Ilosone (Erythromycin)

Erythromycin is a macrolide antibiotic used to treat infections caused by susceptible bacteria. It is available in several dosage forms (oral, IV and topical), and approved uses and directions can vary between products. In Australia, the form prescribed and how it is used can vary depending on the infection being treated and the clinical setting.

Important: Always follow the instructions on your specific product label and your prescriber's advice.

Uses and Administration

Erythromycin is a macrolide antibiotic with a broad spectrum of activity and has been used to treat a wide range of infections caused by susceptible organisms.

When taken by mouth (for example, as tablets, including delayed-release tablets), erythromycin is used to treat certain bacterial infections such as mild to moderate infections of the upper and lower respiratory tract, some skin and soft tissue infections, and other infections when a macrolide antibiotic is appropriate. It may also be used in selected situations, such as treating streptococcal pharyngitis in patients who cannot take penicillin, or preventing recurrent rheumatic fever in patients allergic to penicillin, when directed by a clinician.

For eye use, erythromycin is commonly supplied as a sterile ophthalmic ointment (often called erythromycin ophthalmic ointment or erythromycin eye ointment). In Australia, erythromycin is generally supplied as an ophthalmic ointment rather than an erythromycin eye-drop solution, so drops should not be used instead of ointment unless they have been specifically prescribed.

Other routes

Erythromycin ophthalmic ointment (0.5%) is used for superficial eye infections involving the conjunctiva and/or cornea caused by susceptible organisms, and it is also used for neonatal eye prophylaxis. For infections, an approximately 1 cm (about 1/2 inch) ribbon of ointment may be applied to the affected eye(s) up to 6 times daily, depending on severity; for newborn prophylaxis, a 1 cm ribbon is placed into each lower conjunctival sac as directed on the product label.

For eyelid margin infections such as a stye (hordeolum), Australian clinicians may recommend warm compresses and may prescribe erythromycin ophthalmic ointment to the lid margin when a bacterial component is suspected; ophthalmic ointment is generally preferred over "drops" for this purpose.

It may also be applied topically as a 2 to 4% gel or solution to treat acne vulgaris.

Administration in children

The usual dose for infants and children is the equivalent of about 30 to 50 mg/kg/day of erythromycin in 2 to 4 divided doses, although this may be doubled in severe infections.

Decreased gastrointestinal motility

Erythromycin stimulates gut motility, apparently by acting as a motilin receptor agonist. Use for gastrointestinal stasis or as a prokinetic is not an approved indication for many products and, where it is used, should be considered off-label and guided by a clinician.

Skin disorders

ACNE

Erythromycin may be used topically or orally to treat acne.

To help limit antibiotic resistance, topical antibiotics should not be used on their own and should generally be used for a limited time; they are typically combined with benzoyl peroxide and/or a topical retinoid, with reassessment after about 12 weeks.

Oral erythromycin may be used as an alternative to a tetracycline for moderate acne. However, resistance to erythromycin is increasing, so it may be best reserved for patients in whom other antibacterials are unsuitable.

Precautions

Erythromycin and its derivatives should be avoided in people known to be hypersensitive to it, or in those who have previously developed jaundice. All forms of erythromycin should be used with care in patients with existing liver disease or hepatic impairment, and the estolate is best avoided in these patients; liver function should be monitored. Repeated courses of the estolate or use for longer than 10 days increases the risk of hepatotoxicity.

The lactobionate should be used with caution in patients with severe renal impairment; dose reduction may be necessary, particularly in those who develop toxicity. A reduced dose of the estolate has also been recommended in severe renal impairment. Erythromycin may worsen muscle weakness in patients with myasthenia gravis.

Erythromycin should be used with care in patients with a history of arrhythmias or a predisposition to QT interval prolongationCertain medicines may also increase the risk of cardiac arrhythmias (see Interactions below).

Erythromycin may interfere with some diagnostic tests, including measurements of urinary catecholamines and 17-hydroxycorticosteroids. It has also been associated with falsely elevated serum aspartate aminotransferase values when measured colorimetrically, although genuine elevations of this enzyme, due to hepatotoxicity, also occur, particularly with the estolate. Erythromycin is irritant; solutions for parenteral use should be suitably diluted and given by intravenous infusion over 20 to 60 minutes to reduce the incidence of thrombophlebitis. Rapid infusion is also more likely to be associated with arrhythmias or hypotension.

