Prokinetic dose of erythromycin in adults

• Erythromycin acts as a motilin agonist through its interaction with motilin receptors found in the stomach and upper GI tract. 
• Erythromycin accelerates gastric emptying by increasing the frequency and amplitude of stomach and duodenal contractions
• Both the oral and intravenous (IV) route of erythromycin as a prokinetic agent have been studied, however, there is a lack of evidence from large randomised controlled trials in this area, and studies have tended to include small patient numbers and only consider short term use
• Long term oral use is limited by poor tolerance, modest efficacy and the development of tachyphylaxis

NICE Evidence Summary

• Oral erythromycin has been administered at doses ranging from 125mg three times daily to 500mg four times daily for 2-4 weeks.
• 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 (250mg three times daily) in the short term for improving symptoms of gastroparesis compared with metoclopramide (10mg three times daily).

A clinical guideline for management of gastroparesis

• recommends that erythromycin improves gastric emptying and symptoms from delayed gastric emptying.
• Administration of IV erythromycin should be considered when IV prokinetic therapy is needed in hospitalised patients. 3mg/kg every 8 hours by IV infusion over 45 minutes to avoid sclerosing veins is effective

Other Evidences

• Paw and Shulman advise a dose of 125mg four times a day orally or via a nasogastric tube or 125mg- 250mg intravenously every 6-12 hours

Concerns

• May lead to the development of macrolide resistance and increase the risk of Clostridium difficile (CD) diarrhoea and nosocomial infections
• However, one study in 2008 looked at 183 intensive care patients who had received low dose erythromycin prokinetic therapy and found that diarrhoea was not found to have been caused by CD or bacterial infections but may have been due to the pro-motility effects of erythromycin.
• Other safety considerations such as the numerous drug interactions with erythromycin  due to the inhibition of the cytochrome P450 pathway
• Prevention of cardiovascular complications such as  QTc prolongation and an association with torsades de pointes, should be considered before prescribing erythromycin as a prokinetic agent

Recommendation

• The ideal prokinetic dose of erythromycin is yet to be established but is less than the maximal antibacterial dose of erythromycin
• With intravenous erythromycin, satisfactory outcomes have been achieved with doses of 300mg daily in divided doses, with 250mg four times a day, and with single doses of 70mg and 200mg.
• Oral erythromycin has been used effectively as a prokinetic at doses from 50mg three times daily up to 250mg four times daily

References:

1. What is the optimal prokinetic dose of erythromycin in adults? UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals