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  • CLASSES

    Macrolide Antibiotics
    Ophthalmological Anti-infectives

    DEA CLASS

    Rx

    DESCRIPTION

    Macrolide antibiotic similar in structure to erythromycin, but can be dosed systemically once daily
    Used systemically for otitis media, pharyngitis, community-acquired pneumonia, sexually transmitted diseases, and Mycobacterium avium complex (MAC) prophylaxis and treatment in patients with advanced HIV disease; an ophthalmic solution is used for bacterial conjunctivitis
    Produces less GI intolerance and reaches higher intracellular concentrations than erythromycin

    COMMON BRAND NAMES

    Azasite, Zithromax, Zithromax Tri-Pak, Zithromax Z-Pak, Zmax

    HOW SUPPLIED

    Azasite Ophthalmic Drops: 1%
    Azithromycin/Zithromax Intravenous Inj Pwd F/Sol: 2.5g, 500mg
    Azithromycin/Zithromax Oral Pwd F/Recon: 1g, 5mL, 100mg, 200mg
    Azithromycin/Zithromax/Zithromax Tri-Pak/Zithromax Z-Pak Oral Tab: 250mg, 500mg, 600mg
    Zmax Oral Susp ER: 2g

    DOSAGE & INDICATIONS

    For the treatment of community-acquired pneumonia (CAP).
    Oral dosage (immediate-release)
    Outpatient Adults

    500 mg PO on day 1, followed by 250 mg PO once daily for at least 5 days as monotherapy for patients without comorbidities or risk factors for MRSA or P. aeruginosa and as part of combination therapy for patients with comorbidities. Guide treatment duration by clinical stability.[28855] [34362] [64669] FDA-approved labeling recommends a 5-day treatment course.[28855]

    Hospitalized Adults

    500 mg PO once daily for at least 5 days as part of combination therapy. Guide treatment duration by clinical stability.[34362] [64669]

    Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for HIV-infected patients.[34362] [46963]

    Infants and Children 6 months to 12 years

    10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized HIV-infected patients.[34361] [46963]

    Infants 3 to 5 months†

    10 mg/kg/dose PO for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days. Guidelines recommend azithromycin as oral step-down therapy or as initial oral therapy in patients with atypical pathogens and as part of combination therapy for hospitalized HIV-infected patients.[34361] [46963]

    Oral dosage (extended-release)
    Adults

    2 g PO as a single dose. This dosage form is not recommended for patients with moderate or severe illness or those with other underlying risk factors for which oral therapy is inappropriate.[34473]

    Infants, Children, and Adolescents 6 months to 17 years

    60 mg/kg/dose (Max: 2 g/dose) PO as a single dose. This dosage form is not recommended for patients with moderate or severe illness or those with other underlying risk factors for which oral therapy is inappropriate.[34473]

    Intravenous dosage
    Adults

    500 mg IV once daily for at least 5 days as part of combination therapy for hospitalized patients. Guide treatment duration by clinical stability.[34362] [64669] FDA-approved labeling recommends IV therapy for at least 2 days then step-down to oral therapy to complete a 7- to 10-day treatment course. The switch to oral therapy should be done at the discretion of the physician and based on the clinical response of the patient.[43974]

    Adolescents 16 to 17 years

    500 mg IV once daily for at least 2 days, followed by oral therapy to complete a 7- to 10-day treatment course.[43974] Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including HIV-infected patients, when atypical pathogens are suspected.[34362] [46963]

    Infants, Children, and Adolescents 3 months to 15 years†

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily for 2 days, followed by oral therapy to complete a 5-day treatment course. Guidelines recommend azithromycin as monotherapy for definitive atypical pneumonia and as part of combination therapy for hospitalized patients, including HIV-infected patients, when atypical pathogens are suspected.[34361] [34362] [46963]

    For the treatment of acute bacterial sinusitis.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 3 days.[28855] Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.[49853]

    Infants, Children, and Adolescents 6 months to 17 years

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days.[28855] Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.[49853]

    Oral dosage (extended-release)
    Adults

    2 g PO as a single dose. Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy.

    For the treatment of acute otitis media.
    Oral dosage (immediate-release)
    Infants, Children, and Adolescents 6 months to 17 years

    30 mg/kg/dose (Max: 1,500 mg/dose) PO as a single dose, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days, or 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.[28855] Because macrolides have limited efficacy against both H. influenzae and S. pneumoniae, these agents are not included in guidelines.[53345]

    For the treatment of bacterial conjunctivitis.
    NOTE: For gonococcal conjunctivitis, see gonococcal infections.
    Ophthalmic dosage
    Adults

    1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for 2 days, then 1 drop in the affected eye(s) once daily for 5 days.[43976]

    Children and Adolescents

    1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for 2 days, then 1 drop in the affected eye(s) once daily for 5 days.[43976]

    For the treatment of skin and skin structure infections.
    For the treatment of uncomplicated skin and skin structure infections.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

    For the treatment of cat scratch disease†.
    Oral dosage (immediate-release)
    Adults weighing 45 kg or more

    500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

    Adults weighing less than 45 kg

    10 mg/kg/dose PO once daily for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days.

    For the treatment of pelvic inflammatory disease (PID).
    Intravenous dosage
    Adults

    500 mg IV once daily for 1 to 2 days, followed by oral therapy. Consider adding metronidazole or other anaerobic therapy.

    Adolescents 16 to 17 years

    500 mg IV once daily for 1 to 2 days, followed by oral therapy. Consider adding metronidazole or other anaerobic therapy.

    Adolescents 13 to 15 years†

    500 mg IV once daily for 1 to 2 days, followed by oral therapy. Consider adding metronidazole.

    Oral dosage (immediate-release)
    Adults

    250 mg PO once daily for 7 to 14 days after IV therapy. Consider adding metronidazole or other anaerobic therapy.[43974] [59799] Alternatively, 1 g PO once weekly for 2 weeks plus a single dose of ceftriaxone.[59799]

    Adolescents 16 to 17 years

    250 mg PO once daily for 7 to 14 days after IV therapy. Consider adding metronidazole or other anaerobic therapy.[43974] [59799] Alternatively, 1 g PO once weekly for 2 weeks plus a single dose of ceftriaxone.[59799]

    Adolescents 13 to 15 years†

    250 mg PO once daily for 12 to 14 days after IV therapy. Consider adding metronidazole. Alternatively, 1 g PO once weekly for 2 weeks plus a single dose of ceftriaxone.[59799]

    For the treatment of gonorrhea.
    For the treatment of uncomplicated gonorrhea, including cervicitis, urethritis, and proctitis†.
    Oral dosage (immediate-release)
    Adults

    2 g PO as a single dose plus gentamicin as an alternative in patients with a cephalosporin allergy or when ceftriaxone is not available.

    Children weighing more than 45 kg† and Adolescents†

    2 g PO as a single dose plus gentamicin as an alternative in patients with a cephalosporin allergy or when ceftriaxone is not available.

    For the treatment of disseminated gonorrhea†, including arthritis†, endocarditis†, and meningitis†.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose plus ceftriaxone.[59799]

    Children weighing more than 45 kg and Adolescents

    1 g PO as a single dose plus ceftriaxone.[59799]

    For the treatment of gonococcal conjunctivitis†.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose plus ceftriaxone. Lavage the infected eye(s) with saline to remove accumulated secretions.

    Children weighing more than 45 kg and Adolescents

    1 g PO as a single dose plus ceftriaxone. Lavage the infected eye(s) with saline to remove accumulated secretions.

    For the treatment of chancroid.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose. Data are limited in HIV-infected patients.

    Adolescents†

    1 g PO as a single dose. Data are limited in HIV-infected patients.

    Infants† and Children†

    20 mg/kg/dose (Max: 1 g/dose) PO as a single dose. Data are limited in HIV-infected patients.

    For the treatment of non-gonococcal urethiritis (NGU) and chlamydia infection, including infant pneumonia†.
    NOTE: For ophthalmia neonatorum caused by C. trachomatis, see ophthalmia neonatorum indication.
    For the treatment of non-gonococcal urethritis (NGU) and other urogenital infections (e.g., cervicitis, urethritis, proctitis).
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose.  For recurrent or persistent urethritis, add metronidazole or tinidazole. For recurrent or persistent non-gonococcal urethritis in men initially treated with doxycycline, azithromycin 1 g PO as a single dose for treatment of M. genitalium.

    Adolescents†

    1 g PO as a single dose.  [59799] For recurrent or persistent urethritis, add metronidazole or tinidazole. For recurrent or persistent non-gonococcal urethritis in men initially treated with doxycycline, azithromycin 1 g PO as a single dose for treatment of M. genitalium.[59799]

    Children 8 to 12 years†

    1 g PO as a single dose.[59799]

    Children 1 to 7 years weighing 45 kg or more†

    1 g PO as a single dose.[59799]

    For the treatment of pneumonia caused by Chlamydia trachomatis in neonates and infants†.
    Oral dosage (immediate-release)
    Infants

    20 mg/kg/dose PO once daily for 3 days as an alternative.

    Neonates

    20 mg/kg/dose PO once daily for 3 days as an alternative.