Breastfeeding

There has been a report of a breastfed infant who developed pyloric stenosis thought to be associated with the mother's use of erythromycin.

A milk-to-plasma ratio of about 0.5 has been reported for erythromycin, but values may vary. In general, erythromycin is considered compatible with breastfeeding; monitor the infant for gastrointestinal effects and seek medical advice if you have concerns.

Porphyria

Erythromycin has been associated with acute attacks of porphyria in case reports; use caution in patients with porphyria and follow clinical guidance.

Pregnancy

Of 298 pregnant women who took erythromycin estolate, clindamycin, or placebo for 3 weeks or longer, about 14, 4, and 3% respectively had abnormally high serum aspartate aminotransferase values. Erythromycin estolate should generally be avoided in pregnancy unless clearly needed. (Pregnancy risk information may differ by formulation; follow your product labelling.)

Interactions

Erythromycin and other macrolides can interact with a large number of drugs through their action on hepatic cytochrome P450 isoenzymes, primarily CYP3A4. These interactions can result in severe side effects, including serious cardiac arrhythmias with certain contraindicated medicines.

Erythromycin is contraindicated in patients taking terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine, and should not be used at the same time as lovastatin or simvastatin because of the increased risk of myopathy (including rhabdomyolysis). Check your product labelling for the full list of contraindications and clinically significant interactions.

Cimetidine

Cimetidine may increase plasma concentrations of erythromycin, and deafness occurred in a patient taking both drugs.

Adverse Effects

Erythromycin and its salts and esters are generally well tolerated and serious side effects are rare. Gastrointestinal disturbances such as abdominal discomfort and cramping, nausea, vomiting, and diarrhoea are fairly common after both oral and parenteral use, probably because of erythromycin's stimulant activity on the gut. Gastrointestinal effects are dose related and appear to be more common in younger than in older patients.

Superinfection with resistant organisms may occur, and Clostridioides difficile-associated diarrhoea/colitis has been reported. Hypersensitivity reactions appear to be uncommon, having been reported in about 0.5% of patients, and include pruritus, urticaria, and skin rash, as well as occasional cases of anaphylaxis. Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported very rarely. Hypersensitivity or irritation may occur after topical application of erythromycin.

A hypersensitivity reaction is thought to be responsible for the hepatotoxicity sometimes reported in patients receiving erythromycin or its derivatives, but this has been disputed by some. Most reports of cholestatic hepatitis have been in patients receiving the estolate, and it has been suggested that the propionyl ester linkage is particularly associated with hepatotoxicity, but symptoms have also been reported in patients given the base and most of the other derivatives, both orally and parenterally.

Symptoms indicating cholestasis, including upper abdominal pain (sometimes very severe), nausea and vomiting, abnormal liver function values, raised serum bilirubin, and usually jaundice, may be accompanied by rash, fever, and eosinophilia. Symptoms usually occur in patients who have been taking the drug for more than 10 days, although they may develop more quickly in patients given the drug previously. Hepatic dysfunction seems to be rare in children under 12 years of age.

The effects of erythromycin on the liver are generally reversible after treatment is stopped. Erythromycin may interfere with tests for serum aspartate aminotransferase, which might make hepatotoxicity harder to diagnose.

A generally reversible sensorineural deafness, sometimes with tinnitus, has been reported in patients given erythromycin and appears to be related to serum concentration, with an increased likelihood of such effects in patients given doses of 4 g or more daily of base or its equivalent, in those given intravenous therapy, and in those with renal or hepatic impairment.

Other side effects that have been reported in patients given erythromycin include agranulocytosis, worsening of muscle weakness in patients with myasthenia gravis, and pancreatitis. Prolongation of the QT interval and other arrhythmias, sometimes fatal, including torsade de pointes, have been reported, particularly with intravenous use. There have also been isolated reports of transient CNS side effects including confusion, hallucinations, seizures, and vertigo.

Parenteral formulations of erythromycin are irritant and intravenous dosing may produce thrombophlebitis, particularly at high doses. Intramuscular injection is generally avoided as it may cause severe pain.

