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Special Alerts
Shortage of Erythromycin Ophthalmic Ointment and Suitable Alternatives for Ophthalmia Neonatorum - September, 2009
In conjunction with the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC) are issuing guidance on the recent erythromycin 0.5% ophthalmic ointment shortage, affecting both the 1 g and 3.5 g package sizes. While manufacturers are working to increase production, this guidance provides recommendations for emergency inventory replacement and to reserve the use of erythromycin ophthalmic ointment for neonatal ophthalmia neonatorum prophylaxis. In situations where the ointment is not available, experts recommend AzaSite® (azithromycin ophthalmic solution 1%) as an off-label alternative to be used for neonatal prophylaxis of ophthalmic gonococcal infection. This recommendation is based on general pharmacology and antimicrobial sensitivity data, recognizing that ophthalmic azithromycin is not FDA approved for ophthalmia neonatorum prophylaxis. Additionally, two-person administration is highly recommended to ensure adequate placement of the ophthalmic solution. If AzaSite® is not available, the CDC subsequently recommends use of ophthalmic aminoglycoside 0.3% ointments (gentamicin or tobramycin), and as a last resort due to resistance concerns, ophthalmic ciprofloxacin ointment (Ciloxan® 0.3%) may be used. Use of Betadine® (povidone-iodine) is strongly discouraged due to potential for error if the detergent formulation is used.
Importantly, given the lack of efficacy data with the primary alternatives, the CDC further reinforces following the AAP recommendations of close postnatal follow-up (within 48-72 hours of discharge) and N. gonorrhoeae testing of neonates presenting with ophthalmia neonatorum. Healthcare practitioners are reminded of the 2006 STD Guidelines which describe appropriate neonatal prophylaxis for maternal gonococcal exposure and postdelivery treatment.
Guidance on conserving product and general alternative recommendations may be found at: http://www.cdc.gov/std/treatment/2006/erythromycinOintmentShortage.htm
2006 STD Guidelines and "Dear Colleague" letter may be found at: http://www.cdc.gov/std/treatment/
Medication Safety Issues
Sound-alike/look-alike issues:
Erythromycin may be confused with azithromycin, clarithromycin, Ethmozine®
Akne-Mycin® may be confused with AK-Mycin®
E.E.S.® may be confused with DES®
Eryc® may be confused with Emcyt®, Ery-Tab®
Ery-Tab® may be confused with Eryc®
Erythrocin® may be confused with Ethmozine®
Pronunciation
(er ith roe MYE sin)
U.S. Brand Names
Index Terms
Generic Available
Yes: Capsule, gel, ophthalmic ointment, topical solution, suspension (as ethylsuccinate), swab, tablet (as base, ethylsuccinate, and stearate)
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Systemic: Treatment of susceptible bacterial infections including S. pyogenes, some S. pneumoniae, some S. aureus, M. pneumoniae, Legionella pneumophila, diphtheria, pertussis, Chlamydia, erythrasma, N. gonorrhoeae, E. histolytica, syphilis and nongonococcal urethritis, and Campylobacter gastroenteritis; used in conjunction with neomycin for decontaminating the bowel
Ophthalmic: Treatment of superficial eye infections involving the conjunctiva or cornea; neonatal ophthalmia
Topical: Treatment of acne vulgaris
Use: Dental
Systemic: Alternative to penicillin VK for treatment of orofacial infections
Use: Unlabeled/Investigational
Systemic: Treatment of gastroparesis, chancroid; preoperative gut sterilization
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events were not observed in animal studies; therefore, erythromycin is classified as pregnancy category B. Low levels of erythromycin have been shown to cross the placenta and erythromycin is considered the drug of choice for certain illnesses in pregnant women. Most studies do not support a link between prenatal exposure to erythromycin and pyloric stenosis in the neonate. No increased risk for congenital abnormalities has been documented, with the exception of a possible slight increase in risk for cardiovascular anomalies. No adequate and well-controlled studies have been completed in pregnant women. The estolate form of erythromycin should not be used in pregnancy due to a potential increased risk for hepatic toxicity.
