Azithromycin

What it is

Azithromycin is a macrolide antibiotic given as a tablet, an oral suspension, an injection or eye drops. Its US label lists approved uses in several common bacterial infections, from community-acquired pneumonia to chlamydial urethritis and cervicitis. It has an unusually long tissue half-life, which is why short courses such as five days or a single 1 gram dose are used.

What the research says

For the infections it is approved for, azithromycin works by stopping bacteria making proteins. Where the literature is strongest is not the approved list but two off-label long-term uses: taken several times a week for months it cuts exacerbations in COPD (Cochrane: 61% of control patients had an exacerbation versus 47% on antibiotics, number needed to treat 8) and in persistent uncontrolled asthma (AMAZES: 1.07 versus 1.86 exacerbations per patient-year). Against that sit real costs: significant hearing loss in the COPD trials, diarrhoea in a third of asthma patients, a strong association with infantile pyloric stenosis when given to young babies, warnings about QT prolongation and liver injury, and a sharp rise in macrolide resistance in treated communities.

Evidence grade: Well established.

How it works

Drug class: Macrolide (azalide) antibacterial

Azithromycin gets inside bacteria and sticks to part of the bacterial ribosome, the machine that builds proteins. With the ribosome jammed, the bacterium cannot make the proteins it needs to grow, and cannot assemble new ribosomes either. (Source 1)

What it is used for

• A meta-analysis of 23 randomised trials found azithromycin and doxycycline close in efficacy, with a small edge to doxycycline of up to about 3% overall, and about 7% in men with symptomatic urethral infection. Evidence: established. (Source 2)
• These are the indications the FDA approved, recorded here as a regulatory position with its date (label revised 7/2026). We did not reach systematic reviews for each of these individual indications in this run, so we are not rating the strength of that evidence. Evidence: unknown. (Source 3)
• A Cochrane review found prophylactic antibiotics cut the proportion of people having an exacerbation from 61% to 47%, a number needed to treat of 8, on moderate-quality evidence, and noted the benefit applies only to macrolides given at least three times a week. It did not reduce hospital admissions, lung function decline or deaths, and azithromycin caused significant hearing loss. Evidence: established. (Source 4)
• In the AMAZES randomised trial of 420 adults, azithromycin roughly halved the exacerbation rate and improved asthma quality of life, but diarrhoea affected 34% on azithromycin versus 19% on placebo. This is one large trial, not a body of trials. Evidence: limited. (Source 5)

Interactions

• Food (label): Azithromycin tablets and the oral suspension are not affected enough by food to need timing around meals, according to the label. (Source 6)
• Warfarin and other oral anticoagulants (case reports): Post-marketing reports suggest azithromycin may strengthen the blood-thinning effect, although the dedicated interaction study found no change in prothrombin time. (Source 7)
• Nelfinavir (an HIV protease inhibitor) (pharmacokinetic study): Nelfinavir raises azithromycin blood levels; the label does not change the dose but asks for closer watching for liver enzyme abnormalities and hearing impairment. (Source 8)
• Aluminium- and magnesium-containing antacids (including magnesium and aluminium supplements taken as antacids) (label): The label's pharmacokinetic interaction table reports a mean peak-concentration ratio of 0.765 when a single antacid dose containing 1350 mg aluminium hydroxide and 1200 mg magnesium hydroxide is given with azithromycin, that is a lower peak level; the extent of absorption ratio is 0.984. We could not obtain a narrative sentence from the current label to quote, so the quote below is only the label's general statement about taking azithromycin with or without food, and the antacid figures are reported from the label's Table 14 rather than quoted. (Source 6)

Stopping it

• Azithromycin is not a drug of dependence and we found no withdrawal syndrome described in the sources we reached. The stopping question that the literature does address is long-term prophylactic use: the Cochrane COPD review frames continued use as a trade-off against resistance and specific harms, and asks for monitoring of hearing loss, tinnitus and QTc. (Source 9)
• Stopping mass or prophylactic azithromycin matters at the community level too: a cluster-randomised trial showed macrolide resistance in treated communities climbing from under 4% to nearly half of monitored children in a year. (Source 10)

What goes wrong

Azithromycin caused significant hearing loss in the COPD prophylaxis trials. (Source 11)

• Systematic review, Moderate certainty.
• Size: Trials within the Cochrane review.
• Who: People with COPD, mean age over 65.
• How long: Three to 12 months.
• Result: Rates not given in the recorded passage; described as significant hearing loss, often reversible or partially reversible.
• Funding: not stated.

Azithromycin was associated with significant hearing loss in the treatment group, which was in many cases reversible or partially reversible.

In the same asthma trial, diarrhoea was much more common on azithromycin than placebo. (Source 5)

• Randomized trial, Moderate certainty.
• Size: 420 patients.
• Who: Adults with persistent uncontrolled asthma.
• How long: 48 weeks.
• Result: Diarrhoea 72 (34%) on azithromycin versus 39 (19%) on placebo; p=0·001.
• Funding: not stated in the recorded passage.

Diarrhoea was more common in azithromycin-treated patients (72 [34%] vs 39 [19%]; p=0·001).

Babies given a macrolide antibiotic after birth had about three times the rate of infantile hypertrophic pyloric stenosis. (Source 12)

• Meta-analysis, Moderate certainty.
• Size: 14 papers (12 retrospective cohort studies, two case-control studies); seven cohort studies pooled for postnatal exposure.
• Who: Infants exposed to macrolides directly after birth, in the womb, or through breast milk.
• How long: Early infancy.
• Result: Postnatal exposure RR = 3.17 (95% CI: 2.38-4.23; I2 = 10.0%); prenatal exposure OR = 1.47 (95% CI: 1.03-2.09) in cohorts but OR = 1.02 (95% CI: 0.66-1.58) in case-control studies; breastfeeding OR = 1.31 (95% CI: 0.42-4.1). These are observational associations.
• Funding: not stated.

For postnatal exposure, the overall estimate of seven cohort studies indicated a statistically significant association (RR = 3.17, 95% CI: 2.38–4.23; I2 = 10.0%) with no evidence of publication bias (Egger P = 0.81).

In a cluster-randomised trial, mass azithromycin treatment drove nasopharyngeal pneumococcal azithromycin resistance from under 4% to nearly half of children within a year. (Source 10)

• Randomized trial, Moderate certainty.
• Size: Communities randomised; children monitored for nasopharyngeal carriage.
• Who: Children in treated versus untreated communities.
• How long: 12 months.
• Result: Treated communities 3.6% (95% CI 0.8%-8.9%) at baseline to 46.9% (37.5%-57.5%) at month 12 (p = 0.003); control communities 9.2% (95% CI 6.7%-13.3%) at month 12 (p<0.0001 versus treated)
• Funding: not stated.

In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003).

The US label records, as a regulatory position, that azithromycin has been associated with QT prolongation and reported cases of torsades de pointes. (Source 13)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: Patients receiving azithromycin.
• How long: Label revised 7/2026.
• Result: No rates given; based on postmarketing spontaneous reports.
• Funding: Regulatory document (FDA-approved labelling, Pfizer Laboratories)

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin.

The label also records reports of liver injury, some fatal. (Source 14)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: Patients receiving azithromycin.
• How long: Label revised 7/2026.
• Result: No rates given.
• Funding: Regulatory document (FDA-approved labelling, Pfizer Laboratories)

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

What the evidence supports

Long-term prophylactic antibiotics, in practice macrolides such as azithromycin, reduced the proportion of COPD patients having an exacerbation from 61% to 47%. (Source 4)

• Systematic review, Moderate certainty.
• Size: 2716 participants across 8 studies for the main outcome.
• Who: Mostly frequent exacerbators with at least moderate-severity COPD, mean age over 65.
• How long: Three to 12 months.
• Result: OR 0.57 (95% CI 0.42 to 0.78); absolute fall from 61% to 47% (95% CI 39% to 55%); NNTB 8 (95% CI 5 to 17)
• Funding: not stated.

This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The number needed to treat for an additional beneficial outcome with prophylactic antibiotics given for three to 12 months to prevent one person from experiencing an exacerbation (NNTB) was 8 (95% CI 5 to 17).

In 420 adults with persistent uncontrolled asthma, azithromycin cut the exacerbation rate roughly in half compared with placebo. (Source 5)

• Randomized trial, Moderate certainty.
• Size: 420 patients (213 azithromycin, 207 placebo)
• Who: Adults with persistent uncontrolled asthma.
• How long: 48 weeks of treatment (enrolment June 2009 to January 2015)
• Result: 1·07 versus 1·86 exacerbations per patient-year; IRR 0·59 (95% CI 0·47–0·74); p<0·0001. At least one exacerbation: 44% versus 61%.
• Funding: not stated in the recorded passage.