Effects on the cardiovascular system

QT prolongation and torsade de pointes have been reported with erythromycin, particularly with intravenous use and in patients with additional risk factors and/or interacting medicines.

Effects on the gastrointestinal tract

Comparison in patients with upper respiratory tract infections has suggested that erythromycin ethyl succinate may be associated with less abdominal pain than an equivalent dose of erythromycin base. Another study indicated that there was no significant difference in gastrointestinal symptoms between plain and enteric-coated formulations of erythromycin base.

Severe nausea and vomiting after rapid intravenous infusion of erythromycin lactobionate stopped in 2 patients who switched to oral erythromycin base or ethyl succinate. However, the side effects may have been due to the rate of infusion, since in 2 further patients symptoms resolved when the lactobionate was given more slowly as a more dilute solution. A number of studies have suggested an association between erythromycin use in very young infants and infantile hypertrophic pyloric stenosis, particularly with exposure in the first 14 days of life.

Effects on the neonate

For a suggestion that erythromycin or other macrolides might be associated with an increased risk of infantile hypertrophic pyloric stenosis in neonates, see under Effects on the gastrointestinal tract, above.

Effects on the skin

Skin reactions ranging from mild eruptions to erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have rarely been reported with macrolides.

Overdosage

Acute pancreatitis was reported in a 12-year-old girl after ingestion of about 5 g of erythromycin base. Transient pancreatitis has also been reported in another 15-year-old girl who took 5.328 g of erythromycin base. Erythromycin causes contraction of the sphincter of Oddi, resulting in reflux of bile into the pancreas, but the resulting pancreatitis is self-limiting and resolves when sphincter tone returns to normal after erythromycin is eliminated from the body.

Antimicrobial Action

Erythromycin is a macrolide antibiotic with a broad and essentially bacteriostatic action against many Gram-positive and, to a lesser extent, some Gram-negative bacteria, as well as other organisms including some Mycoplasma spp., Chlamydiaceae, Rickettsia spp., and spirochaetes.

Mechanism of action

Erythromycin and other macrolides bind reversibly to the 50S subunit of the ribosome, resulting in blockage of the transpeptidation or translocation reactions, inhibition of protein synthesis, and therefore inhibition of cell growth. Its action is mainly bacteriostatic, but high concentrations are slowly bactericidal against the more sensitive strains.

The actions of erythromycin are increased at moderately alkaline pH (up to about 8.5), particularly in Gram-negative species, probably because of improved cellular penetration of the non-ionised form of the drug.

Resistance

A meta-analysis found that reported macrolide resistance in Streptococcus pneumoniae varied greatly from country to country. Reported erythromycin-resistant Streptococcus pneumoniae rates in Australia, as in other countries, can differ substantially depending on the setting and time period; in the analysis, the USA was 20.7% compared with Europe at 32.0%, although this difference was not considered statistically significant, while higher levels were found in Asia (57.3%).

Pharmacokinetics

Erythromycin base is unstable in gastric acid, so absorption is variable and unreliable. Consequently, the base is usually given in film- or enteric-coated preparations, or one of the more acid-stable salts or esters is used. Food may reduce absorption of the base or the stearate, although this depends to some extent on the formulation.

Peak plasma concentrations generally occur between 1 and 4 hours after a dose and have been reported to range from about 0.3 to 1.0 mcg/mL after 250 mg of erythromycin base, and from 0.3 to 1.9 mcg/mL after 500 mg. Similar concentrations have been seen after equivalent doses of the stearate.

Higher total concentrations are achieved after oral doses of the estolate or ethyl succinate, but only about 20 to 30% of estolate or 55% of ethyl succinate is present as the active base, the rest being present as the inactive ester (in the case of the estolate as the propionate). Peak concentrations of about 500 ng/mL of erythromycin base have been reported after 250 mg of the estolate or 500 mg of the ethyl succinate.

If you are prescribed erythromycin, take it exactly as directed and do not skip doses. For antibiotics, completing the full course helps reduce the risk of treatment failure and resistance. Seek medical help straight away for severe allergic reactions, severe diarrhoea, or symptoms of heart rhythm problems (such as fainting or palpitations).