Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Reviewed/Revised May 2022
Topic Resources





Oral or parenteral




Oral or parenteral




Macrolides are relatively poorly absorbed orally. Fidaxomicin is minimally absorbed and active only locally in the gastrointestinal tract. Food has the following effects on macrolide absorption:

  • For extended-release clarithromycin, increased absorption

  • For immediate-release clarithromycin tablet or suspension, no effect

  • For azithromycin capsules and erythromycin (including base and stearate formulations), decreased absorption

  • For fidaxomicin, minimal effects

Once absorbed macrolides diffuse well into body fluids, except cerebrospinal fluid, and are concentrated in phagocytes. Excretion is mainly in bile.

Indications for Macrolides

Macrolides are active against

Macrolides have been considered the drug of choice for group A streptococcal Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more Streptococcal Infections and pneumococcal infections Pneumococcal Infections Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis... read more when penicillin cannot be used. However, pneumococci with reduced penicillin sensitivity are often resistant to macrolides, and macrolide resistance among S. pyogenes varies globally. Because they are active against atypical respiratory pathogens, they are often used empirically for lower respiratory tract infections, but another drug is often necessary to cover macrolide-resistant pneumococci. Macrolides have other clinical uses (see table Some Clinical Uses of Macrolides Some Clinical Uses of Macrolides Some Clinical Uses of Macrolides ). Macrolides are not used to treat meningitis.


Contraindications to Macrolides

Macrolides are contraindicated in patients who have had an allergic reaction to them.

Concomitant administration of macrolides with astemizole, cisapride, pimozide, or terfenadine is contraindicated because potentially fatal cardiac arrhythmias (eg, QT prolongation, ventricular tachycardia, ventricular fibrillation, torsades de pointes) may occur when clarithromycin or erythromycin is given with these drugs. This effect is most likely due to inhibition of metabolism of these drugs by erythromycin and clarithromycin.

Use During Pregnancy and Breastfeeding

Animal reproduction studies with erythromycin or azithromycin have not shown risk to the fetus. A higher rate of cardiovascular anomalies has been observed after exposure to erythromycin during early pregnancy than after exposure to penicillin exposure; however, in other studies this increased risk was not observed. Erythromycin is considered safer than azithromycin because clinical use has been much more extensive.

Animal reproduction studies with clarithromycin show some risk. Clarithromycin should not be used in pregnant women except when there is no alternative therapy.

Erythromycin is considered compatible with breastfeeding. Safety of other macrolides during breastfeeding is unknown.

Adverse Effects of Macrolides

Main concerns with macrolides include

  • Gastrointestinal (GI) disturbances (mainly with erythromycin)

  • QT-interval prolongation

  • Inhibition of hepatic metabolism, leading to numerous drug interactions

Erythromycin commonly causes dose-related GI disturbances, including nausea, vomiting, abdominal cramps, and diarrhea; disturbances are less common with clarithromycin and azithromycin. Taking the drug with food may help decrease GI disturbances. Erythromycin may cause dose-related tinnitus, dizziness, and reversible hearing loss. Cholestatic jaundice occurs most commonly with erythromycin estolate. Jaundice usually appears after 10 days of use, primarily in adults but can occur earlier if the drug has been given previously. Erythromycin is not given IM because it causes severe pain; when given IV, it may cause phlebitis or pain. Hypersensitivity reactions are rare.

Erythromycin causes QT-interval prolongation and predisposes to ventricular tachyarrhythmia, especially in women, in patients who have QT-interval prolongation or electrolyte abnormalities, and in patients taking another drug that may prolong the QT interval.

Clarithromycin and azithromycin may also cause QT-interval prolongation but are less likely to cause arrhythmias.

Dosing Considerations for Macrolides

For azithromycin, no dosage adjustment is required for renal insufficiency.

Erythromycin and, to some extent, clarithromycin interact with numerous drugs because they inhibit hepatic metabolism via the cytochrome P-450 (CYP450) system. Azithromycin is the least likely to interact with other drugs.

Interactions may occur when erythromycin or clarithromycin is taken with the following:

  • Warfarin: Further elevation of the prothrombin time/international normalized ratio (PT/INR)

  • Lovastatin and simvastatin: Rhabdomyolysis

  • Midazolam and triazolam: Somnolence

  • Theophylline: Nausea, vomiting, and seizures

  • Tacrolimus, cyclosporine, and ergot alkaloids: Elevated serum levels of these drugs

Drugs Mentioned In This Article

Drug Name Select Trade
Biaxin, Biaxin XL
Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose , Zithromax Tri-Pak, Zithromax Z-Pak, Zmax, Zmax Pediatric
A/T/S, Akne-mycin, E.E.S., Emcin Clear , EMGEL, E-Mycin, ERYC, Erycette, Eryderm , Erygel, Erymax, EryPed, Ery-Tab, Erythra Derm , Erythrocin, Erythrocin Lactobionate, Erythrocin Stearate, Ilosone, Ilotycin, My-E, PCE, PCE Dispertab , Romycin, Staticin, T-Stat
Coumadin, Jantoven
Altoprev, Mevacor
FloLipid, Zocor
Nayzilam, Versed, Versed Syrup
Elixophyllin, Quibron T, Quibron T/SR, Respbid, Slo-Bid, Slo-Phyllin, Theo X, Theo-24, Theo-Bid Duracap, TheoCap, Theochron, Theo-Dur, Theo-Dur Sprinkle , Theolair, Theolair SR, Theovent LA, T-Phyl, Uni-Dur, Uniphyl
Cequa, Gengraf , Klarity-C, Neoral, Restasis, Sandimmune, SangCya, Verkazia, Vevye
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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