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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; produces less GI intolerance and reaches higher intracellular concentrations than erythromycin; used systemically for STDs, otitis media, pharyngitis, community-acquired pneumonia, PID, and Mycobacterium avium complex (MAC) prophylaxis in patients with advanced HIV disease. An ophthalmic solution is used for bacterial conjunctivitis.

    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 mild to moderate acute bacterial exacerbations of chronic bronchitis in patients with COPD caused by susceptible strains of Haemophilus influenza, Moraxella catarrhalis, or Streptococcus pneumoniae.
    Oral dosage
    Adults

    The recommended dose is either 500 mg PO once daily for 3 days (e.g., Zithromax Tri-Pak) or 500 mg PO on first day of therapy, followed by 250 mg PO once daily for 4 days (e.g., Z-Pak). (Total cumulative dose: 1,500 mg).

    Oral dosage (extended release oral suspension, e.g., Zmax)†

    NOTE: 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, alternative therapy should be considered. In patients with normal gastric emptying, if vomiting occurs 60 minutes or longer after administration, no additional antibiotic therapy is warranted. In patients with delayed gastric emptying, consider alternative therapy.

    Adults

    2 g PO single dose given at least 1 hour before or 2 hours following a meal. 2 g PO as a single dose was reported to be as effective as a 7-day course of levofloxacin in a multicenter, randomized, double-blind, double-dummy study.

    For the treatment of acute otitis media.
    NOTE: Various dosing regimens are FDA-approved. Because macrolides, including azithromycin, have limited efficacy against both H. influenzae and S. pneumoniae, these agents are not included in the preferred or alternative options recommended by the American Academy of Pediatrics (AAP) in the treatment guidelines for acute otitis media.
    Oral dosage (immediate-release formulations)
    Infants 6 months and older, Children, and Adolescents

    30 mg/kg PO as a single dose (Max: 1,500 mg/dose), OR 10 mg/kg/day PO once daily for 3 days (Max: 500 mg/day), OR 10 mg/kg PO as a single dose (Max: 500 mg/dose) on day 1, followed by 5 mg/kg/day on days 2 to 5 (Max: 250 mg/day). In a clinical trial of 242 children, the 30 mg/kg single dose regimen resulted in clinical cure rates consistent with those seen with the 3- or 5-day regimen.

    For the treatment of bacterial conjunctivitis caused by susceptible strains of CDC coryneform group G, H. influenzae, S. aureus, S. mitis group, and S. pneumoniae.
    Ophthalmic dosage (AzaSite)
    Adults, Adolescents, and Children >= 1 year

    1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for the first 2 days, followed by 1 drop in the affected eye(s) once daily for the next 5 days.

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

    500 mg PO on first day of therapy, followed by 250 mg PO once daily on days 2 to 5. Guidelines recommend azithromycin as a monotherapy option in previously healthy outpatients with no risk factors for drug-resistant S. pneumoniae and without therapy in the preceding 3 months. An oral beta-lactam should be added in outpatients with comorbidities, previous antibiotic use in the preceding 3 months, or risk factors for drug-resistant S. pneumoniae. Patients should be treated for at least 5 days and should be afebrile for 48 to 72 hours with no more than 1 CAP-associated sign of clinical instability before discontinuing therapy. A longer duration may be needed if the initial therapy is not active against identified pathogens or if there are complications.

    Infants 6 months and older months, Children, and Adolescents

    10 mg/kg PO on day 1, followed by 5 mg/kg/day on days 2 through 5. All doses given once daily. Max daily dose: 500 mg/day. The IDSA recommends as oral stepdown therapy or as initial oral therapy in patients with atypical pathogens as young as 3 months.

    Oral dosage (extended release oral suspension)
    Adults

    2 g PO as a single dose given at least 1 hour before or 2 hours following a meal. The manufacturer states that 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.

    Infants 6 months and older, Children, and Adolescents

    60 mg/kg/dose (Max: 2 g/dose) PO as a single dose at least 1 hour before or 2 hours following a meal. The manufacturer states that 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.

    Intravenous dosage
    Adults and Adolescents 16 years and older

    Initially, 500 mg IV infusion as a single daily dose for at least 2 days then 500 mg PO once daily to complete a 7 to 10 day course of therapy. The switch to oral therapy should be done at the discretion of the physician and based on the clinical response of the patient. Guidelines recommend azithromycin in combination with an IV beta-lactam for inpatients with community-acquired pneumonia. Azithromycin with an aminoglycoside with an antipseudomonal beta-lactam is as an option in CAP patients with suspected Pseudomonas aeruginosa infection. Azithromycin treatment should continue for at least 5 days, and patients should be afebrile for 48 to 72 hours with no more than 1 CAP-associated sign of clinical instability before discontinuing therapy. A longer duration may be needed in the initial therapy is not active against identified pathogens or if there are complications.

    Infants older than 3 months†, Children†, and Adolescents less than 16 years†

    10 mg/kg/dose (Max: 500 mg/dose) IV once daily for the first 2 days then conversion to oral therapy if possible to complete a 5 day course. After the IV loading doses have been given, the oral dosage is 5 mg/kg/day (Max: 250 mg/day). Azithromycin may be used alone for diagnosed atypical pneumonia or in combination with an IV beta-lactam for inpatients when atypical pathogens are suspected.

    For the treatment of uncomplicated skin and skin structure infections caused by S. aureus, S. pyogenes or S. agalactiae.
    Oral dosage (includes Z-pak packaging)
    Adults

    The recommended dose is 500 mg PO on first day of therapy, followed by 250 mg PO once daily for 4 days. (Total cumulative dose 1,500 mg). In a comparative study (n = 296), this dosing regimen for azithromycin was shown to be as effective as a 10-day course of cefadroxil (500 mg PO twice daily).

    For the treatment of pelvic inflammatory disease (PID).
    Intravenous and Oral dosage
    Adults and Adolescents >= 16 years

    500 mg IV infusion as a single daily dose for 1 or 2 days, then oral therapy at 250 mg PO once daily to complete a 7 day course of therapy. The CDC suggests monotherapy or with the addition of a 12 to 14 day course of metronidazole. Additionally, azithromycin 1 g PO administered once weekly for 2 weeks plus a single dose of ceftriaxone IM has been studied. According to the manufacturer, an antimicrobial agent with anaerobic activity should be administered in combination with azithromycin if anaerobic microorganisms are suspected.

    For the treatment of gonorrhea.
    For the treatment of uncomplicated gonorrhea of the cervix, urethra, rectum, and pharynx.
    Oral dosage (immediate-release formulations)
    Adults, Adolescents†, and Children 8 years and older weighing 45 kg or more†

    1 g PO as a single dose plus ceftriaxone 250 mg IM as a single dose (or cefixime 400 mg PO as a single dose if ceftriaxone not available). Dual treatment with azithromycin 2 g PO as a single dose plus gemifloxacin 320 mg PO as a single dose or gentamicin 240 mg IM as a single dose are options for patients with severe cephalosporin allergy or those with treatment failure after retreatment with preferred regimen. Azithromycin 2 g PO as a single dose plus ceftriaxone 250 mg IM as a single dose should be used in those with treatment failure after treatment with the alternative regimen of cefixime and azithromycin. Monotherapy with azithromycin is no longer recommended by the CDC. In patients with cephalosporin-resistant N. gonorrhoeae who have failed high dose ceftriaxone, the World Health Organization (WHO) suggests that 2 g PO once plus either gentamicin 240 mg IM as a single dose or spectinomycin 2 g IM as a single may be appropriate. Appropriate treatment of sexual partners is necessary.

    For the treatment of disseminated (e.g., bacteremia, arthritis) gonococcal infection†, including meningitis† and endocarditis†.
    Oral dosage (immediate-release formulations)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    1 g PO as a single dose in combination with ceftriaxone administered as an extended duration dependent upon disease state. For meningitis, give ceftriaxone IV for 10 to 14 days; for endocarditis, give ceftriaxone IV for at least 28 days. For disseminated infections, continue ceftriaxone IM/IV (or alternatively cefotaxime or ceftizoxime) for 24 to 48 hours after clinical improvement begins at which time therapy may then be switched to an oral regimen (e.g., cefixime) to complete 7 days of cephalosporin therapy.

    For the treatment of gonococcal conjunctivitis†.
    Oral dosage (immediate-release formulations)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    For the treatment of chancroid due to Haemophilus ducreyi.
    Oral dosage (immediate-release formulations)
    Adults and Adolescents†

    The CDC and manufacturer recommend 1 g PO as a single dose. A longer course of therapy may be required in HIV-infected patients and uncircumcised men. If azithromycin is used in HIV-infected patients, follow-up must be ensured; otherwise, an erythromycin 7-day regimen or a ciprofloxacin 3-day may be preferred.

    Infants† and Children†

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

    For the treatment of Mycobacterium avium complex infection (MAC).
    Oral dosage
    Adults

    The FDA-approved dose is 600 mg PO once daily. The HIV guidelines recommend azithromycin 500 to 600 mg PO daily plus ethambutol as an alternative to clarithromycin when drug interactions or intolerance precludes the use of clarithromycin. A third or fourth drug (rifabutin, amikacin, streptomycin, levofloxacin, or moxifloxacin) should be considered for patients with 50 CD4 cells/mm3 or less, high mycobacterial loads (more than 2 log CFU/mL of blood), or in the absence of effective antiretroviral therapy. Adjunctive steroids can be considered for patients with moderate to severe immune reconstitution inflammatory syndrome (IRIS). Duration of treatment depends on clinical response, but should continue for at least 12 months.

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

    The FDA-approved dose is 1,200 mg PO once weekly, with or without rifabutin. However, the HIV guidelines recommend azithromycin alone as preferred therapy and do not recommend routine administration of azithromycin and rifabutin. The guidelines suggest 600 mg PO twice weekly as an alternative regimen. Prophylaxis is recommended in patients with with a 50 CD4 cells/mm3 or less after ruling out active disease. Primary MAC prophylaxis may be discontinued in adult patients whose CD4 counts are more than 100 cells/mm3 for more than 3 months and who exhibit sustained suppression of HIV plasma RNA. Primary MAC prophylaxis should be restarted if CD4 counts fall to less than 50 cells/mm3.

