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Erythromycin is a macrolide antibiotic.

Erythromycin: Organs and Systems


Erythromycin has antidysrhythmic properties similar to those of Class IA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization. High-doses intravenously have caused ventricular fibrillation and torsade de pointes. Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal.

In an FDA database analysis, 346 cases of cardiac dysrhythmias associated with erythromycin were identified. There was a preponderance of women, as there was among those with life-threatening ventricular dysrhythmias and deaths after intravenous erythromycin lactobionate. A sex difference in cardiac repolarization response to erythromycin is a potential contributing factor, since in an in vitro experiment on rabbit hearts, erythromycin caused significantly greater QT prolongation in female than in male hearts.

In 35 women and 28 men erythromycin caused QT interval prolongation after the first few doses of erythromycin. Similarly, in a prospective, comparative study in 19 patients with uncomplicated community-acquired pneumonia, a single dose of intravenous erythromycin 500 mg increased the heart rate and prolonged the QT interval. These effects were seen after 15 minutes of infusion and disappeared 5 minutes after the infusion had been stopped.

Owing to prolongation of the QT interval, a newborn with congenital AV block developed ventricular extra beats and non-sustained ventricular tachycardia after intravenous erythromycin; the QT interval normalized after withdrawal.

Intravenous erythromycin (1 g 6-hourly by intravenous infusion over 30 minutes) resulted in QT interval prolongation, ventricular fibrillation, and torsade de pointes in a 32-year-old woman.

Intravenous administration of erythromycin into peripheral veins relatively commonly causes thrombophlebitis, although the lactobionate form of erythromycin may be less irritating to veins than other parenteral forms. In a prospective study of 550 patients with 1386 peripheral venous catheters, the incidence of phlebitis was 19% with antibiotics and 8.8% without; erythromycin was associated with an increased risk.


Adverse effects involving the respiratory system were reported in 2% of patients taking erythromycin stearate. A beneficial effect of erythromycin on sputum volume has been reported in a patient with severe airways obstruction due to bronchorrhea.

Nervous system

In patients without neuromuscular disease erythromycin caused subclinical loss of motor unit contractions, which improved with intravenous edrophonium or neostigmine

Sensory systems

Ototoxicity, resulting in hearing loss, and usually reversible, has been reported in patients treated with erythromycin lactobionate 4 g/day or more or large oral doses of erythromycin estolate. Ototoxic reactions have also been seen after the use of esters of erythromycin, such as the ethylsuccinate, stearate, and propionate. High parenteral doses of erythromycin have resulted in transient perceptive deafness. Since renal and hepatic disease was a prominent feature in these patients, ototoxicity was thought to result from high blood concentrations. Recovery occurred within a few days after withdrawal. The phenomenon differs from the permanent type of ototoxicity caused by aminoglycosides. Erythromycin should not be given together with other potentially ototoxic drugs and hearing acuity should be monitored during erythromycin therapy, especially in the elderly. Acute psychotic reactions have been related to ototoxicity and high-dose erythromycin therapy.

Psychological, psychiatric

Erythromycin has been associated with complications such as confusion, paranoia, visual hallucinations, fear, lack of control, and nightmares. These suspected psychiatric adverse effects were seen within 12-48 hours of starting therapy with conventional doses. Such complications may even be under-reported.


Erythromycin is a motilin receptor agonist. This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides.

Pylorospasm and hypertrophic pyloric stenosis is associated with early postnatal erythromycin exposure and has been observed in neonates after 1-2 days of oral erythromycin therapy. The prominent gastrokinetic properties of erythromycin have been postulated as the mechanism.

Pyloric stenosis has also been reported in a boy born at 23 weeks gestation, weight 690 g, after treatment of the child with three doses of oral erythromycin 10 mg/kg/day.