    For the treatment of Mycobacterium avium complex infection (MAC) in HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    500 to 600 mg PO once daily as part of combination therapy as an alternative.[34362] [43975] Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Adolescents†

    500 to 600 mg PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Infants† and Children†

    10 to 12 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy as an alternative. Duration of treatment depends on clinical response but should continue for at least 12 months.[34361]

    For Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients.
    For primary Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    1,200 mg PO once weekly or 600 mg PO twice weekly as preferred therapy.[34362] [43975] Discontinue primary prophylaxis upon initiation of effective antiretroviral therapy (ART). Restart primary prophylaxis if the CD4 count decreases to less than 50 cells/mm3 and not on fully suppressive ART.[34362]

    Adolescents†

    1,200 mg PO once weekly or 600 mg PO twice weekly as preferred therapy. Primary prophylaxis is only recommended for patients not on fully suppressive antiretroviral therapy (ART) with CD4 counts less than 50 cells/mm3 after ruling out disseminated MAC. Discontinue primary prophylaxis upon initiation of effective ART. Restart primary prophylaxis if the CD4 count decreases to less than 50 cells/mm3 and not on fully suppressive ART.[34362]

    Children 6 to 12 years†

    20 mg/kg/dose (Max: 1,200 mg/dose) PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose (Max: 250 mg/dose) PO once daily. Primary prophylaxis is recommended in children 6 years and older with a CD4 count less than 50 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 100 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34361]

    Children 2 to 5 years†

    20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 2 to 5 years with a CD4 count less than 75 cells/mm3. Primary prophylaxis may be discontinued after 6 months or more of antiretroviral therapy (ART) and a CD4 count more than 200 cells/mm3 for more than 3 consecutive months. Restart primary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.[34361]

    Children 1 year†

    20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in children 1 to 2 years with a CD4 count less than 500 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.[34361]

    Infants†

    20 mg/kg/dose PO once weekly as preferred therapy, or alternatively, 5 mg/kg/dose PO once daily. Primary prophylaxis is recommended in infants with a CD4 count less than 750 cells/mm3. Do not discontinue primary prophylaxis for children younger than 2 years.[34361]

    For secondary Mycobacterium avium complex (MAC) prophylaxis† (i.e., long-term suppressive therapy) in HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    500 to 600 mg PO once daily as part of combination therapy and preferred therapy. Consider discontinuing secondary prophylaxis in patients who have completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for more than 6 months in response to antiretroviral therapy (ART). Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

    Adolescents

    500 to 600 mg PO once daily as part of combination therapy and preferred therapy. Consider discontinuing secondary prophylaxis in patients who have completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for more than 6 months in response to antiretroviral therapy (ART). Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

    Children 6 to 12 years

    5 mg/kg/dose (Max: 250 mg/dose) PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in patients who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 100 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34361]

    Children 2 to 5 years

    5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Consider discontinuing secondary prophylaxis in children who have completed 6 months or more of antiretroviral therapy (ART), completed 12 months or more of MAC treatment, have no signs or symptoms of MAC disease, and have a CD4 count more than 200 cells/mm3 for 6 consecutive months or more. Restart secondary prophylaxis if the CD4 count decreases to less than 200 cells/mm3.[34361]

    Infants and Children 1 year

    5 mg/kg/dose PO once daily as part of combination therapy as an alternative. Do not discontinue secondary prophylaxis for children younger than 2 years.[34361]

    INVESTIGATIONAL USE: For adjunctive use in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, the virus that causes coronavirus disease 2019 (COVID-19)†.
    Oral dosage (immediate-release)
    Adults

    Data are limited and inconclusive. Due to the potential for toxicities, the National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of azithromycin. Doses studied include 500 mg PO on day 1 then 250 mg PO once daily for 5 days and 500 mg PO once daily for 7 days in combination with hydroxychloroquine.[65147]

    For the treatment of acute bacterial exacerbations of chronic bronchitis and for maintenance treatment of chronic obstructive pulmonary disease (COPD)† (e.g., chronic bronchitis† or emphysema†).
    For the treatment of acute bacterial exacerbations of chronic bronchitis.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 3 days, or 500 mg PO once daily for 1 day followed by 250 mg PO once daily for 4 days.

    For maintenance treatment of chronic obstructive pulmonary disease (COPD)† (e.g., chronic bronchitis† or emphysema†).
    Oral dosage (immediate release)
    Adults

    250 to 500 mg PO 3 days per week has been recommended to reduce exacerbation rates in patients with more than 3 exacerbations requiring steroid therapy and at least one exacerbation requiring hospitalization per year. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. It is not necessary to stop prophylactic azithromycin during acute exacerbations of COPD.

    For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis†) and tonsillitis.
    NOTE: Guidelines recommend azithromycin for secondary rheumatic fever prophylaxis in patients allergic to penicillin or sulfadiazine, although no dosage recommendations are given. Secondary prophylaxis is recommended for 10 years or until age 40 (whichever is longer) in patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease); for 10 years or until age 21 (whichever is longer) in patients who have experienced rheumatic fever with carditis, but have no residual heart disease; and for 5 years or until age 21 (whichever is longer) in patients who have experienced rheumatic fever without carditis.[35507]
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 5 days as an alternative in patients allergic to penicillin is recommended in guidelines. The FDA-approved dose is 500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days.

    Children and Adolescents 2 to 17 years

    12 mg/kg/dose (Max: 500 mg/dose) PO once daily for 5 days as an alternative in patients allergic to penicillin.[28855] [35507] [52889]

    Infants† and Children 1 year†

    12 mg/kg/dose PO once daily for 5 days as an alternative in patients allergic to penicillin.

    For the treatment of primary†, secondary†, or early latent syphilis† in nonpregnant, penicillin-allergic patients.
    For the treatment of primary† or secondary syphilis† in nonpregnant, penicillin-allergic patients.
    Oral dosage (immediate-release)
    Adults

    2 g PO as a single dose as an alternative when penicillin and doxycycline are not feasible options. Do not use azithromycin in pregnant females or in males who have sex with males (MSM). Use in HIV-infected patients is controversial and not well-studied.

    Adolescents

    2 g PO as a single dose as an alternative when penicillin and doxycycline are not feasible options. Do not use azithromycin in pregnant females or in males who have sex with males (MSM). Use in HIV-infected patients is controversial and not well-studied.

    For the treatment of early latent syphilis† in nonpregnant, penicillin-allergic HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    2 g PO as a single dose as an alternative when penicillin and doxycycline are not feasible options. Do not use azithromycin in pregnant females or in males who have sex with males (MSM). Use in HIV-infected patients is controversial and not well-studied.

    Adolescents

    2 g PO as a single dose as an alternative when penicillin and doxycycline are not feasible options. Do not use azithromycin in pregnant females or in males who have sex with males (MSM). Use in HIV-infected patients is controversial and not well-studied.

    For the treatment of ophthalmia neonatorum†.
    Oral dosage (immediate-release)
    Neonates

    20 mg/kg/dose PO once daily for 3 days as an alternative.

    For chlamydial infection prophylaxis† and gonorrhea prophylaxis† in victims of sexual assault.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose in combination with ceftriaxone plus either metronidazole or tinidazole (for trichomoniasis and bacterial vaginosis prophylaxis).

    Adolescents

    1 g PO as a single dose in combination with ceftriaxone plus either metronidazole or tinidazole (for trichomoniasis and bacterial vaginosis prophylaxis).

    For the treatment of lymphogranuloma venereum†.
    For the primary treatment of lymphogranuloma venereum†.
    Oral dosage (immediate-release)
    Adults

    1 g PO once weekly for 3 weeks as an alternative.

    Adolescents

    1 g PO once weekly for 3 weeks as an alternative.

    For the presumptive treatment of chlamydia in the sex partner(s) of a patient with lymphogranuloma venereum†.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose.

    Adolescents

    1 g PO as a single dose.

    For the treatment of granuloma inguinale† (Donovanosis).
    Oral dosage (immediate-release)
    Adults

    1 g PO once weekly or 500 mg PO once daily for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    Adolescents

    1 g PO once weekly or 500 mg PO once daily for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    Children weighing 45 kg or more

    1 g PO once weekly or 500 mg PO once daily for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    For the treatment of bartonellosis† in HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for at least 3 months as an alternative for Bartonella angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.[34362]

    Adolescents

    500 mg PO once daily for at least 3 months as an alternative for Bartonella angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.[34362]

    For secondary bartonellosis prophylaxis† (i.e., long-term suppressive therapy) in HIV-infected patients.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily. Discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing of suppressive therapy.[34362]

    Adolescents

    500 mg PO once daily. Discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing of suppressive therapy.

    For the treatment of non-invasive shigellosis† in immunocompromised patients.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 5 days as an alternative. Recurrent infection may require treating for up to 6 weeks. Azithromycin is not recommended for Shigella bacteremia. Most Shigella infections are self-limiting and do not require treatment.[34362] [65199] [65200]

    Adolescents

    500 mg PO once daily for 5 days as an alternative. Recurrent infection may require treating for up to 6 weeks. Azithromycin is not recommended for Shigella bacteremia. Most Shigella infections are self-limiting and do not require treatment.

    Infants and Children

    12 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 6 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days has been used; however, data are limited. Most Shigella infections are self-limiting and do not require treatment.

    For the treatment of mild-to-moderate campylobacteriosis†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 3 days as preferred therapy. Many acute cases do not need treatment.

    HIV-infected Adults

    500 mg PO once daily for 5 days as preferred therapy. Azithromycin is not recommended for Campylobacter bacteremia.[34362]

    Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days. Many acute cases do not need treatment.

    HIV-infected Adolescents

    500 mg PO once daily for 5 days as preferred therapy. Azithromycin is not recommended for Campylobacter bacteremia.

    Children

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days. Many acute cases do not need treatment.

    For the treatment of cholera†.
    Oral dosage (immediate-release)
    Adults

    1 g PO as a single dose as an alternative. Azithromycin may be considered as preferred therapy in pregnant women.

    Children and Adolescents

    20 mg/kg/dose (Max: 1 g/dose) PO as a single dose as preferred therapy.

    For the treatment of traveler's diarrhea†.
    Oral dosage (immediate-release)
    Adults

    1,000 mg PO as a single dose or in 2 divided doses for 1 day or 500 mg PO once daily for 3 days as first-line therapy for dysentery or acute watery diarrhea with greater than mild fever. If symptoms are not resolved after single dose, continue treatment for up to 3 days. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.[62855] [62856]

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days as first-line therapy. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.

    For the treatment of typhoid fever†.
    For the treatment of multidrug-resistant uncomplicated typhoid fever† or quinolone-resistant uncomplicated typhoid fever†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 7 days or 1 g PO once daily PO once daily for 5 to 7 days. 

    Infants, Children, and Adolescents

    8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 7 days.  

    For the treatment of extensively drug-resistant typhoid fever†.
    Oral dosage (immediate-release)
    Adults

    1 g PO once daily for 1 day, followed by 500 mg to 1 g PO once daily for 5 to 10 days. Use as a single agent for uncomplicated disease or in combination with a carbapenem for complicated disease.

    Infants, Children, and Adolescents

    20 mg/kg/dose (Max: 1 g/dose) PO once daily for 1 day, followed by 8 to 20 mg/kg/dose (Max: 1 g/dose) PO once daily for 5 to 10 days. Use as a single agent for uncomplicated disease or in combination with a carbapenem for complicated disease.

    For the treatment of early Lyme disease† (erythema migrans†), including solitary and multiple erythema migrans† as second line therapy.
    For the treatment of early Lyme disease† (erythema migrans†) in adults as second line therapy.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 7 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.

    For the treatment of early Lyme disease† (erythema migrans†) in pediatric patients as second line therapy.
    Oral dosage (immediate-release)
    Infants, Children, and Adolescents

    10 mg/kg/day (Max: 500 mg/day) PO once daily for 7 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.

    For the treatment of babesiosis†.
    For the treatment of babesiosis† in immunocompetent ambulatory patients with mild to moderate disease in combination with atovaquone.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 7 to 10 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 7 to 10 days.

    For the treatment of babesiosis† in immunocompromised ambulatory patients with mild to moderate disease in combination with atovaquone.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 1 day, followed by 250 mg PO once daily for at least 7 to 10 days; duration may need to be extended in these patients.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for at least 7 to 10 days; duration may need to be extended in these patients.

    For the initial treatment of babesiosis† in immunocompetent hospitalized patients with acute, severe disease in combination with atovaquone.
    Intravenous dosage
    Adults

    500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of 7 to 10 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of 7 to 10 days.

    For the initial treatment of babesiosis† in immunocompromised hospitalized patients with acute, severe disease in combination with atovaquone.
    Intravenous dosage
    Adults

    500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

    For oral stepdown treatment of babesiosis† in immunocompetent hospitalized patients in combination with atovaquone after initial IV therapy.
    Oral dosage (immediate-release)
    Adults

    250 to 500 mg PO once daily for a total treatment duration of 7 to 10 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of 7 to 10 days.

    For oral stepdown treatment of babesiosis† in immunocompromised hospitalized patients in combination with atovaquone after initial IV therapy.
    Oral dosage (immediate-release)
    Adults

    500 to 1,000 mg PO once daily for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total treatment duration of at least 7 to 10 days; duration may need to be extended in these patients.

    For oral stepdown treatment of babesiosis† in highly immunocompromised patients in combination with atovaquone after initial IV therapy.
    Oral dosage (immediate-release)
    Adults

    500 to 1,000 mg PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    Adolescents

    10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    Infants and Children

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    For oral stepdown treatment of refractory or relapsed babesiosis† as part of combination therapy after initial IV therapy.
    Oral dosage (immediate-release)
    Adults

    500 to 1,000 mg PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    Adolescents

    10 mg/kg/dose (Max: 1,000 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    Infants and Children

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    For the initial treatment of babesiosis† in highly immunocompromised patients in combination with atovaquone.
    Intravenous dosage
    Adults

    500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    Adolescents

    10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    Infants and Children

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy for a total duration of at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

    For the initial treatment of refractory or relapsed babesiosis† as part of combination therapy.
    Intravenous dosage
    Adults

    500 to 1,000 mg IV once then 500 mg IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    Adolescents

    10 mg/kg/dose (Max: 1,000 mg/dose) IV once then 10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    Infants and Children

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily until symptoms abate, followed by oral stepdown therapy as part of combination therapy which may include atovaquone; proguanil, atovaquone plus clindamycin, or atovaquone plus clindamycin plus quinine.

    For the treatment of dental infection† or dentoalveolar infection†, including periodontitis†, acute dental abscess (apical)†, and dental abscess (periapical)†.
    For the treatment of chronic periodontitis† after scaling and root planing.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 4 to 7 days.

    For the treatment of acute dental abscess in combination with surgical incision and drainage in patients with beta-lactam allergy.
    Oral dosage (immediate-release)
    Adults

    1 g PO once daily for 1 day, followed by 500 mg PO once daily for 2 days.

    For bacterial endocarditis prophylaxis†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

    Children and Adolescents

    15 mg/kg/dose (Max: 500 mg/dose) PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

    For improving pulmonary function in cystic fibrosis† patients chronically colonized with Pseudomonas aeruginosa.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 times weekly is a common regimen.[27654] [51769] However, optimal dosing is not well established and various regimens are used; some centers prefer daily dosing, and once weekly therapy has also been studied.[27655] [27656] [56856] Guidelines recommend azithromycin to improve lung function and decrease pulmonary exacerbations in CF patients 6 years and older who have sputum cultures persistently positive for P. aeruginosa.[51770]

    Children and Adolescents 6 to 17 years weighing 40 kg or more

    500 mg PO 3 times weekly is a common regimen.[27654] [51769] However, optimal dosing is not well established and various regimens are used; some centers prefer daily dosing, and once weekly therapy has also been studied.[27655] [27656]  [56856] Guidelines recommend azithromycin to improve lung function and decrease pulmonary exacerbations in CF patients 6 years and older who have sputum cultures persistently positive for P. aeruginosa.[51770]

    Children and Adolescents 6 to 17 years weighing less than 40 kg

    250 mg PO 3 times weekly is a common regimen.[27654] [51769] However, optimal dosing is not well established and various regimens are used; some centers prefer daily dosing, and once weekly therapy has also been studied.[27655] [27656]  [56856] Guidelines recommend azithromycin to improve lung function and decrease pulmonary exacerbations in CF patients 6 years and older who have sputum cultures persistently positive for P. aeruginosa.[51770]

    For the treatment of pertussis (whooping cough)† or for postexposure pertussis prophylaxis†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 1 day, followed by 250 mg PO once daily for 4 days. For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure.[31752]

    Infants, Children, and Adolescents 6 months to 17 years

    10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days. For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure.

    Infants 1 to 5 months

    10 mg/kg/dose PO once daily for 5 days. For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure.

    Neonates

    10 mg/kg/dose PO once daily for 5 days. For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure.

    For asthma maintenance† add-on therapy in patients with uncontrolled or severe asthma.
    Oral dosage (immediate-release)
    Adults

    250 to 500 mg PO 3 days per week has been recommended to reduce the incidence of asthma exacerbations in patients with severe asthma who are optimized on inhaled corticosteroids/long-acting beta agonist therapy but who continue to have exacerbations.   Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. Breaks in therapy may be considered to reduce treatment burden. Fewer asthma exacerbations and improved quality of life were reported in patients (n = 213) treated with azithromycin 500 mg PO 3 days per week for 48 weeks. The rate of severe exacerbations and lower respiratory tract infections were not reduced in patients (n = 55) with severe asthma treated with azithromycin 250 mg PO 3 days per week.

    For the treatment of bronchiectasis† to reduce exacerbations in patients with high exacerbation rates.
    Oral dosage (immediate-release)
    Adults

    250 to 500 mg PO 3 days per week has been recommended to reduce exacerbation rates. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. Breaks in therapy may be considered to reduce treatment burden.

    For the treatment of bronchiolitis obliterans† in lung transplant recipients..
    Oral dosage (immediate-release)
    Adults

    250 mg PO 3 days per week for a trial period of 3 months has been recommended.

    For bronchiolitis obliterans prevention after transplantation† in lung transplant patients.
    Oral dosage (immediate-release)
    Adults

    250 mg PO 3 days per week has been recommended to prevent occurrence of bronchiolitis obliterans.

    For the adjunctive treatment of diphtheria†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 14 days as an adjunct to diphtheria antitoxin.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 14 days as an adjunct to diphtheria antitoxin.

    For the post-exposure diphtheria prophylaxis† of close contacts of persons with diphtheria.
    Oral dosage (immediate-release)
    Adults

    500 mg PO once daily for 7 days.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose (Max: 500 mg/dose) PO once daily for 7 days.

    For post-exposure meningococcal infection prophylaxis†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO as a single dose. Not recommended for first-line use; use in the rare circumstance of sustained ciprofloxacin-resistance in a community. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value. 

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO as a single dose. Not recommended for first-line use; use in the rare circumstance of sustained ciprofloxacin-resistance in a community. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.

    Geriatric

    500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.

    Adolescents

    16 to 17 years: 500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose; 500 mg/day IV infusion.
    13 to 15 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) or 1,200 mg/day are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.

    Children

    2 to 12 years: For the immediate-release oral suspension or tablets, 12 mg/kg/day PO (Max: 500 mg/dose) and single doses up to 30 mg/kg PO (Max: 1.5 g/dose) are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO (Max: 1,000 mg/day) are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO (Max: 2 g/dose). Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day (Max: 500 mg/dose) have been used off-label.
    1 year: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.

    Infants

    6 to 11 months: For the immediate-release oral suspension or tablets, 10 mg/kg/day PO and single doses up to 30 mg/kg PO are the maximum FDA-approved dosages; however, doses up to 20 mg/kg/day PO are used off-label. For extended-release oral suspension, 60 mg/kg single dose PO. Safety and efficacy have not been established for IV; however, doses up to 10 mg/kg/day have been used off-label.
    3 to 5 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO or 10 mg/kg/day IV have been used off-label.
    1 to 2 months: Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.

    Neonates

    Safety and efficacy have not been established; however, doses up to 20 mg/kg/day PO have been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage adjustment recommendations are not available; azithromycin has not been studied in patients with impaired hepatic function.

    Renal Impairment

    CrCl more than 80 mL/min: No dosage adjustment is needed.
    CrCl 10 to 80 mL/min: No dosage adjustment is recommended.
    CrCl less than 10 mL/min: No dosage adjustment is recommended; however, the manufacturer recommends caution in patients with severe renal impairment since mean AUC is increased roughly 35%.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    May be taken with or without food; however, increased tolerability has been observed when the tablets are taken with food.

    Oral Liquid Formulations

    Oral suspension (immediate-release, bottles for reconstitution):
    Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution may vary from manufacturer to manufacturer.
    Tap the bottle to loosen the powder. Add water in 2 portions and shake well after each portion.
    Azithromycin for oral suspension (100 mg/5 mL or 200 mg/5 mL strengths) may be taken with or without food.
    Measure dosage with a calibrated spoon, cup, or oral syringe.
    Storage after reconstitution: Store at 5 to 30 degrees C (41 to 86 degrees F). Discard any unused portion per manufacturer recommendations.[28855]
     
    Oral suspension (1 gram single-dose packet):
    Do not use for administration of doses other than 1 gram.
    Zithromax for oral suspension (1-g single-dose packet) may be taken with or without food; however, administration with food may increase tolerability.
    Mix the entire contents of the packet in 60 mL (approximately 2 ounces) of water. Administer the entire contents immediately, then add an additional 60 mL of water, mix and administer to assure complete administration of the dosage.[43975]
     
    Oral suspension (extended-release, bottles for reconstitution):
    Extended-release oral suspension (2 grams azithromycin) should be taken as a single dose at least 1 hour before or 2 hours after a meal.
    If a patient vomits within 5 minutes of the dose, the manufacturer recommends additional antibiotic treatment due to minimal absorption of the azithromycin dose. If a patient vomits between 5 to 60 minutes following the dose, consider alternate therapy. In patients with normal gastric emptying, if vomiting occurs 60 minutes or later after the dose, no additional antibiotic therapy is warranted. In patients with delayed gastric emptying, consider alternative therapy.
    Constitute with 60 mL of water, replace cap, and shake bottle well.
    Storage after reconstitution: Do not refrigerate. Use within 12 hours.[34473]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution:
    NOTE: When using the Vial-Mate drug reconstitution device, please refer to the Vial-Mate instructions for assembly and reconstitution.[43974]
    Add 4.8 mL of Sterile Water Injection to a concentration of 100 mg/mL.
    Because the vial is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of sterile water is dispensed.
    Shake until all of the drug is dissolved.
    Further dilution is required.
    Storage: The reconstituted solution is stable for 24 hours when stored below 30 degrees C (86 degrees F).[43974]
     
    Dilution:
    Dilute by transferring 5 mL of the reconstituted solution into a compatible diluent; use 500 mL of diluent for a concentration of 1 mg/mL and 250 mL of diluent for a concentration of 2 mg/mL.
    Compatible diluents include: 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and 0.45% Sodium Chloride Injection with 20 mEq KCl, 5% Dextrose and Lactated Ringer's Injection, 5% Dextrose and 0.3% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, Normosol-M and 5% Dextrose Injection, and Normosol-R and 5% Dextrose Injection.
    Storage: Diluted solutions are stable for 24 hours at or below room temperature (30 degrees C or 86 degrees F) or for 7 days if stored under refrigeration (5 degrees C or 41 degrees F).[43974]
     
    Intravenous infusion:
    Do not administer intramuscularly or via IV bolus.
    Other intravenous substances, additives, or medications should not be added to azithromycin or infused simultaneously through the same IV line.
    For a dose of 500 mg in 250 mL (concentration = 2 mg/mL), infuse over 1 hour. For a dose of 500 mg in 500 mL (concentration = 1 mg/mL), infuse over 3 hours.[43974]

    Ophthalmic Administration

    For ophthalmic use only. Apply topically only to the eye.
    Instruct patient on proper instillation of eye solution.
    Avoid contamination of the eye solution; do not touch the tip of the eye dropper to the eye, fingertips, or other surface.
    Due to the difficulty of administering eye drops to pediatric patients, consider a 2 person administration approach to ensure proper installation of the drops (1 person to hold the eyelids open and 1 person to administer the drops).
    To avoid contamination, do not share an opened bottle among patients.[43976]

    STORAGE

    Generic:
    - Reconstituted product is stable for up to 24 hours at or below 86 degrees F, or for up to 7 days if refrigerated (41 degrees F)
    Azasite:
    - Avoid excessive heat (above 104 degrees F)
    - Discard within 14 days after first use
    - Store opened container between 36 to 77 degrees F for up to 14 days
    - Store unopened containers in refrigerator (36 to 46 degrees F)
    Zithromax:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zithromax Tri-Pak:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zithromax Z-Pak:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zmax:
    - Do not freeze
    - Do not refrigerate
    - Store below 86 degrees F
    - Store reconstituted product at 77 degrees F; excursions permitted to 59-86 degrees F
    - Use within 12 hours after reconstitution

    CONTRAINDICATIONS / PRECAUTIONS

    Viral infection

    Azithromycin does not treat viral infection (e.g., common cold). Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier.

    Macrolide hypersensitivity, risk of serious hypersensitivity reactions or anaphylaxis

    Azithromycin is contraindicated in patients with a known azithromycin or macrolide hypersensitivity. Azithromycin has a rare risk of serious hypersensitivity reactions or anaphylaxis, including angioedema and severe dermatologic reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis. Fatalities associated with these severe reactions have been reported. There is a risk of cross sensitivity with other macrolide antibiotics. Some patients have a recurrence of allergic symptoms once symptomatic treatment is withdrawn, even though azithromycin therapy is not reinstated.

    Hepatic disease, hepatitis, jaundice

    Systemic azithromycin is contraindicated in patients with a history of jaundice and/or hepatic dysfunction associated with the prior use of azithromycin. Systemically administered azithromycin should be used with caution in patients who have hepatic disease. In addition, abnormal hepatic function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported with use, including cases that have resulted in death. Monitor liver function tests in patients receiving systemic azithromycin. Discontinue treatment immediately if signs and symptoms of hepatitis and liver dysfunction occur.

    Renal failure, renal impairment

    Safe use of systemically-administered azithromycin in patients with severe renal impairment has not been determined; limited data are available. Azithromycin should be used cautiously in patients with preexisting severe renal impairment or renal failure (CrCl less than 10 ml/min).

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including azithromycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Macrolides are associated with QT prolongation; cases of cardiac arrhythmias and torsade de pointes (TdP) have been reported during postmarketing surveillance.[34473] Caution is warranted when using the drug in high-risk patients, including those with known prolongation of the QT interval or a history of TdP.[34473] Use azithromycin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457]  [56592] [65180] In patients taking azithromycin with another drug that prolongs the QT interval (see Therapeutic Drug Monitoring for recommendations specific to using azithromycin with chloroquine or hydroxychloroquine in the treatment of COVID-19), obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device. Obtain baseline electrolytes, including calcium, magnesium, and potassium. Determine if the patient is currently on any QT-prolonging medications that can be discontinued. Document high-risk cardiovascular and comorbid conditions. If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then again at 48 and 96 hours after treatment initiation. If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpuberal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. Data from a cohort study in adults have associated azithromycin with an increased risk of cardiovascular death. The study included persons receiving prescriptions for azithromycin (n = 347,795), amoxicillin (n = 1,348,672), ciprofloxacin (n = 264,626), levofloxacin (n = 193,906), and matched persons receiving no antibiotics (n = 1,391,180). Analysis of the data found those persons receiving a 5-day course of azithromycin had a significantly greater risk of cardiovascular death than persons not treated with antibiotics (HR: 2.88; 95% CI: 1.79 to 4.63; p less than 0.001), persons treated with 5 days of amoxicillin (HR: 2.49; 95% CI: 1.38 to 4.50; p = 0.002), and persons in the first 5 days of ciprofloxacin therapy (HR: 3.49; 95% CI: 1.32 to 9.26; p = 0.01); mortality rate did not differ from levofloxacin.[50182] [50183]

    Geriatric

    Clinical trials of oral and intravenous azithromycin and other reported clinical experience has not identified overall differences in safety and effectiveness between geriatric and younger adult subjects. Greater sensitivity of some older individuals cannot be ruled out. Health care providers are advised that geriatric patients may be more susceptible to drug-associated effects on the QT interval. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Pregnancy

