Bacteriostatic macrolide (azalide)
Azithromycin is a macrolide antibiotic used to treat various respiratory, skin and sexually transmitted infections, among others. It is taken orally, usually in short courses (3 to 5 days), because it persists for a long time in tissues. It is generally well tolerated; the most common effects are gastrointestinal.
Also known as: Zitromax, Azitromax
Azithromycin may raise plasma Digoxin levels by inhibiting P-glycoprotein, with a risk of digitalis toxicity.
Azithromycin, like other macrolides, can raise digoxin concentrations through two mechanisms: inhibition of P-glycoprotein (which eliminates digoxin) and reduction of the gut bacterial flora that inactivates digoxin (about 10% of patients have flora that metabolises the drug). The effect is variable, but reports of digitalis toxicity after macrolide courses exist. Monitor for toxicity symptoms (nausea, vomiting, bradycardia, arrhythmias, confusion, visual disturbances) and consider monitoring digoxin levels, especially in the elderly and in patients with reduced renal function.
Macrolides can raise digoxin levels (P-gp inhibition and reduction of the gut flora that metabolises digoxin). Monitor for signs of digitalis toxicity.
Azithromycin inhibits P-glycoprotein, the efflux transporter that clears Digoxin; inhibition raises serum digoxin and may trigger digitalis toxicity.
Monitor nausea, anorexia, visual disturbances, bradycardia/arrhythmias and digoxin and potassium levels.
Bradyarrhythmias, persistent nausea, confusion or visual changes require immediate evaluation.
Watch for digitalis toxicity and, when possible, check serum digoxin levels during the combination.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Azithromycin may potentiate the anticoagulant effect of Warfarin, raising the INR and the bleeding risk (variable and sometimes delayed effect).
Azithromycin, like other macrolides, can increase the effect of warfarin through two mechanisms: reduction of the gut flora that produces vitamin K and inhibition (milder than clarithromycin and erythromycin) of CYP3A4, which participates in warfarin metabolism. Clinical reports with azithromycin are less consistent, but cases of elevated INR and bleeding exist. The warfarin label lists macrolides as drugs that can increase the anticoagulant effect. The INR should be monitored during the antibiotic course and in the following weeks, with dose adjustment if needed.
Macrolides can potentiate warfarin (gut flora + enzyme inhibition). Azithromycin's effect is less consistent than clarithromycin/erythromycin, but INR monitoring during and after the antibiotic is still required.
Mechanism not fully established; Azithromycin appears to alter metabolism or gut flora, potentiating Warfarin anticoagulation, usually within the first days or weeks of combined use.
Monitor the INR more frequently and watch for bleeding signs during therapy.
Bleeding, an elevated INR or spontaneous bruising require urgent evaluation.
Monitor the INR and adjust warfarin as needed; watch for bleeding signs during and after the combination.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Food reduces absorption of azithromycin capsules; tablets may be taken with or without food.
Take capsules on an empty stomach; tablets may be taken with food.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45
Grapefruit may slightly raise azithromycin concentrations, with limited clinical relevance.
Limit grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45
Azithromycin can cause hepatotoxicity, including hepatic necrosis, especially with prior liver disease.
Use with caution; monitor for signs of liver injury.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45
Azithromycin may prolong the QT interval and increase the arrhythmia risk, especially in at-risk patients.
Avoid in known QT prolongation or with QT-prolonging drugs.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45
Azithromycin has not been associated with an increase in major malformations; it is used in pregnancy when a macrolide is indicated.
May be used in pregnancy when indicated.
Excreted into breast milk; compatible with breastfeeding.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Broad-spectrum macrolide antibacterial (respiratory tract, skin and soft tissue, uncomplicated urethritis/cervicitis). Penetrates extensively into tissues (tissue concentrations far above serum), with a long terminal half-life allowing short courses (3-5 days). Prolongs the QTc interval in a dose- and concentration-dependent manner (maximum mean +9 ms with 1500 mg co-administered with chloroquine).
Macrolide antibacterial; in animal infection models the antibacterial activity correlates with the AUC/MIC ratio (area under the curve/minimum inhibitory concentration) for certain pathogens (S. pneumoniae and S. aureus). The pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been fully elucidated in clinical trials.
Absolute oral bioavailability of 38% (250 mg capsules). After a single 500 mg oral dose under fasting conditions: mean Cmax 0.5 mcg/mL, Tmax 2.2 hours. Serum protein binding is variable, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. Food increases Cmax (23-56% depending on formulation) without changing AUC.
Minimal metabolism (no formal in vitro/in vivo metabolism studies were performed). Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination; over the course of a week only about 6% of the administered dose appears unchanged in urine. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.
Terminal elimination half-life of approximately 68 hours (polyphasic pattern; mean apparent plasma clearance 630 mL/min) — the prolonged half-life is due to extensive tissue uptake rather than slow elimination of circulating drug. Serum terminal half-life after 3- or 5-day regimens is 68.9-71.8 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