The use of erythromycin in postexposure prophylaxis for pertussis in 200 infants was followed by an increased number of cases of infantile hypertrophic pyloric stenosis, and all seven cases had taken erythromycin prophylacti-cally. A case review and cohort study supported these preliminary findings. In a retrospective study in 314 029 children, very early exposure to erythromycin (at 3-13 days of life) was associated with a nearly eightfold increased risk of pyloric stenosis. There was no increased risk in infants exposed to erythromycin after 13 days of life or in infants exposed to antibiotics other than erythromycin.

Intravenous erythromycin should be restricted to as few patients as possible. It can cause severe abdominal cramps, probably by a direct action on smooth muscle.


Erythromycin can cause two different types of liver damage. Administration of erythromycin as base or salt can be followed in 0-10% of cases by apparently benign increases in serum transaminases, which may or may not recur on rechallenge. In children, raised transaminases were noted at dosages of 40 mg/kg/day but not 20 mg/kg/day.

Cholestatic hepatitis, which is associated primarily with erythromycin estolate, can be caused by all forms of erythromycin, including the base, estolate, ethylsuccinate, propionate, and stearate. Although it was originally speculated that a hypersensitivity reaction to the estolate ester rather than to the erythromycin itself was responsible for this adverse reaction, erythromycin does inhibit bile flow. Most probably the differences in hepatotoxicity between the various erythromycin derivatives are of a quantitative rather than a qualitative nature, perhaps because of better intestinal absorption of the estolate. Potentially severe but rare cholestatic liver injury occurs in perhaps up to 2-4% of treated patients. Erythromycin-induced cholestasis is rare in children under the age of 12 years, but has occurred in infants at 6 weeks of age, in whom it can mimic acute cholecystitis, biliary atresia, or neonatal hepatitis.

A young woman developed severe cholestasis and jaundice after taking erythromycin stearate. A second severe episode of jaundice and malaise occurred after treatment with erythromycin succinate 2 years later pointing to erythromycin itself as the culprit.

The syndrome generally starts 10-14 days after the start of therapy, but earlier after re-exposure, sometimes within 12-24 hours. At all ages it often begins with abdominal pain, nausea, vomiting, pyrexia, pruritus, and jaundice; fever, rash, leukocytosis, raised serum transaminases, and eosinophilia can also occur. However, it can be ushered in with severe acute upper abdominal pain or right subcostal tenderness, simulating an acute abdomen, or it can resemble obstructive jaundice. Serum bilirubin, alkaline phosphatase, and transaminases are raised. Histological examination typically shows intrahepatic cholestasis and periportal inflammatory infiltration, with lymphocytes, neutrophils, and disproportionate numbers of eosinophils. These histological findings could be interpreted as reflecting a hypersensitivity reaction, but this hypothesis has been rejected. If erythromycin is promptly withdrawn, the clinical signs often improve rapidly, although prolonged jaundice has been reported.

Urinary tract

Acute renal insufficiency has been observed in a patient with Henoch-Schonlein syndrome. Another case presented as interstitial nephritis with acute renal insufficiency.


Topical erythromycin in benzoylperoxide, marketed for acne treatment, must be compounded by a pharmacist and requires subsequent refrigeration, warranting the development of alternative formulations. In a double-blind, parallel-group, multicenter study in 327 patients, a single-use erythromycin in benzoylperoxide combination package was compared with the vehicle alone and the original, reconstituted formulation packaged in a jar. Dry skin was the most frequently reported skin-related adverse event; it occurred in 3.2% of patients who used the preformulated erythromycin in benzoylperoxide and 5.0% of those who used the reconstituted erythromycin in benzoylperoxide.

A fixed drug eruption due to erythromycin has been observed. In another case skin tests with erythromycin were positive for the immediate and or delayed types of hypersensitivity.

A 27-year-old woman developed urticaria 30 minutes after taking a single dose of erythromycin. An identical episode had occurred three years before. Erythromycin-specific IgE was detected in her serum by radioimmunoassay.

Stevens-Johnson syndrome developed in a 64-year-old man who took erythromycin stearate for non-specific upper respiratory tract symptoms. After four doses of 250 mg, he developed a fever and typical lesions in the mouth and conjunctivae and on the lips. He was treated with prednisolone and recovered rapidly.