Lactation
Enters breast milk/use caution (AAP considers “compatible”)
Breast-Feeding Considerations
Erythromycin is excreted in breast milk; therefore, the manufacturer recommends that caution be exercised when administering erythromycin to breast-feeding women.
Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. One case report and a cohort study raise the possibility for a connection with pyloric stenosis in neonates exposed to erythromycin via breast milk and an alternative antibiotic may be preferred for breast-feeding mothers of infants in this age group. Nondose-related effects could include modification of bowel flora. The AAP considers erythromycin to be “usually compatible with breast-feeding.”
Contraindications
Hypersensitivity to erythromycin or any component of the formulation
Systemic: Concomitant use with pimozide or cisapride
Warnings/Precautions
Concerns related to adverse effects:
• Altered cardiac conduction: Macrolides have been associated with rare QTc prolongation and ventricular arrhythmias, including torsade de pointes; use with caution in patients at risk of prolonged cardiac repolarization.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with pre-existing liver disease; hepatic impairment, including hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been observed. Discontinue if symptoms of malaise, nausea, vomiting, abdominal colic, and fever.
• Myasthenia gravis: Erythromycin has been associated with aggravation of weakness associated with myasthenia gravis.
Concurrent drug therapy issues:
• Major inhibitor of CYP3A4: Use caution with any agents with substantial metabolism through the CYP3A4 pathway; high potential for drug interactions exists.
Special populations:
•Infants: Use of erythromycin has been associated with infantile hypertrophic pyloric stenosis (IHPS); observe for non-bilious vomiting or irritability with feeding.
• Elderly: May be at increased risk of adverse events, including hearing loss and/or torsade de pointes when dosage ?4 g/day, particularly if concurrent renal/hepatic impairment.
Adverse Reactions
Frequency not defined. Incidence may vary with formulation.
Systemic:
Cardiovascular: QTc prolongation, torsade de pointes, ventricular arrhythmia, ventricular tachycardia
Central nervous system: Seizure
Dermatitis: Pruritus, rash
Gastrointestinal: Abdominal pain, anorexia, diarrhea, infantile hypertrophic pyloric stenosis, nausea, oral candidiasis, pancreatitis, pseudomembranous colitis, vomiting
Hepatic: Cholestatic jaundice (most common with estolate), hepatitis, liver function tests abnormal
Local: Phlebitis at the injection site, thrombophlebitis
Neuromuscular & skeletal: Weakness
Otic: Hearing loss
Miscellaneous: Allergic reactions, anaphylaxis, hypersensitivity reactions, urticaria
Topical: 1% to 10%: Dermatologic: Erythema, desquamation, dryness, pruritus
Metabolism/Transport Effects
Substrate of CYP2B6 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 3A4 (moderate)
Drug Interactions
Alfentanil: Macrolide Antibiotics may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): Macrolide Antibiotics may decrease the metabolism of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Macrolide Antibiotics. Risk D: Consider therapy modification
Antineoplastic Agents (Vinca Alkaloids): Macrolide Antibiotics may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an alternative to using a macrolide antibiotic when possible in order to avoid the potential for increased vinca alkaloid toxicity. Risk D: Consider therapy modification
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Macrolide Antibiotics may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
BusPIRone: Macrolide Antibiotics may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers: Macrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
CarBAMazepine: Macrolide Antibiotics may decrease the metabolism of CarBAMazepine. Risk D: Consider therapy modification
Cardiac Glycosides: Macrolide Antibiotics may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cilostazol: Macrolide Antibiotics may decrease the metabolism of Cilostazol. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cisapride: Macrolide Antibiotics may decrease the metabolism of Cisapride. Risk X: Avoid combination
Clopidogrel: Macrolide Antibiotics may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Clozapine: Macrolide Antibiotics may decrease the metabolism of Clozapine. Risk D: Consider therapy modification
Colchicine: P-Glycoprotein Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine (adult) dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
Corticosteroids (Systemic): Macrolide Antibiotics may decrease the metabolism of Corticosteroids (Systemic). Risk D: Consider therapy modification