    For secondary Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients with disseminated disease, after treatment of the acute illness.
    Oral dosage
    Adults

    As an alternative to clarithromycin, 500 to 600 mg PO once daily plus ethambutol. It may be reasonable to consider discontinuation of secondary prophylaxis in patients who have completed at least 12 months of treatment for MAC, remain asymptomatic with respect to MAC signs and symptoms, and have a sustained increase (6 months or more) in the CD4 count more than 100 cells/mm3 following highly active antiretroviral therapy. Secondary prophylaxis should be restarted if the CD4 count decreases to less than 100 cells/mm3.

    For the treatment of acute bacterial sinusitis.
    NOTE: Due to the high rate of resistance among S. pneumoniae isolates, macrolides are not recommended as empiric therapy. Amoxicillin/clavulanate is recommended as the first-line empiric therapy.
    Oral dosage (immediate-release formulations)
    Adults

    500 mg PO once daily for 3 days.

    Infants 6 months and older, Children, and Adolescents

    10 mg/kg/day PO once daily (Max: 500 mg/day) for 3 days.

    Oral dosage (extended-release oral suspension, e.g., Zmax)
    Adults

    2 g PO as a single dose.

    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 formulations)
    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. 1 g PO as a single dose has been found as effective as 7 days of doxycycline in adults with a positive C. trachomatis antigen test.

    Adolescents†

    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. 1 g PO as a single dose has been found as effective as 7 days of doxycycline in adolescents with a positive C. trachomatis antigen test.

    Children 8 years and older or weighing 45 kg or more†

    1 g PO as a single dose.

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

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

    For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis†) and tonsillitis.
    NOTE: For secondary prophylaxis of rheumatic fever, the American Heart Association (AHA) recommends prophylaxis for 10 years or until age 40 (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis, but have no residual heart disease, the AHA recommends prophylaxis for 10 years or until age 21 (whichever is longer). For patients who have experienced rheumatic fever without carditis, the AHA recommends prophylaxis for 5 years or until age 21 (whichever is longer).
    Oral dosage (immediate-release formulations)
    Adults

    500 mg PO once daily for 5 days is recommended by the American Heart Association (AHA) and the Infectious Diseases Society of America (IDSA) as an alternative in patients allergic to penicillin. The FDA-approved dosage is 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days. Additionally, the AHA recommends azithromycin as an option for secondary rheumatic fever prophylaxis (prevent recurrent attacks) in patients allergic to penicillin or sulfadiazine, although no dosage recommendations are given.

    Children and Adolescents 2 to 17 years

    12 mg/kg/dose PO once daily (Max: 500 mg/day) for 5 days for a total course of 60 mg/kg azithromycin. The American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend azithromycin as an alternative in patients allergic to penicillin. Additionally, the AHA recommends azithromycin as an option for secondary rheumatic fever prophylaxis (prevent recurrent attacks) in patients allergic to penicillin or sulfadiazine, although no dosage recommendations are given.

    Infants† and Children younger than 2 years†

    12 mg/kg/dose PO once daily for 5 days is recommended by the American Heart Association (AHA) and the Infectious Diseases Society of America (IDSA) as an alternative in patients allergic to penicillin. Additionally, the AHA recommends azithromycin as an option for secondary rheumatic fever prophylaxis (prevent recurrent attacks) in patients allergic to penicillin or sulfadiazine, although no dosage recommendations are given.

    For the treatment of primary, secondary, or early latent syphilis† (caused by Treponema pallidum) in nonpregnant, penicillin-allergic patients.
    NOTE: A Jarisch-Herxheimer reaction may occur within the first 24 hours of therapy.
    NOTE: While the HIV guidelines recommend non-penicillin alternatives for the treatment of syphilis in HIV-infected patients, their efficacy has not been evaluated and should only be used with close clinical and serologic monitoring.
    Oral dosage
    Adults

    Due to documented resistance and treatment failures, azithromycin should only be used when penicillin and doxycycline are not feasible options; guidelines recommend a single 2 g oral dose. Azithromycin should not be used in pregnant women or in men who have sex with men (MSM). Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis with in the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed > 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    For the treatment of chronic prostatitis† due to Ureaplasma urealyticum.
    Oral dosage
    Adults

    In a pilot study, azithromycin 500 mg PO daily for 3 days repeated every week for 3 weeks (total dose = 4,500 mg) was compared to doxycycline 100 mg PO twice daily for 21 days. Patients were randomized to the doxycycline (n = 31) or azithromycin (n = 32) regimen; sexual partners were also treated at the same time. Eradication rates and clinical cure rates were similar between the groups.

    For the treatment of Legionnaire's disease†.
    Oral dosage
    Adults

    A dose of 500 mg PO once daily has been recommended.

    For the treatment of shigellosis† diarrhea.
    For the treatment of shigellosis† diarrhea in non-immunocompromised patients.
    Oral dosage
    Adults

    Both ciprofloxacin and azithromycin were found to be highly effective in the treatment of men in Bangladesh with shigellosis lasting less than 72 hours. The dose of azithromycin in this double-blind, randomized study was 500 mg PO on day 1, followed by 250 mg PO once daily for the next 4 days.

    For the treatment of shigellosis† in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    500 mg PO once daily for 5 days as an alternative in patients without bacteremia by the HIV guidelines. Recurrent infection may require treating for up to 6 weeks.

    For the treatment of mild-to-moderate campylobacteriosis† in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    500 mg PO once daily for 5 days in patients without bacteremia is recommended by the HIV guidelines.

    For the treatment of toxoplasmosis†, including toxoplasmic encephalitis†, in HIV-positive patients.
    Oral dosage
    Adults

    900—1200 mg PO daily in combination with pyrimethamine and leucovorin is recommended as alternative therapy in the HIV guidelines. Start chronic maintenance therapy after treatment. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however they should not be used prophylactically.

    For the treatment of early Lyme disease†.
    For the treatment of early Lyme disease† in adults.
    Oral dosage (immediate-release formulations)
    Adults

    500 mg PO once daily for 7 to 10 days. Macrolides are not recommended as first-line agents for early Lyme disease and are only recommended for patients who are intolerant of, or are unable to take amoxicillin, doxycycline, or cefuroxime.

    For the treatment of early Lyme disease† in children and adolescents.
    Oral dosage (immediate-release formulations)
    Children and Adolescents

    10 mg/kg/day PO once daily (Max: 500 mg/day) for 7 to 10 days. Macrolides are not recommended as first-line agents for early Lyme disease and are only recommended for patients who are intolerant of, or are unable to take amoxicillin, doxycycline, or cefuroxime.

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

    500 mg PO once daily for 4 to 7 days.

    For acute dental abscess (apical)† and/or dental abscess (periapical)† in combination with surgical incision and drainage in patients with beta-lactam allergy.
    Oral dosage (immediate-release formulations)
    Adults

    1 g PO as a loading dose on day 1, followed by 500 mg PO once daily on days 2 and 3.

    For bacterial endocarditis prophylaxis†.
    Oral dosage (immediate-release formulations)
    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. Cardiac patients that are considered to be at highest risk include those with prosthetic cardiac valves or prosthetic material used for cardiac valve repair, previous infective endocarditis, select types of congenital heart disease (CHD), and cardiac transplantation with valvulopathy.

    Children and Adolescents

    15 mg/kg PO as a single dose (Max: 500 mg/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. Cardiac patients that are considered to be at highest risk include those with prosthetic cardiac valves or prosthetic material used for cardiac valve repair, previous infective endocarditis, select types of congenital heart disease (CHD), and cardiac transplantation with valvulopathy.

    For the treatment of babesiosis† in combination with atovaquone.
    Oral dosage
    Adults

    A prospective, unblinded, randomized trial compared the efficacy of an atovaquone/azithromycin regimen with the standard quinine/clindamycin regimen for treatment of babesiosis. Patients received either atovaquone (750 mg PO every 12 hours) plus azithromycin (500 mg PO on day 1, followed by 250 mg PO once daily for 7 days) or the quinine/clindamycin regimen. The atovaquone/azithromycin regimen was as effective as the quinine/clindamycin regimen but with less adverse reactions.

    For the treatment of granuloma inguinale† (Donovanosis) caused by Klebsiella granulomatis.
    Oral dosage
    Adults

    As primary therapy, the CDC recommends 1 g PO once per week for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside such as gentamicin should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. For pregnant and lactating patients, the CDC recommends azithromycin as an option.

    Adolescents†

    The American Academy of Pediatrics (AAP) recommends 1 g PO once weekly for at least 3 weeks until all lesions have healed.

    For use in improving pulmonary function in cystic fibrosis† patients chronically infected with Pseudomonas aeruginosa.
    Oral dosage
    Adults, Adolescents, and Children >= 6 years

    A randomized clinical trial evaluated whether azithromycin improves pulmonary function in patients with cystic fibrosis infected with Pseudomonas aeruginosa. Patients received either azithromycin 250 mg PO or placebo 3 days per week (Mon, Wed, Fri) for 168 days. At the end of the study, those receiving azithromycin showed greater improvements in FEV1 and had a decrease in pulmonary exacerbations. The azithromycin patient group also weighed an average of 0.7 kg more than placebo patients which suggests an improvement in nutritional status. The results of this study are consistent with 2 other studies suggesting benefits of azithromycin in CF patients.

    For the treatment of mild scrub typhus† due to Orientia tsutsugamushi† (formerly Rickettsia tsutsugamushi†).
    Oral dosage
    Adults

    Azithromycin 500 mg PO as a single dose was as effective as a standard 1-week doxycycline regimen. A prospective, open-label, randomized study (n = 93) compared azithromycin with doxycycline for treatment of mild scrub typhus which is an endemic infection in the Asia-Pacific region. All patients (100%, n = 47) receiving azithromycin were cured whereas 43 of 46 patients (93.5%) receiving doxycycline were cured. Azithromycin-treated patients were afebrile at a median time of 21 hours after initiation and those treated with doxycycline at 29 hours. Relapses did not occur in either of the groups during a 1-month follow-up.

    For the treatment of pertussis (whooping cough)† caused by Bordetella pertussis or for postexposure pertussis prophylaxis†.
    NOTE: For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure, especially in high-risk patients (e.g., pregnant women in third trimester, infants younger than 12 months). Symptomatic contacts (coughing) should be treated as if they have pertussis.
    Oral dosage (immediate-release formulations)
    Adults

    500 mg PO on day 1, followed by 250 mg PO once daily on days 2 to 5.

    Infants 6 months and older, Children, and Adolescents

    10 mg/kg/day PO on day 1 (Max: 500 mg), then 5 mg/kg/day PO on days 2 to 5 (Max: 250 mg/day).

