Erythromycin is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome p enzyme system CYP3A. Coadministration of erythromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving erythromycin.
The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible. The following CYP3A based drug interactions have been observed with erythromycin products in post-marketing experience: Triazolobenzodiazepines such as triazolam and alprazolam and related benzodiazepines Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.
Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Sildenafil Viagra Erythromycin has been reported to increase the systemic exposure AUC of sildenafil. Reduction of sildenafil dosage should be considered. See Viagra package insert. There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine.
Concomitant administration of erythromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated. In addition, there have been reports of interactions of erythromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate.
Erythromycin has been reported to significantly alter the metabolism of the nonsedating antihistamines terfenadine and astemizole when taken concomitantly.
In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin. There have been post-marketing reports of drug interactions when erythromycin is co-administered with cisapride, resulting in QT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, most likely due to inhibition of hepatic metabolism of cisapride by erythromycin.
Fatalities have been reported. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term 2-year oral studies in rats with erythromycin ethylsuccinate and erythromycin base did not provide evidence of tumorigenicity.
Mutagenicity studies have not been conducted. There was no apparent effect on male or female fertility in rats fed erythromycin base at levels up to 0. Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Syphilis in Pregnancy There have been reports suggesting that 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 an appropriate penicillin regimen. Clostridium difficile Associated Diarrhea Clostridium difficile associated diarrhea CDAD has been reported with use of nearly all antibacterial agents, including Ery-Ped, 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. Hypertoxin producing strains of C. 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 the administration of antibacterial agents. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
Drug Interactions Serious adverse reactions have been reported in patients taking erythromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 e.
There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine. Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin.
Therefore, patients receiving concomitant lovastatin and erythromycin should be carefully monitored for creatine kinase CK and serum transaminase levels. Syphilis in Pregnancy There have been reports suggesting that 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 an appropriate penicillin regimen. Clostridium difficile Associated Diarrhea Clostridium difficile associated diarrhea CDAD has been reported with use of nearly all antibacterial agents, including Ery-Ped, 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.
Hypertoxin producing strains of C. 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 the administration of antibacterial agents.
There have been reports of infantile hypertrophic pyloric stenosis IHPS occurring in infants following erythromycin therapy. Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity such as pertussis or chlamydia , the benefit of erythromycin therapy needs to be weighed against the potential risk of developing IHPS.
Parents should be informed to contact their physician if vomiting or irritability with feeding occurs. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary. Particular care should be taken with medications known to prolong the QTc interval of the electrocardiogram.
Drugs that induce CYP3A4 such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John's Wort may induce the metabolism of erythromycin. This may lead to sub-therapeutic levels of erythromycin and a decreased effect. The induction decreases gradually during two weeks after discontinued treatment with CYP3A4 inducers.
Erythromycin should not be used during and two weeks after treatment with CYP3A4 inducers. During prolonged treatment of infections, the development of resistant strains is common. Erythromycin is an agent for use in individuals unable to take penicillin because of previous reactions. Pharyngitis, Scarlet Fever anderysipelas produced by group-A Streptococcus pyogenes respond to erythromycin.
Erythromycin is useful in cases in which the presence of penicillinase-producing staphylococci may be responsible for relapse of streptococcal pharyngitis after adequate treatment with penicillin G, and other infections due to enterococci may also respond well to the drug.
Erythromycin is effective in eradicating the acute or chronic diphtheria bacillus carrier state.
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