What side effects or serious risks should I watch for?

The burden of proof is on the people asking you to accept a drug, and for cisapride, that burden has not been met.

You are asking about a drug that was pulled from the market in most of the world because it caused heart rhythm problems, including sudden death. The systematic review you cite is honest about the core problem: the evidence for benefit is weak, and the evidence for harm is real. Let me walk you through the mechanism, the data, and what you should actually watch for if you or someone you care about is still taking it.

Cisapride works by stimulating serotonin receptors in the gut, which pushes food and stool along. That sounds good in theory. But those same receptors exist in the heart muscle, specifically in the electrical system that controls the heartbeat. The drug blocks a potassium channel called hERG. When that channel is blocked, the electrical repolarization of the heart slows down. On an ECG, that shows up as a prolonged QT interval. A prolonged QT interval is a direct risk factor for torsades de pointes, a chaotic heart rhythm that can degenerate into ventricular fibrillation and stop the heart. This is not a theoretical risk. It is a documented, dose-dependent, and often fatal one.

The systematic review you cite concludes that cisapride does not provide clear benefits for constipation or constipation-predominant IBS. That is the honest reading of the trials. The studies that exist are small, short, and mostly funded by the manufacturer. They measure surrogate endpoints like stool frequency or transit time, not hard outcomes like quality of life or avoidance of surgery. And the safety data is worse than thin. The trials were not powered to detect rare cardiac events. The post-marketing surveillance that did catch the problem came from spontaneous reports, which are the weakest form of evidence, and even then, the signal was strong enough to get the drug withdrawn in many countries.

So what should you watch for? If someone is still taking cisapride, the first thing is palpitations, a racing or skipping heart, dizziness, fainting, or seizures. Those are signs of a heart rhythm problem, and they are emergencies. The second thing is any drug interaction. Cisapride is metabolized by the liver enzyme CYP3A4. Anything that inhibits that enzyme, like certain antifungals, macrolide antibiotics, or grapefruit juice, will raise cisapride levels in the blood and increase the risk of QT prolongation. The third thing is electrolyte imbalances. Low potassium, low magnesium, or low calcium all make the heart more vulnerable to the drug's effect. If the person has kidney disease, liver disease, or is on diuretics, the risk goes up further.

Here is where the evidence is genuinely weak. There is no long-term safety data on cisapride in children, which is a population where it was sometimes used off-label for reflux or constipation. There is no data on cumulative dose effects over years. There is no data on what happens to the heart months after stopping the drug, because the studies that exist are short and industry-funded. The systematic review you cite is not a conspiracy. It is a rare piece of honest literature that says what the data shows: no clear benefit, real cardiac risk.

My confidence in this assessment is high. The mechanism is proven biochemistry. The cardiac risk is documented in multiple case series and pharmacovigilance databases. The lack of benefit is what the systematic review says, and it aligns with the fact that the drug was withdrawn from the market for safety, not for lack of efficacy. If you are weighing whether to start or continue cisapride, the honest answer is that the risk is known and the benefit is not. The evidence is not clear on benefit, and it is clear on harm. That is not a hedge. That is the state of the science.