    Available data over several decades with systemic azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Developmental toxicity studies in animals showed no drug-induced fetal malformations at doses up to 4 times the adult human daily dose of 500 mg based on body surface area; however, decreased viability and delayed development were observed in the offspring of pregnant rats given azithromycin at a dose equivalent to 4 times the adult human daily dose from day 6 of pregnancy through weaning.[28855] In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, systemic azithromycin use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 1.65, 95% CI 1.34 to 2.02, 110 exposed cases); residual confounding by severity of infection may be a potential limitation of this study.[62176] In a large population-based cohort study (n = 104,605 live births) assessing systemic macrolide (n = 8,632) or penicillin (n = 95,973) use during pregnancy and the risk of major malformations, macrolide use in the first trimester was associated with increased risk of any malformation (27.7 vs. 17.7 per 1,000 live births; adjusted risk ratio 1.55, 95% CI 1.19 to 2.03), and in particular, cardiovascular malformations (10.6 vs. 6.6 per 1,000 live births; adjusted risk ratio 1.62, 95% CI 1.05 to 2.51). Specific findings for azithromycin use during the first trimester were precluded due to few events. Macrolide use during the second and third trimesters showed no increased risk of any major malformation (19.5 vs. 17.3 per 1,000 live births; adjusted risk ratio 1.13, 95% CI 0.94 to 1.36); however, a borderline association with gastrointestinal malformations was observed (adjusted risk ratio 1.89, 95% CI 1 to 3.58). Macrolide use in any trimester was associated with an increased risk of genital malformations (adjusted risk ratio 1.58, 95% CI 1.14 to 2.19), mainly hypospadias.[65012] Additionally, in another large population-based cohort study (n = 139,938 live births) assessing systemic antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, macrolide exposure was associated with an increased risk of digestive system malformations (adjusted odds ratio (aOR) 1.46, 95% CI 1.04 to 2.06, 35 exposed cases).[62177]

    Infants, neonates

    Use azithromycin with caution and with proper monitoring in young infants and neonates; there have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in young infants after azithromycin therapy. Because azithromycin is sometimes used for the treatment of conditions that are associated with significant mortality or morbidity (e.g., pertussis), weigh the benefit of azithromycin therapy against the potential risk of developing IHPS. Inform parents and other caregivers to contact their physician if vomiting or irritability with feeding occurs. In a retrospective study of 148 infants given azithromycin during the first 14 days of life, IHPS developed in 3 patients (2%) for an odds ratio of 8.26 (95% CI: 2.62 to 26; p less than 0.001). Of 729 infants aged 15 to 42 days at the time of azithromycin exposure, 5 patients developed IHPS for an OR of 2.98 (95% CI: 1.24 to 7.2; p = 0.015). A male predominance was also observed, as all 8 infants who developed IHPS were boys. No infants aged 43 to 90 days at the time of azithromycin exposure developed IHPS; however, there have been 2 case reports of older infants developing IHPS (89 and 94 days old at diagnosis, respectively).

    Breast-feeding

    Azithromycin is present in human breast milk. Non-serious adverse reactions have been reported in breast-fed infants after maternal administration of azithromycin. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for azithromycin and any potential adverse effects on the breast-fed infant from azithromycin or the underlying maternal condition. Monitor the breast-fed infant for diarrhea, vomiting, or rash. There are no available data on the effects of azithromycin on milk production. Azithromycin breast milk concentrations were measured in 20 women receiving a single 2 g oral dose during labor. Azithromycin was present in breast milk up to 4 weeks after dosing. Another study of 8 women receiving azithromycin IV before incision of cesarean section showed azithromycin was present in breast milk up to 48 hours later.[28855] A prospective observational study assessing the safety of macrolide antibiotics during lactation found that 12.7% (n = 55) of babies exposed to macrolides via breast milk experienced adverse events including rash, diarrhea, loss of appetite, and somnolence. The adverse event rate was similar to that seen in babies in a control group whose mothers were treated with amoxicillin (8.3%). Only 10 mothers in the study received azithromycin, 6 received clarithromycin, 2 received erythromycin, and the remainder were treated with roxythromycin.[45767] A population-based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3 to 3 times more likely to have been exposed to a macrolide antibiotic through breast milk during the first 90 days of life than babies not exposed during that same time period. The study did not specify which antibiotic the mothers of affected babies were prescribed; however, the majority of macrolide prescriptions were for erythromycin (72%), with 7% for azithromycin and 1.7% for clarithromycin.[45779] Previous American Academy of Pediatrics (AAP) recommendations consider erythromycin to be usually compatible with breast-feeding; azithromycin has not been evaluated by the AAP.[27500]

    Sunlight (UV) exposure

    Direct sunlight (UV) exposure should be minimized during therapy with systemic azithromycin. Photosensitivity has been reported as an adverse reaction to azithromycin.

    Sodium restriction

    Some intravenous formulations of azithromycin contain a total of 4.96 mEq (114 mg) of sodium per 500-mg vial. The sodium amounts should be considered in patients with requirements for sodium restriction or blunted natriuresis to salt loading (i.e., cardiac disease or hypertension).

    Contact lenses

    Patients who wear contact lenses should avoid wearing them while being treated for an ocular infection with azithromycin ophthalmic solution.

    Myasthenia gravis

    Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving systemic azithromycin therapy.

    Sexually transmitted disease

    While azithromycin may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Allogeneic stem cell transplant, leukemia, lymphoma

    Do not use azithromycin for long-term prophylaxis of bronchiolitis obliterans syndrome (BOS) in patients with cancers of the blood or lymph nodes (i.e. leukemia, lymphoma) who undergo an allogeneic stem cell transplant because of the increased risk for cancer relapse or death.

    ADVERSE REACTIONS

    Severe

    hyperkalemia / Delayed / 1.0-2.0
    pleural effusion / Delayed / 0-1.0
    uveitis / Delayed / 0-1.0
    eczema vaccinatum / Delayed / 0-1.0
    angioedema / Rapid / 0-1.0
    bronchospasm / Rapid / 0-1.0
    keratitis / Delayed / 0-1.0
    corneal erosion / Delayed / 0-1.0
    visual impairment / Early / 0-1.0
    lymphoma / Delayed / 0-1.0
    leukemia / Delayed / 0-1.0
    azotemia / Delayed / 0-1.0
    pancreatitis / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    hearing loss / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    pyloric stenosis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 1.0-6.0
    erythema / Early / 3.1-3.1
    hyperbilirubinemia / Delayed / 0-3.0
    vaginitis / Delayed / 0-2.8
    stomatitis / Delayed / 1.9-1.9
    dyspnea / Early / 0-1.9
    melena / Delayed / 0-1.0
    gastritis / Delayed / 0-1.0
    constipation / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    jaundice / Delayed / 0-1.0
    superinfection / Delayed / 0-1.0
    anemia / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    palpitations / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    conjunctivitis / Delayed / 0-1.0
    contact dermatitis / Delayed / 0-1.0
    atopic dermatitis / Delayed / 0-1.0
    blurred vision / Early / 0-1.0
    hyponatremia / Delayed / 0-1.0
    hypokalemia / Delayed / 0-1.0
    dysuria / Early / 0-1.0
    lymphocytosis / Delayed / 1.0
    eosinophilia / Delayed / 1.0
    lymphopenia / Delayed / 1.0
    hypoglycemia / Early / 1.0
    hyperglycemia / Delayed / 1.0
    hepatitis / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    edema / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known