Dosage and Administration


Erythromycin base is administered orally. The manufacturers of erythromycin delayed-release tablets state that these tablets are well absorbed and may be given without regard to meals. The manufacturers of erythromycin delayed-release capsules (containing enteric-coated pellets) and erythromycin film-coated tablets state that optimal absorption generally occurs when these preparations are administered in the fasting state (at least 30 minutes and, preferably, 2 hours before or after meals). Delayed-release tablets containing enteric-coated particles are well absorbed in most patients and may be given without regard to meals, but the manufacturer states that optimal absorption still occurs if such tablets are administered in the fasting state (at least 30 minutes and, preferably, 2 hours before meals). The commercially available delayed-release capsules containing enteric-coated pellets of erythromycin (ERYC®) may be swallowed intact or the entire contents of a capsule(s) may be sprinkled on a small amount of applesauce immediately prior to administration; subdividing the contents of a capsule is not recommended. The enteric-coated pellets contained in the capsules should not be chewed or crushed. If the capsule contents are administered by sprinkling on applesauce, the patient should drink some water after swallowing the applesauce to ensure that the pellets are swallowed. If the pellets are accidentally spilled, the dose preparation should be started over with a new capsule.


The usual adult oral dosage of erythromycin is 250 mg every 6 hours, 333 mg every 8 hours, or 500 mg every 12 hours. In severe infections, dosage may be increased up to 4 g daily; however, a twice-daily dosing schedule is not recommended when dosages exceeding 1 g daily are administered. The usual oral erythromycin dosage in children is 30-50 mg/kg daily given in 2-4 equally divided doses. For more severe infections, this dosage may be doubled but should not exceed 4 g daily. A twice-daily dosing schedule is not recommended when dosages exceeding 1 g daily are administered.

Pharyngitis and Tonsillitis

If erythromycin is used for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci), the drug should be given in the usual dosage for 10 days or longer.

Prophylaxis of Recurrent Rheumatic Fever

For continuous prophylaxis to prevent recurrences in patients with a history of rheumatic heart disease, the usual oral dosage of erythromycin is 250 mg twice daily. When selecting anti-infectives for prophylaxis of recurrent rheumatic fever, the current recommendations published by the American Heart Association (AHA) should be consulted.


Although penicillin G is the drug of choice for all stages of syphilis, the manufacturers state that 30-40 g of oral erythromycin has been given in divided doses over 10-15 days for the treatment of primary syphilis. Erythromycin is no longer included in US Centers for Disease Control and Prevention (CDC) recommendations for the treatment of any form of syphilis in adults or adolescents (including primary, secondary, latent, or tertiary syphilis or neurosyphilis) and is not recommended for the treatment of congenital syphilis or syphilis in older infants and children. In addition, erythromycin is no longer recommended by the CDC or American Academy of Pediatrics (AAP) for the treatment of syphilis in pregnant women who are hypersensitive to penicillin since numerous treatment failures (including in the fetus) have been reported with the drug.

Lyme Disease

For the treatment of early localized or early disseminated Lyme disease associated with erythema migrans (but without neurologic involvement or third-degree AV heart block) in adults who are allergic to or intolerant of penicillins and cephalosporins and in whom tetracyclines are contraindicated, the Infectious Diseases Society of America (IDSA) suggests an oral erythromycin dosage of 500 mg 4 times daily for 14-21 days. For the treatment of early localized or early disseminated Lyme disease associated with erythema migrans (but without neurologic involvement or third-degree AV heart block) in children who are allergic to or intolerant of penicillins or cephalosporins and cannot receive a tetracycline (e.g., younger than 8 years of age), the IDSA suggests an oral erythromycin dosage of 12. mg/kg (maximum dose: 500 mg) 4 times daily for 14-21 days. Some clinicians suggest that if erythromycin is used in the treatment of early Lyme disease, adults should receive 250 mg 4 times daily for 14-21 days and children should receive 30 mg/kg daily in 3 divided doses (or 250 mg 3 times daily) for 14-21 days. However, erythromycin may not be as effective as other recommended agents (e.g., oral doxycycline, oral amoxicillin) for the treatment of Lyme disease, and patients treated with macrolides should be monitored closely. For additional details on the manifestations of Lyme disease and the efficacy of various anti-infective regimens in early or late Lyme disease, see Lyme Disease in Uses: Spirochetal Infections, in the Tetracyclines General Statement 8:12.24.

