indication

For use in the treatment of infections caused by susceptible strains of microorganisms in the following diseases: respiratory tract infections (upper and lower) of mild to moderate degree, pertussis (whooping cough), as adjunct to antitoxin in infections due to Corynebacterium diphtheriae, in the treatment of infections due to Corynebacterium minutissimum, intestinal amebiasis caused by Entamoeba histolytica, acute pelvic inflammatory disease caused by Neisseria gonorrhoeae, skin and soft tissue infections of mild to moderate severity caused by Streptococcus pyogenes and Staphylococcus aureus, primary syphilis caused by Treponema pallidum, infections caused by Chlamydia trachomatis, nongonococcal urethritis caused by Ureaplasma urealyticum, and Legionnaires' disease caused by Legionella pneumophila.

pharmacology

Erythromycin is produced by a strain of Streptomyces erythraeus and belongs to the macrolide group of antibiotics. After absorption, erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid, but the passage of the drug across the blood-brain barrier increases in meningitis. Erythromycin is excreted in breast milk. The drug crosses the placental barrier with fetal serum drug levels reaching 5 - 20% of maternal serum concentrations. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

mechanism of action

Erythromycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the “P” or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the “A” or acceptor site to the “P” or donor site is prevented, and subsequent protein synthesis is inhibited. Erythromycin is effective only against actively dividing organisms. The exact mechanism by which erythmromycin reduces lesions of acne vulgaris is not fully known: however, the effect appears to be due in part to the antibacterial activity of the drug.

toxicity

Symptoms of overdose include diarrhea, nausea, stomach cramps, and vomiting.

biotransformation

Hepatic. Extensively metabolized - after oral administration, less than 5% of the administered dose can be recovered in the active form in the urine. Erythromycin is partially metabolized by CYP3A4 resulting in numerous drug interactions.

absorption

Orally administered erythromycin base and its salts are readily absorbed in the microbiologically active form. Topical application of the ophthalmic ointment to the eye may result in absorption into the cornea and aqueous humor.

half life

0.8 - 3 hours

drug interactions

Acenocoumarol: The macrolide, erythromycin, may increase the anticoagulant effect of acenocoumarol.

Alfentanil: The macrolide, erythromycin, may increase the effect and toxicity of alfentanil.

Alprazolam: The macrolide, erythromycin, may increase the effect of the benzodiazepine, alprazolam.

Aminophylline: The macrolide, erythromycin, may increase the effect and toxicity of the theophylline derivative, aminophylline.

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Anisindione: The macrolide, erythromycin, may increase the anticoagulant effect of anisindione.

Aprepitant: Erythromycin, a moderate CYP3A4 inhibitor, may increase the effect and toxicity of aprepitant.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atorvastatin: The macrolide, erythromycin, may increase the toxicity of the statin, atorvastatin.

Bretylium: Increased risk of cardiotoxicity and arryhthmias

Bromazepam: Erythromcyin may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if erythromycin is initiated, discontinued or dose changed. Dosage adjustments may be required.

Bromocriptine: Erythromycin increases serum levels of bromocriptine

Buspirone: The macrolide, erythromycin, may increase the effect and toxicity of buspirone.

Cabergoline: Erythromycin increases serum levels and toxicity of cabergoline

Carbamazepine: The macrolide, erythromycin, may increase the effect of carbamazepine.

Cerivastatin: The macrolide, erythromycin, may increase the toxicity of the statin, cerivastatin.

Cilostazol: Erythromycin increases the effect of cilostazol

Cinacalcet: The macrolide, erythromycin, may increase the serum concentration and toxicity of cinacalcet.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Citalopram: Possible serotoninergic syndrome with this combination

Clozapine: Erythromycin increases the effect of clozapine

Colchicine: Severe colchicine toxicity can occur

Cyclosporine: The macrolide, erythromycin, may increase the effect of cyclosporine.

Diazepam: The macrolide, erythromycin, may increase the effect of the benzodiazepine, diazepam.

Dicumarol: The macrolide, erythromycin, may increase the anticoagulant effect of dicumarol..

Digoxin: The macrolide, erythromycin, may increase the effect of digoxin in 10% of patients.

Dihydroergotamine: Possible ergotism and severe ischemia with this combination

Dihydroergotoxine: Possible ergotism and severe ischemia with this combination

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Docetaxel: Erythromycin may increase the serum levels and toxicity of docetaxel.

