Macrolides
ATC code: J01FA10 (Azithromycin)
Binds the 50S ribosomal subunit and inhibits bacterial protein synthesis. Bacteriostatic at standard concentrations, bactericidal at high levels. Broad spectrum: gram-positive cocci, select gram-negatives, and atypical pathogens – Mycoplasma pneumoniae, Chlamydia trachomatis, Legionella pneumophila. Accumulates intracellularly, providing a prolonged effect after a short course.
First line
First-line when atypical etiology is suspected in community-acquired pneumonia – Mycoplasma, Chlamydophila, Legionella. Also used in penicillin-allergic patients. Per /ATS 2019, azithromycin is given as outpatient monotherapy in patients without comorbidities or combined with a beta-lactam.
Second line
Second-line for acute bacterial sinusitis. First-line is amoxicillin or amoxicillin-clavulanate. Macrolides are given in penicillin allergy, but growing pneumococcal macrolide resistance limits their use.
Second line
Per the current CDC STI Treatment Guidelines 2021, first-line for uncomplicated chlamydial infection is doxycycline 100 mg twice daily for 7 days (better eradication, especially in rectal chlamydia and LGV). Azithromycin 1 g single oral dose is an alternative when doxycycline cannot be used (pregnancy, intolerance). Eradication with the single dose exceeds 90 % but is lower than with doxycycline.
Second line
Second-line for streptococcal pharyngitis, indicated only when the patient has a penicillin allergy. A 5-day course is standard. Penicillin V or amoxicillin remain first-choice per 2012.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Azithromycin is prescribed for upper respiratory infections, influenza and mild COVID-19 without bacterial complication. 2024 AWaRe and ESCMID 2020 state antibiotics do not act on viruses and are not indicated for viral URIs. The Hinks 2021 (PRINCIPLE), Furtado 2020 (COALITION II) and Cavalcanti 2020 RCTs did not show azithromycin benefit in COVID-19. CDC Antibiotic Use Tracking 2024 lists azithromycin as the most overprescribed outpatient pediatric agent. QT prolongation risk applies ( Drug Safety Communication 2013).
28 pairs found. Sorted from critical to minor.
Mechanism
Additive QT prolongation. Azithromycin received a 2013 warning for fatal ventricular arrhythmia risk, particularly in patients with risk factors. Amiodarone is a potent QT-prolonging drug.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin. If azithromycin is needed, ECG before start and potassium and magnesium in range.
Mechanism
Additive QT prolongation. Less dangerous than citalopram with clarithromycin (azithromycin prolongs QT less), but risk persists, especially with risk factors.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In atrial fibrillation, hypokalaemia, or prior QT prolongation, alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Azithromycin inhibits the P-glycoprotein transporter less than clarithromycin but still blocks a colchicine clearance route. Colchicine plasma levels rise moderately; toxicity has been reported with prolonged combination, especially in older patients and chronic kidney disease.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain as first signs. With prolonged combination, muscle weakness, peripheral neuropathy, and pancytopenia follow.
Management
For short azithromycin courses (3–5 days), no special measures are needed. In chronic kidney disease or hepatic impairment, temporarily halve the colchicine dose. For prolonged azithromycin therapy, switch antibiotic (doxycycline) or replace colchicine with allopurinol.
Mechanism
Additive QT prolongation. Azithromycin received a dedicated warning in 2013 for fatal ventricular arrhythmia risk. Dronedarone itself prolongs QT, and combined the effects add up.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin (no QT effect). If azithromycin is needed, ECG before start and potassium and magnesium in range.
Mechanism
Additive QT prolongation. Azithromycin received a 2013 warning for fatal arrhythmia risk. Haloperidol (especially IV) also has a pronounced QT effect.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Azithromycin weakly prolongs QT, additively with the TCA amitriptyline (a pronounced QT prolonger). Clinically significant arrhythmia is rare in young patients without cardiovascular disease.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) in young patients, the combination is acceptable. In older patients, cardiac disease, or hypokalaemia: ECG before start, alternative antibiotics (doxycycline, a cephalosporin), or replace amitriptyline with gabapentin/pregabalin for neuropathic pain.
Mechanism
Dual antibiotic therapy with additive QT prolongation. Used in severe infections (e.g., empirical therapy for community-acquired pneumonia in older patients at risk of atypical flora).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is appropriate in inpatient settings for indications (severe pneumonia, abdominal sepsis). ECG before start and at day 2 of therapy. Maintain potassium and magnesium. Avoid dual therapy in outpatient infections.
Mechanism
Dual macrolide therapy – doubled QT effect and redundant antibacterial activity without clinical rationale.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is not prescribed. Choose one macrolide: azithromycin for upper respiratory infections and chlamydia (short course); clarithromycin for H. pylori and atypical pneumonia. When choosing, mind the interaction profile (clarithromycin is a strong CYP3A4 inhibitor).
Mechanism
Macrolides suppress the gut bacteria Eggerthella lenta that inactivate digoxin. Digoxin plasma levels rise within days of co-administration.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias. Older patients: confusion.
Management
For short azithromycin courses (3–5 days), check digoxin level at 5–7 days. If it rises, temporarily reduce digoxin. Alternative antibiotics without gut flora effect: a cephalosporin or doxycycline.
Mechanism
Both prolong QT. Escitalopram dose-dependently ( Lexapro caps at 20 mg/day), azithromycin dose-dependently (FDA warning 2013).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In atrial fibrillation, hypokalaemia, or prior QT prolongation: alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Additive QT prolongation – both drugs prolong QTc dose-dependently.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short courses of both (azithromycin 3–5 days, fluconazole single dose for candidiasis), the combination is acceptable. For prolonged systemic fluconazole therapy: alternative antibiotics (doxycycline, a cephalosporin) or antifungals (terbinafine, echinocandins).
Mechanism
Additive QT prolongation (fluoxetine weakly prolongs QT at high doses).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In cardiovascular disease or fluoxetine doses above 40 mg: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Additive QT prolongation.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. Alternative antibiotics: a cephalosporin or doxycycline (no QT effect).
Mechanism
Antibiotics may affect methotrexate gut absorption. Low clinical significance at rheumatological methotrexate doses (5–25 mg weekly).
Symptoms
Mostly no changes. At high oncologic methotrexate doses: risk of rising levels with toxicity symptoms (stomatitis, diarrhoea, falling leukocyte count).
Management
At low rheumatological methotrexate doses, the combination is acceptable without adjustment. At high oncologic doses: avoid azithromycin; alternative antibiotics (a cephalosporin, nitrofurantoin for UTI).
Mechanism
Additive QT prolongation (mirtazapine weakly prolongs QT, especially above 30 mg).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with mirtazapine ≤30 mg, the combination is acceptable. In older patients and cardiovascular disease: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Additive QT prolongation (quetiapine prolongs QT at high doses).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with quetiapine ≤300 mg, the combination is acceptable. On high quetiapine doses or cardiovascular disease: ECG before start or alternative antibiotics.
Mechanism
Azithromycin is a weak P-glycoprotein inhibitor; rivaroxaban is a P-glycoprotein substrate. Rivaroxaban plasma levels may rise modestly, raising bleeding risk.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools. Higher risk in older patients and chronic kidney disease.
Management
For short azithromycin courses (3–5 days), the combination is acceptable without dose change. In older patients and creatinine clearance below 50 mL/min: monitor for bleeding signs. Alternative antibiotics without P-glycoprotein effect: a cephalosporin, amoxicillin-clavulanate, doxycycline.
Mechanism
Additive QT prolongation (sertraline minimally prolongs QT at standard doses, azithromycin dose-dependently).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with sertraline ≤150 mg, the combination is acceptable. In cardiovascular disease: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Additive QT prolongation (tacrolimus prolongs QT in hypomagnesaemia, common on calcineurin inhibitors).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses post-transplant: check magnesium and replete if needed. ECG before start if other QT-prolonging drugs are on board. Alternative antibiotics: a cephalosporin or doxycycline.
Mechanism
Azithromycin is a weak CYP1A2 inhibitor (theophylline is a substrate). Theophylline plasma levels may rise slightly. The effect is much smaller than with erythromycin or clarithromycin.
Symptoms
Mostly no changes. In patients with borderline theophylline levels: rare nausea, tachycardia, insomnia.