Gonorrhea and Associated Infections

When an oral erythromycin is indicated for the treatment of coexisting chlamydial infections in conjunction with therapy of uncomplicated or disseminated gonococcal infections, the CDC recommends that adults and adolescents receive 500 mg of erythromycin orally 4 times daily for 7 days. Erythromycins generally are indicated for these infections in pregnant women and in other adults when tetracyclines are contraindicated or not tolerated. (See Uses: Gonorrhea and Associated Infections, in the Erythromycins General Statement 8:12..04.) The AAP currently recommends that all children beyond the neonatal period being treated for uncomplicated vulvovaginal, urethral, or pharyngeal gonorrhea, epididymitis, proctitis, or disseminated gonococcal infections including meningitis or endocarditis receive presumptive treatment for possible coexisting chlamydial infections. If oral erythromycin is used for presumptive treatment of chlamydial infection in children who weigh less than 45 kg, the AAP recommends a dosage of 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 7 days. Although erythromycin is not included in the current CDC recommendations for the treatment of acute pelvic inflammatory disease (PID) caused by N. gonorrhoeae, some manufacturers recommend a regimen of 500 mg of erythromycin (as the lactobionate) IV every 6 hours for 3 days followed by an oral regimen of 333 mg of erythromycin (as the base or stearate) every 8 hours for 7 days or 500 mg every 12 hours for 7 days for the treatment of these infections. However, some clinicians believe this oral dosage is inadequate and recommend 500 mg every 6 hours for 7-10 days.

Nongonococcal Urethritis

When oral erythromycin is used as an alternative to azithromycin or doxycycline for the treatment of nongonococcal urethritis in adults and adolescents, the CDC recommends a regimen of 500 mg of erythromycin 4 times daily for 7 days. Alternatively, a regimen of 666 mg of erythromycin may be given every 8 hours for at least 7 days. Patients with recurrent and persistent urethritis who were not compliant with the full course of erythromycin therapy or who were reexposed to untreated sexual partner(s) should receive a second course of oral erythromycin. If the patient has recurrent and persistent urethritis, was compliant with the regimen, and reexposure can be excluded, the CDC recommends a regimen of 500 mg of oral erythromycin 4 times daily for 7 days given in conjunction with a single 2-g dose of oral metronidazole.

