Key points from the evidence

Key points from the evidence

Summary

Only 1 small single-blind, crossover study (n=13) identified in a systematic review (5 studies, varying designs, n = 60) found a statistically significant benefit for erythromycin in the short term for improving symptoms of gastroparesis compared with metoclopramide. The other studies identified in the systematic review did not provide reliable evidence of the effectiveness, safety and tolerability of erythromycin for gastroparesis in either the short or longer term.

Regulatory status: Off-label for treating symptoms of gastroparesis.

Effectiveness

  • Five small studies (n=60), 4 of which reported on symptoms as an outcome.

  • Only 1 study found a statistically significant benefit of oral erythromycin on symptoms compared with metoclopramide. Another controlled study found no benefit compared with placebo. Two uncontrolled studies found no benefit compared with baseline symptoms.

Safety

Erythromycin:

  • Can rarely cause serious adverse effects such as hearing loss, allergic reactions, skin reactions, hepatic dysfunction and cardiac arrhythmias.

  • Is associated with many drug interactions.

  • Is contraindicated in people with known hypersensitivity, and in those taking astemizole, terfenadine, cisapride, pimozide, ergotamine, dihydroergotamine and simvastatin.

Patient factors

  • Gastrointestinal adverse effects, including nausea, vomiting, diarrhoea and abdominal pain, are common with erythromycin.

Cost

  • Erythromycin is available in various strengths and formulations with costs ranging from £1.91 to £12.70 for 28 capsules or tablets.

Key points

Erythromycin is a macrolide antibiotic that is licensed for treating and preventing infections. It does not have UK marketing authorisation for treating gastroparesis and so this indication is an off-label use of erythromycin.

Managing gastroparesis centres on nutrition and fluid balance. If pharmacological treatment is required, metoclopramide, domperidone or erythromycin may be considered as motility agents.

There is limited evidence reviewing the efficacy of oral erythromycin in people with gastroparesis. One systematic review (Maganti et al. 2003) including 5 studies (n=60), and 1 retrospective chart review (n=25) were identified.

Of the 5 studies in the systematic review, only 4 reported on change in symptom scores, and none assessed symptom improvement as the primary end point. Of the 4 studies which reported symptom scores, 1 was a double-blind, placebo-controlled, crossover study, 1 was a single-blind, active-controlled (metoclopramide) crossover study, and 2 were open-label uncontrolled studies.

Erythromycin improved measures of gastric emptying compared with baseline in all the studies. However, of the 4 studies that reported on symptoms, 1 found that oral erythromycin did not statistically significantly improve symptoms compared with placebo (Samsom et al. 1997); 1 study found statistically significant improvement compared with metoclopramide (Erbas et al. 1993), and 2 open-label uncontrolled studies found no statistically significant improvement in symptoms compared with baseline (Richards et al.1993 and Ramirez et al. 1994). One of the uncontrolled studies found a statistically significant improvement in global assessment score (Richards et al.1993).

The retrospective chart review (Dhir and Richter 2004) included a series of patients with dyspepsia and gastroparesis treated with a low-bulk diet and 50 to 100 mg oral erythromycin suspension 3 times a day and at bedtime. The chart review collected data on responses at 6 to 8 weeks; longer term responses were collected by telephone follow up. Of the 25 patients, 18 were assessed by chart review, and 18 had longer term telephone follow up. Fifteen out of 18 patients had "some" (<50% of baseline) or "dramatic" (>50% of baseline) reduction in symptoms on the 6 to 8 week chart review. Twelve out of 18 patients had "some" or "dramatic" improvement in the longer term (up to 2 years) follow up. Retrospective chart reviews and case series rarely provide evidence which is sufficiently strong to confidently guide clinical practice.

Erythromycin is often associated with gastrointestinal adverse effects, including abdominal discomfort, nausea, vomiting and diarrhoea. Rare adverse effects include hearing loss, allergic reactions (including anaphylaxis), skin reactions (including erythema multiforme and Stevens-Johnson syndrome), hepatitis and hepatic dysfunction, cardiac arrhythmias and pseudomembranous colitis. Erythromycin is contraindicated in people with known hypersensitivity, and in those taking certain medications including astemizole, terfenadine, cisapride and pimozide (increased risk of cardiotoxicity), ergotamine and dihydroergotamine (increased risk of ergot toxicity), and simvastatin (increased risk of myopathy and rhabdomyolysis).

Erythromycin may interact with various other medications, including increasing serum concentrations of drugs metabolised by the cytochrome P450 system. The relevant summaries of product characteristics contain more information on drug interactions and adverse effects of erythromycin.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.