Cisapride gastrointestinal effects

Despite the rigorous process for drug approval and regulation, several important medications have been removed from the market because of serious ADEs over the past 30 years. Examples of serious but uncommon effects include acute flank syndrome associated with suprofen," the gastrointestinal effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) in the elderly," troglitazone and the risk of hepatotoxicity," and the adverse effects of cisapride... 

Cisapride is structurally similar to metoclopramide, but has no dopamine receptor antagonist activity and hence no central antiemetic effect. However, because it stimulates the release of acetylcholine in the gastrointestinal tract it is effective in conditions such as reflux esophagitis and gastroparesis. During clinical trials, the most frequent unwanted effects were diarrhea (5-11%) and abdominal pain (16% with 20 mg bd). 

The effect of cisapride 0.8 mg/kg/day for 14 days on the QTc interval has been stndied prospectively in 50 infants with feeding intolerance, apnea, and bradycardia episodes secondary to gastro-esophageal reflux and gastrointestinal dysmotUity (9). In 15 infants there was prolongation of the QTc interval at some time during the 14 days. Infants with a QTc interval on day 3 at least two standard deviations above the mean baseline QTc interval were more likely to develop a prolonged QTc interval. 

Fig. 6. Top Effects of (A) EM574 and (B) porcine motilin on gastrointestinal contractile activity in the interdigestive state in the conscious dog. Both agents induced IMC-like migrating contractions. Bottom Effect of cisapride on gastrointestinal contractile activity in the fasting dog [(A), 0.3 mg/kg (B), 1 mg/kg]. The contractile pattern of cisapride-evoked contractions was different from those induced by EM574 and motilin. (From Inatomi et al. [15] with permission of the editor.)...

Antiepileptics e.g. Phenytoin Increase in gastrointestinal motility caused by cisapride may affect the rate and/or extent of absorption, which may be important for some drugs with a narrow therapeutic index, such as some antiepileptics. However, no available case reports to suggest this is a problem, and one case reporting no interaction. Uncertain. Monitor antiepileptic drug levels as usual practice. Advise the patient to report any increase in adverse effects. 1,7... 

Kuroda T, Yoshihara Y, Nakamura H, Azumi T, Inatome T, Fukuzaki H, Takanashi H, Yogo K, Akima M. Effects of cisapride on gastrointestinal motor activity and gastric emptying of disopyramide. J Pharmacobiodyn (1992) 15, 395-402. 

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