Chlamydial Infections

For the treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis in nonpregnant adults and adolescents when azithromycin or doxycycline cannot be used, the CDC and others recommend oral erythromycin in a dosage of 500 mg 4 times daily for 7 days. Alternatively, a dosage of 666 mg every 8 hours for 7 days can be used. The dosage of oral erythromycin recommended by the CDC for the treatment of these infections in children weighing 45 kg or less is 50 mg/kg daily given in 4 divided doses for 14 days. For the treatment of chlamydial urogenital infections during pregnancy, the recommended dosage of oral erythromycin is 500 mg 4 times daily or 666 mg every 8 hours for at least 7 days. Women who cannot tolerate this regimen may receive a dosage of 500 mg every 12 hours, 333 mg every 8 hours, or 250 mg 4 times daily for at least 14 days. For the treatment of pneumonia caused by C. trachomatis in infants, the recommended dosage of oral erythromycin is 50 mg/kg daily given in 4 divided doses for 14 days; follow-up is recommended and a second course of therapy may be necessary. For the treatment of ophthalmia neonatorum caused by C. trachomatis, the recommended dosage of oral erythromycin is 50 mg/kg daily given in 4 divided doses for 14 days; follow-up is recommended and a second course of therapy may be necessary. If erythromycin is used as an alternative to doxycycline for the treatment of genital, inguinal, or anorectal infections caused by a lymphogranuloma venereum serotype of C. trachomatis, the CDC and others recommend that adults and adolescents receive an oral dosage of 500 mg 4 times daily for 21 days. Chancroid For the treatment of chancroid (genital ulcers caused by Haemophilus ducreyi), the CDC and many clinicians recommend that adults receive an oral erythromycin dosage of 500 mg 3-4 times daily for 7 days. The CDC recommends that patients with chancroid be examined 3-7 days after initiation of anti-infective therapy. If the regimen was effective, symptomatic improvement in the ulcers is evident within 3 days and objective improvement is evident within 7 days. The time required for complete healing is related to the size of the ulcer; large ulcers may require more than 2 weeks to heal. Healing of ulcers may be slower in uncircumcised men who have ulcers under the foreskin. Resolution of fluctuant lymphadenopathy is slower than that of ulcers, and needle aspiration or incision and drainage may be necessary even during otherwise effective anti-infective therapy. While needle aspiration of buboes is a simpler procedure, incision and drainage of buboes may be preferred. If clinical improvement is not evident within 3-7 days, consideration should be given to the possibility that the diagnosis was incorrect, there is coinfection with another sexually transmitted disease, the patient was noncompliant with the regimen, the strain of H. ducreyi is resistant to the anti-infective agent used, or the patient is HIV seropositive. (See Uses: Chancroid in the Erythromycins General Statement 8:12.12.04.)

Granuloma Inguinale (Donovanosis)

When oral erythromycin is used as an alternative to co-trimoxazole or doxycycline for the treatment of granuloma inguinale (Donovanosis) caused by Calymmatobacterium granulomatis (e.g., in pregnant or lactating women), the CDC recommends a dosage of 500 mg orally 4 times daily for at least 3 weeks. If lesions do not respond within the first few days of therapy, some experts recommend that a parenteral aminoglycoside (e.g., 1 mg/kg of gentamicin IV every 8 hours) be added to the regimen. Addition of an aminoglycoside should be strongly considered when treating donovanosis in pregnant or lactating women or in patients with human immunodeficiency virus (HIV) infection. Despite effective anti-infective therapy, donovanosis may relapse 6-18 months later.

Intestinal Amebiasis

Although erythromycin is not considered a drug of choice for the treatment of intestinal amebiasis caused by Entamoeba histolytica, the manufacturers state that adults may receive 250 mg of erythromycin every 6 hours, 333 mg every 8 hours, or 500 mg every 12 hours for 10-14 days and that children may be given 30-50 mg/kg daily in divided doses for 10-14 days.

Diphtheria Treatment

When used as an adjunct to diphtheria antitoxin for the treatment of diphtheria, the usual dosage of erythromycin is 40-50 mg/kg daily (maximum 2 g daily) for 14 days. Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy. Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.


For prevention of diphtheria in household or intimate contacts of patients with respiratory or cutaneous diphtheria, the CDC and US Public Health Service Advisory Committee on Immunization Practices (ACIP) recommend that children receive erythromycin in a dosage of 40 mg/kg daily and that adults receive 1 g daily for 7-10 days. The American Academy of Pediatrics (AAP) recommends that these contacts receive an erythromycin dosage of 40-50 mg/kg daily (maximum 2 g daily) for 7 days. Household or intimate contacts of patients with diphtheria should receive anti-infective prophylaxis regardless of their immunization status and should be closely monitored for symptoms of diphtheria for 7 days. In addition, contacts who are inadequately immunized against diphtheria (i.e., have previously received fewer than 3 doses of diphtheria toxoid) or whose immunization status is unknown should receive an immediate dose of an age-appropriate diphtheria toxoid preparation and the primary series should be completed according to the recommended schedule. Contacts who are fully immunized should receive an immediate booster dose of an age-appropriate diphtheria toxoid preparation if it has been 5 years or longer since their last booster dose.