    Neonates and Infants 1 to 5 months

    10 mg/kg/day PO for 5 days. Although limited data are available for azithromycin, it is the preferred agent in neonates. Monitor for infantile hypertrophic pyloric stenosis (IHPS) in patients younger than 1 month of age.

    For the treatment of cholera†.
    Oral dosage
    Adults

    1 g PO as a single dose in conjunction with fluid and electrolyte replacement. Azithromycin (1 g PO single dose; n = 97) was compared to ciprofloxacin (1 g PO single dose; n = 98) in a double-blind, randomized trial of patients with severe cholera. Patients treated with azithromycin had a shorter duration of diarrhea, lower frequency of vomiting, and a lower stool volume than those receiving ciprofloxacin.

    Children

    20 mg/kg PO as a single dose in conjunction with fluid and electrolyte replacement was as effective as a 3-day regimen of erythromycin (12.5 mg/kg PO every 6 hours). Azithromycin (10 mg/kg PO once daily for 3-days) was superior to erythromycin (50 mg/kg/day in 4 divided doses for 3 days) in treating male children aged 2 to 10 years with cholera and severe dehydration.

    For the treatment of uncomplicated typhoid fever†.
    Oral dosage
    Adults

    8 to 10 mg/kg/day PO once daily for 7 days is recommended by WHO. In a comparative study, a dose of 1,000 mg PO on first day of therapy, followed by 500 mg PO once daily for 6 days was as effective as ciprofloxacin (500 mg PO twice daily for 7 days).

    Children

    10 mg/kg/day PO once daily for 7 days was used in 1 study. A 5-day regimen of 20 mg/kg/day has also been shown to be effective.

    For the treatment of bartonellosis† (Bartonella bacilliformis) and other Bartonella sp.† infections in HIV-infected patients.
    For the treatment of angiomatosis infections†, peliosis hepatis†, bacteremia†, and osteomyelitis† caused by Bartonella sp.†.
    Oral dosage (immediate-release formulations)
    Adults and Adolescents

    500 mg PO once daily for at least 3 months is recommended by the HIV guidelines as an alternative to erythromycin or doxycycline therapy. Severe Jarisch-Herxheimer-like reactions can occur during the first 48 hours of therapy.

    For long term suppression† of infections caused by Bartonella sp.† in HIV-infected patients with relapse or reinfection and with CD4 count less than 200 cells/mm3.
    Oral dosage (immediate-release formulations)
    Adults and Adolescents

    500 mg PO once daily is recommended as an alternative by the HIV guidelines. Discontinuation of suppressive therapy 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 prior to discontinuation of suppressive therapy.

    For the treatment of ophthalmia neonatorum† due to C. trachomatis.
    Oral dosage (immediate-release formulations)
    Neonates

    20 mg/kg/dose PO once daily for 3 days as an alternative to erythromycin. Limited data for azithromycin use suggest that a short course of azithromycin therapy may be effective for neonatal chlamydia infection.

    For the treatment of lymphogranuloma venereum† caused by C. trachomatis.
    Oral dosage (immediate-release formulations)
    Adults

    1 g PO once weekly for 21 as an alternative to doxycycline. Erythromycin is preferred in pregnant/lactating women. Although clinical data are lacking, azithromycin is probably effective based on its chlamydial antimicrobial activity.

    Adolescents

    1 g PO once weekly for 21 as an alternative to doxycycline. Erythromycin is preferred in pregnant/lactating women. Although clinical data are lacking, azithromycin is probably effective based on its chlamydial antimicrobial activity.

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

    †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

    No dosage adjustment recommendations can be made; azithromycin has not been studied in patients with impaired hepatic function.

    Renal Impairment

    CrCl > 80 mL/min: No dosage adjustment is needed.
    CrCl 10—80 mL/min: No dosage adjustment is recommended.
    CrCl < 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

    Azithromycin is administered orally.

    Oral Solid Formulations

    Tablets: 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 (Zithromax 1 gram single-dose packet):
    Review the manufacturer reconstitution instructions for the particular product and package size.
    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.
    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.
    Oral suspension (immediate-release, bottles for reconstitution):
    Review the manufacturer reconstitution instructions for the particular product and package size.
    Zithromax for oral suspension (100 mg/5 mL or 200 mg/5 mL strengths) may be taken with or without food.
    Add water in 2 portions and shake well after each addition.
    Storage: After mixing, store suspension at 5—30 degrees C (41—86 degrees F) and use within 10 days.
    Administer using a calibrated measuring device.
    Oral suspension (extended release, bottles for reconstitution):
    Review the manufacturer reconstitution instructions for the particular product and package size.
    Zmax extended release oral suspension (2 grams azithromycin) should be taken as a single dose at least 1 hour before or 2 hours following 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—60 minutes following the dose, consider alternate therapy. In patients with normal gastric emptying, if vomiting occurs >= 60 minutes 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 mixing, store suspension at 15—30 degrees C (59—86 degrees F) and use within 12 hours.

    Injectable Administration

    For intravenous infusion after dilution only; do not administer IM or via IV bolus.
    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.
    Add 4.8 mL of Sterile Water for Injection to the 500-mg vial and shake until all of the drug is dissolved. 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.
    The reconstituted solution contains 100 mg/mL azithromycin. The reconstituted solution is stable for 24 hours when stored below 30 degrees C (86 degrees F). Dilute further prior to administration.
     
    Dilution:
    To provide a concentration of 1 mg/mL azithromycin, transfer 5 mL of the 100 mg/mL reconstituted azithromycin solution into 500 mL of a compatible diluent. For a 2 mg/mL azithromycin infusion solution, use 250 mL of a compatible diluent.
    Compatible diluents include: 0.9% NaCl, 0.45% NaCl, 5% Dextrose, Lactated Ringer's solution, 5% Dextrose and 0.45% NaCl with 20 mEq KCl, 5% Dextrose and Lactated Ringer's solution, 5% Dextrose and 0.3% NaCl, 5% Dextrose and 0.45% NaCl,  Normosol-M and 5% Dextrose, and Normosol-R and 5% Dextrose.
    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).
     
    Intravenous infusion:
    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.

    Ophthalmic Administration

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

    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 at controlled room temperature (between 68 and 77 degrees F)
    Zithromax Tri-Pak:
    - Store at controlled room temperature (between 68 and 77 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

    General Information

    Oral therapy with azithromycin is not recommend in patients with serious infections (e.g., pneumonia) who are considered to be inappropriate candidates for oral therapy. This includes patients with moderate or severe illness or risk factors such as patients with cystic fibrosis, with nosocomially acquired infections, with known or suspected bacteremia, who require hospitalization, who are elderly or debilitated, or who have significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

    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

    Since it is primarily eliminated via the liver, 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. Also, systemic azithromycin is contraindicated in patients with a history of jaundice and/or hepatic dysfunction associated with the prior use of azithromycin.

    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 < 10 ml/min).

    Colitis, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Data from a cohort study has 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 significantly greater risk of cardiovascular death than persons not treated with antibiotics (HR: 2.88; 95% CI: 1.79—4.63; P<0.001), persons treated with 5 days of amoxicillin (HR: 2.49; 95% CI: 1.38—4.50; P=0.002), and persons in the first 5 days of ciprofloxacin therapy (HR: 3.49; 95% CI: 1.32—9.26; P=0.01); mortality rate did not differ from levofloxacin. In addition, cases of torsade de pointes (TdP) have been noted during azithromycin post-marketing surveillance. Based on these data, the FDA has issued a Drug Safety Communication to alert health care professionals that azithromycin is associated with QT prolongation, imparting a risk of developing fatal cardiac arrhythmias such as TdP. Although this Drug Safety Communication focused on azithromycin, the FDA reminds prescribers that QT prolongation has also been associated with other macrolide and non-macrolide antibiotics, including fluoroquinolones. Health care providers should assess the risks and benefits of prescribing these drugs to at-risk groups, including patients with known prolongation of the QT interval or a history of TdP. Use azithromycin with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation.

    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

    Azithromycin is classified as FDA pregnancy risk category B. Animal data reveal no teratogenic effects. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Azithromycin has not been studied for use during labor and obstetric delivery. Treatment should be given only if clearly needed.

    Breast-feeding

    According to the manufacturer, azithromycin should be used cautiously in women who are breast-feeding. 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. A population based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3—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. The American Academy of Pediatric considers erythromycin to be a medication that is usually compatible with breast-feeding; azithromycin and clarithromycin have not been evaluated by the AAP. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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 < 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).

    Sunlight (UV) exposure

    Direct sunlight (UV) exposure should be minimized during therapy with systemic azithromycin. Photosensitivity has been reported as an allergic reaction to azithromycin. Azithromycin should be discontinued at the first sign of erythema.

    Sodium restriction

    Zithromax (azithromycin for injection) contains a total of 4.96 mEq (114 mg) of sodium per vial. At the usual recommended doses, patients would receive 4.96 mEq (114 mg) of sodium. The sodium amounts should be considered in patients with requirements for sodium restriction or blunted natriuresis to salt loading (i.e., cardiac disease, elderly, or hypertension).

    Contact lenses

    Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. Thus, patients who wear contact lenses should avoid wearing them while being treated with azithromycin ophthalmic solution (Azasite) for an ocular infection.

    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.

    ADVERSE REACTIONS

    Severe

    pleural effusion / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    eczema vaccinatum / Delayed / 0-1.0
    angioedema / Rapid / 0-1.0
    corneal erosion / Delayed / 0-1.0
    keratitis / Delayed / 0-1.0
    azotemia / Delayed / 1.0
    hyperkalemia / Delayed / 1.0
    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    pyloric stenosis / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    hearing loss / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / 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

    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
    dyspnea / Early / 0-1.9
    gastritis / Delayed / 0-1.0
    constipation / Delayed / 0-1.0
    dysuria / Early / 0-1.0
    melena / 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
    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
    vomiting / Early / 0-14.0
    diarrhea / Early / 1.8-12.0
    injection site reaction / Rapid / 1.9-12.0
    abdominal pain / Early / 1.2-7.0
    rash (unspecified) / Early / 0-5.0
    dizziness / Early / 0-3.9
    headache / Early / 0-3.0
    fever / Early / 0-2.1
    anorexia / Delayed / 0-2.0
    ocular irritation / Rapid / 1.0-2.0
    pruritus / Rapid / 0-1.9
    flatulence / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    nasal congestion / Early / 0-1.0
    pharyngitis / Delayed / 0-1.0
    sinusitis / Delayed / 0-1.0
    cough / Delayed / 0-1.0
    rhinitis / Early / 0-1.0
    asthenia / Delayed / 0-1.0
    fatigue / Early / 0-1.0
    malaise / Early / 0-1.0
    chills / Rapid / 0-1.0
    drowsiness / Early / 0-1.0
    emotional lability / Early / 0-1.0
    hyperkinesis / Delayed / 0-1.0
    vertigo / Early / 0-1.0
    insomnia / Early / 0-1.0
    agitation / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    vesicular rash / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    photosensitivity / Delayed / 0-1.0
    ocular pain / Early / 0-1.0
    ocular discharge / Delayed / 0-1.0
    xerophthalmia / Early / 0-1.0
    tongue discoloration / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    anxiety / Delayed / Incidence not known
    syncope / Early / Incidence not known
    anosmia / Delayed / Incidence not known
    dysosmia / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    diaphoresis / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. If azithromycin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Abarelix is associated with a possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    Afatinib: (Major) If the concomitant use of azithromycin and afatinib is necessary, consider reducing the afatinib dose by 10 mg per day if the original dose is not tolerated; resume the previous dose of afatinib as tolerated after discontinuation of azithromycin. Afatinib is a P-glycoprotein (P-gp) substrate and inhibitor in vitro, and azithromycin is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration of another P-gp inhibitor, ritonavir (200 mg twice daily for 3 days), 1 hour before afatinib (single dose) increased the afatinib AUC and Cmax by 48% and 39%, respectively; there was no change in the afatinib AUC when ritonavir was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with ritonavir, and 111% and 105% when ritonavir was administered 6 hours after afatinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise.
    Albuterol: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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; Ipratropium: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering alfuzosin with azithromycin. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Reports of QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance. Concurrent use may increase the risk of QT prolongation.
    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) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. 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.
    Amitriptyline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Amitriptyline; Chlordiazepoxide: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Amlodipine; Atorvastatin: (Moderate) Monitor for evidence of rhabdomyolysis if atorvastatin is coadministered with azithromycin. A clinically significant pharmacokinetic interaction was not observed when atorvastatin was administered with azithromycin in a drug interaction study. However, a case series in the World Health Organization Adverse Drug Reaction (WHO-ADR) database was suggestive of a possible drug interaction resulting in rhabdomyolysis between statins, incuding atorvastatin, and azithromycin.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Both clarithromycin and azithromycin are macrolide antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin. (Minor) Both lansoprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Both clarithromycin and azithromycin are macrolide antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin. (Minor) Both omeprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Anagrelide: (Major) Torsades de pointes (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. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include azithromycin.
    Apomorphine: (Major) Due to the increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering apomorphine with azithromycin. There have been case reports of QT prolongation and TdP with the post-market use of azithromycin. Limited data indicate that QT prolongation is also possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to 10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Arformoterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Due to the risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering aripiprazole with azithromycin. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. There have also been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Arsenic Trioxide: (Major) If possible, use of azithromycin should be discontinued prior to initiating arsenic trioxide therapy, as coadministration may lead to increased risk for QT prolongation and torsade de pointes (TdP). Azithromycin has been associated with cases of QT prolongation and TdP during post-marketing use. Cases of TdP and complete atrioventricular block have also been reported with arsenic trioxide; QT prolongation should be expected with the use of arsenic trioxide.
    Artemether; Lumefantrine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), concurrent use of azithromycin with artemether; lumefantrine should be avoided. Consider ECG monitoring if azithromycin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval, and rare cases of QT prolongation and TdP have been reported during post-market use of azithromycin. Although no studies have examined the effects of administering these medications together, their concurrent use may result in additive QT prolongation and should be avoided. (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), concurrent use of azithromycin with artemether; lumefantrine should be avoided. Consider ECG monitoring if other QT prolonging drugs must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval, and cases of QT prolongation and TdP have been reported during post-market use of azithromycin. Although no studies have examined the effects of administering these medications together, their concurrent use may result in additive QT prolongation and should be avoided.
    Asenapine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), the manufacturer of asenapine recommends avoiding its use in combination with agents known to prolong the QT interval, such as azithromycin. Asenapine has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin.
    Aspirin, ASA; Omeprazole: (Minor) Both omeprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and atomoxetine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Concurrent use may increase the risk of QT prolongation.
    Atorvastatin: (Moderate) Monitor for evidence of rhabdomyolysis if atorvastatin is coadministered with azithromycin. A clinically significant pharmacokinetic interaction was not observed when atorvastatin was administered with azithromycin in a drug interaction study. However, a case series in the World Health Organization Adverse Drug Reaction (WHO-ADR) database was suggestive of a possible drug interaction resulting in rhabdomyolysis between statins, incuding atorvastatin, and azithromycin.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for evidence of rhabdomyolysis if atorvastatin is coadministered with azithromycin. A clinically significant pharmacokinetic interaction was not observed when atorvastatin was administered with azithromycin in a drug interaction study. However, a case series in the World Health Organization Adverse Drug Reaction (WHO-ADR) database was suggestive of a possible drug interaction resulting in rhabdomyolysis between statins, incuding atorvastatin, and azithromycin.
    Bedaquiline: (Major) Coadministration of bedaquiline with other QT prolonging drugs, such as azithromycin, may result in additive or synergistic prolongation of the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) The manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin and ergotamine, because simultaneous use of ergotamine with other macrolides may produce ergot toxicity.
    Bepridil: (Severe) There have been rare case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in postmarketing reports. Other drugs, such as bepridil, have been specifically established to have a causal association with QT prolongation and TdP and are contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving azithromycin. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving azithromycin. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; azithromycin inhibits P-gp.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and metronidazole should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Potential QT prolongation has been reported in limited case reports with metronidazole. Concurrent use may increase the risk of QT prolongation.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and metronidazole should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Potential QT prolongation has been reported in limited case reports with metronidazole. Concurrent use may increase the risk of QT prolongation.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering azithromycin with boceprevir due to an increased potential for azithromycin-related adverse events. If azithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of azithromycin and boceprevir. Both azithromycin and boceprevir are substrates and inhibitors of drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
    Budesonide: (Minor) Both budesonide and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates; coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Budesonide; Formoterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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. (Minor) Both budesonide and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates; coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Buprenorphine: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of azithromycin and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as azithromycin may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of azithromycin and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as azithromycin may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Cabazitaxel: (Minor) Cabazitaxel is a substrate for P-glycoprotein (Pgp). No formal drug interaction studies have been conducted with Pgp inhibitors, such as azithromycin. Use caution when cabazitaxel is administered concomitantly with Pgp inhibitors.
    Cabozantinib: (Moderate) Monitor for an increase in azithromycin-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of azithromycin may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and azithromycin is a substrate of P-gp; the clinical relevance of this finding is unknown.
    Caffeine; Ergotamine: (Minor) The manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin and ergotamine, because simultaneous use of ergotamine with other macrolides may produce ergot toxicity.
    Calcium Carbonate; 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.
    Canagliflozin: (Moderate) Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Azithromycin is a P-gp inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Canagliflozin; Metformin: (Moderate) Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Azithromycin is a P-gp inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Carvedilol: (Moderate) Carvedilol and azithromycin are both substrates and inhibitors of P-glycoprotein (PGP); therefore, increased concentrations of either drug may occur with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and azithromycin; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Prolongation of the QT interval and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Chloroquine: (Major) The need to coadminister chloroquine with other drugs known to prolong the QT interval, such as azithromycin, should be done with a careful assessment of risks versus benefits and should be avoided when possible. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP). Cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin.
    Chlorpromazine: (Major) Agents that prolong the QT interval, such as azithromycin, could lead to torsade de pointes (TdP) when combined with a phenothiazine, and therefore are generally not recommended for combined use. Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Cases of QT prolongation and TdP were also reported during the post-marketing use of azithromycin.
    Ciprofloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and ciprofloxacin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Concurrent use may increase the risk of QT prolongation.
    Cisapride: (Severe) 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) Concurrent use of citalopram with azithromycin is not recommended due to an increased risk for QT prolongation and torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation, and azithromycin has been associated with cases of QT prolongation and TdP. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Both clarithromycin and azithromycin are macrolide antibiotics and coadministration would represent duplicate therapy. Additionally, coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin.
    Clomipramine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Clozapine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and clozapine should be used together cautiously. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as azithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Cobimetinib: (Minor) If concurrent use of cobimetinib and azithromycin is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and azithromycin is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
    Codeine; Phenylephrine; Promethazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Codeine; Promethazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and azithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Azithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like azithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Conivaptan: (Moderate) Use caution when administering conivaptan and azithromycin concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as azithromycin, may increase azithromycin exposure leading to increased or prolonged therapeutic effects and adverse events.
    Conjugated Estrogens; Bazedoxifene: (Moderate) In clinical evaluation, azithromycin 500 mg was given once daily for 8 consecutive days in 30 postmenopausal women. Azithromycin 500 mg and a bazedoxifene 40 mg tablet were co-administered on Day 9. Azithromycin 250 mg administration once daily continued on Days 10 to 13. Co-administration increased the Cmax of bazedoxifene by 6% and decreased AUC of bazedoxifene by 15%. The clinical effect of this change is not known. A reduction in bazedoxifene exposure may be associated with an increased risk of endometrial hyperplasia. Monitor patients for loss of efficacy and increased side effects during conjugated estrogens; bazedoxifene therapy.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with azithromycin. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Reports of QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Crizotinib has also been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and cyclobenzaprine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Cyclobenzaprine is associated with a possible risk of QT prolongation and TdP, particularly in the event of acute overdose. Concurrent use may increase the risk of QT prolongation.
    Cyclosporine: (Moderate) Both cyclosporine and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates; coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together. In a case report, one patient had increased cyclosporine concentrations after administration of azithromycin and decreased cyclosporine concentrations after azithromycin discontinuation.
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with azithromycin, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like azithromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with azithromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Daclatasvir: (Moderate) Systemic exposure of azithromycin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of azithromycin; monitor patients for potential adverse effects.
    Darunavir: (Major) Increased concentrations of azithromycin may occur if it is coadministered with darunavir; exercise caution. Darunavir is an inhibitor of the efflux transporter P-glycoprotein (PGP) and azithromycin may be a P-glycoprotein substrate.
    Darunavir; Cobicistat: (Major) Increased concentrations of azithromycin may occur if it is coadministered with darunavir; exercise caution. Darunavir is an inhibitor of the efflux transporter P-glycoprotein (PGP) and azithromycin may be a P-glycoprotein substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Both ritonavir and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together. In addition, the use of ritonavir could result in QT prolongation; QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Concurrent use may result in additive risk of QT prolongation. (Major) Concurrent administration of azithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of all 5 drugs. Increased plasma concentrations increases the risk of adverse effects, some of which may be serious; azithromycin and ritonavir both have been associated with QT-prolongation. Azithromycin and ritonavir are inhibitors of the drug transporter P-glycoprotein (P-gp), and all 5 drugs are P-gp substrates. Caution and close monitoring are advised if these drugs are administered together. (Major) Concurrent administration of azithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of azithromycin and the components of the hepatitis C regimen. Increased plasma concentrations increases the risk of adverse effects, some of which may be serious; azithromycin and ritonavir both have been associated with QT-prolongation. Azithromycin and ritonavir are inhibitors of the drug transporter P-glycoprotein (P-gp), and azithromycin, dasabuvir, ombitasvir, paritaprevir, and ritonavir are P-gp substrates. Caution and close monitoring are advised if these drugs are administered together.
    Dasatinib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised during coadministration of dasatinib and azithromycin. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Additionally, cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin.