CycloSPORINE: Macrolide Antibiotics may decrease the metabolism of CycloSPORINE. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dabigatran Etexilate: P-Glycoprotein Inhibitors may increase the serum concentration of Dabigatran Etexilate. Risk X: Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disopyramide: Macrolide Antibiotics may enhance the QTc-prolonging effect of Disopyramide. Macrolide Antibiotics may decrease the metabolism of Disopyramide. Risk X: Avoid combination
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Eletriptan: Macrolide Antibiotics may decrease the metabolism of Eletriptan. Risk D: Consider therapy modification
Eplerenone: Macrolide Antibiotics may decrease the metabolism of Eplerenone. Risk C: Monitor therapy
Ergot Derivatives: Macrolide Antibiotics may enhance the adverse/toxic effect of Ergot Derivatives. Specifically leading the development of ergotism. Exceptions: Cabergoline. Risk D: Consider therapy modification
Etravirine: May decrease the serum concentration of Macrolide Antibiotics. Clarithromycin AUC is reduced and levels of the active metabolite (14-hydroxy-clarithromycin) are modestly increased. Management: For the treatment of Mycobacterium avium complex, consider changing to alternative agent, such as azithromycin. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Risk D: Consider therapy modification
Fexofenadine: Erythromycin may increase the serum concentration of Fexofenadine. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Macrolide Antibiotics may decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Limit pitavastatin to a maximum adult dose of 1 mg/day when used with erythromycin. Dose adjustments for lovastatin, simvastatin, or atorvastatin may also be required. Increase monitoring for toxicity with any such combination. Exceptions: Fluvastatin; Pravastatin; Rosuvastatin. Risk D: Consider therapy modification
Lincosamide Antibiotics: May diminish the therapeutic effect of Erythromycin. Risk X: Avoid combination
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: Macrolide Antibiotics may decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Macrolide Antibiotics may enhance the QTc-prolonging effect of Pimozide. Macrolide Antibiotics may decrease the metabolism of Pimozide. QTc prolongation is a risk. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QuiNIDine: Macrolide Antibiotics may decrease the metabolism of QuiNIDine. Risk D: Consider therapy modification
QuiNINE: Macrolide Antibiotics may increase the serum concentration of QuiNINE. Risk X: Avoid combination
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Repaglinide: Macrolide Antibiotics may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Rifamycin Derivatives: Macrolide Antibiotics may decrease the metabolism of Rifamycin Derivatives. Exceptions: Rifapentine. Risk D: Consider therapy modification
Rivaroxaban: Erythromycin may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Macrolide Antibiotics may decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Exceptions: Fluvoxamine; PARoxetine. Risk C: Monitor therapy
Silodosin: P-Glycoprotein Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination
Sirolimus: Macrolide Antibiotics may decrease the metabolism of Sirolimus. Risk D: Consider therapy modification
Tacrolimus: Macrolide Antibiotics may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
Temsirolimus: Macrolide Antibiotics may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Theophylline Derivatives: Macrolide Antibiotics may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Zafirlukast: Erythromycin may decrease the serum concentration of Zafirlukast. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Zopiclone: Macrolide Antibiotics may increase the serum concentration of Zopiclone. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may decrease absorption of erythromycin or enhance ethanol effects).
Food: Erythromycin serum levels may be altered if taken with food (formulation-dependent).
Herb/Nutraceutical: St John's wort may decrease erythromycin levels.
Storage
Injection: Store unreconstituted vials at 15°C to 30°C (59°F to 86°F). Reconstituted solution is stable for 2 weeks when refrigerated or for 8 hours at room temperature. Erythromycin I.V. infusion solution is stable at pH 6-8; stability of lactobionate is pH dependent; I.V. form has longest stability in NS. Stability of parenteral admixture at room temperature (25°C) and at refrigeration temperature (4°C) is 24 hours.
Oral suspension:
Granules: After mixing, store under refrigeration and use within 10 days.
Powder: Refrigerate to preserve taste. Erythromycin ethylsuccinate may be stored at room temperature if used within 14 days. EryPed® drops should be used within 35 days following reconstitution. May store at room temperature or under refrigeration.
Tablet and capsule formulations: Store at <30°C (<86°F).
Topical and ophthalmic formulations: Store at room temperature.
Reconstitution
Erythromycin lactobionate should be reconstituted with sterile water for injection without preservatives to avoid gel formation. I.V. form has the longest stability in NS and should be prepared in this base solution whenever possible. Do not use D5W as a diluent unless sodium bicarbonate is added to solution. If I.V. must be prepared in D5W, 0.5 mL of the 8.4% sodium bicarbonate solution should be added per each 100 mL of D5W.
Standard diluent: 500 mg/250 mL D5W/NS; 750 mg/250 mL D5W/NS; 1 g/250 mL D5W/NS.
Compatibility
Erythromycin lactobionate: Stable in NS; incompatible with D5LR, D10W; variable stability (consult detailed reference) in D5NS, D5W, LR.
Y-site administration: Compatible: Acyclovir, amiodarone, cyclophosphamide, diltiazem, enalaprilat, esmolol, famotidine, foscarnet, heparin, hydromorphone, idarubicin, labetalol, lorazepam, magnesium sulfate, meperidine, midazolam, morphine, multivitamins, perphenazine, tacrolimus, theophylline, vitamin B complex with C, zidovudine. Incompatible: Fluconazole.
Compatibility in syringe: Incompatible: Ampicillin, heparin.
Compatibility when admixed: Compatible: Aminophylline, ampicillin, cimetidine, diphenhydramine, hydrocortisone sodium succinate, lidocaine, penicillin G potassium, penicillin G sodium, pentobarbital, polymyxin B sulfate, potassium chloride, prochlorperazine edisylate, promazine, ranitidine, sodium bicarbonate, verapamil. Incompatible: Colistimethate, floxacillin, furosemide, heparin, metaraminol, metoclopramide, riboflavin, vitamin B complex with C. Variable (consult detailed reference): Ascorbic acid injection.
Mechanism of Action
Inhibits RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation
Pharmacodynamics/Kinetics
Absorption: Oral: Variable but better with salt forms than with base form; 18% to 45%; ethylsuccinate may be better absorbed with food
Distribution:
Relative diffusion from blood into CSF: Minimal even with inflammation
CSF:blood level ratio: Normal meninges: 2% to 13%; Inflamed meninges: 7% to 25%
Protein binding: Base: 73% to 81%
Metabolism: Demethylation primarily via hepatic CYP3A4
Half-life elimination: Peak: 1.5-2 hours; End-stage renal disease: 5-6 hours
Time to peak, serum: Base: 4 hours; Ethylsuccinate: 0.5-2.5 hours; delayed with food due to differences in absorption
Excretion: Primarily feces; urine (2% to 15% as unchanged drug)
Dosage
Note: Due to differences in absorption, 400 mg erythromycin ethylsuccinate produces the same serum levels as 250 mg erythromycin base or stearate.
Usual dosage range:
Neonates: Ophthalmic: Prophylaxis of neonatal gonococcal or chlamydial conjunctivitis: 0.5-1 cm ribbon of ointment should be instilled into each conjunctival sac
Infants and Children:
Oral:
Base: 30-50 mg/kg/day in 2-4 divided doses; maximum: 2 g/day
Ethylsuccinate: 30-50 mg/kg/day in 2-4 divided doses; maximum: 3.2 g/day
Stearate: 30-50 mg/kg/day in 2-4 divided doses; maximum: 2 g/day
I.V.: Lactobionate: 15-50 mg/kg/day divided every 6 hours, not to exceed 4 g/day
Children and Adults:
Ophthalmic: Instill 1/2” (1.25 cm) 2-6 times/day depending on the severity of the infection
Topical: Acne: Apply over the affected area twice daily after the skin has been thoroughly washed and patted dry
Adults:
Oral:
Base: 250-500 mg every 6-12 hours; maximum 4 g/day
Ethylsuccinate: 400-800 mg every 6-12 hours; maximum: 4 g/day
I.V.: Lactobionate: 15-20 mg/kg/day divided every 6 hours or 500 mg to 1 g every 6 hours, or given as a continuous infusion over 24 hours; maximum: 4 g/24 hours
Indication-specific dosing:
Children:
Bartonella sp
infections (bacillary angiomatosis [BA], peliosis hepatis [PH]) (unlabeled use): Oral: 40 mg/kg/day (ethylsuccinate) in 4 divided doses (maximum: 2 g/day) for 3 months (BA) or 4 months (PH)
Conjunctivitis, neonatal
(C. trachomatis):
Oral: 50 mg/kg/day (base or ethylsuccinate) in 4 divided doses for 14 days
Mild/moderate infection: Oral: 30-50 mg/kg/day in divided doses every 6-12 hours
Pertussis: Oral: 40-50 mg/kg/day in 4 divided doses for 14 days; maximum 2 g/day (not preferred agent for infants <1 month due to IHPS)
Pharyngitis, tonsillitis (streptococcal): Oral: 20 mg (base)/kg/day or 40 mg (ethylsuccinate)/kg/day in 2 divided doses for 10 days. Note: No longer preferred therapy due to increased organism resistance.
