erythromycin stearate (Rx)

1-10%

Abdominal pain (8%)

Headache (8%)

Nausea (8%)

Diarrhea (7%)

Rash (3%)

Vomiting (3%)

Dyspepsia (2%)

Flatulence (2%)

Pain (2%)

Pruritus (1%)

Pseudomembranous colitis

Hypertrophic pyloric stenosis

Anaphylaxis

Fever

Mild allergic reactions

Urticaria

Skin eruptions

Tinnitus

<1%

Cholestatic hepatitis

Confusion

Hallucinations

Hearing loss

Hypotension

Nervous system effects including seizures

Torsade de pointes

Ventricular tachycardia

Vertigo

Postmarketing reports

Interstitial nephritis

Contraindications

Documented hypersensitivity

Coadministration with terfenadine

Coadministration with HMG-CoA reductase inhibitors that are extensively metabolized by CYP3A4 (lovastatin or simvastatin)

Co-administration of erythromycin with ergotamine or dihydroergotamine

Cautions

Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice reported in patients receiving oral erythromycin products

Prescribing therapy in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

Since erythromycin is principally excreted by the liver, caution should be exercised when erythromycin is administered to patients with impaired hepatic function

Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome reported in patients receiving erythromycin therapy

Infantile hypertrophic pyloric stenosis (IHPS) in infants following erythromycin therapy reported; a possible dose-response effect reported; since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (such as pertussis or neonatal Chlamydia trachomatis infections), the benefit of therapy needs to be weighed against potential risk of developing IHPS; parents should be informed to contact their physician if vomiting or irritability with feeding occurs

Prolonged or repeated use of erythromycin may result in an overgrowth of nonsusceptible bacteria or fungi; if superinfection occurs, erythromycin should be discontinued, and appropriate therapy instituted

When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy; observational studies in humans have reported cardiovascular malformations after exposure to drug products containing erythromycin during early pregnancy

QT Prolongation

• Therapy has been associated with prolongation of QT interval and infrequent cases of arrhythmia; elderly patients may be more susceptible to drug-associated effects on QT interval
• Cases of torsades de pointes spontaneously reported during postmarketing surveillance in patients receiving erythromycin; fatalities reported
• Therapy should be avoided in patients with known prolongation of QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Syphilis in pregnancy

• There have been reports suggesting erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis; infants born to women treated during pregnancy with oral erythromycin for early syphilis should be treated with appropriate penicillin regimen

Clostridium difficile associated diarrhea

• Clostridium difficile associated diarrhea (CDAD) reported with use of nearly all antibacterial agents, including erythromycin and may range in severity from mild diarrhea to fatal colitis
• Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile; C. difficile produces toxins A and B which contribute to development of CDAD
• Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
• CDAD must be considered in all patients who present with diarrhea following antibiotic use; careful medical history is necessary since CDAD has been reported to occur over two months after administration of antibacterial agents
• If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated

Drug interaction overview

• There have been post-marketing reports of cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, caused by coadministration of drugs that result in QT prolongation; fatalities reported
• Increased anticoagulant effects, which may be more pronounced in elderly when erythromycin and oral anticoagulants (eg, warfarin) are used concomitantly, reported
• Colchicine is a substrate for both CYP3A4 and the efflux transporter P-glycoprotein (P-gp); erythromycin is considered moderate inhibitor of CYP3A4; a significant increase in colchicine plasma concentration is anticipated when co-administered with moderate CYP3A4 inhibitors such as erythromycin; if coadministration of colchicine and erythromycin is necessary, may need to reduce starting dose of colchicine, and maximum colchicine dose lowered; monitor patients for clinical symptoms of colchicine toxicity
• Erythromycin may increase systemic exposure (AUC) of sildenafil; consider reduction of sildenafil dosage
• Erythromycin may decrease clearance of triazolam, midazolam and related benzodiazepines, increasing their effect
• Post-marketing reports indicate that co-administration with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of central nervous system, extremities and other tissues

Pregnancy Category: B

Lactation: distributed in breast milk, use with caution; AAP categorizes as compatible with breastfeeding

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest

Absorption

Oral: variable but better with salt forms than with base form

Peak Plasma Time: 4 hr (base)

Distribution

Protein Bound: 75-80%

Crosses placenta; enters breast milk

Relative diffusion from blood into CSF: minimal even with inflammation

Metabolism

Via P450 enzyme CYP3A4

Enzymes inhibited: CYP1A2, CYP3A4

Elimination

Half-Life: 1.4 hr

Excretion: Primarily feces; urine (2-15% as unchanged drug)