What is the role of prokinetic agents for constipation?
Erythromycin has a limited role in treating pediatric patients (strength of recommendation [SOR]: B, limited-quality, patient-oriented evidence). Tegaserod and cisapride are the only prokinetic agents available for constipated adults (SOR: A, consistent, good-quality, patient-oriented evidence for tegaserod; SOR: B, for cisapride), but cardiovascular risk restricts prescribing of both medications.
Evidence summary
Prokinetic agents promote transit of intestinal contents by increasing the frequency or strength of small intestine contractions. Available prokinetics include erythromycin and metoclopramide. Metoclopramide has been tested only for upper gastrointestinal mobility. The only randomized controlled trials (RCTs) of erythromycin for constipation have been conducted in children. Cisapride and tegaserod have been withdrawn from general use because of adverse side effects. The TABLE summarizes the available data.
,TABLE
Prokinetics for constipation: What the research tells us
| DRUG | DESIGN (N) | DOSE | OUTCOME | NNT |
|---|---|---|---|---|
| Erythromycin estolate1 | Crossover children (14) | 20 mg/kg/day divided qid | †Constipation and laxative use | 10 |
| Cisapride5 | RCT adults (69) | 5-10 mg tid | ü Spontaneous BM † Abdominal pain | 4 |
| Cisapride6 | RCT adults (82) | 5-10 mg tid | Abdominal pain and constipation, drug=placebo | N/A |
| Tegaserod7 | RCT adults (1348) | 2 mg or 6 mg bid | † Constipation ü Spontaneous BM | 6 (2 mg) 5 (6 mg) |
| Tegaserod8 | RCT adults (1264) | 2 mg or 6 mg bid | † Constipation and abdominal pain | 11 (2 mg) 7 (6 mg) |
| Renzapride11 | Pilot study adults (17) | Escalating dose: 2 mg daily to 2 mg bid | † Abdominal pain and bloating | Not enough information to calculate |
| Renzapride12 | Parallel group adults (48) | 1, 2, or 4 mg daily | ü Colonic transit; stool form and ease of passage, drug=placebo | N/A |
| BM, bowel movement; N/A, not available; NNT, number needed to treat; RCT, randomized controlled trial. | ||||
Pediatric constipation: Erythromycin helps; watch dosage
A small RCT of 14 children between 4 and 13 years of age showed that erythromycin improved symptoms of constipation and decreased laxative use (number needed to treat [NNT]=10).1 Two RCTs in neonates demonstrated that erythromycin shortened intestinal transit time and improved feeding tolerance.2,3
The erythromycin dose used in these studies was lower than the dosage for antibiotic purposes; no adverse effects were reported. However, cardiac arrhythmias and death have occurred when erythromycin is given to adults and children at the usual antibiotic doses.4