Azithromycin reduced asthma exacerbations (1·07 per patient-year [95% CI 0·85–1·29]) compared with placebo (1·86 per patient-year [1·54–2·18]; incidence rate ratio [IRR] 0·59 [95% CI 0·47–0·74]; p<0·0001).

What the evidence does not support

In the same review, prophylactic antibiotics did not reduce hospital admissions, lung function decline, serious adverse events or deaths. (Source 15)

• Systematic review, Moderate certainty.
• Size: Up to 2716 participants.
• Who: People with COPD.
• How long: Three to 12 months.
• Result: No significant effect on hospital admissions, change in FEV1, serious adverse events or all-cause mortality.
• Funding: not stated.

Prophylactic antibiotics showed no significant effect on the secondary outcomes of frequency of hospital admissions, change in forced expiratory volume in one second (FEV1), serious adverse events or all-cause mortality (moderate-quality evidence).

Pooled randomised trials found no increase in death or cardiovascular events with azithromycin compared with placebo. (Source 16)

• Meta-analysis, Moderate certainty.
• Size: 15,588 patients across 12 randomised clinical trials.
• Who: Trial participants given azithromycin or placebo.
• How long: Varies by trial.
• Result: Risk ratio of death 0.877 (95% CI 0.752-1.024; P = .097); hospitalisation RR 1.005 (95% CI 0.922-1.094); clinical intervention for CV events RR 0.999 (95% CI 0.896-1.125)
• Funding: not stated.

Compared with patients who had not received azithromycin, patients who had received azithromycin had an overall risk ratio (RR) of death of 0.877 (95% confidence interval [CI], 0.752-1.024; P = .097).

Where the evidence is mixed

For genital chlamydia, pooled trials favoured doxycycline over azithromycin by up to about 3% overall and about 7% in men with symptomatic urethral infection, on evidence the authors describe as of variable quality. (Source 2)

• Meta-analysis, Low certainty.
• Size: 23 studies; 1147 patients on azithromycin and 912 on doxycycline.
• Who: Patients with genital chlamydia infection.
• How long: not stated in the abstract.
• Result: Pooled efficacy difference favouring doxycycline 1.5% (95% CI -.1% to 3.1%, random effects) to 2.6% (95% CI .5%-4.7%, fixed effects); symptomatic men 7.4% (95% CI 2.0%-12.9%, fixed effects)
• Funding: not stated.

We found a pooled efficacy difference in favor of doxycycline of 1.5% (95% confidence interval [CI], -.1% to 3.1%; I(2) = 1.9%; P = .435; random effects) to 2.6% (95% CI, .5%-4.7%; fixed effects).

An observational analysis found cardiac deaths in the first five days highest after azithromycin among the antibiotics compared, but the difference from the other antibiotics was not statistically significant. (Source 17)

• Cohort study, Low certainty.
• Size: Not given in the recorded passage.
• Who: Patients dispensed azithromycin, amoxicillin, clindamycin, clarithromycin or a quinolone (levofloxacin, ciprofloxacin or moxifloxacin), excluding patients at high risk of death from other causes.
• How long: 0-5, 6-10, 0-10 and 0-30 day windows.
• Result: Cardiac deaths per million within the first 5 days: 84.6 azithromycin, 78.3 clarithromycin, 69.4 amoxicillin, 61.6 quinolones, 15.0 clindamycin.
• Funding: not stated.

After propensity score weighting, cardiac deaths per million within the first 5 days were: 84.6 for azithromycin, 78.3 for clarithromycin, 69.4 for amoxicillin, 61.6 for quinolones and 15.0 for clindamycin.

The same authors conclude that cardiovascular mortality did not differ significantly between azithromycin and the other antibiotics, while saying they cannot rule out an increased risk of cardiovascular death from azithromycin in people otherwise at low risk of death. (Source 18)

• Cohort study, Low certainty.
• Size: Not given in the recorded passage.
• Who: General population of antibiotic users.
• How long: Up to 30 days.
• Result: No statistically significant difference between the study antibiotics and azithromycin in any time window (days: 0-5, 6-10, 0-10 and 0-30)
• Funding: not stated.

Additionally our results suggest that while we cannot rule out the increased risk of cardiovascular death from azithromycin in patients at low risk of death, the risk may not be as large initial studies suggest.