Diphtheria Carrier State


When erythromycin is used to eliminate the diphtheria carrier state in identified carriers of toxigenic Corynebacterium diphtheriae, the ACIP and AAP recommend that adults and children receive 7-10 days of the drug in the dosages specified above for prevention of diphtheria. Follow-up cultures should be obtained at least 2 weeks after completion of therapy; if cultures are positive, an additional 10-day course of oral erythromycin should be given and additional follow-up cultures obtained.


Although the optimum dosage and duration of erythromycin for the treatment of pertussis or prevention in susceptible contacts have not been established, a dosage of 1 g daily in adults and 40-50 mg/kg daily (maximum 2 g daily) in children given in divided doses for 14 days usually is recommended. While a shorter duration of erythromycin therapy (e.g., 7 or 10 days) may be effective in some patients, 107, 112 prophylaxis failures and bacteriologic relapse of pertussis have been reported with erythromycin regimens shorter than 14 days. Therefore, the CDC, ACIP, AAP, and some clinicians recommend that a 14-day course of erythromycin therapy be used for treatment or prevention of pertussis. Although data from controlled studies are lacking, the CDC recommends that all household and other close contacts of individuals with pertussis receive a 14-day regimen of prophylaxis (regardless of age and vaccination status) since this may prevent or minimize transmission of the disease. In addition, all close contacts younger than 7 years of age who are not fully immunized against pertussis should receive the remaining required doses of a preparation containing pertussis vaccine (using minimal intervals between doses) and those who are fully immunized but have not received a vaccine dose within the last 3 years should receive a booster dose of a pertussis vaccine preparation.

Legionnaires’ Disease

Although the optimum dosage and duration of erythromycin for the treatment of Legionnaires’ disease have not been established, dosages of 1-4 g daily in divided doses have been given alone or in combination with rifampin. A parenteral regimen usually is necessary for the initial treatment of severe Legionnaires’ disease and the addition of rifampin is recommended during the first 3-5 days of therapy in severely ill and/or immunocompromised patients; after a response is obtained, rifampin can be discontinued and therapy changed to oral erythromycin. The duration of therapy in patients with Legionnaires’s disease usually is 10-21 days; some clinicians recommend 14 days of therapy for patients with mild disease and 21 days for those who are immunocompromised or have severe disease.

Preoperative Intestinal Antisepsis

For preoperative intestinal antisepsis in patients undergoing colorectal surgery, oral erythromycin is usually given in conjunction with oral neomycin sulfate as an adjunct to mechanical cleansing of the large intestine. It is generally recommended that if surgery is scheduled for 8 a.m., 1 g of erythromycin and 1 g of neomycin sulfate should be administered at 1 p.m., 2 p.m., and 11 p.m. on the day preceding surgery.

Chemistry and Stability


Erythromycin occurs as a white or slightly yellow, odorless or practically odorless, bitter, crystalline powder. The drug has a solubility of approximately 1 mg/mL in water and is soluble in alcohol at 25°C.


Erythromycin delayed-release capsules (containing enteric-coated pellets), delayed-release tablets (containing enteric-coated particles), delayed-release (enteric coated) tablets, and film-coated tablets should be stored at a temperature not exceeding 30°C. The delayed-release capsules should be protected from moisture and excessive heat. For further information on chemistry, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of erythromycin, see the Erythromycins General Statement 8:12.12.04.


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Erythromycin: Side Effects

See also Macrolide antibiotics

For some decades erythromycin was the only macrolide antibiotic available, but with the development of new macrolides with remarkable pharmacokinetic and safety features, it has met fierce competition and has, at least in some health-care systems, lost its place as the most important macrolide.

Comparative studies

In a direct comparison of clarithromycin with erythromycin stearate, the rate of adverse events was 19% in 96 patients taking clarithromycin and 35% in 112 patients taking erythromycin . Most of the adverse events associated with clarithromycin affect the gastrointestinal tract (7%).

