Drug Shortages
| Prep | Started At | Notes |
|---|---|---|
| Oral susp, 1 gm packets | 2024-11-20 |
Usage and Dosing
- Azithromycin, approved in 1991, is an azalide antibiotic used to treat a wide range of clinical conditions, including bacterial conjunctivitis, upper respiratory tract bacterial infections, community-acquired pneumonia (CAP), disseminated Mycobacterium avium complex (MAC), pertussis, Chlamydia, gonococcal STI, and cat scratch disease.
- Azithromycin binds to the 50S ribosomal subunit to interfere with protein synthesis. It was originally thought to simply block the exit tunnel for the new polypeptide being synthesized, but it is probably more complicated than that. The drug may also affect the catalytic center of the ribosome to prevent polymerization of specific amino acid sequences.
- Mechanisms of resistance: Methylation of ribosomal target, activation of efflux pumps.
- Available in multiple pharmaceutical preparations (see Pharmacology).
- Evaluate risk of prolongation of QTc before prescribing; details under adverse effects.
Adult Dose
| Usual oral dose* | 500 mg po day 1, then 250 mg po q24h days 2-5 |
| Usual IV dose* | 500 mg IV q24h |
| Other uses (partial list) |
*NOTE: Different oral or IV dosage regimens are sometimes used. Refer to disease syndrome pages for specifics.
Pediatric Dose
| Dose (Age >28 Days) | See syndrome pages for dosing details Oral: 5-12 mg/kg/day (once daily) IV: 5-10 mg/kg/day (once daily) |
| Max/Day | - |
Renal Adjustment
- Body weight and Creatinine Clearance calculations
- CrCl = Creatinine clearance (mL/min)
- CAPD = Continuous Ambulatory Peritoneal Dialysis
- CRRT = Continuous Renal Replacement Therapy
- AD = after hemodialysis
- SLED = sustained low efficiency dialysis
| Half-life, hrs (renal function normal) | 68 |
| Half-life, hrs (ESRD) | Unchanged |
| Dose (renal function normal) | 250-500 mg IV/po q24h |
| CrCl or eGFR | No dosage adjustment for renal impairment |
| Hemodialysis | No dosage adjustment |
| CAPD | No dosage adjustment |
| CRRT | No dosage adjustment |
| SLED | No data |
Hepatic Adjustment
| Mild impairment (Child-Pugh Class A) | No dosage adjustment |
| Moderate impairment (Child-Pugh Class B) | No dosage adjustment |
| Severe impairment (Child-Pugh Class C) | No dosage adjustment |
Other Adjustment
- ECMO: See ECMO Drug Dosing Adjustment.
Adverse Effects
- GI (nausea, vomiting, diarrhea). Taking the drug with food lessens the chance of nausea.
- Rash (rare)
- Hematologic (rare): neutropenia, thrombocytopenia
- LFT abnormalities (rare)
- Transient reversible hearing loss (J Otolaryngol 2007;36:257).
- Possible induction of a manic episode with psychotic features in an adolescent: Innov Clin Neurosci 2025;22:54.
- QTc interval prolongation: Any of the macrolides (azithromycin, clarithromycin, erythromycin) has the potential of increasing the QTc interval and predisposing to ventricular arrhythmias.
- In retrospective controlled study from Tennessee, 5 days of azithromycin increased the risk of cardiovascular death (hazard ratio 2.88, p<0.001); compared to amoxicillin, estimated 47 additional cardiovascular deaths per 1 million courses of therapy (N Engl J Med 2012;366:1881). Subsequent larger study in generally younger population from Denmark showed CV mortality in azithromycin recipients was only 15.4/million courses vs. 85.2/million courses in the Tennessee study (N Engl J Med 2013;368:1704; N Engl J Med 2013;368:1665).
- Risk of ventricular arrhythmia and/or cardiac death in 2 million Taiwanese outpatients occurring within 7 days after the initiation of treatment with amoxicillin-clavulanate, oral FQ, or oral macrolide (azithromycin/clarithromycin). Although the number of events was low, compared to amoxicillin-clavulanate, the highest propensity score adjusted odds ratios were 2.74 for moxifloxacin, and 3.4 for azithromycin (Clin Infect Dis 2015;60:566).
- Hence, azithromycin may increase risk of CV death in patients with congenital or acquired cardiovascular disease risk factors. Caution indicated in patients with history of unexplained syncope, family history of unexplained sudden cardiac death, known electrolyte abnormalities, or the need for concomitant administration of other drugs known to potentially prolong the QTc.
- Review: Am J Med 2015;128:1362.e1.
Pregnancy Risk
| FDA Risk Category 1 |
Humans: no evidence of toxicity. Animals: some evidence of decreased viability and delayed development in rats. |
| Use during Lactation | Safe, monitor infant for GI toxicity |
Footnotes:
| 1 | : | Capital letter = Old FDA risk category; Text = New FDA risk category |
Antimicrobial Spectrum
Preferred ++ ( 10 )
Agent is a first line therapy: reliably active in vitro, clinically effective, guideline recommended, recommended as a primary or acceptable alternative agent in the Sanford Guide. See pathogen page for specific recommendations.