Where the research disagrees

Whether azithromycin raises the risk of cardiovascular death

• Meta-analysis of 12 randomised trials (American Health & Drug Benefits, 2014), meta-analysis of randomised trials, 15,588 patients: No increased risks for mortality or for CV events associated with azithromycin therapy compared with placebo were found among patients included in the 12 randomized clinical trials reviewed in this analysis. (Source 19)
• Observational analysis of antibiotic users (Journal of Comparative Effectiveness Research, 2017), cohort, propensity-score weighted observational data: Additionally our results suggest that while we cannot rule out the increased risk of cardiovascular death from azithromycin in patients at low risk of death, the risk may not be as large initial studies suggest. (Source 18)

How much

• Reference intake: There is no reference intake for an antibiotic. Dosing is set by the prescriber and depends on the infection. As a regulatory position, the US label (revised 7/2026) gives for community-acquired pneumonia of mild severity in adults: "500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5". (Source 20)
• Upper limit: No upper limit in the nutrition sense exists. The largest single approved adult dose on the label is for urethritis and cervicitis: "One single 1 gram dose". Recorded as a regulatory position of the label revised 7/2026. (Source 21)
• Studied: The Cochrane COPD review notes that all the continuous and intermittent prophylaxis trials used macrolides given at least three times a week, for three to 12 months. (Source 9)
• Studied: AMAZES randomised 213 adults with persistent uncontrolled asthma to azithromycin and 207 to placebo, with enrolment between June 12, 2009 and Jan 31, 2015. (Source 5)

A common belief, and what the research shows

The belief: A course of azithromycin is a harmless way to clear up any chest infection or cough.

What the research shows: It is not harmless at the population level. In a cluster-randomised trial, "In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003)." And at the individual level the label records that "Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin."

Questions and answers

What is it?

Azithromycin is a macrolide antibiotic, sold as Zithromax and often as a five-day 'Z-Pak'. It is approved in the US for a defined list of bacterial infections in people with mild to moderate disease caused by bacteria known to be susceptible. It comes as tablets, a suspension, an injection and eye drops. (Source 3)

What does it do in the body?

It binds to part of the bacterial ribosome, the structure bacteria use to build proteins. That blocks protein production and also stops the bacterium assembling new ribosomes, so the bacteria cannot grow. (Source 1)

Is it good or bad for you?

Good when there is a bacterial infection it treats, and genuinely useful taken long-term in COPD, where it cut the share of people having a flare-up from 61% to 47%. Bad when it is used for infections that are not bacterial, because the harms are real: hearing loss in the long-term trials, diarrhoea in a third of asthma trial patients, liver injury and QT warnings on the label, and a large rise in resistant bacteria in treated communities. (Source 4)

How do you get more of it?

Azithromycin is prescription-only and there is no food or supplement source. The amount a person takes is fixed by the prescription: for adult community-acquired pneumonia of mild severity the label gives a 5-day course starting with a double dose. (Source 20)

If it is harmful, what reduces it?

If azithromycin is causing a problem, it is simply stopped; the label tells prescribers to stop it immediately if signs of hepatitis appear. There is no taper and no withdrawal syndrome described in the sources we reached. The harm that does not disappear when you stop is the resistant bacteria the course selects for. (Source 14)

Why might someone be low in it or missing it?

This question does not apply. Azithromycin is a manufactured antibiotic, not a nutrient or a resident organism, so nobody is naturally short of it. The nearest equivalent problem is the opposite one: bacteria that have become resistant so the drug no longer works, which the trial evidence shows rises sharply in treated communities. (Source 10)

Which whole foods contain it or feed it?

No whole food contains azithromycin. The only food-related fact in the label is that tablets and suspension can be taken with or without a meal, so there is nothing to time around. (Source 6)

What happens if you do not have it?

Nothing happens to a healthy person who never takes it. Where it matters is when a condition it treats goes untreated or is treated with something less effective: for genital chlamydia, for instance, the pooled trials show the alternative doxycycline is slightly more effective, by up to about 3% overall and about 7% in men with symptomatic urethral infection. The same review authors add that the quality of that evidence varies considerably and that few of the trials were double-blind and placebo-controlled, so the size of the gap is uncertain. (Source 22)

How can you test for it?

There is no blood test for azithromycin levels in routine use. What is tested is the bacterium: laboratories measure whether an isolate is susceptible or resistant to azithromycin. The cluster-randomised trial we cite measured exactly that in nasopharyngeal pneumococci, so the test exists and is used in research and in clinical microbiology, but no source we fetched describes a validated test of azithromycin levels in a person. (Source 10)

We searched: DailyMed ZITHROMAX label (Microbiology, Drug Interactions, Warnings), Cochrane CD009764, PLOS Medicine cluster-randomised resistance trial

References

1. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - CLINICAL PHARMACOLOGY, Microbiology (Pfizer Laboratories). 2026. Read the source
2. Clinical Infectious Diseases (structured abstract, NIHR Database of Abstracts of Reviews of Effects). Azithromycin versus doxycycline for the treatment of genital chlamydia infection: a meta-analysis of randomised controlled trials (Results). 2014. PMID 24729507, DOI 10.1093/cid/ciu220. Read the source
3. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) tablet / powder for suspension - INDICATIONS AND USAGE (Pfizer Laboratories). 2026. Read the source
4. Cochrane Database of Systematic Reviews. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD) (Main results, exacerbations). 2018. DOI 10.1002/14651858.CD009764.pub3. Read the source
5. The Lancet. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. 2017. DOI 10.1016/S0140-6736(17)31281-3. Read the source
6. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - DOSAGE AND ADMINISTRATION 2.1, statement that tablets and oral suspension may be taken with or without food (Pfizer Laboratories). 2026. Read the source
7. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - DRUG INTERACTIONS, oral anticoagulants (Pfizer Laboratories). 2026. Read the source
8. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - DRUG INTERACTIONS, nelfinavir (Pfizer Laboratories). 2026. Read the source
9. Cochrane Database of Systematic Reviews. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD) (Authors' conclusions). 2018. DOI 10.1002/14651858.CD009764.pub3. Read the source
10. PLOS Medicine. Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial. 2010. PMID 21179434, DOI 10.1371/journal.pmed.1000377. Read the source
11. Cochrane Database of Systematic Reviews. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD) (Main results, adverse events). 2018. DOI 10.1002/14651858.CD009764.pub3. Read the source
12. Italian Journal of Pediatrics. The association of prenatal and postnatal macrolide exposure with subsequent development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis (Results). 2019. DOI 10.1186/s13052-019-0613-2. Read the source
13. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - WARNINGS AND PRECAUTIONS, QT prolongation (Pfizer Laboratories). 2026. Read the source
14. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - WARNINGS AND PRECAUTIONS, hepatotoxicity (Pfizer Laboratories). 2026. Read the source
15. Cochrane Database of Systematic Reviews. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD) (Main results, secondary outcomes). 2018. DOI 10.1002/14651858.CD009764.pub3. Read the source
16. American Health & Drug Benefits. Cardiovascular Events and Safety Outcomes Associated with Azithromycin Therapy: A Meta-Analysis of Randomized Controlled Trials (Results). 2014. Read the source
17. Journal of Comparative Effectiveness Research. Appraisal of the cardiovascular risks of azithromycin: an observational analysis (abstract, Results). 2017. DOI 10.2217/cer-2016-0080. Read the source
18. Journal of Comparative Effectiveness Research. Appraisal of the cardiovascular risks of azithromycin: an observational analysis (abstract, Conclusion). 2017. DOI 10.2217/cer-2016-0080. Read the source
19. American Health & Drug Benefits. Cardiovascular Events and Safety Outcomes Associated with Azithromycin Therapy: A Meta-Analysis of Randomized Controlled Trials (Conclusion). 2014. Read the source
20. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - DOSAGE AND ADMINISTRATION, adult dosage table row for community-acquired pneumonia (mild severity), pharyngitis/tonsillitis (second-line therapy) and skin/skin structure (uncomplicated) (Pfizer Laboratories). 2026. Read the source
21. DailyMed, U.S. National Library of Medicine (FDA Structured Product Label). ZITHROMAX (azithromycin dihydrate) - DOSAGE AND ADMINISTRATION, adult dosage table row for genital ulcer disease (chancroid) and non-gonococcal urethritis and cervicitis (Pfizer Laboratories). 2026. Read the source
22. Clinical Infectious Diseases (structured abstract, NIHR Database of Abstracts of Reviews of Effects). Azithromycin versus doxycycline for the treatment of genital chlamydia infection: a meta-analysis of randomised controlled trials (Conclusions). 2014. PMID 24729507, DOI 10.1093/cid/ciu220. Read the source