    Daunorubicin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and daunorubicin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Acute cardiotoxicity can occur during the administration of daunorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. In addition, daunorubicin is a P-glycoprotein (P-gp) substrate and azithromycin is a P-gp inhibitor, so coadministration may lead to increased anthracycline concentrations.
    Degarelix: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering degarelix and azithromycin. Degarelix can cause QT prolongation, and azithromycin has been associated with cases of QT prolongation and TdP during the post-marketing period. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking azithromycin.
    Desflurane: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Desipramine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Desloratadine: (Minor) Desloratadine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, desloratadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Desloratadine; Pseudoephedrine: (Minor) Desloratadine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, desloratadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with azithromycin, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Reports of QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Dexamethasone: (Moderate) Dexamethasone is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, dexamethasone concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Dextromethorphan; Promethazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Dextromethorphan; Quinidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering quinidine with azithromycin. Quinidine is associated with QT prolongation and TdP, and rare cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin. In addition, both quinidine and azithromycin are P-glycoprotein (P-gp) substrates and inhibitors, which may lead to increased serum concentrations of either drug when given concomitantly.
    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) Elevated digoxin concentrations have been observed when certain macrolide antibiotics, including azithromycin, have been coadministered with digoxin. Monitor patients who take both azithromycin and digoxin for possible digoxin toxicity and reduce digoxin dose as necessary. Digoxin is a substrate for the drug efflux pump P-glycoprotein (P-gp); azithromycin is a substrate and inhibitor of P-gp. Inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption and decreased renal and non-renal clearance of digoxin.
    Dihydroergotamine: (Minor) Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin and either ergotamine or dihydroergotamine concurrently. The simultaneous use of certain ergot alkaloids with certain macrolides may produce ergot toxicity.
    Diltiazem: (Moderate) Both diltiazem and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Disopyramide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering disopyramide with azithromycin. Disopyramide is associated with QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin.
    Docetaxel: (Minor) Docetaxel is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, docetaxel concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Dofetilide: (Severe) Coadministration of dofetilide and azithromycin is contraindicated since there is an increased risk for QT prolongation and torsade de pointes (TdP). Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Azithromycin has been associated with cases of QT prolongation and TdP, reported during the post-marketing period.
    Dolasetron: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering dolasetron with azithromycin. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk fo QT prolongation.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include azithromycin.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include azithromycin.
    Doxepin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Doxorubicin: (Major) Avoid coadministration of azithromycin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. Azithromycin inhibits P-glycoprotein (P-gp) and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentrations and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Azithromycin also has a possible risk for QT prolongation and torsades de pointes (TdP). Concurrent use may increase the risk of QT prolongation.
    Dronedarone: (Severe) 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. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. There have been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports. Additionally, dronedarone may inhibit P-glycoprotein (P-gp) and azithromycin is a P-gp substrate; therefore, increased concentrations of azithromycin may occur with concomitant administration.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as azithromycin. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Additionally, azithromycin may inhibit P-glycoprotein (P-gp) and droperidol is a P-gp substrate; therefore, increased concentrations of droperidol may occur with concomitant administration.
    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.
    Edoxaban: (Major) Reduce the dose of edoxaban to 30 mg/day PO in patients being treated for deep venous thrombosis (DVT) or pulmonary embolism and receiving concomitant therapy with azithromycin. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein (P-gp) substrate and azithromycin is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of azithromycin; monitor for increased adverse effects of edoxaban.
    Efavirenz: (Major) According to the manufacturer, clinically significant interactions are not expected with efavirenz and azithromycin. However, use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. There have also been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports.
    Efavirenz; Emtricitabine; Tenofovir: (Major) According to the manufacturer, clinically significant interactions are not expected with efavirenz and azithromycin. However, use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. There have also been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as azithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Eletriptan: (Moderate) Eletriptan is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, eletriptan concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Eliglustat: (Major) Coadministration of azithromycin and eliglustat may result in increased concentrations of azithromycin and an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Azithromycin is a P-glycoprotein (P-gp) substrate associated with post-marketing case reports of QT prolongation and torsade de pointes (TdP). Eliglustat is a P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with azithromycin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with azithromycin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as azithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as azithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enflurane: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Epirubicin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering azithromycin with epirubicin. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Acute cardiotoxicity can occur during the administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concurrent use may increase the risk of QT prolongation.
    Ergotamine: (Minor) The manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin and ergotamine, because simultaneous use of ergotamine with other macrolides may produce ergot toxicity.
    Eribulin: (Major) Concurrent use of eribulin and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the use of azithromycin during the post-marketing period.
    Erythromycin: (Major) Avoid use of azithromycin and erythromycin together as this would be considered duplicate therapy. Cross-resistance with gram-positive organisms would be expected. Additionally, the risk for QT prolongation and torsade de pointes (TdP) increases if these drugs are administered together. Erythromycin has been associated with QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin.
    Erythromycin; Sulfisoxazole: (Major) Avoid use of azithromycin and erythromycin together as this would be considered duplicate therapy. Cross-resistance with gram-positive organisms would be expected. Additionally, the risk for QT prolongation and torsade de pointes (TdP) increases if these drugs are administered together. Erythromycin has been associated with QT prolongation and TdP, and cases of QT prolongation and TdP have been reported during post-marketing use of azithromycin.
    Escitalopram: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and escitalopram should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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; Desogestrel: (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; Ethynodiol Diacetate: (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; Etonogestrel: (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: (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; Norethindrone Acetate; 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.
    Ethinyl 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.
    Ethinyl Estradiol; Norethindrone; 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.
    Ethinyl 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; 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.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with azithromycin. Azithromycin is an inhibitor of P-glycoprotein (P-gp) and etoposide, VP-16 is a P-gp substrate. Coadministration may increase etoposide concentrations.
    Etravirine: (Moderate) Etravirine is an inhibitor of the efflux transporter P-glycoprotein (PGP). Azithromycin may be a P-glycoprotein substrate. Increased concentrations of azithromycin may occur if it is coadministered with etravirine; exercise caution.
    Ezetimibe; Simvastatin: (Moderate) Both simvastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Ezogabine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering ezogabine with azithromycin. Ezogabine has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Fentanyl: (Moderate) Fentanyl is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, fentanyl concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Fexofenadine: (Minor) Fexofenadine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, fexofenadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Fexofenadine; Pseudoephedrine: (Minor) Fexofenadine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, fexofenadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Fingolimod: (Major) Cautious use of fingolimod with azithromycin is advised, as azithromycin has been associated with post-marketing reports of QT prolongation and torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP. 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: (Moderate) Cautious use of flecainide with azithromycin is advised, as azithromycin has been associated with post-marketing reports of QT prolongation and torsade de pointes (TdP). 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) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering fluconazole with azithromycin. Fluconazole has been associated with QT prolongation and rare cases of TdP, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin. An open-label, randomized, three-way crossover study evaluated 800 mg fluconazole and a single 1200 mg oral dose of azithromycin. There was no significant pharmacokinetic interaction between the two agents.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include azithromycin.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include azithromycin. (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with azithromycin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. During postmarketing use, azithromycin has also been associated with case reports of QT prolongation and TdP. Concurrent use may increase the risk of QT prolongation.
    Fluphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and fluphenazine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and azithromycin. Coadminister with caution. QT prolongation and TdP have been reported during postmarketing use of both fluvoxamine and azithromycin.
    Food: (Moderate) The effect of food on the oral bioavailability of azithromycin is variable depending on the specific azithromycin dosage form. Azithromycin capsules (no longer marketed) have an oral bioavailability of 37%; food reduces the extent of absorption (AUC) by about 43%. Therefore, azithromycin capsules should be administered 1 hour before or 2 hours after meals. In contrast, azithromycin serum concentrations increase by about 23%, while AUC remains unchanged, when tablets are administered with a high-fat meal. Therefore, azithromycin tablets can be taken with or without food. Food increases the rate of absorption (Cmax) of the suspension by about 56%; however, the extent of absorption is unchanged. Because peak azithromycin serum concentrations are increased substantially when the suspension is taken with food, the suspension should be taken on an empty stomach.
    Formoterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Fosamprenavir: (Moderate) Caution is advised when administering azithromycin with fosamprenavir, as concurrent use may result in elevated fosamprenavir and reduced azithromycin plasma concentrations. Azithromycin is an inhibitor and substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer and substrate.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as azithromycin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). There have also been case reports of QT prolongation and TdP with postmarketing use of azithromycin. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Minor) Of the macrolides, azithromycin does not inhibit cytochrome P450 enzymes and is not likely to be implicated in clinically significant drug-drug interactions involving the CYP450 system. However, azithromycin is a substrate of p-glycoprotein (P-gp), and may undergo increased efflux resulting in lowered serum concentrations if administered with P-gp inducers such as phenytoin or fosphenytoin. 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. Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with phenytoin.
    Gemifloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of gemifloxacin with azithromycin is advised. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. 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) Use gemtuzumab ozogamicin and azithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and azithromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and azithromycin are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and azithromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and azithromycin are substrates and inhibitors of P-glycoprotein (P-gp).
    Glyburide: (Moderate) Glyburide is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, glyburide concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Glyburide; Metformin: (Moderate) Glyburide is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, glyburide concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Glycopyrrolate; Formoterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and goserelin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with azithromycin. Granisetron has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Grapefruit juice: (Moderate) Increased concentrations of azithromycin may occur if it is coadministered with grapefruit juice; exercise caution. Grapefruit juice is an inhibitor of the efflux transporter P-glycoprotein (P-gp) and azithromycin may be a P-glycoprotein substrate.
    Halofantrine: (Severe) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in postmarketing reports. Other drugs, such as halofantrine, have been specifically established to have a causal association with QT prolongation and TdP and are contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    Halogenated Anesthetics: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Haloperidol: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of haloperidol with azithromycin is advised. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Halothane: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and azithromycin. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include azithromycin.
    Ibutilide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of ibutilide with azithromycin is advised. 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. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP.
    Idarubicin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and idarubicin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concurrent use may increase the risk of QT prolongation.
    Iloperidone: (Major) Concurrent use of iloperidone and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Iloperidone has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Imatinib: (Minor) Imatinib, STI-571 is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, imatinib concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Imipramine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Indacaterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Indinavir: (Moderate) Indinavir is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, indinavir concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    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. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance.
    Irinotecan: (Major) Irinotecan is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, irinotecan concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Isoflurane: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin may decrease serum concentrations and potentially the effectiveness of azithromycin, while azithromycin may increase serum concentrations of rifampin. Rifampin is a substrate and inducer of P-glycoprotein (P-gp), while azithromycin is a substrate and inhibitor of P-gp. Monitor patients for increased side effects of rifampin and for signs of antimicrobial efficacy with azithromycin use.
    Isoniazid, INH; Rifampin: (Moderate) Rifampin may decrease serum concentrations and potentially the effectiveness of azithromycin, while azithromycin may increase serum concentrations of rifampin. Rifampin is a substrate and inducer of P-glycoprotein (P-gp), while azithromycin is a substrate and inhibitor of P-gp. Monitor patients for increased side effects of rifampin and for signs of antimicrobial efficacy with azithromycin use.
    Itraconazole: (Moderate) Both itraconazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and azithromycin concurrently. Ivacaftor is an inhibitor of P-glycoprotein (Pgp). Co-administration of ivacaftor with Pgp substrates, such as azithromycin, may increase azithromycin exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ixabepilone: (Minor) Azithromycin is a mild inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in azithromycin concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Ketoconazole: (Moderate) Increased concentrations of azithromycin may occur if it is coadministered with ketoconazole; exercise caution. Ketoconazole is an inhibitor of the efflux transporter P-glycoprotein (P-gp) and azithromycin may be a P-gp substrate.
    Lansoprazole: (Minor) Both lansoprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Lansoprazole; Naproxen: (Minor) Both lansoprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like macrolides, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Lapatinib: (Major) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Lapatinib is also associated with a possible risk for QT prolongation and TdP; therefore, concomitant use may have additive risk. Also, lapatinib is a P-glycoprotein (P-gp) inhibitor and azithromycin is a P-gp substrate, so coadministration may lead to increased azithromycin concentrations.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of azithromycin and ledipasvir; sofosbuvir. Both ledipasvir and azithromycin are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