Alternative + ( 13 )
Agent is a potential alternative agent (active in vitro, possesses class activity comparable to known effective agents or a therapeutically interchangeable agents and hence likely to be clinically effective, but second line due to overly broad spectrum, toxicity, limited clinical experience, or paucity of direct evidence of effectiveness).
- Actinomyces sp.
- Borrelia burgdorferi
- Chlamydophila psittaci, C. pneumoniae
- Clostridium perfringens, C. sordellii
- Coxiella burnetii
- Haemophilus influenzae
- Moraxella catarrhalis
- Pasteurella multocida
- Salmonella sp.
- Shigella sp.
- Staphylococcus lugdunensis
- Vibrio cholera, toxigenic
- Vibrio parahemolyticus
- Mycoplasma species are generally susceptible to azithromycin and other macrolides. The exception is Mycoplasma hominis which is resistant to macrolides.
Pharmacology
| PK/PD Index | 24-hr AUC/MIC |
| Pharmaceutical Preparations |
Tab (250, 500, 600 mg) Oral susp (1 gm pkt) Oral susp (100 mg/5 mL, 200 mg/5 mL) 1% oph soln Injection |
| Food Rec (PO Drugs) 1 | All preps ± food |
| Oral Absorption (%) | 37 |
| Tmax (hr) | po 2.5 |
| Peak Serum Conc (µg/mL) 2 |
0.4 (500 mg po, SD) 3.6 (500 mg IV, SD) |
| Peak Urine Conc (µg/mL) | No data |
| Protein Binding (%) | 7-51 |
| Volume of Distribution (Vd) 3 | 31.1-33.3 L/kg |
| Avg Serum T½ (hr) 4 | 68 |
| Elimination | Biliary |
| Bile Penetration (%) 5 | High |
| CSF/blood (%) 6 | No data |
| Therapeutic Levels in CSF 7 | No data |
| AUC (µg*hr/mL) 8 |
4.3 (500 mg po, 0-inf) 9.6 (500 mg IV, 0-24 hr, pre-SS) |
Footnotes:
| 1 | : | Refers to adult oral preparations unless otherwise noted; + food = take with food, no food = take without food, ± food = take with or without food |
| 2 | : | SD = after a single dose, SS = at steady state |
| 3 | : | V/F = Vd/oral bioavailability; Vss = Vd at steady state; Vss/F = Vd at steady state/oral bioavailability |
| 4 | : | Assumes CrCl >80 mL/min |
| 5 | : | (Peak concentration in bile/peak concentration in serum) x 100. If blank, no data. |
| 6 | : | CSF concentrations with inflammation. |
| 7 | : | Judgment based on drug dose and organism susceptibility. CSF concentration ideally ≥10x MIC. |
| 8 | : | AUC = area under serum concentration vs. time curve. KEY: 0-inf = AUC 0 to infinity; 0-xh = AUC 0 to x hours. |
Enzyme- Transporter-mediated Interactions
| CYP450s that drug is a substrate for: | - |
| Transporters that drug is a substrate for: | PGP |
| UGTs that drug is a substrate for: | - |
| CYP450s inhibited by drug: | - |
| Transporters inhibited by drug: | PGP (weak) |
| UGTs inhibited by drug: | - |
| CYP450s induced by drug: | - |
| Transporters induced by drug: | - |
| UGTs induced by drug: | - |
| Impact on serum drug concentrations 1 | mild ↑ |
Footnotes:
| 1 | : | Refers to serum concentrations of companion drugs that may be affected by the listed antimicrobial. ↑=increase, ↓=decrease. |
Major Drug Interactions
| Drug | Effect on concentration (or other) | Suggested management |
|---|---|---|
| Amiodarone | ↑QT interval | Monitor or avoid |
| Apixaban | ↑apixaban | Monitor or avoid |
| Betrixaban | ↑betrixaban | Monitor or avoid |
| Cyclosporine | ↑cyclosporine | Monitor or avoid |
| Dabigatran | ↑dabigatran | Monitor or avoid |
| Digoxin | ↑digoxin | Monitor, adjust dosage |
| Dofetilide | ↑QT interval | Monitor or avoid |
| Edoxaban | ↑edoxaban | Monitor or avoid |
| Everolimus | ↑everolimus | Monitor or avoid |
| Nelfinavir | ↑azithromycin | Monitor |
| Procainamide | ↑QT interval | Monitor or avoid |
| Quinidine | ↑QT interval | Monitor or avoid |
| Rivaroxaban | ↑rivaroxaban | Monitor or avoid |
| Sirolimus | ↑sirolimus | Monitor or avoid |
| Sotalol | ↑QT interval | Monitor or avoid |
| Tacrolimus | ↑tacrolimus | Monitor or avoid |