    Mild

    nausea / Early / 0.4-18.0
    diarrhea / Early / 1.8-14.0
    abdominal pain / Early / 1.2-14.0
    vomiting / Early / 0-14.0
    injection site reaction / Rapid / 1.9-12.0
    rash / Early / 0-8.1
    flatulence / Early / 0-5.0
    headache / Early / 0-5.0
    fatigue / Early / 0-3.9
    dizziness / Early / 0-3.9
    pruritus / Rapid / 0-3.9
    tinnitus / Delayed / 0.9-3.4
    arthralgia / Delayed / 0-3.0
    fever / Early / 0-2.1
    anorexia / Delayed / 0-2.0
    ocular irritation / Rapid / 1.0-2.0
    dysgeusia / Early / 0-1.3
    malaise / Early / 0-1.1
    dyspepsia / Early / 0-1.0
    pharyngitis / Delayed / 0-1.0
    cough / Delayed / 0-1.0
    sinusitis / Delayed / 0-1.0
    rhinitis / Early / 0-1.0
    nasal congestion / Early / 0-1.0
    paresthesias / Delayed / 0-1.0
    chills / Rapid / 0-1.0
    asthenia / Delayed / 0-1.0
    agitation / Early / 0-1.0
    vertigo / Early / 0-1.0
    insomnia / Early / 0-1.0
    drowsiness / Early / 0-1.0
    hyperkinesis / Delayed / 0-1.0
    emotional lability / Early / 0-1.0
    irritability / Delayed / 0-1.0
    vesicular rash / Delayed / 0-1.0
    diaphoresis / Early / 0-1.0
    maculopapular rash / Early / 0-1.0
    photosensitivity / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    ocular pruritus / Rapid / 0-1.0
    xerophthalmia / Early / 0-1.0
    ocular pain / Early / 0-1.0
    ocular discharge / Delayed / 0-1.0
    tongue discoloration / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    syncope / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    dysosmia / Delayed / Incidence not known
    anosmia / Delayed / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    Aclidinium; Formoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Alfuzosin: (Major) Avoid coadministration of azithromycin with alfuzosin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Alfuzosin may prolong the QT interval in a dose-dependent manner.
    Aluminum Hydroxide: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Amiodarone: (Major) Avoid coadministration of amiodarone and azithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Reports of QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation was reported in a 68-year old woman receiving azithromycin and amiodarone. The patient had a history of stable congestive heart failure and a posterior communicating artery aneurysm. She was receiving amiodarone (200 mg/day) for over a year for paroxysmal atrial fibrillation. Additional medications included furosemide, enalapril, and aspirin. A regular sinus rhythm with normal P-R, QRST, and QTc intervals was noted prior to initiation of azithromycin therapy. Therapy with azithromycin was started at 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days. Sinus bradycardia with marked QT prolongation and increased QT dispersion were noted on day 3 of treatment. Azithromycin was discontinued; QT and QTc intervals and QT dispersion returned to baseline in 4 days. Hypokalemia or hypomagnesemia were not noted in the patient and the amiodarone dose remained consistent at 200 mg/day.
    Amisulpride: (Major) Avoid coadministration of azithromycin with amisulpride due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Amisulpride causes dose- and concentration- dependent QT prolongation.
    Amitriptyline: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Anagrelide: (Major) Avoid coadministration of azithromycin with anagrelide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects.
    Apomorphine: (Major) Avoid coadministration of azithromycin with apomorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Arformoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Major) Avoid coadministration of azithromycin with aripiprazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) Avoid coadministration of azithromycin with arsenic trioxide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
    Artemether; Lumefantrine: (Major) Avoid coadministration of azithromycin with artemether; lumefantrine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Artemether; lumefantrine is associated with prolongation of the QT interval.
    Asenapine: (Major) Avoid coadministration of azithromycin with asenapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Asenapine has been associated with QT prolongation.
    Aspirin, ASA; Pravastatin: (Moderate) Azithromycin has the potential to increase pravastatin exposure when used concomitantly. Coadminister pravastatin and azithromycin cautiously due to a potential increased risk of myopathies.
    Atomoxetine: (Major) Avoid coadministration of azithromycin with atomoxetine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Bedaquiline: (Major) Avoid coadministration of azithromycin with bedaquiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 ms. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Bedaquiline prolongs the QT interval.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Carefully monitor patients when azithromycin and ergotamine are used concomitantly. Pharmacokinetic and/or pharmacodynamic interactions with ergotamine have been observed with other macrolides.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Budesonide; Formoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Buprenorphine: (Major) Avoid coadministration of azithromycin with buprenorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
    Buprenorphine; Naloxone: (Major) Avoid coadministration of azithromycin with buprenorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
    Cabotegravir; Rilpivirine: (Major) Avoid coadministration of azithromycin with rilpivirine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Ceritinib: (Major) Avoid coadministration of azithromycin with ceritinib if possible due to the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Chlordiazepoxide; Amitriptyline: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Chloroquine: (Major) Avoid coadministration of chloroquine with azithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances (See Therapeutic Drug Monitoring for recommendations specific to COVID-19). Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Chlorpromazine: (Major) Avoid coadministration of azithromycin with chlorpromazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Chlorpromazine is associated with an established risk of QT prolongation and TdP.
    Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received azithromycin within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as azithromycin, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
    Ciprofloxacin: (Major) Avoid coadministration of azithromycin with ciprofloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Contraindicated) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Azithromycin is contraindicated with other drugs that have been specifically established that have a causal association with QT prolongation and torsade de pointes, such as cisapride.
    Citalopram: (Major) Avoid coadministration of azithromycin with citalopram due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Citalopram causes dose-dependent QT interval prolongation.
    Clofazimine: (Major) Avoid coadministration of azithromycin with clofazimine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and TdP have been reported in patients receiving clofazimine in combination with QT prolonging medications.
    Clomipramine: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Clozapine: (Major) Avoid coadministration of azithromycin with clozapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
    Codeine; Phenylephrine; Promethazine: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Codeine; Promethazine: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Colchicine: (Moderate) Caution is warranted with the concomitant use of colchicine and azithromycin as increased colchicine concentrations may occur. Monitor for colchicine toxicity. Colchicine accumulation may be greater in patients with renal or hepatic impairment. Coadministration with azithromycin resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
    Conjugated Estrogens; Bazedoxifene: (Moderate) Coadministration of azithromycin and bazedoxifene increased the Cmax of bazedoxifene by 6% and decreased AUC of bazedoxifene by 15%. The clinical effect of these changes is not described.
    Crizotinib: (Major) Avoid coadministration of crizotinib with azithromycin due to the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Cyclosporine: (Moderate) Caution is warranted with the concomitant use of azithromycin and cyclosporine as increased cyclosporine concentrations may occur. Dose adjustment of cyclosporine may be necessary; monitor cyclosporine serum concentrations during use with azithromycin and after discontinuation of azithromycin.
    Dasatinib: (Major) Avoid coadministration of azithromycin with dasatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Degarelix: (Major) Avoid coadministration of azithromycin with degarelix due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
    Desflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Desipramine: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Deutetrabenazine: (Major) Avoid coadministration of azithromycin with deutetrabenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Avoid coadministration of azithromycin with quinidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinidine administration is associated with QT prolongation and TdP.
    Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Digoxin: (Moderate) Monitor digoxin concentrations before and during concomitant use of azithromycin and reduce the digoxin dose if necessary. Elevated digoxin concentrations have been observed when azithromycin has been coadministered with digoxin.
    Dihydroergotamine: (Minor) Carefully monitor patients when azithromycin and dihydroergotamine are used concomitantly. Pharmacokinetic and/or pharmacodynamic interactions with dihydroergotamine have been observed with other macrolides.
    Disopyramide: (Major) Avoid coadministration of azithromycin with disopyramide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Disopyramide is associated with QT prolongation and TdP.
    Dofetilide: (Major) Avoid coadministration of azithromycin with dofetilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP.
    Dolasetron: (Major) Avoid coadministration of azithromycin with dolasetron due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Major) Avoid coadministration of azithromycin with rilpivirine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Donepezil: (Major) Avoid coadministration of azithromycin with donepezil due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
    Donepezil; Memantine: (Major) Avoid coadministration of azithromycin with donepezil due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
    Doxepin: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Dronedarone: (Contraindicated) Coadministration of dronedarone and azithromycin is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). There have been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Avoid coadministration of azithromycin with droperidol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Droperidol administration is associated with an established risk for QT prolongation and TdP. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Efavirenz: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of azithromycin with efavirenz due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QTc prolongation has been observed with the use of efavirenz.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Eliglustat: (Major) Avoid coadministration of azithromycin with eliglustat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of azithromycin with rilpivirine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Avoid coadministration of azithromycin with rilpivirine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Encorafenib: (Major) Avoid coadministration of azithromycin with encorafenib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Enflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Entrectinib: (Major) Avoid coadministration of azithromycin with entrectinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Entrectinib has been associated with QT prolongation.
    Ergotamine: (Minor) Carefully monitor patients when azithromycin and ergotamine are used concomitantly. Pharmacokinetic and/or pharmacodynamic interactions with ergotamine have been observed with other macrolides.
    Ergotamine; Caffeine: (Minor) Carefully monitor patients when azithromycin and ergotamine are used concomitantly. Pharmacokinetic and/or pharmacodynamic interactions with ergotamine have been observed with other macrolides.
    Eribulin: (Major) Avoid coadministration of azithromycin with eribulin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eribulin has been associated with QT prolongation.
    Escitalopram: (Major) Avoid coadministration of azithromycin with escitalopram due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Escitalopram has been associated with a risk of QT prolongation and TdP.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ezogabine: (Major) Avoid coadministration of azithromycin with ezogabine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ezogabine has been associated with QT prolongation.
    Fingolimod: (Major) Avoid coadministration of azithromycin with fingolimod due to the increased risk of QT prolongation. If concomitant use is unavoidable, overnight monitoring with continuous ECG in a medical facility is advised after the first dose of fingolimod; monitor ECG closely throughout therapy, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Avoid coadministration of azithromycin with flecainide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Flecainide is a Class IC antiarrhythmic and is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as azithromycin, may have an increased risk of developing proarrhythmias.
    Fluconazole: (Major) Avoid coadministration of azithromycin with fluconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Fluoxetine: (Major) Avoid coadministration of azithromycin with fluoxetine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and TdP have been reported in patients treated with fluoxetine.
    Fluphenazine: (Major) Avoid coadministration of azithromycin with fluphenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Fluticasone; Salmeterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvoxamine: (Major) Avoid coadministration of azithromycin with fluvoxamine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and TdP have been reported during fluvoxamine postmarketing use.
    Formoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Foscarnet: (Major) Avoid coadministration of azithromycin with foscarnet due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Both QT prolongation and TdP have been reported during postmarketing use of foscarnet.
    Fosphenytoin: (Minor) Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with fosphenytoin. Azithromycin was not implicated in clinical trials with drug interactions with fosphenytoin. However, specific drug interaction studies have not been performed with the combination of azithromycin and fosphenytoin.
    Fostemsavir: (Major) Avoid coadministration of azithromycin with fostemsavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gemifloxacin: (Major) Avoid coadministration of azithromycin with gemifloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of azithromycin with gemtuzumab due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
    Gilteritinib: (Major) Avoid coadministration of azithromycin with gilteritinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Gilteritinib has been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of azithromycin with glasdegib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
    Glycopyrrolate; Formoterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Goserelin: (Major) Avoid coadministration of azithromycin with goserelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
    Granisetron: (Major) Avoid coadministration of azithromycin with granisetron due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Granisetron has been associated with QT prolongation.
    Halogenated Anesthetics: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Haloperidol: (Major) Avoid coadministration of azithromycin with haloperidol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Halothane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Histrelin: (Major) Avoid coadministration of azithromycin with histrelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and azithromycin due the risk of additive QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances (See Therapeutic Drug Monitoring for recommendations specific to COVID-19). Hydroxychloroquine prolongs the QT interval. QT prolongation and torsade de pointe (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Hydroxyzine: (Major) Avoid coadministration of azithromycin with hydroxyzine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Ibutilide: (Major) Avoid coadministration of azithromycin with ibutilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Iloperidone: (Major) Avoid coadministration of azithromycin with iloperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Iloperidone has been associated with QT prolongation.
    Imipramine: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Indacaterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with azithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Avoid any non-essential QT prolonging drugs and correct electrolyte imbalances. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance.
    Ipratropium; Albuterol: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Isoflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Itraconazole: (Major) Avoid coadministration of azithromycin with itraconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Itraconazole has been associated with prolongation of the QT interval.
    Ivosidenib: (Major) Avoid coadministration of azithromycin with ivosidenib due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Ketoconazole: (Major) Avoid coadministration of azithromycin with ketoconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ketoconazole has been associated with prolongation of the QT interval.
    Lapatinib: (Major) Avoid coadministration of azithromycin with lapatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
    Lefamulin: (Major) Avoid coadministration of azithromycin with lefamulin as concurrent use may increase the risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs. and correct electrolyte imbalances. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Lenvatinib: (Major) Avoid coadministration of azithromycin with lenvatinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Prolongation of the QT interval has been reported with lenvatinib therapy.
    Leuprolide: (Major) Avoid coadministration of azithromycin with leuprolide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of azithromycin with leuprolide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levalbuterol: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levofloxacin: (Major) Avoid coadministration of azithromycin with levofloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Lithium: (Major) Avoid coadministration of azithromycin with lithium due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lithium has also been associated with QT prolongation.
    Lofexidine: (Major) Avoid coadministration of azithromycin with lofexidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lofexidine prolongs the QT interval.
    Long-acting beta-agonists: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Major) Avoid coadministration of azithromycin with loperamide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Loperamide; Simethicone: (Major) Avoid coadministration of azithromycin with loperamide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of azithromycin with lopinavir; ritonavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Lopinavir; ritonavir is associated with QT prolongation.
    Macimorelin: (Major) Avoid coadministration of azithromycin with macimorelin due to the increased risk of QT prolongation and torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval.
    Magnesium Hydroxide: (Moderate) Antacids containing aluminum salts and/or magnesium salts can decrease the oral absorption of immediate-release azithromycin, resulting in lower peak plasma concentrations. If antacids must be taken, stagger the administration of the antacid and azithromycin. The extended-release suspension may be taken without regard to antacids containing magnesium hydroxide and/or aluminum hydroxide.
    Maprotiline: (Major) Avoid coadministration of azithromycin with maprotiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Major) Avoid coadministration of azithromycin with mefloquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
    Meperidine; Promethazine: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Metaproterenol: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Methadone: (Major) Avoid coadministration of azithromycin with methadone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Metronidazole: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midostaurin: (Major) Avoid coadministration of azithromycin with midostaurin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs. and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation was reported in patients who received midostaurin in clinical trials.
    Mifepristone: (Major) Avoid coadministration of azithromycin with mifepristone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Mirtazapine: (Major) Avoid coadministration of azithromycin with mirtazapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. TdP has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation.
    Mobocertinib: (Major) Concomitant use of mobocertinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Avoid coadministration of azithromycin with moxifloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nelfinavir: (Moderate) Coadministration of nelfinavir and azithromycin results in increased azithromycin concentrations. Dosage adjustments are not necessary, although patients should be monitored for azithromycin related adverse effects such as increased hepatic enzymes and hearing impairment.
    Nilotinib: (Major) Avoid coadministration of azithromycin with nilotinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Nortriptyline: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Octreotide: (Major) Avoid coadministration of azithromycin with octreotide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Avoid coadministration of azithromycin with ofloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Major) Avoid coadministration of azithromycin with olanzapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Olanzapine; Fluoxetine: (Major) Avoid coadministration of azithromycin with fluoxetine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and TdP have been reported in patients treated with fluoxetine. (Major) Avoid coadministration of azithromycin with olanzapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Olanzapine; Samidorphan: (Major) Avoid coadministration of azithromycin with olanzapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Olodaterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ondansetron: (Major) Avoid coadministration of azithromycin with ondansetron due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Osilodrostat: (Major) Avoid coadministration of azithromycin with osilodrostat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Major) Avoid coadministration of azithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
    Oxaliplatin: (Major) Avoid coadministration of azithromycin with oxaliplatin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Ozanimod: (Major) Avoid coadministration of azithromycin with ozanimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
    Paliperidone: (Major) Avoid coadministration of azithromycin with paliperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose.
    Panobinostat: (Major) Avoid coadministration of azithromycin with panobinostat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation has been reported with panobinostat.
    Pasireotide: (Major) Avoid coadministration of azithromycin with pasireotide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
    Pazopanib: (Major) Avoid coadministration of azithromycin with pazopanib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Pazopanib has been reported to prolong the QT interval.
    Pentamidine: (Major) Avoid coadministration of azithromycin with pentamidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Systemic pentamidine has been associated with QT prolongation.
    Perphenazine: (Major) Avoid coadministration of azithromycin with perphenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Perphenazine; Amitriptyline: (Major) Avoid coadministration of azithromycin with perphenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Phenytoin: (Minor) Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with phenytoin. Azithromycin was not implicated in clinical trials with drug interactions with phenytoin. However, specific drug interaction studies have not been performed with the combination of azithromycin and phenytoin.
    Pimavanserin: (Major) Avoid coadministration of azithromycin with pimavanserin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Pimavanserin prolongs the QT interval.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
    Pirbuterol: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Pitolisant: (Major) Avoid coadministration of azithromycin with pitolisant due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Pitolisant prolongs the QT interval.
    Ponesimod: (Major) Avoid coadministration of azithromycin with ponesimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia
    Posaconazole: (Major) Avoid coadministration of azithromycin with posaconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
    Pravastatin: (Moderate) Azithromycin has the potential to increase pravastatin exposure when used concomitantly. Coadminister pravastatin and azithromycin cautiously due to a potential increased risk of myopathies.
    Primaquine: (Major) Avoid coadministration of azithromycin with primaquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Primaquine has the potential for QT interval prolongation.
    Probenecid; Colchicine: (Moderate) Caution is warranted with the concomitant use of colchicine and azithromycin as increased colchicine concentrations may occur. Monitor for colchicine toxicity. Colchicine accumulation may be greater in patients with renal or hepatic impairment. Coadministration with azithromycin resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
    Procainamide: (Major) Avoid coadministration of azithromycin with procainamide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Prochlorperazine: (Major) Avoid coadministration of azithromycin with prochlorperazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Promethazine: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Promethazine; Dextromethorphan: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Promethazine; Phenylephrine: (Major) Avoid coadministration of azithromycin with promethazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Promethazine is associated with possible risk for QT prolongation.
    Propafenone: (Major) Avoid coadministration of azithromycin with propafenone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
    Protriptyline: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Quetiapine: (Major) Avoid coadministration of azithromycin with quetiapine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Quinidine: (Major) Avoid coadministration of azithromycin with quinidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinidine administration is associated with QT prolongation and TdP.
    Quinine: (Major) Avoid coadministration of azithromycin with quinine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinine has been associated with QT prolongation and rare cases of TdP.
    Ranolazine: (Major) Avoid coadministration of azithromycin with ranolazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Relugolix: (Major) Avoid coadministration of azithromycin with relugolix due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of azithromycin with relugolix due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ribociclib: (Major) Avoid coadministration of azithromycin with ribociclib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
    Ribociclib; Letrozole: (Major) Avoid coadministration of azithromycin with ribociclib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
    Rilpivirine: (Major) Avoid coadministration of azithromycin with rilpivirine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Risperidone: (Major) Avoid coadministration of azithromycin with risperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Romidepsin: (Major) Avoid coadministration of azithromycin with romidepsin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Romidepsin has been reported to prolong the QT interval.
    Salmeterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Saquinavir: (Major) Avoid coadministration of azithromycin with saquinavir boosted with ritonavir due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Selpercatinib: (Major) Avoid coadministration of azithromycin and selpercatinib due to the risk of additive QT prolongation. Monitor ECG and electrolytes and avoid other non-essential QT prolonging drugs if use together is required. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
    Sertraline: (Major) Avoid coadministration of azithromycin with sertraline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
    Short-acting beta-agonists: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Siponimod: (Major) Avoid coadministration of azithromycin with siponimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Solifenacin: (Major) Avoid coadministration of azithromycin with solifenacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Sorafenib: (Major) Avoid coadministration of azithromycin with sorafenib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sorafenib is also associated with QTc prolongation.
    Sotalol: (Major) Avoid coadministration of azithromycin with sotalol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sunitinib: (Major) Avoid coadministration of azithromycin with sunitinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Tacrolimus: (Major) Avoid coadministration of azithromycin with tacrolimus due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Tacrolimus may prolong the QT interval and cause TdP.
    Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with azithromycin is necessary. In clinical trials, coadministration with azithromycin increased talazoparib exposure by approximately 8%.
    Tamoxifen: (Major) Avoid coadministration of azithromycin with tamoxifen due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    Telavancin: (Major) Avoid coadministration of azithromycin with telavancin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Avoid coadministration of azithromycin with telithromycin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Telithromycin is also associated with QT prolongation and TdP.
    Terbutaline: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tetrabenazine: (Major) Avoid coadministration of azithromycin with tetrabenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Thioridazine: (Contraindicated) Coadministration of thioridazine and azithromycin is contraindicated due to an increased risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
    Tiotropium; Olodaterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tolterodine: (Major) Avoid coadministration of azithromycin with tolterodine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
    Toremifene: (Major) Avoid coadministration of azithromycin with toremifene if possible due to the risk of additive QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Trazodone: (Major) Avoid coadministration of azithromycin with trazodone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP.
    Triclabendazole: (Major) Avoid coadministration of azithromycin with triclabendazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole.
    Tricyclic antidepressants: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Trifluoperazine: (Major) Avoid coadministration of azithromycin with trifluoperazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Trimipramine: (Major) Avoid coadministration of azithromycin with tricyclic antidepressants (TCAs) due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Triptorelin: (Major) Avoid coadministration of azithromycin with triptorelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
    Umeclidinium; Vilanterol: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Vandetanib: (Major) Avoid coadministration of azithromycin with vandetanib due to an increased risk of QT prolongation and torsade de pointes (TdP). If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
    Vardenafil: (Major) Avoid coadministration of azithromycin with vardenafil due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    Vemurafenib: (Major) Avoid coadministration of azithromycin with vemurafenib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Vemurafenib has been associated with QT prolongation.
    Venlafaxine: (Major) Avoid coadministration of azithromycin with venlafaxine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has reported with postmarketing use.
    Voclosporin: (Major) Avoid concomitant use of azithromycin and voclosporin due to the risk of additive QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    Voriconazole: (Major) Avoid coadministration of azithromycin with voriconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP.
    Vorinostat: (Major) Avoid coadministration of azithromycin with vorinostat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Vorinostat is associated with a risk of QT prolongation.
    Warfarin: (Moderate) Carefully monitor the PT/INR in patients who receive warfarin and azithromycin concomitantly. Postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin.
    Ziprasidone: (Major) Avoid coadministration of azithromycin with ziprasidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data over several decades with systemic azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Developmental toxicity studies in animals showed no drug-induced fetal malformations at doses up to 4 times the adult human daily dose of 500 mg based on body surface area; however, decreased viability and delayed development were observed in the offspring of pregnant rats given azithromycin at a dose equivalent to 4 times the adult human daily dose from day 6 of pregnancy through weaning.[28855] In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, systemic azithromycin use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 1.65, 95% CI 1.34 to 2.02, 110 exposed cases); residual confounding by severity of infection may be a potential limitation of this study.[62176] In a large population-based cohort study (n = 104,605 live births) assessing systemic macrolide (n = 8,632) or penicillin (n = 95,973) use during pregnancy and the risk of major malformations, macrolide use in the first trimester was associated with increased risk of any malformation (27.7 vs. 17.7 per 1,000 live births; adjusted risk ratio 1.55, 95% CI 1.19 to 2.03), and in particular, cardiovascular malformations (10.6 vs. 6.6 per 1,000 live births; adjusted risk ratio 1.62, 95% CI 1.05 to 2.51). Specific findings for azithromycin use during the first trimester were precluded due to few events. Macrolide use during the second and third trimesters showed no increased risk of any major malformation (19.5 vs. 17.3 per 1,000 live births; adjusted risk ratio 1.13, 95% CI 0.94 to 1.36); however, a borderline association with gastrointestinal malformations was observed (adjusted risk ratio 1.89, 95% CI 1 to 3.58). Macrolide use in any trimester was associated with an increased risk of genital malformations (adjusted risk ratio 1.58, 95% CI 1.14 to 2.19), mainly hypospadias.[65012] Additionally, in another large population-based cohort study (n = 139,938 live births) assessing systemic antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, macrolide exposure was associated with an increased risk of digestive system malformations (adjusted odds ratio (aOR) 1.46, 95% CI 1.04 to 2.06, 35 exposed cases).[62177]