    Lenvatinib: (Major) Lenvatinib should be used cautiously and with close monitoring with azithromycin. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and leuprolide should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Leuprolide; Norethindrone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and leuprolide should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT 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: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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 concurrent use of levofloxacin and azithromycin due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been reported during postmarketing surveillance in patients receiving levofloxacin. During the postmarketing period, cases of QT prolongation and TdP were associated with azithromycin.
    Levomethadyl: (Severe) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in postmarketing reports. Other drugs, such as levomethadyl, have been specifically established to have a causal association with QT prolongation and torsade de pointes and are contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    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.
    Lincomycin: (Major) Lincomycin and macrolide antimicrobials are bactericidal or bacteriostatic via the same or similar mechanisms of action. Antagonism in vitro has been demonstrated when lincomycin was coadministered with erythromycin. It is not recommended to administer these agents together in any combination due to potential antagonism. The manufacturer of lincomycin does not recommend concurrent use of lincomycin with macrolides.
    Lithium: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and lithium should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Lithium has also been associated with QT prolongation. Concurrent use may increase the risk of QT prolongation.
    Long-acting beta-agonists: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Loperamide should be used cautiously and with close monitoring with azithromycin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. In addition, the plasma concentrations of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with azithromycin, a P-gp inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Major) Loperamide should be used cautiously and with close monitoring with azithromycin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. In addition, the plasma concentrations of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with azithromycin, a P-gp inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Both ritonavir and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together. In addition, the use of ritonavir could result in QT prolongation; QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Concurrent use may result in additive risk of QT prolongation. (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering azithromycin with lopinavir; ritonavir. There have been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports, and lopinavir; ritonavir has been associated with QT prolongation.
    Loratadine: (Minor) Loratadine is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, loratadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Loratadine; Pseudoephedrine: (Minor) Loratadine is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, loratadine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Lovastatin: (Moderate) Both lovastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Lovastatin; Niacin: (Moderate) Both lovastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Lumacaftor; Ivacaftor: (Minor) Although the clinical significance of this interaction is unknown, concurrent use of azithromycin and lumacaftor; ivacaftor may alter azithromycin exposure; caution and monitoring are advised if these drugs are used together. Azithromycin is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased adverse events.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and azithromycin concurrently. Ivacaftor is an inhibitor of P-glycoprotein (Pgp). Co-administration of ivacaftor with Pgp substrates, such as azithromycin, may increase azithromycin exposure leading to increased or prolonged therapeutic effects and adverse events.
    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) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of maprotiline with azithromycin is advised. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. 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.
    Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and azithromycin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); azithromycin is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Mefloquine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering mefloquine with azithromycin. There is evidence that use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as azithromycin. Post-marketing use of azithromycin has been associated with cases of QT prolongation and TdP. Also, both mefloquine and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent.
    Meperidine; Promethazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Mesoridazine: (Severe) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Other drugs, such as mesoridazine, have been specifically established to have a causal association with QT prolongation and torsade de pointes and are contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    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: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Use of azithromycin during the post-marketing period has been associated with cases of QT prolongation and torsade de pointes (TdP). The need to coadminister methadone with drugs known to prolong the QT interval, such as azithromycin, should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, methadone is a substrate for P-glycoprotein (P-gp). Concurrent use of methadone with azithromycin (an inhibitor of P-gp) may result in increased methadone serum concentrations.
    Methylprednisolone: (Minor) Methylprednisolone is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, methylprednisolone concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Metronidazole: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and metronidazole should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Potential QT prolongation has been reported in limited case reports with metronidazole. Concurrent use may increase the risk of QT prolongation.
    Midostaurin: (Major) The concomitant use of midostaurin and azithromycin may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Reports of QT prolongation and torsade de pointes have been reported during postmarketing surveillance of azithromycin.
    Mifepristone, RU-486: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering mifepristone with azithromycin. Mifepristone has been associated with dose-dependent prolongation of the QT interval, and rare cases of QT prolongation and TdP have been reported with azithromycin during postmarketing use. To minimize the risk of QT prolongation, the lowest effective mifepristone dose should always be used. In addition, increased concentrations of azithromycin may occur if it is coadministered with mifepristone. Mifepristone is an inhibitor of the efflux transporter P-glycoprotein (P-gp) and azithromycin is a P-gp substrate.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and azithromycin. Coadminister with caution. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitomycin: (Moderate) Mitomycin is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, mitomycin concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Morphine: (Moderate) Monitor patients for increased side effects if morphine and azithromycin are coadministered. Morphine concentrations could be increased with coadministration. Morphine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor.
    Morphine; Naltrexone: (Moderate) Monitor patients for increased side effects if morphine and azithromycin are coadministered. Morphine concentrations could be increased with coadministration. Morphine is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor.
    Moxifloxacin: (Major) Concurrent use of moxifloxacin and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval, such as azithromycin. During the post-marketing period, cases of QT prolongation and TdP were associated with azithromycin.
    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.
    Niacin; Simvastatin: (Moderate) Both simvastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Nicardipine: (Moderate) Both nicardipine and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Nifedipine: (Moderate) Increased concentrations of azithromycin may occur if it is coadministered with nifedipine; exercise caution. Nifedipine is a mild inhibitor of the efflux transporter P-glycoprotein (P-gp) and azithromycin may be a P-gp substrate.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Nilotinib is a substrate and inhibitor of P-glycoprotein (P-gp) and azithromycin is also a substrate and inhibitor of P-gp; therefore, levels of nilotinib and/or azithromycin may increase. If the use of azithromycin is required, hold nilotinib therapy. If the use of nilotinib and azithromycin cannot be avoided, exercise caution; close monitoring of the QT interval is recommended.
    Nintedanib: (Moderate) Azithromycin is a moderate inhibitor of P-glycoprotein (P-gp) and nintedanib is a P-gp substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of azithromycin and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
    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.
    Norfloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and norfloxacin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Additionally, quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Octreotide: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and octreotide should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval.
    Ofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering ofloxacin with azithromycin. Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of TdP. Cases of QT prolongation and TdP have also been reported with the post-marketing use of azithromycin.
    Olanzapine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with azithromycin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. During postmarketing use, azithromycin has also been associated with case reports of QT prolongation and TdP. Concurrent use may increase the risk of QT prolongation.
    Olodaterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Both ritonavir and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together. In addition, the use of ritonavir could result in QT prolongation; QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Concurrent use may result in additive risk of QT prolongation. (Major) Concurrent administration of azithromycin with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of azithromycin and the components of the hepatitis C regimen. Increased plasma concentrations increases the risk of adverse effects, some of which may be serious; azithromycin and ritonavir both have been associated with QT-prolongation. Azithromycin and ritonavir are inhibitors of the drug transporter P-glycoprotein (P-gp), and azithromycin, dasabuvir, ombitasvir, paritaprevir, and ritonavir are P-gp substrates. Caution and close monitoring are advised if these drugs are administered together.
    Omeprazole: (Minor) Both omeprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Omeprazole; Sodium Bicarbonate: (Minor) Both omeprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Ondansetron: (Major) If azithromycin and ondansetron must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Azithromycin has also been associated with cases of QT prolongation and TdP during the post-marketing period.
    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.
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of azithromycin with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Both QT prolongation and TdP have been spontaneously reported with azithromycin use in postmarketing surveillance.
    Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and azithromycin concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. QT prolongation and TdP have also been spontaneously reported during azithromycin postmarketing surveillance.
    Paclitaxel: (Moderate) Paclitaxel is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, paclitaxel concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Paliperidone: (Major) Concurrent use of paliperidone and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, close monitoring for QT interval prolongation is advised. Paliperidone has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the use of azithromycin during the post-marketing period.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include azithromycin.
    Pantoprazole: (Minor) Both pantoprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Pasireotide: (Major) Cautious use of pasireotide and azithromycin is needed, as coadministration may have additive effects on the prolongation of the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Pazopanib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), coadministration of pazopanib and azithromycin is not advised; both pazopanib and azithromycin have been reported to prolong the QT interval. If these drugs must be given together, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for P-glycoprotein (P-gp). Azithromycin is an inhibitor of P-gp. Concurrent administration may result in increased pazopanib concentrations.
    Pentamidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with azithromycin. Pentamidine has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Perphenazine: (Minor) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering perphenazine with azithromycin. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Perphenazine is also 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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation. (Minor) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering perphenazine with azithromycin. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Perphenazine is also 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.
    Phenicol Derivatives: (Major) Chloramphenicol and macrolides are bactericidal or bacteriostatic via the same or similar mechanisms of action. Antagonism in vitro has been demonstrated. It is not recommended to administer these agents together in any combination due to potential antagonism.
    Phenylephrine; Promethazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Phenytoin: (Minor) Of the macrolides, azithromycin does not inhibit cytochrome P450 enzymes and is not likely to be implicated in clinically significant drug-drug interactions involving the CYP450 system. However, azithromycin is a substrate of p-glycoprotein (P-gp), and may undergo increased efflux resulting in lowered serum concentrations if administered with P-gp inducers such as 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. Until more data are available, the manufacturer of azithromycin recommends caution and careful monitoring of patients who receive azithromycin with phenytoin.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as azithromycin. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Concurrent use of pimozide and macrolides is contraindicated. Pimozide is metabolized primarily through CYP3A4, and macrolide antibiotics are CYP3A4 inhibitors. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Two sudden deaths have been reported when clarithromycin was added to pimozide therapy.
    Pirbuterol: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Posaconazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with azithromycin. Reports of QT prolongation and 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 torsade de pointes. Also, both posaconazole and azithromycin are P-glycoprotein (P-gp) substrates and inhibitors, which may lead to increased serum concentrations of either drug when given concomitantly. Concurrent use may increase the risk of QT prolongation.
    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.
    Prednisone: (Minor) Prednisone is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, prednisone concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include azithromycin.
    Procainamide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with azithromycin. Procainamide is associated with a well-established risk of QT prolongation and TdP, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Prochlorperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and prochlorperazine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and promethazine should be used together cautiously. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Propafenone: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with azithromycin. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Azithromycin has been associated with cases of QT prolongation and TdP, reported during the post-marketing period. Additionally, propafenone may inhibit P-glycoprotein (P-gp) and azithromycin is a P-gp substrate; therefore, increased concentrations of azithromycin may occur with concomitant administration.
    Protriptyline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Quetiapine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quetiapine with azithromycin. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, azithromycin has been associated with cases of QT prolongation and TdP, reported during the post-marketing period.
    Quinidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering quinidine with azithromycin. Quinidine is associated with QT prolongation and TdP, and rare cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin. In addition, both quinidine and azithromycin are P-glycoprotein (P-gp) substrates and inhibitors, which may lead to increased serum concentrations of either drug when given concomitantly.
    Quinine: (Major) Concurrent use of quinine and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. There have also been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports. In addition, concentrations of quinine may be increased during concomitant use. Azithromycin is a P-glycoprotein (P-gp) inhibitor and quinine is a P-gp substrate.
    Ranolazine: (Major) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Ranolazine is also associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, concomitant use may have additive risk. Azithromycin is also a substrate for and an inhibitor of P-glycoprotein transport, an energy-dependent drug efflux pump. The inhibition of P-glycoprotein, by drugs such as ranolazine may result in an increase in the concentration of azithromycin. Similarly, ranolazine also is a substrate for and an inhibitor of P-glycoprotein transport. Coadministration with azithromycin may result in an increase in the plasma concentration of ranolazine. If ranolazine and azithromycin are coadministered, patients should be monitored closely for adverse effects of each agent.
    Regadenoson: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and regadenoson should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Regadenoson has been associated with QT prolongation. Concurrent use may increase the risk of QT prolongation.