Pneumonia
(C. trachomatis):
Oral: 50 mg/kg/day (base or ethylsuccinate) in 4 divided doses for 14-21 days
Preop bowel preparation: Oral: 20 mg (base)/kg at 1, 2, and 11 PM on the day before surgery combined with mechanical cleansing of the large intestine and oral neomycin
Severe infection: I.V.: 15-50 mg/kg/day; maximum: 4 g/day
Adults:
Bartonella sp
infections (bacillary angiomatosis [BA], peliosis hepatis [PH]) (unlabeled use): Oral: 500 mg (base) 4 times/day for 3 months (BA) or 4 months (PH)
Chancroid (unlabeled use): Oral: 500 mg (base) 3 times/day for 7 days; Note: Not a preferred agent; isolates with intermediate resistance have been documented
Gastrointestinal prokinetic (unlabeled use): I.V.: 200 mg initially followed by 250 mg (base) orally 3 times/day 30 minutes before meals. Lower dosages have been used in some trials.
Granuloma inguinale
(K. granulomatis)
(unlabeled use): Oral: 500 mg (base) 4 times/day for 21 days
Legionnaires' disease: Oral: 1.6-4 g (ethylsuccinate)/day or 1-4 g (base)/day in divided doses for 21 days. Note: No longer preferred therapy and only used in nonhospitalized patients.
Lymphogranuloma venereum: Oral: 500 mg (base) 4 times/day for 21 days
Nongonococcal urethritis (including coinfection with
C. trachomatis):
Oral: 500 mg (base) 4 times/day for 7 days or 800 mg (ethylsuccinate) 4 times/day for 7 days. Note: May use 250 mg (base) or 400 mg (ethylsuccinate) 4 times/day for 14 days if gastrointestinal intolerance.
Pelvic inflammatory disease: I.V.: 500 mg every 6 hours for 3 days, followed by 1000 mg (base)/day orally in 2-4 divided doses for 7 days. Note: Not recommended therapy per current treatment guidelines.
Pertussis: Oral: 500 mg (base) every 6 hours for 14 days
Preop bowel preparation (unlabeled use): Oral: 1 g erythromycin base at 1, 2, and 11 PM on the day before surgery combined with mechanical cleansing of the large intestine and oral neomycin
Syphilis, primary: Oral: 48-64 g (ethylsuccinate) or 30-40 g (base) in divided doses over 10-15 days. Note: Not recommended therapy per current treatment guidelines.
Dosage adjustment in renal impairment: Dialysis: Slightly dialyzable (5% to 20%); no supplemental dosage necessary in hemo- or peritoneal dialysis or in continuous arteriovenous or venovenous hemofiltration
Dental Usual Dosing
Treatment of orofacial infections: Adults: Oral:
Base: 250-500 mg every 6-12 hours
Ethylsuccinate: 400-800 mg every 6-12 hours
Administration: Oral
Do not crush enteric coated drug product. GI upset, including diarrhea, is common. May be administered with food to decrease GI upset. Do not give with milk or acidic beverages.
Administration: I.V.
Infuse 1 g over 20-60 minutes.
Administration: Other
Avoid contact of tip of ophthalmic ointment tube with affected eye.