    Azithromycin is present in human breast milk. Non-serious adverse reactions have been reported in breast-fed infants after maternal administration of azithromycin. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for azithromycin and any potential adverse effects on the breast-fed infant from azithromycin or the underlying maternal condition. Monitor the breast-fed infant for diarrhea, vomiting, or rash. There are no available data on the effects of azithromycin on milk production. Azithromycin breast milk concentrations were measured in 20 women receiving a single 2 g oral dose during labor. Azithromycin was present in breast milk up to 4 weeks after dosing. Another study of 8 women receiving azithromycin IV before incision of cesarean section showed azithromycin was present in breast milk up to 48 hours later.[28855] A prospective observational study assessing the safety of macrolide antibiotics during lactation found that 12.7% (n = 55) of babies exposed to macrolides via breast milk experienced adverse events including rash, diarrhea, loss of appetite, and somnolence. The adverse event rate was similar to that seen in babies in a control group whose mothers were treated with amoxicillin (8.3%). Only 10 mothers in the study received azithromycin, 6 received clarithromycin, 2 received erythromycin, and the remainder were treated with roxythromycin.[45767] A population-based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3 to 3 times more likely to have been exposed to a macrolide antibiotic through breast milk during the first 90 days of life than babies not exposed during that same time period. The study did not specify which antibiotic the mothers of affected babies were prescribed; however, the majority of macrolide prescriptions were for erythromycin (72%), with 7% for azithromycin and 1.7% for clarithromycin.[45779] Previous American Academy of Pediatrics (AAP) recommendations consider erythromycin to be usually compatible with breast-feeding; azithromycin has not been evaluated by the AAP.[27500]