    Ribociclib: (Major) Avoid coadministration of ribociclib with azithromycin due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. There have been case reports of QT prolongation and Td with the use of azithromycin in postmarketing reports. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with azithromycin due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. There have been case reports of QT prolongation and Td with the use of azithromycin in postmarketing reports. Concomitant use may increase the risk for QT prolongation.
    Rifampin: (Moderate) Rifampin may decrease serum concentrations and potentially the effectiveness of azithromycin, while azithromycin may increase serum concentrations of rifampin. Rifampin is a substrate and inducer of P-glycoprotein (P-gp), while azithromycin is a substrate and inhibitor of P-gp. Monitor patients for increased side effects of rifampin and for signs of antimicrobial efficacy with azithromycin use.
    Rifaximin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and azithromycin, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
    Rilpivirine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with azithromycin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Risperidone: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of risperidone with azithromycin is advised. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Ritonavir: (Major) Both ritonavir and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together. In addition, the use of ritonavir could result in QT prolongation; QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Concurrent use may result in additive risk of QT prolongation.
    Rivaroxaban: (Minor) The coadministration of rivaroxaban and azithromycin should be undertaken with caution in patients with renal impairment; it is unclear whether a clinically significant interaction occurs when these two drugs are coadministered to patients with normal renal function. Azithromycin is a combined mild CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor. Rivaroxaban is a substrate of CYP3A4/5 and the P-gp transporter. Coadministration in patients with renal impairment may result in increased exposure to rivaroxaban compared with patients with normal renal function and no inhibitor use since both pathways of elimination are affected. While an increase in exposure to rivaroxaban may be expected, results from an analysis of the ROCKET-AF trial which allowed concomitant administration of rivaroxaban and a combined P-gp inhibitor and weak or moderate CYP3A4 inhibitor did not show an increased risk of bleeding in patients with CrCl 30 to < 50 ml/min [HR (95% CI): 1.05 (0.77, 1.42)].
    Romidepsin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering romidepsin with azithromycin. If these drugs must be coadministered, periodic ECG and electrolyte monitoring is recommended. Romidepsin has been reported to prolong the QT interval, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin. Additionally, romidepsin is a substrate for P-glycoprotein (P-gp). Azithromycin is an inhibitor of P-gp. Concurrent administration of romidepsin with an inhibitor of P-gp may cause an increase in systemic romidepsin concentrations.
    Salmeterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Sapropterin: (Moderate) Caution is advised with the concomitant use of sapropterin and azithromycin as coadministration may result in increased systemic exposure of azithromycin. Azithromycin is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of azithromycin.
    Saquinavir: (Severe) The concurrent use of azithromycin and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsades de pointes (TdP). Both saquinavir and azithromycin are P-glycoprotein (P-gp) substrates and inhibitors, which may lead to increased serum concentrations of either drug when given concomitantly, thus increasing the risk of drug toxicity and proarrhythmic effects. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as azithromycin. There have been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports.
    Sertraline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and sertraline should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of both azithromycin and sertraline in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Sevoflurane: (Major) Halogenated Anesthetics should be used cautiously and with close monitoring with azithromycin. Halogenated Anesthetics can prolong the QT interval. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Short-acting beta-agonists: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Silodosin: (Moderate) Silodosin is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, silodosin concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Simvastatin: (Moderate) Both simvastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Simvastatin; Sitagliptin: (Moderate) Both simvastatin and azithromycin are P-glycoprotein (P-gp) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Sirolimus: (Moderate) Sirolimus is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, sirolimus concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    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.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with azithromycin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of azithromycin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with azithromycin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Solifenacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and solifenacin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Sorafenib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering sorafenib with azithromycin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Sorafenib has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the use of azithromycin during the post-marketing period.
    Sotalol: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), cautious use of sotalol with azithromycin is advised. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    Soy Isoflavones: (Minor) Bacteria in the intestine produce enzymes which hydrolyze the soy isoflavones to the active isoflavonoids genistein and daidzein; alterations in gut microflora have been correlated with effects on soy isoflavone bioavailability. Macrolides significantly reduce the GI microflora and could theoretically prevent the formation of the active components of the soy isoflavones.
    Sparfloxacin: (Severe) There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports. Other drugs, such as sparfloxacin, have been specifically established to have a causal association with QT prolongation and torsade de pointes and are contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. In addition to avoiding concurrent drug interactions, the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
    St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort, Hypericum perforatum may decrease serum concentrations and potentially the effectiveness of azithromycin. St. John's wort may increase the expression of P-glycoprotein (P-gp), resulting in increased efflux and lowered serum concentrations of interacting medications that are substrates for P-gp, such as azithromycin. Clinicians should observe patients closely if St. John's wort is used.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and sulfamethoxazole; trimethoprim should be used together cautiously. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. In addition, there have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Sunitinib: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering sunitinib with azithromycin. Sunitinib can prolong the QT interval, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Tacrolimus: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering tacrolimus with azithromycin. Tacrolimus causes QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen with azithromycin due to an increased risk of QT prolongation and torsade de pointes (TdP); increased azithromycin exposure is also possible. 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. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance. Tamoxifen may increase exposure to azithromycin via inhibition of P-glycoprotein (P-gp).
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering azithromycin with telaprevir due to an increased potential for azithromycin-related adverse events. If azithromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of azithromycin and telaprevir. Both azithromycin and telaprevir are substrates and inhibitors of drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
    Telavancin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with azithromycin. Telavancin has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Telithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering telithromycin with azithromycin. Telithromycin is associated with QT prolongation and TdP, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Telotristat Ethyl: (Moderate) Use caution if azithromycin is coadministered with telotristat ethyl, and monitor for an increase in telotristat ethyl-related adverse reactions. Telotristat, the active metabolite of telotristat ethyl, is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor. Exposure to telotristat ethyl may increase.
    Temsirolimus: (Moderate) Use caution if coadministration of temsirolimus with azithromycin is necessary, and monitor for an increase in temsirolimus- and azithromycin-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) substrate/inhibitor in vitro, while azithromycin is also a P-gp substrate/inhibitor. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp inhibitors or substrates, but exposure to both azithromycin and temsirolimus (and active metabolite, sirolimus) is likely to increase.
    Teniposide: (Major) Concomitant use of teniposide with azithromycin may result in increased serum concentrations of teniposide and increase the risk for adverse reactions. Teniposide is a substrate of P-glycoprotein (P-gp); azithromycin is an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
    Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as azithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Terbutaline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Terfenadine: (Severe) Coadministration is contraindicated due to the risk for QT prolongation and torsade de pointes (TdP). Consider alternative antihistamine therapy.Terfenadine has been specifically established to have a causal association with QT prolongation and TdP and is contraindicated for use with drugs that potentially cause QT prolongation, such as azithromycin. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in postmarketing reports.
    Testosterone: (Minor) Both testosterone and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Tetrabenazine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering tetrabenazine with azithromycin. Tetrabenazine causes a small increase in the corrected QT interval (QTc), and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Thioridazine: (Severe) Because of the potential for torsade de pointes (TdP), use of azithromycin with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP. There have been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports.
    Ticagrelor: (Moderate) Coadministration of ticagrelor and azithromycin may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and azithromycin is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
    Tiotropium; Olodaterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Tipranavir: (Moderate) Tipranavir may alter serum concentrations and potentially the effectiveness of azithromycin, while azithromycin may increase serum concentrations of tipranavir. Tipranavir's effects on intestinal and hepatic P-glycoprotein (P-gp) are currently inconclusive. It appears that P-gp is inhibited with the first dose of tipranavir, followed by induction over time. The clinical effects will vary depending on the relative affinity of the coadministered drug for P-gp and the extent of intestinal first-pass metabolism/efflux. Azithromycin is a P-gp substrate and inhibitor. Monitor patients for increased side effects of tipranavir and for signs of antimicrobial efficacy with azithromycin use.
    Tizanidine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tizanidine should be used together cautiously. Tizanidine administration may result in QT prolongation. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Tolterodine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tolterodine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Concurrent use may increase the risk of QT prolongation.
    Tolvaptan: (Major) Both tolvaptan and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for side effects if these drugs are given together. If tolvaptan and azithromycin are coadministered, a reduction in the dose of tolvaptan may be required. For tolvaptan, monitor serum electrolytes and clinical response.
    Topotecan: (Major) Avoid the concomitant use of azithromycin, a P-glycoprotein (P-gp) inhibitor, with oral topotecan, a P-gp substrate; P-gp inhibitors have less of an effect on intravenous topotecan and these may be coadministered with caution. If coadministration of azithromycin and oral topotecan is necessary, carefully monitor for increased toxicity of topotecan, including severe myelosuppression and diarrhea. In a pharmacokinetic cohort study, coadministration of oral topotecan with a potent P-gp inhibitor (n = 8) increased the Cmax and AUC of topotecan by 2 to 3 fold (p = 0.008); coadministration with intravenous topotecan (n = 8) increased total topotecan exposure by 1.2-fold (p = 0.02) and topotecan lactone by 1.1-fold (not significant).
    Toremifene: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering toremifene with azithromycin. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Trandolapril; Verapamil: (Moderate) Both verapamil and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Trazodone: (Major) Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval, such as azithromycin. There have been case reports of QT prolongation and torsade de pointes (TdP) with the use of azithromycin in post-marketing reports.
    Tricyclic antidepressants: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Trifluoperazine: (Minor) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering trifluoperazine with azithromycin. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    Trimethoprim: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and sulfamethoxazole; trimethoprim should be used together cautiously. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. In addition, there have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Trimipramine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and tricyclic antidepressants (TCAs) should be used together cautiously. 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).There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Triptorelin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and triptorelin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Ulipristal: (Minor) In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as azithromycin may increase azithromycin concentrations. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Umeclidinium; Vilanterol: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and long-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP); additionally, an increase in azithromycin-related adverse reactions is possible. Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; azithromycin also has a possible risk for QT prolongation and TdP. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose. Generally, azithromycin is not metabolized, although some data indicate that it is a substrate of P-glycoprotein (P-gp). Coadministration with vandetanib increased the Cmax and AUC of another P-gp substrate by 29% and 23%, respectively. Increased concentrations of azithromycin are also possible.
    Vardenafil: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vardenafil with azithromycin. Azithromycin has been associated with post-marketing reports of QT prolongation and TdP. Vardenafil, at therapeutic (10 mg) and supratherapeutic (80 mg) doses, produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as azithromycin, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, concomitant use may result in increased concentrations of azithromycin and vemurafenib. Both vemurafenib and azithromycin are substrates/inhibitors of P-glycoprotein (P-gp). Use caution and monitor patients for toxicity.
    Venetoclax: (Major) Avoid the concomitant use of venetoclax and azithromycin; venetoclax is a substrate of P-glycoprotein (P-gp) and azithromycin is an inhibitor of P-gp. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day). If azithromycin is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a P-gp inhibitor was co-administered in healthy subjects.
    Venlafaxine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering venlafaxine with azithromycin. Venlafaxine is associated with a possible risk of QT prolongation; TdP has been reported with postmarketing use. Azithromycin has also been associated with postmarketing reports of QT prolongation and TdP. Concurrent use may increase the risk of QT prolongation.
    Verapamil: (Moderate) Both verapamil and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Vinblastine: (Minor) Vinblastine is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, vinblastine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Vincristine Liposomal: (Minor) Vincristine is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, vincristine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Minor) Vincristine is a substrate of P-glycoprotein (PGP) and azithromycin is a PGP inhibitor; therefore, vincristine concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    Vinorelbine: (Moderate) Caution is warranted when azithromycin is administered with vinorelbine as there is a potential for elevated vinorelbine concentrations. Monitor patients for an earlier onset and/or an increased severity of adverse effects including neurotoxicity and myelosuppression. Vinorelbine is a substrate of P-glycoprotein (P-gp) and azithromycin is an inhibitor of P-gp.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with azithromycin. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. There have also been case reports of QT prolongation and TdP with azithromycin.
    Vorinostat: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vorinostat with azithromycin. Vorinostat is associated with a risk of QT prolongation, and cases of QT prolongation and TdP have been reported with the postmarketing use of azithromycin. Concurrent use may increase the risk of QT prolongation.
    Warfarin: (Moderate) Azithromycin did not affect the prothrombin time response to a single dose of warfarin. Compared to other macrolides, azithromycin has less of an effect on cytochrome P450 isoenzymes. Reports of an interaction between azithromycin and warfarin have been made to the manufacturers suggesting that concomitant administration may potentiate the effects of warfarin. Monitor the INR in patients who receive warfarin and azithromycin concurrently as a potential interaction may occur. The concurrent use of other macrolides and warfarin in medical practice has been associated with increased anticoagulant effects.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including azithromycin.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and azithromycin is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Azithromycin is classified as FDA pregnancy risk category B. Animal data reveal no teratogenic effects. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Azithromycin has not been studied for use during labor and obstetric delivery. Treatment should be given only if clearly needed.

