Is There a Replacement for Propulsid? Exploring Safer Alternatives in 2025

October 9, 2025 •

3 min read

In July 2000, Propulsid (cisapride) was removed from the U.S. market due to reports of serious cardiac arrhythmias and death. For patients wondering, 'Is there a replacement for Propulsid?', the answer lies in modern, safer prokinetic agents.

Quick Summary

Propulsid (cisapride) was discontinued due to risks of severe cardiac events. Safer alternatives now exist for treating conditions like gastroparesis, including metoclopramide and the more selective drug prucalopride.

Key Points

Withdrawn Due to Safety: Propulsid (cisapride) was removed from the U.S. market in 2000 because it could cause serious, sometimes fatal, cardiac arrhythmias.
FDA-Approved Alternative: Metoclopramide is the only drug currently FDA-approved for gastroparesis but has a black box warning for the risk of tardive dyskinesia, a serious movement disorder.
A Modern, Safer Option: Prucalopride (Motegrity) is a highly selective 5-HT4 agonist that promotes gut motility without the significant cardiac risks associated with Propulsid.
Restricted Access Drug: Domperidone is effective and has fewer neurological side effects than metoclopramide but is not FDA-approved in the U.S. due to its own cardiac risks and is only available through a special access program.
Off-Label Antibiotic Use: Erythromycin can be used short-term as a prokinetic agent, but its effectiveness can wane over time, and it carries the risk of antibiotic resistance.
Consult a Professional: Choosing a replacement for Propulsid requires careful consideration of individual health factors and must be done in consultation with a qualified healthcare provider.

The Story of Propulsid (Cisapride)

Propulsid (cisapride) was a prokinetic agent used for conditions like nocturnal heartburn from GERD and off-label for gastroparesis. It worked by increasing gastrointestinal motility through stimulating acetylcholine release.

Why Was Propulsid Taken Off the Market?

Propulsid was voluntarily withdrawn from the U.S. market in July 2000 due to a link with serious cardiac arrhythmias, including a fatal rhythm called Torsades de Pointes. This was caused by the drug's effect on cardiac potassium channels. The risk was higher in patients with existing heart conditions or those taking medications that affected cisapride's metabolism. The FDA received reports of 38 deaths by 2000, leading to its removal from general use. It is now only available in the U.S. through a limited-access program.

Modern Alternatives: Is There a Replacement for Propulsid?

Several medications are used as alternatives to Propulsid, each with unique benefits and risks, chosen based on the patient's condition and health.

Metoclopramide (Reglan)

Metoclopramide is the only FDA-approved drug for treating gastroparesis in the U.S.. It enhances stomach emptying by blocking dopamine-2 receptors.

Warning: A significant risk is tardive dyskinesia (TD), an irreversible movement disorder. The FDA issued a black box warning in 2009 for this risk, recommending use be limited to 12 weeks.

Prucalopride (Motegrity)

Prucalopride is a newer, highly selective 5-HT4 receptor agonist, similar to cisapride. Its selectivity means it does not significantly affect the hERG potassium channels, avoiding the cardiac risks of cisapride. Clinical trials have not shown significant QT prolongation. While primarily for chronic constipation, it's used and studied for gastroparesis.

Domperidone (Motilium)

Domperidone is a peripheral dopamine antagonist, similar to metoclopramide but with fewer central nervous system side effects. It is used for gastroparesis outside the U.S..

Availability: Not FDA-approved in the U.S. due to cardiac risks. It can be accessed for severe cases in patients aged 12+ through a special Expanded Access IND program.

Erythromycin

This antibiotic is used off-label short-term for its prokinetic effect, stimulating motilin receptors to aid gastric emptying. Its effectiveness can decrease over time, and long-term use can lead to antibiotic resistance.

Comparison of Propulsid Alternatives


Medication	Mechanism of Action	Primary Use	Key Safety Concern(s)
Cisapride (Propulsid)	Non-selective 5-HT4 agonist	GERD, Gastroparesis (historically)	Severe cardiac arrhythmias (QT prolongation)
Metoclopramide (Reglan)	Dopamine-2 receptor antagonist	Gastroparesis, GERD	Black box warning for tardive dyskinesia
Prucalopride (Motegrity)	Selective 5-HT4 agonist	Chronic Constipation, Gastroparesis (off-label)	Lacks the cardiac risks of cisapride due to high selectivity
Domperidone (Motilium)	Peripheral dopamine antagonist	Gastroparesis (outside U.S.)	Not FDA-approved; cardiac risks; only available via special program
Erythromycin	Motilin receptor agonist	Gastroparesis (off-label)	Diminishing effectiveness over time (tachyphylaxis), antibiotic resistance

Conclusion: Navigating Treatment After Propulsid

Since Propulsid's withdrawal, the treatment of GI motility disorders relies on various alternatives. Metoclopramide is FDA-approved for gastroparesis but has a significant warning. Prucalopride offers a safer, more selective approach without the cardiac risks of cisapride. Other options like domperidone and erythromycin have restrictions or limitations. Determining the best replacement for Propulsid requires medical consultation to evaluate individual needs and risks.

Authoritative Link: For more information on the risks that led to Propulsid's withdrawal, you can review materials from the U.S. Food and Drug Administration. (Link is for informational purposes and does not imply an endorsement of the content of this article.)

Frequently Asked Questions

Propulsid was officially approved to treat nocturnal heartburn caused by GERD, but it was also widely used to treat other gastrointestinal motility disorders like gastroparesis and dyspepsia.

Propulsid was withdrawn from the market in 2000 due to its association with serious cardiac side effects, including irregular heart rhythms (QT prolongation) and sudden death.

Prucalopride (Motegrity) is pharmacologically similar to Propulsid as a 5-HT4 agonist, but it is much more selective and does not carry the same significant cardiac risks, making it a safer modern alternative.

Metoclopramide is an effective prokinetic agent and the only one FDA-approved for gastroparesis. However, its long-term use is discouraged due to a black box warning for tardive dyskinesia, a potentially irreversible movement disorder.

No, Domperidone is not approved for sale in the U.S. It can only be obtained for severe GI conditions through a special Expanded Access program managed by the FDA for patients who have not responded to other therapies.

Gastroparesis, also called delayed gastric emptying, is a disorder where the stomach takes too long to empty its contents into the small intestine, without any physical blockage. Symptoms can include nausea, vomiting, and feeling full quickly.

QT prolongation is a condition affecting the heart's electrical system, where the heart muscle takes longer than normal to recharge between beats. It can increase the risk of a dangerous and chaotic heart rhythm called Torsades de Pointes, which was the primary concern with Propulsid.