Erythromycin: update on known risk of infantile hypertrophic pyloric stenosis

Updates have been made to the magnitude of the known risk of infantile hypertrophic pyloric stenosis following exposure to erythromycin in infancy as a result of new epidemiological data. The risk is particularly increased in the first 14 days after birth. Weigh the benefit of erythromycin therapy in infants against the potential risk of infantile hypertrophic pyloric stenosis.

Advice for healthcare professionals:

  • an increased risk of infantile hypertrophic pyloric stenosis following exposure to erythromycin in infancy has been reflected in the product information for some time
  • data from three recent meta-analyses has led to updates for the magnitude of increased risk with erythromycin use during infancy in general, and to reflect that the risk is highest in the first 14 days after birth
  • consider the benefit of erythromycin therapy against the potential risk of developing infantile hypertrophic pyloric stenosis
  • advise parents to seek advice from their doctor if vomiting or irritability with feeding occurs in infants during treatment with erythromycin
  • report suspected adverse drug reactions (ADRs) associated with erythromycin to the Yellow Card scheme

New data for risk of infantile hypertrophic pyloric stenosis

Use of the antibiotic erythromycin in infancy has been associated with an increased risk of infantile hypertrophic pyloric stenosis.

A recent European review of safety data assessed published literature studies, including data from three meta-analyses [footnote 1] [footnote 2] [footnote 3] that support an association between exposure to erythromycin in infants and the risk of infantile hypertrophic pyloric stenosis.

Although this risk was already included in the Summary of Product Characteristics (SmPC) for erythromycin medicines, the review recommended that information on the magnitude of the increased risk should be added to the sections on precautions and potential side effects.

The background incidence of infantile hypertrophic pyloric stenosis is thought to be 0.1–0.2% livebirths. The studies show that the risk of infantile hypertrophic pyloric stenosis following exposure to erythromycin is highest in the first 14 days after birth. Available data suggests an incidence of 2.6% (95% CI 1.5 to 4.2) for infants younger than 14 days following exposure to erythromycin.

The studies suggest an overall 2–3-fold increase in risk of infantile hypertrophic pyloric stenosis following exposure to erythromycin in infancy in general. It is noted that the meta-analyses used different age limits to identify studies in infants, with two using a cut-off age for studies of 6 months[footnote 1][footnote 2] and one using a cut off of 120 days old (around 4 months).[footnote 3]

Since erythromycin may be used in the treatment of conditions in infants that are associated with significant mortality or morbidity (such as pertussis or chlamydia), the benefit of erythromycin therapy should be weighed against the potential risk of developing infantile hypertrophic pyloric stenosis. Parents should be informed to contact their doctor if vomiting or irritability with feeding occurs.

About infantile hypertrophic pyloric stenosis

Infantile hypertrophic pyloric stenosis is characterised by hypotrophy and subsequent narrowing of the pylorus between the stomach and duodenum. Signs and symptoms in infants can include vomiting (sometimes forceful) and irritability after feeding. Treatment is usually pyloromyotomy, a surgical procedure where incisions are made in the muscle walls of the pylorus.

About erythromycin

Erythromycin is a macrolide antibiotic that is active against gram-positive cocci and gram-positive bacilli, some gram-negative cocci and some gram-negative bacilli. It is widely used to treat chest infections such as pneumonia, skin problems and sexually transmitted diseases. It is used in children, often to treat ear or chest infections. Erythromycin is licensed for use in both adults and children (including infants and babies).

As for all antibiotic medicines, consideration should be given to official guidance on the appropriate use of antimicrobial agents.

Report suspected reactions on a Yellow Card

Please continue to report suspected adverse drug reactions (ADRs) to the Yellow Card scheme. Reporting suspected ADRs, even those known to occur, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 14, issue 5: December 2020: 3.

Post-publication note: March 2022

In February 2022, we published advice on the increased risk of cardiovascular events when systemic macrolide antibiotics are used concurrently with hydroxychloroquine or chloroquine. See Drug Safety Update February 2022 for more information.

Published 17 December 2020