    According to the manufacturer, azithromycin should be used cautiously in women who are breast-feeding. 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. A population based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3—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. The American Academy of Pediatric considers erythromycin to be a medication that is usually compatible with breast-feeding; azithromycin and clarithromycin have not been evaluated by the AAP. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Azithromycin inhibits protein synthesis in bacterial cells by binding to the 50 S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms. It 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. It is not clear if azithromycin, like erythromycin, is effective in the treatment of diabetic gastroparesis.

    PHARMACOKINETICS

    Azithromycin is administered orally, intravenously, and topically to the eye. Distribution occurs extensively throughout the body with systemic administration. It 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). It has a long half-life (68 hours), which is partially explained by its extensive tissue uptake and slow release. Generally, it is not metabolized, although some data indicate that it is a substrate and inhibitor of P-glycoprotein. Elimination is largely in the feces, following excretion into the bile, with less than 10% excreted in the urine.
     
    Affected cytochrome P450 isoenzymes and drug transporter: P-gp
    Some data indicate that azithromycin is a substrate and inhibitor of P-glycoprotein.
     

    Oral Route

    Following oral administration, absorption of azithromycin is rapid. The absolute bioavailability of azithromycin capsules (no longer commercially available) is 38%. Food increases the mean serum concentration (Cmax) of azithromycin tablets and immediate-release oral suspension by about 23% and 56%, respectively; however, the AUC remains unchanged. In clinical trials with pediatric patients, azithromycin immediate-release oral suspension was routinely administered following a low-fat breakfast. After administration of the extended-release (ER) oral suspension, the mean Cmax and AUC of azithromycin were lower by 57% and 17%, respectively, compared to azithromycin immediate-release oral suspension. The bioavailability of azithromycin from the ER oral suspension relative to the immediate-release oral suspension was 83%. Therefore, the ER oral suspension is not bioequivalent and is not interchangeable with the immediate-release oral suspension. Administration of the ER oral suspension with a high-fat meal increases azithromycin mean Cmax by 115% and mean AUC by 23% compared to administration in the fasting state; a standard meal increased the Cmax by 119% and the mean AUC by 12% compared to the fasted state. Per the manufacturer, both azithromycin tablets and the immediate-release oral suspension may be taken with or without food. The extended-release oral suspension should be taken on an empty stomach, 1 hour before or 2 hours after a meal. Antacids containing aluminum and magnesium hydroxide did not alter the rate or extent of absorption from the ER oral suspension. 

    Intravenous Route

    In patients hospitalized with community-acquired pneumonia (CAP) receiving single daily 1-hour intravenous (IV) infusions for 2 to 5 days of 500 mg azithromycin at a concentration of 2 mg/mL, the mean Cmax +/- SD achieved was 3.63 +/- 1.60 mcg/mL, while the 24-hour trough level was 0.20 +/- 0.15 mcg/mL, and the AUC24 was 9.60 +/- 4.80 mcg x h/mL. The mean Cmax, 24-hour trough and AUC24 values were 1.14 +/- 0.14 mcg/mL, 0.18 +/- 0.02 mcg/mL, and 8.03 +/- 0.86 mcg x h/mL, respectively, in normal volunteers receiving a 3-hour IV infusion of 500 mg azithromycin at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with CAP that received the same 3-hour IV infusion regimen for 2 to 5 days.

    Other Route(s)

    Ophthalmic Route
    Following application of one drop of azithromycin ophthalmic solution to each eye, the systemic concentration of azithromycin is estimated to be below quantifiable limits.