triazolam)

Modest effect on pharmacokinetics of midazolam or triazolam; decreased clearance of triazolam and increased pharmacologic effect reported with other macrolides

No dosage adjustment recommended

Carbamazepine

Modest effect on pharmacokinetics of carbamazepine; increased carbamazepine concentrations reported with other macrolides

No dosage adjustment recommended; monitor closely

Cetirizine

Modest effect on pharmacokinetics of cetirizine

No dosage adjustment recommended

Chloroquine

No clinically important pharmacokinetic interactions between chloroquine and azithromycin

In vitro evidence of additive to synergistic effects against P. falciparum, including multidrug-resistant strains

Cimetidine

No effect on azithromycin absorption if cimetidine given 2 hours prior to azithromycin

Co-trimoxazole

Modest effect on pharmacokinetics of co-trimoxazole; no clinically important effect on pharmacokinetics of azithromycin

No dosage adjustment recommended

Cyclosporine

No interaction studies with azithromycin; increased cyclosporine concentrations reported with other macrolides

Monitor carefully

Didanosine

Modest or no effect on pharmacokinetics of didanosine

No dosage adjustment recommended

Digoxin

No interaction studies with azithromycin; increased digoxin concentrations reported with other macrolides

Monitor carefully

Efavirenz

Modest or no effect on efavirenz and azithromycin pharmacokinetics

No dosage adjustment recommended

Ergot alkaloids (ergotamine, dihydroergotamine)

No interaction studies with azithromycin; acute ergot toxicity (severe peripheral vasospasm and dysesthesia)reported with other macrolides

Monitor carefully

Fluconazole

Modest or no effect on pharmacokinetics of azithromycin and fluconazole

No dosage adjustment recommended

Hexobarbital

No interaction studies with azithromycin; increased hexobarbital concentrations reported with other macrolides

Monitor carefully

HMG-CoA reductase inhibitors (atorvastatin)

Modest effect on pharmacokinetics of atorvastatin

Rhabdomyolysis reported with lovastatin

No dosage adjustment recommended; monitor closely

Indinavir

Modest or no effect on pharmacokinetics of indinavir

No dosage adjustment recommended

Ivermectin

Increased peak plasma concentrations and AUC of azithromycin and ivermectin when azithromycin, ivermectin, and albendazole given concomitantly

Effect on azithromycin not considered clinically important; additional study needed regarding effect on pharmacokinetics of ivermectin

Lopinavir

Clinically important pharmacokinetic interactions not expected

Nelfinavir

Decreased AUC of nelfinavir and its M8 metabolite; increased plasma concentrations and AUC of azithromycin

No dosage adjustment recommended; closely monitor for adverse effects of azithromycin (e.g., liver enzyme abnormalities, hearing impairment)

Phenytoin

No interaction studies with azithromycin; increased phenytoin concentrations reported with other macrolides

Monitor carefully

Pimozide

Potential increased pimozide plasma concentrations and risk of prolonged QT interval and serious cardiac arrhythmias reported with other macrolides

Manufacturer of pimozide states concomitant use contraindicated

Quinine

In vitro evidence of additive to synergistic effects against P. falciparum, including multidrug-resistant strains

Sildenafil

Modest effect on sildenafil pharmacokinetics

No dosage adjustment recommended

Theophylline

Modest or no effect on theophylline pharmacokinetics; increased theophylline concentrations have been reported with other macrolides

No dosage adjustment recommended; closely monitor theophylline concentrations

Zidovudine

Modest effect on zidovudine pharmacokinetics

No dosage adjustment recommended

Azithromycin Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract.

Conventional tablets or oral suspension: Absolute oral bioavailability is 34–52%. Peak serum concentrations attained about 2 hours after an oral dose.

Extended-release oral suspension: Bioavailability is approximately 83% of that reported with conventional oral suspension. 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).

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

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

Food

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

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.

Distribution

Extent

Distributed into most tissues and fluids following oral or IV administration, including skin, lungs, sputum, tonsils, and cervix. Tissue concentrations generally exceed plasma concentrations by at least 10- to 100-fold.

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

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

Distributed into milk.

Plasma Protein Binding

51% at plasma azithromycin concentration of 0.02 mcg/mL; 7% at concentration of 2 mcg/mL.

Elimination

Metabolism

At least 10 microbiologically inactive metabolites identified.

Elimination Route

Biliary excretion as unchanged drug is a major route of elimination. Excreted in feces principally as unchanged drug.

Only a small portion (approximately 6%) of a dose excreted in urine as unchanged drug.

Half-life

Conventional tablets or oral suspension: Terminal serum half-life averages 68–72 hours.

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

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

Tissue half-life averages 1–4 days; half-life in peripheral leukocytes averages 34–57 hours.

Special Populations

Pharmacokinetics of conventional oral preparations in men 65–85 years of age similar to that in younger adults. 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. Pharmacokinetics of extended-release oral suspension not evaluated in geriatric patients.

Pharmacokinetics in hepatic impairment not fully established. 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.

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).

Stability

Storage

Oral

Conventional Powder For Suspension

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

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

Conventional Tablets

15–30°C.

Extended-release Microspheres For Suspension

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

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.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

For dilution of reconstituted azithromycin injection:

Compatible

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.3 or 0.45%

Dextrose 5% in sodium chloride 0.45% with 20 mEq KCl

Dextrose 5% in water

Normosol M in dextrose 5%

Normosol R in dextrose 5%

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

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).

  • Usually bacteriostatic, but may be bactericidal against some organisms at high concentrations.

  • Like other macrolide antibacterials, inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits.

  • 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]).

  • More active than erythromycin or clarithromycin against gram-negative bacteria; activity comparable to erythromycin against gram-positive bacteria.

  • Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus aureus, S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and S. agalactiae (group B streptococci). Also active in vitro against some other streptococci (e.g., groups C, F, and G streptococci, viridans streptococci). Enterococci (e.g., Enterococcus faecalis) and oxacillin-resistant (methicillin-resistant) staphylococci are resistant.

  • Gram-negative aerobes: Active in vitro and in clinical infections against Haemophilus influenzae, H. ducreyi, Moraxella catarrhalis, and Neisseria gonorrhoeae. Also active in vitro against N. meningitidis and some strains of Bordetella pertussis and Legionella pneumophila.

  • Other organisms: Active in vitro and in clinical infections against C. pneumoniae, C. trachomatis, M. pneumoniae, and M. hominis. Also active against MAC, Borrelia burgdorferi, Toxoplasma gondii, Plasmodium falciparum, Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi), Rickettsia conorii, R. typhi, and Coxiella burnettii.

  • Streptococci and staphylococci resistant to erythromycin usually are cross-resistant to azithromycin.

  • Complete cross-resistance occurs between azithromycin and clarithromycin in MAC.

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).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • 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.

  • Conventional tablets or oral suspension can be taken without regard to meals. Extended-release oral suspension should be taken on an empty stomach (at least 1 hour before or 2 hours after a meal).

  • Importance of not taking aluminum- or magnesium-containing antacids at the same time as conventional tablets or oral suspension. Extended-release oral suspension can be taken without regard to aluminum- or magnesium-containing antacids.

  • 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.

  • Importance of discontinuing azithromycin and informing clinician if an allergic reaction occurs.

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. 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.

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

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

AHFS DI Essentials™. © Copyright 2021, Selected Revisions August 7, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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