    MECHANISM OF ACTION

    Azithromycin inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms. Azithromycin is more active against gram-negative organisms but has less activity against streptococci and staphylococci than does erythromycin; erythromycin-resistant gram-positive isolates demonstrate cross-resistance to azithromycin.[34473] [50470] Azithromycin concentrates in phagocytes and fibroblasts leading to high intracellular concentrations. Drug distribution to inflamed tissues is thought to occur from the concentration in phagocytes.[43975]
     
    The susceptibility interpretive criteria for azithromycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, S. viridans group, and S. pneumoniae as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for S. enterica ser. Typhi as susceptible at 16 mcg/mL or less and resistant at 32 mcg/mL or more. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 4 mcg/mL or less. The MICs are defined for N. meningitidis as susceptible at 2 mcg/mL or less, which may be only appropriate for prophylaxis of meningococcal case contacts and does not apply to treatment of invasive disease. The MICs are defined for N. gonorrhoeae as susceptible at 1 mcg/mL or less, presuming use of a 1 g single dose regimen that includes an additional antimicrobial agent.[63320] [63321]
     
    Macrolides have been reported to have immunomodulatory properties in pulmonary inflammatory disorders. They may downregulate inflammatory responses and reduce the excessive cytokine production associated with respiratory viral infections; however, their direct effects on viral clearance are uncertain. Immunomodulatory mechanisms may include reducing chemotaxis of neutrophils (PMNs) to the lungs by inhibiting cytokines (i.e., IL-8), inhibition of mucus hypersecretion, decreased bacterial adhesion to the epithelium, decreased production of reactive oxygen species, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors.[65149] [65150] [65151] [65152] [65153]

    PHARMACOKINETICS

    Azithromycin is administered orally, intravenously, and topically to the eye. Following systemic administration, it is widely distributed to body tissues and fluids including bone, prostate, ovary, uterus, stomach, liver, middle ear, lung, tonsils and adenoids, and sputum. Azithromycin exhibits significant intracellular penetration and concentrates within fibroblasts and phagocytes. As a result, tissue concentrations are significantly higher than are plasma concentrations. Azithromycin is distributed widely into brain tissue but not into cerebrospinal fluid or the aqueous humor of the eye. Protein binding varies with plasma concentration; 51% of the drug is bound at low concentrations (0.02 mcg/ml) and this binding decreases to 7% at higher concentrations (2 mcg/ml). Azithromycin has a long half-life in both adults (40 to 68 hours) and children (32 to 64 hours), which is partially explained by its extensive tissue uptake and slow release. Elimination is largely in the feces, following excretion into the bile, with less than 14% excreted in the urine.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Oral Route

    Immediate-release suspension
    Peak concentrations of azithromycin occur approximately 2 hours after administration.[51753] Food increases the Cmax by approximately 56%, but the extent of absorption is unaltered.[28855]
     
    Single-dose (1 g) immediate-release suspension
    Administration with food increased the Cmax by 46% and the AUC by 14%.[43975]
     
    250 mg and 500 mg immediate-release tablets
    The absolute bioavailability is approximately 38%. The Cmax for a 5-day regimen of 250 mg PO ranged from 0.24 to 0.43 mcg/mL and the AUC was 14.9 mcg x hour/mL. The Cmax for 3-day regimen of 500 mg PO ranged from 0.44 to 0.54 mcg/mL and the AUC was 17.4 mcg x hour/mL. Food increases the Cmax by approximately 23%, but the extent of absorption is unaltered.[28855]
     
    600 mg immediate-release tablets
    The absolute bioavailability is 34%. For a 1,200 mg dose, the Cmax is 0.33 mcg/mL, the Tmax is 2.5 hours, and the AUC is 6.8 mcg x hour/mL. Administration with food increased the Cmax by 31%; however, the AUC was unchanged.[43975]
     
    Extended-release suspension
    The bioavailability of the extended-release suspension compared to the immediate-release suspension is 83%. Food increases absorption. Administration with a high-fat meal increased the Cmax by 115% and the AUC by 23% compared to the fasted state. Administration with a standard meal increased the Cmax by 119% and the AUC by 12%.[34473] Peak concentrations occur approximately 3 hours (range 2 to 8 hours) after administration.[51753] Extended-release suspension and immediate-release formulations are not bioequivalent and cannot be interchanged.[34473]

    Intravenous Route

    Azithromycin doses of 500 mg IV daily administered over 1 hour for 2 to 5 days resulted in a mean Cmax +/- SD of 3.63 +/- 1.60 mcg/mL, a 24-hour trough of 0.20 +/- 0.15 mcg/mL, and an AUC24 of 9.60 +/- 4.80 mcg x hour/mL. Doses of 500 mg IV administered over 3 hours resulted in a mean Cmax of 1.14 +/- 0.14 mcg/mL, a 24-hour trough of 0.18 +/- 0.02 mcg/mL, and an AUC24 of 8.03 +/- 0.86 mcg x hour/mL. Similar pharmacokinetic values were obtained in patients that received the same 3-hour IV infusion regimen for 2 to 5 days. A comparison of the pharmacokinetics after the first and fifth daily doses showed an increase in AUC24 of 61%, reflecting a 3-fold rise in trough concentrations. Cmax increased by 8%.[43974]

    Other Route(s)

    Ophthalmic Route
    The systemic concentration of azithromycin after ocular administration is estimated to be below quantifiable limits (10 ng/mL or less).