Exacerbation of Myasthenia gravis
There have been reports that erythromycin may aggravate the weakness of patients with myasthenia gravis.
Development of Drug-Resistant Bacteria
Prolonged or repeated use of erythromycin may result in an overgrowth of non-susceptible 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.
Prescribing erythromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Laboratory Tests
Erythromycin interferes with the fluorometric determination of urinary catecholamines.
Drug Interactions
Erythromycin administration in patients receiving 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins) that are extensively metabolized by cytochrome P450 isoform 3A4 (e.g., lovastatin or simvastatin) has been reported to cause increased risk of myopathy, including rhabdomyolysis. Do not administer erythromycin with lovastatin or simvastatin (See CONTRAINDICATIONS).
Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase of serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.
There have been published reports suggesting that when oral erythromycin is given concurrently with theophylline there is a significant decrease in erythromycin serum concentrations. This decrease could result in subtherapeutic concentrations of erythromycin.
Erythromycin administration in patients receiving carbamazepine has been reported to cause increased serum levels of carbamazepine with subsequent development of signs of carbamazepine toxicity.
Concomitant administration of erythromycin and digoxin has been reported to result in elevated serum digoxin levels.
There have been reports of increased anticoagulant effects, which may be more pronounced in elderly when erythromycin and oral anticoagulants (e.g., warfarin) are used concomitantly.
Colchicine is a substrate for both CYP3A4 and the efflux transporter P-glycoprotein (P-gp). Erythromycin is considered a moderate inhibitor of CYP3A4. A significant increase in colchicine plasma concentration is anticipated when co-administered with moderate CYP3A4 inhibitors such as erythromycin. If co-administration of colchicine and erythromycin is necessary, the starting dose of colchicine may need to be reduced, and the maximum colchicine dose should be lowered. Patients should be monitored for clinical symptoms of colchicine toxicity (See WARNINGS).
Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered (See sildenafil prescribing information).
Erythromycin has been reported to decrease the clearance of triazolam, midazolam and related benzodiazepines, and thus may increase the pharmacological effect of these benzodiazepines.
Post-marketing reports indicate that co-administration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the central nervous system, extremities and other tissues (See CONTRAINDICATIONS).
Erythromycin has been reported to significantly alter the metabolism of the nonsedating antihistamines, terfenadine and astemizole, when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QTc interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed (See CONTRAINDICATIONS). In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin.
The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, disopyramide, bromocriptine, valproate, terfenadine, and astemizole. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.
Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients receiving concurrent verapamil, a calcium-channel blocker.
Cimetidine may inhibit the metabolism of erythromycin, which may lead to an increased plasma concentration.
Erythromycin has been reported to decrease the clearance of racemic zopiclone and, thus, may also decrease the clearance of eszopiclone, the S-enantiomer of racemic zopiclone. Accordingly, erythromycin may increase the pharmacodynamic effects of eszopiclone. Dose reduction of eszopiclone may be necessary (See eszopiclone prescribing information).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal data with erythromycin lactobionate for use in determination of possible carcinogenic effects are not available. However, long-term 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 0.25% of diet.
Pregnancy
There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation, and through weaning of two successive litters. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low.
Labor and Delivery
The effect of erythromycin on labor and delivery is unknown.
Nursing Mothers
Erythromycin is excreted in breast milk. Caution should be exercised when erythromycin is administered to a nursing woman.
Pediatric Use
(See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION).
Geriatric Use
Elderly patients, particularly those with reduced renal or hepatic function, may be at increased risk for developing erythromycin-induced hearing loss, when ErythrocinTM doses of 4 grams/day or higher are given (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).
Elderly patients may be more susceptible to the development of torsades de pointes arrhythmias than younger patients (See ADVERSE REACTIONS).
Elderly patients may experience increased effects of oral anticoagulant therapy while undergoing treatment with ErythrocinTM (See PRECAUTIONS – Drug Interactions).
Erythromycin Lactobionate does not contain sodium.
Information for Patients
Patients should be counseled that antibacterial drugs including erythromycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When erythromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by erythromycin or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.