Dofetilide: Increased risk of cardiotoxicity and arrhythmias

Dyphylline: The macrolide, erythromycin, may increase the effect and toxicity of the theophylline derivative, dyphylline.

Eletriptan: The macrolide, erythromycin, may increase the effect and toxicity of eletriptan.

Eplerenone: This CYP3A4 inhibitor increases the effect and toxicity of eplerenone

Ergonovine: Possible ergotism and severe ischemia with this combination

Ergotamine: Possible ergotism and severe ischemia with this combination

Erlotinib: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Everolimus: The macrolide, erythromycin, may increase the serum concentration and toxicity of everolimus.

Felodipine: Erythromycin increases the effect of felodipine

Fluoxetine: Possible serotoninergic syndrome with this combination

Gefitinib: This CYP3A4 inhibitor increases levels/toxicity of gefitinib

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Imatinib: The macrolide, erythromycin, may increase the serum concentration of imatinib.

Itraconazole: The macrolide, erythromycin, may increase the effect and toxicity of itraconazole.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Lincomycin: Possible antagonism of action with this combination.

Lovastatin: The macrolide, erythromycin, may increase the toxicity of the statin, lovastatin.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methylergonovine: Possible ergotism and severe ischemia with this combination

Methylprednisolone: The macrolide, erythromycin, may increase the effect of corticosteroid, methylprednisolone.

Methysergide: Possible ergotism and severe ischemia with this combination

Midazolam: The macrolide, erythromycin, may increase the effect of the benzodiazepine, midazolam.

Moxifloxacin: Increased risk of cardiotoxicity and arrhythmias

Oxtriphylline: The macrolide, erythromycin, may increase the effect and toxicity of the theophylline derivative, oxtriphylline.

Pimozide: Increased risk of cardiotoxicity and arrhythmias

Quetiapine: The macrolide, erythromycin, may increase the effect and toxicity of quetiapine.

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Quinupristin: This combination presents an increased risk of toxicity

Ranolazine: Increased levels of ranolazine - risk of toxicity

Repaglinide: The macrolide, erythromycin, may increase the effect of repaglinide.

Rifabutin: The rifamycin, rifabutin, may decrease the effect of the macrolide, erythromycin.

Rifampin: The rifamycin, rifampin, may decrease the effect of the macrolide, erythromycin.

Ritonavir: Increased toxicity of both agents

Sertraline: Possible serotoninergic syndrome with this combination

Sibutramine: Erythromycin increases the effect and toxicity of sibutramine

Sildenafil: The macrolide, erythromycin, may increase the effect and toxicity of sildenafil.

Simvastatin: The macrolide, erythromycin, may increase the toxicity of the statin, simvastatin.

Sirolimus: The macrolide, erythromycin, may increase the serum concentration of sirolimus.

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, erythromycin, may also increase the blood concentration of tacrolimus.

Tamsulosin: Erythromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Erythromycin is initiated, discontinued, or dose changed.

Telithromycin: Telithromycin may reduce clearance of Erythromycin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Erythromycin if Telithromycin is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Theophylline: The macrolide, erythromycin, may increase the effect and toxicity of theophylline.

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Topotecan: The p-glycoprotein inhibitor, Erythromycin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Tramadol: Erythromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inhibitor, Erythromycin , may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Erythromycin is initiated, discontinued or dose changed.

Triazolam: The macrolide, erythromycin, may increase the effect of the benzodiazepine, triazolam.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Valproic Acid: The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Erythromycin is initiated, discontinued or dose changed.

Vardenafil: Erythromycin, a moderate CYP3A4 inhibitor, may reduce the metabolism and clearance of vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of vardenafil if erythromycin is initiated, discontinued or dose changed.

Verapamil: Erythromycin, a moderate CYP3A4 inhibitor, may increase the serum concentration of veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of verapamil if erythromycin is initiated, discontinued or dose changed.

Vinblastine: Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of vinblastine if erythromycin is initiated, discontinued or dose changed.

Vincristine: Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Erythromycin is initiated, discontinued or dose changed.

Vinorelbine: Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Erythromycin is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of erythromycin by decreasing its metabolism. Erythromycin may increase the serum concentration of voriconazole by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for QTc prolongation and changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Warfarin: The macrolide, erythromycin, may increase the anticoagulant effect of warfarin.

Zafirlukast: Erythromycin may decrease the serum concentration and effect of zafirlukast.

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zopiclone: The macrolide antibiotic, erythromycin, may increase the serum concentration of zopiclone. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if erythromycin is initiated, discontinued or dose changed.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).