In a prospective, single-blind, randomized study of a 7-day course of clarithromycin (7.5 mg/kg bd) and a 14-day course of erythromycin (13.3 mg/kg tds) in 153 children with pertussis, the incidence of treatment-emergent drug-related adverse events was significantly higher with erythromycin than with clarithromycin (62 versus 45%). Three subjects given erythromycin withdrew prematurely because of adverse events: one because of a rash; one with vomiting and diarrhea; and one with vomiting, abdominal pain, and rash.

In a double-blind, randomized, multicenter trial in 302 children, a 10-day course of erythromycin estolate (40 mg/kg/day in two doses) was as safe and effective as amoxicillin (50 mg/kg/day in two doses) in acute otitis media. Treatment-related adverse events occurred in 5.3% of patients given erythromycin and in 7.3% of patients given amoxicillin.

General adverse effects

Erythromycin is relatively well tolerated, with the exception of gastrointestinal adverse effects. Cholestasis resulting from the use of all forms of erythromycin is virtually the only serious effect. However, local irritation (affecting the gastrointestinal system, the muscles, or the veins, depending on the route of administration) is common. Erythromycin can increase serum theophylline concentrations and occasionally causes theophylline toxicity. Hypersensitivity reactions are rare, unless cholestasis is to be regarded as allergic. They probably have clinical effects in under 0.5% of treated patients, and consist mainly of maculopapular rashes, pruritus, urticaria, and angioedema; anaphylaxis and acute respiratory distress have also been reported. Fixed drug eruptions, urticaria, and Stevens-Johnson syndrome have also been reported.

Erythromycin: Organs and Systems

Second-Generation Effects


In a retrospective study there was no evidence of an increased risk of pyloric stenosis among infants born to mothers exposed to erythromycin during pregnancy.

Erythromycin: Drug-Drug Interactions


The association of ventricular dysrhythmias with co-administration of erythromycin and terfenadine is thought to be due to inhibition of CYP3A4 by erythromycin. This combination should be avoided.

Erythromycin increases concentrations of astemizole. This combination should be avoided.

A double-blind, crossover study of the potential interaction between erythromycin and loratadine in 24 healthy volunteers showed that the AUCs of loratadine and its metabolite descarboethoxyloratadine were increased 40% and 46% respectively by erythromycin, but with no discernible effect on the QT interval.

Combined desloratadine 7.5 mg/day plus erythromycin 500 mg qds in 24 healthy volunteers was well tolerated and had no clinically important electrocardiographic effects. Although co-administration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with prolongation of the QT interval, and there was no toxicity.


Erythromycin can increase concentrations of midazolam and triazolam by inhibition of CYP3A4, and dosage reductions of 50% have been proposed if concomitant therapy is unavoidable.


Co-administration of erythromycin with the anxiolytic drug buspirone increased the plasma concentration of buspirone.


Erythromycin can cause acute carbamazepine intoxication, probably by inhibiting its hepatic metabolism. Erythromycin may also directly inhibit the conversion of carbamazepine to its epoxide. In a controlled study of the effects of erythromycin on carbamazepine pharmacoki-netics in healthy volunteers, the clearance of a single dose of carbamazepine was reduced by 19% during erythromycin treatment. In contrast, the single-dose pharmacokinetics of phenytoin were not affected by erythromycin. After withdrawal of the macrolide, carbamazepine concentrations quickly return to normal. If co-administration of erythromycin and carbamazepine cannot be avoided, a dosage reduction of carbamazepine of around 25% should be considered, with careful monitoring of serum concentrations.


When erythromycin was given to 16 healthy non-smoking male volunteers taking cilostazol, the Cmax and AUC of cilostazol increased significantly by 47 and 73% respectively, and the unbound clearance of the major metabolite of cilostazol, OPC-13015, fell by about 50%.


• QT interval prolongation and torsade de pointes occurred after co-administration of cisapride and erythromycin 500 mg qds for 1 week in a 47-year-old woman.