Management
For short azithromycin courses (3–5 days), no special adjustment. In patients on high theophylline doses (or with renal/hepatic impairment): check theophylline level at 3–5 days.
Mechanism
Additive QT prolongation (tramadol weakly prolongs QT). Weak serotonergic risk (tramadol inhibits serotonin reuptake).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) in patients without cardiovascular disease, the combination is acceptable. In epilepsy: watch tramadol-related seizure threshold reduction. Alternative analgesic: paracetamol or morphine/oxycodone (no QT effect).
Mechanism
Additive QT prolongation (venlafaxine prolongs QT at doses above 150 mg).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with venlafaxine ≤150 mg, the combination is acceptable. At higher venlafaxine doses or cardiovascular disease: ECG before start or alternative antibiotics.
Mechanism
Azithromycin suppresses vitamin K-producing gut flora, raising INR. Bleeding cases have been reported.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools. Higher risk in older patients and prior peptic ulcer disease.
Management
For short azithromycin courses (3–5 days), check INR 3–5 days after start and 5 days after stopping the antibiotic. If INR rises above target, reduce warfarin by 10–20%. Alternative antibiotics: a cephalosporin (minimal gut flora effect).
Mechanism
Azithromycin does not clinically significantly inhibit CYP3A4 (Indiana Flockhart Table). Atorvastatin AUC is unchanged.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. When a macrolide is needed in a patient on atorvastatin, azithromycin remains the preferred choice (unlike clarithromycin and erythromycin — strong CYP3A4 inhibitors).
Mechanism
Azithromycin has minimal effect on CYP3A4 and does not affect hepatic oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. In women on menopausal hormone therapy, azithromycin remains an antibiotic of choice for respiratory infections.
Mechanism
Azithromycin has minimal effect on CYP3A4 (unlike clarithromycin and erythromycin). No clinically significant reduction in ethinylestradiol levels has been reported.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
Additional contraception during short azithromycin courses (3–5 days) is not needed. In women on combined oral contraceptives with respiratory or urogenital infections, azithromycin remains an antibiotic of choice.
Mechanism
Rosuvastatin is minimally metabolised by CYP2C9 and excreted mainly unchanged via the liver and kidneys. Azithromycin does not affect these routes.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. The combination is standard when a macrolide is needed on rosuvastatin.
Mechanism
Azithromycin does not significantly inhibit CYP3A4, unlike clarithromycin and erythromycin (the labels these as absolute contraindications with simvastatin due to rhabdomyolysis risk). Simvastatin does not accumulate.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. When a macrolide is needed on simvastatin, azithromycin is the preferred choice. Clarithromycin and erythromycin are not combined with simvastatin — switch to azithromycin or to pravastatin/rosuvastatin (minimal CYP3A4 metabolism).
Sources
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FDA category B. Observational data have not shown an increased risk of congenital anomalies. Used when the benefit outweighs potential risk.
Compatible. Hale L2. Transfers into milk (RID about 3-5%); the long half-life (~68 h) does not produce clinically meaningful infant exposure. Possible mild diarrhoea, candidiasis or rash. Short courses (5-7 days) do not require breastfeeding interruption; longer therapy warrants observation of the infant's stools. eLactancia rates the risk as very low.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Azithromycin is evaluated for the following indications with varying evidence strength: Community-acquired pneumonia (evidence tier A), Streptococcal pharyngitis (evidence tier B), Acute bacterial rhinosinusitis (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Azithromycin (≥ 1 in 100): Diarrhea, Nausea, Abdominal pain, Flatulence. See the Safety section for uncommon and serious reactions.
FDA category B. FDA category B. Observational data have not shown an increased risk of congenital anomalies. Used when the benefit outweighs potential risk.
Compatible. Hale L2. Transfers into milk (RID about 3-5%); the long half-life (~68 h) does not produce clinically meaningful infant exposure. Possible mild diarrhoea, candidiasis or rash. Short courses (5-7 days) do not require breastfeeding interruption; longer therapy warrants observation of the infant's stools. eLactancia rates the risk as very low.
Azithromycin is contraindicated in: Hypersensitivity to macrolides; Severe hepatic impairment. Full list in the Safety section.