Administration: I.V. Detail
I.V. infusion may be very irritating to the vein. If phlebitis/pain occurs with used dilution, consider diluting further (eg, 1:5) if fluid status of the patient will tolerate, or consider administering in larger available vein. The addition of lidocaine or bicarbonate does not decrease the irritation of erythromycin infusions.
pH: Erythromycin lactobionate: 6.5-7.5 (reconstituted with sterile water for injection or D5W to a 50 mg/mL concentration)
Test Interactions
False-positive urinary catecholamines
Dietary Considerations
Systemic: Drug may cause GI upset; may take with food.
Some products may contain sodium.
Patient Education
Do not take any new prescription or OTC medications, or herbal products during therapy without consulting prescriber. Take exactly as directed:
Ophthalmic: Preparations should be used exactly as directed. Always wash hands before applying ophthalmic preparations and do not let tip of applicator touch eye or become contaminated.
Suspension: Mix granules exactly as directed and store in refrigerator after mixing; mix powder as directed; store at room temperature or in refrigerator.
Tablets/capsules: Take as directed, around-the-clock, with a full glass of water (not juice or milk); may take with food to reduce GI upset. Do not chew or crush extended release capsules or tablets.
Topical: Apply as directed after skin has been cleansed and gently dried.
Take complete prescription even if you are feeling better. Avoid alcohol (may cause adverse response). May cause nausea, vomiting, or mouth sores (small, frequent meals, frequent mouth care may help). Report immediately any unusual malaise, nausea, vomiting, abdominal colic, or fever; skin rash or itching; easy bruising or bleeding; vaginal itching or discharge; watery or bloody diarrhea; yellowing of skin or eyes, pale stool or dark urine; persistent diarrhea; white plaques, sores, or fuzziness in mouth; or any change in hearing.
Geriatric Considerations
Dose does not need to be adjusted unless there is severe renal or hepatic impairment. Elderly may be at an increased risk for torsade de pointes, ototoxicity (particularly when dose is ?4 g/day in conjunction with renal or hepatic impairment).
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Erythromycin, when used with drugs that affect the QT interval (eg, cisapride, ergot derivatives, pimozide) or when administered to patients with a prolonged QT interval, may further increase the QT interval and the risk of torsade de pointes (proarrhythmias).
Cardiovascular Considerations
Erythromycin, when used with drugs that affect the QT interval (eg, cisapride, quinidine) or when administered to patients with a prolonged QT interval, may further increase the QT interval and the risk of torsade de pointes (proarrhythmias).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral candidiasis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Erythromycin is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution. See Dental Health Professional Considerations.
Dental Comment
Erythromycin is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Erythromycin is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Many patients cannot tolerate erythromycin because of abdominal pain and nausea; the mechanism of this adverse effect appears to be the motilin agonistic properties of erythromycin in the GI tract. For these patients, clindamycin is indicated as the alternative antibiotic for treatment of orofacial infections.
HMG-CoA reductase inhibitors, also known as the statins, effectively decrease the hepatic cholesterol biosynthesis resulting in the reduction of blood LDL-cholesterol concentrations. The AUC of atorvastatin (Lipitor®) was increased 33% by erythromycin administration. Combination of erythromycin and lovastatin (Mevacor®) has been associated with rhabdomyolysis (Ayanian, et al). The mechanism of erythromycin is inhibiting the CYP3A4 metabolism of atorvastatin, lovastatin, and cerivastatin. Simvastatin (Zocor®) would likely be affected in a similar manner by the coadministration of erythromycin. Clarithromycin (Biaxin®) may exert a similar effect as erythromycin on atorvastatin, lovastatin, cerivastatin, and simvastatin.
Mental Health: Effects on Mental Status
Systemic: Macrolides have been reported to cause nightmares, confusion, anxiety, and mood lability
Mental Health: Effects on Psychiatric Treatment
Systemic: Contraindicated with pimozide; may increase concentration of bromocriptine, carbamazepine, and triazolam
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and patient's previous allergy history prior to therapy. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking. Assess therapeutic effectiveness and adverse reactions. Teach patient proper use (according to formulation and purpose for use), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Note: Strength expressed as base
Capsule, delayed release, enteric-coated pellets, as base: 250 mg
Eryc®: 250 mg [DSC]
Gel, topical: 2% (30 g, 60 g)
Erygel®: 2% (30 g, 60 g) [DSC] [contains alcohol 92%]
Granules for oral suspension, as ethylsuccinate:
E.E.S.®: 200 mg/5 mL (100 mL, 200 mL) [contains sodium 25.9 mg (1.1 mEq)/5 mL; cherry flavor]
Injection, powder for reconstitution, as lactobionate:
Erythrocin®: 500 mg, 1 g
Ointment, ophthalmic: 0.5% [5 mg/g] (1 g, 3.5 g)
Romycin®: 0.5% [5 mg/g] (3.5 g)
Ointment, topical:
Akne-Mycin®: 2% (25 g)
Powder for oral suspension, as ethylsuccinate:
EryPed®: 200 mg/5 mL (100 mL, 200 mL [DSC]) [contains sodium 117.5 mg (5.1 mEq)/5 mL; fruit flavor]; 400 mg/5 mL (100 mL, 200 mL [DSC]) [contains sodium 117.5 mg (5.1 mEq)/5 mL; banana flavor]
Powder for oral suspension, as ethylsuccinate [drops]:
EryPed®: 100 mg/2.5 mL (50 mL) [DSC] [contains sodium 58.8 mg (2.6 mEq)/dropperful; fruit flavor]
Powder, for prescription compounding:
Erythro-RX: USP (50 g)
Solution, topical: 2% (60 mL)
Eryderm®: 2% (60 mL) [contain alcohol] [DSC]
Sans acne [CAN]: 2% (60 mL) [contains ethyl alcohol 44%; not available in U.S.]
Suspension, oral, as ethylsuccinate: 200 mg/5 mL (480 mL) [DSC]; 400 mg/5 mL (480 mL) [DSC]
E.E.S.®: 200 mg/5 mL (100 mL, 480 mL) [fruit flavor] [DSC]; 400 mg/5 mL (100 mL, 480 mL) [orange flavor]
Tablet, as base: 250 mg, 500 mg
Tablet, as base [polymer-coated particles]:
PCE®: 333 mg, 500 mg
Tablet, as ethylsuccinate: 400 mg
E.E.S.®: 400 mg [DSC]
Tablet, as stearate: 250 mg, 500 mg
Erythrocin®: 250 mg, 500 mg
Tablet, delayed release, enteric coated, as base:
Ery-Tab®: 250 mg, 333 mg, 500 mg
Pricing: U.S. (www.drugstore.com)
Capsule, enteric pellets (Erythromycin Base)
250 mg (30): $14.68
Gel (Erythromycin)
2% (30): $18.65
2% (60): $38.65
Ointment (Erythromycin)
5 mg/g (3.5): $12.99
Solution (Eryderm)
2% (60): $25.99
Solution (Erythromycin)
2% (60): $26.13
Suspension (E.E.S. 200)
200 mg/5 mL (473): $31.17
Suspension (E.E.S. 400)
400 mg/5 mL (100): $12.99
Suspension (Erythromycin Ethylsuccinate)
200 mg/5 mL (200): $15.00
400 mg/5 mL (100): $10.99
Suspension (reconstituted) (E.E.S. Granules)
200 mg/5 mL (100): $13.62
200 mg/5 mL (200): $24.12
Suspension (reconstituted) (EryPed 200)
200 mg/5 mL (100): $19.96
Tablet, EC (Ery-Tab)
250 mg (40): $17.99
333 mg (30): $19.99
500 mg (20): $17.99
Tablet, EC (PCE)
333 mg (30): $72.13
500 mg (20): $63.64
Tablets (E.E.S. 400)
400 mg (40): $16.78
Tablets (Erythrocin Stearate)
250 mg (30): $13.99
500 mg (20): $13.99
Tablets (Erythromycin Base)
250 mg (30): $13.99
500 mg (30): $17.83
Tablets (Erythromycin Ethylsuccinate)
400 mg (40): $17.83
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International Brand Names
Lexi-Comp.com
Last full review/revision October 2009
Content last modified October 2009
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