The interaction of erythromycin with digoxin is probably due to inhibition of its presystemic metabolism by inhibition of the growth of Eubacterium glenum.


Disopyramide altered protein binding of erythromycin and this resulted in increased plasma erythromycin concentrations in vitro. The interaction between erythromycin and disopyramide was potentially fatal in two cases

Ergot alkaloids

The interaction of erythromycin with ergotamine or di-hydroergotamine can cause ergotism, sometimes leading to gangrene, by inhibition of the metabolism of the ergo-peptides.


Erythromycin (333 mg tds for 10 days) had no effect on the pharmacokinetics of felbamate (3.0 or 3.6 g/d) used as monotherapy in epilepsy.


Erythromycin inhibited halofantrine metabolism in vitro, suggesting that increased cardiotoxicity might be clinically important.


Erythromycin can increase the plasma concentration and toxicity of oral lidocaine, as shown in a crossover study in nine volunteers who took erythromycin orally (500 mg tds) for 4 days and 1 mg/kg of oral lidocaine on day 4.

Oral anticoagulants

Erythromycin can interact with warfarin, resulting in a modest increase in blood concentrations and a rise in the prothrombin time of around 8%.

Erythromycin may potentiate acenocoumarol anticoagulant treatment, as reported in a 68-year-old man on stable anticoagulation with acenocoumarol 3 mg/day who took erythromycin ethylsuccinate 1.5 g/day.


Erythromycin reduced the total clearance of quinidine, reduced its partial clearance by 3-hydroxylation, and increased its maximal serum concentration in an open study in 30 healthy young volunteers.


Erythromycin is a competitive in vitro inhibitor of quinine 3-hydroxylation and may therefore interact with quinine.

Selective serotonin re-uptake inhibitors (SSRIs)

A 12-year-old boy developed the serotonin syndrome, which is normally associated with the interaction of two or more serotonergic agents, after the co-administration of erythromycin and sertraline.

This could have been due to erythromycin-induced inhibition of sertraline metabolism by CYP3A.


It has been proposed that the risk of myotoxicity increases when statins are prescribed concurrently with erythromycin. There are no data for any pharmacokinetic interaction with fluvastatin or pravastatin, but as in the case of simvastatin the major route of metabolism of these drugs is by CYP3A4 and there is potential for an adverse interaction.


When erythromycin was co-administered with atorvastatin, the mean Cmax and AUC of atorvastatin increased by more than 30%.


Rhabdomyolysis with or without renal impairment has been reported in patients taking both erythromycin and lovastatin. The exact mechanism is unknown, but lovastatin is extensively metabolized by CYP3A4 and its metabolism may therefore be inhibited by erythromycin. The manufacturers have advised that careful monitoring is required when these two drugs are given together.


A case-control analysis of 7405 cases and 28 327 controls suggested that concomitant use of simvastatin and erythromycin is associated with an increased risk of cataract. Studies in dogs have shown that some statins are associated with cataract when given in excessive doses.

Theophylline and other xanthines

Erythromycin can increase the serum concentrations of theophylline by 20-25%. However, patients with an average serum concentration of theophylline under 15 µg/ml will probably only experience a small increase in their serum theophylline concentration during erythromycin therapy, whereas patients with steady-state concentrations above 15 µg/ml deserve careful monitoring and close observation for symptoms of theophylline toxicity during treatment with erythromycin.


Both tiagabine and erythromycin are metabolized by cytochrome P450. In an open, crossover study in 13 healthy volunteers, tiagabine (4 mg bd) and erythromycin (500 mg bd) were co-administered for 4 days. Maximum plasma concentration, AUC, and half-life of tiagabine were comparable when tiagabine was administered alone or in combination with erythromycin. The tmax was prolonged after administration with erythromycin in women; this effect may be due to a differential effect of erythromycin on gastric emptying. The interpretation of these findings is limited by the rather low doses of tiagabine used in the study and the short time of co-administration.

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