Gastroparesis in adults: oral erythromycin

Efficacy

One systematic review (Maganti et al. 2003) was identified. It reviewed studies evaluating the efficacy of oral erythromycin for the symptomatic relief of gastroparesis.

Four of the 5 studies in the review investigated the effect of oral erythromycin on symptoms, although none of these assessed symptom improvement as the primary end point. One study was a double-blind, placebo-controlled, crossover study (Samsom et al. 1997); 1 was a single-blind, active-controlled (metoclopramide), crossover study (Erbas et al. 1993); and 2 were open-label uncontrolled studies (Richards et al.1993, and Ramirez et al. 1994). The included populations were people with gastroparesis associated with diabetes (2 studies), diabetes or of unknown cause (idiopathic) (1 study), and surgery (1 study).

Erythromycin was administered orally with dosages ranging from 125 mg 3 times daily to 500 mg 4 times daily, and treatment periods ranging from 2 to 4 weeks. All studies were small including 14 or fewer participants in each, and all were of poor methodological quality with high risk of bias. The studies included a total of 60 participants.

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 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). Erythromycin improved measures of gastric emptying compared with baseline in all studies. In the 2 controlled studies, oral erythromycin statistically significantly improved gastric emptying compared with placebo and both erythromycin and metoclopramide improved gastric emptying parameters.

Table 1 Summary of the studies included in the Maganti et al. (2003) systematic review

Safety

The studies included in the systematic review do not provide reliable evidence of the risk of adverse effects with erythromycin.

The summaries of product characteristics for erythromycin state that the drug 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).

Caution is advised when using erythromycin in people with hepatic impairment or in those receiving potentially hepatotoxic agents (hepatic dysfunction has been infrequently reported); those with myasthenia gravis (weakness may be aggravated); and in seriously ill people receiving erythromycin concomitantly with statins (rhabdomyolysis has been reported). The summaries of product characteristics also warn that, as with other broad spectrum antibiotics, pseudomembranous colitis has been rarely reported with erythromycin. Erythromycin may interact with various other medications, including increasing serum concentrations of drugs metabolised by the cytochrome P450 system (including acenocoumarol, carbamazepine, ciclosporin, digoxin, midazolam, omeprazole, phenytoin, sildenafil, tacrolimus, theophylline and valproate). The summaries of product characteristics for erythromycin describe common adverse effects including nausea, abdominal discomfort, vomiting and diarrhoea.

There have been isolated reports of reversible hearing loss occurring with high doses of erythromycin or in people with renal insufficiency.

The following adverse effects have been rarely reported:

The relevant summaries of product characteristics contain more information on drug interactions and adverse effects of erythromycin.

Cost effectiveness and cost

No cost-effectiveness studies of erythromycin for use in gastroparesis were identified.

The NHS Electronic Drug Tariff (May 2013) lists the price for erythromycin oral capsules or tablets as follows: