The History and Recall of Propulsid (Cisapride)
Propulsid, known generically as cisapride, was a prokinetic medication used to treat gastrointestinal (GI) issues such as severe nighttime heartburn associated with gastroesophageal reflux disease (GERD) and gastroparesis. Approved by the FDA in 1993, the drug worked by increasing muscle contractions in the upper GI tract, helping to move food more efficiently and prevent acid reflux. For a period, it was a valuable treatment option for patients with debilitating GI conditions unresponsive to other therapies.
However, a dark side to the medication soon became apparent. By March 2000, mounting data revealed a significant and alarming risk of serious cardiac arrhythmias, including a potentially fatal irregular heartbeat known as torsade de pointes. This risk was particularly high in patients with pre-existing heart conditions, electrolyte imbalances, or those taking other medications that interfered with cisapride's metabolism. In consultation with the FDA, Janssen Pharmaceutica decided to stop marketing Propulsid in the United States, officially removing it from retail shelves on July 14, 2000.
Cardiac Risks and the Danger of QT Prolongation
The primary reason for the recall was Propulsid's effect on the heart's electrical system, specifically its ability to prolong the QT interval. The QT interval is a measure on an electrocardiogram (ECG) that represents the time it takes for the heart's ventricles to contract and then recover. A prolonged QT interval can lead to dangerous and potentially lethal arrhythmias. The risk was heightened by several factors, which contributed to an elevated level of cisapride in the bloodstream:
- Drug-drug interactions: Medications that inhibit the cytochrome P450 3A4 enzyme, such as certain antibiotics (e.g., erythromycin) and antifungals (e.g., ketoconazole), were contraindicated with Propulsid as they could significantly increase cisapride levels.
- Underlying medical conditions: Patients with a history of prolonged QT intervals, heart disease, or renal failure were at higher risk.
- Electrolyte imbalances: Uncorrected low levels of potassium or magnesium could predispose patients to arrhythmias when taking cisapride.
Discontinued Medications That Interacted with Propulsid
Numerous medications were identified as interacting negatively with cisapride. Many of these are no longer on the market or are used with extreme caution. This extensive list further complicated safe administration of the drug, leading to continued inappropriate use despite multiple warnings.
The Limited Access Program and Its End
For a small, specific group of patients with severe, debilitating GI conditions who had no other treatment options, Propulsid was made available through a special "Limited Access Program". This program required strict patient monitoring, including regular ECGs and blood tests, and was administered by the manufacturer, Janssen Pharmaceuticals. However, even this last-resort program has concluded. As of September 8, 2025, Janssen Pharmaceuticals stopped accepting new patient enrollment requests for the program, effectively making Propulsid unavailable for new human patients in the U.S..
Safer and More Common Alternatives for GI Motility Issues
For individuals with gastroparesis, GERD, or other motility disorders, several safer and highly effective alternatives are available today. The choice of treatment depends on the specific condition, its severity, and the patient's overall health profile. Some common alternatives include:
- Metoclopramide (Reglan®): A prokinetic agent and dopamine receptor antagonist that, like Propulsid, can increase stomach and intestinal contractions. It is used to treat gastroparesis but has potential side effects, including neurological ones.
- Domperidone: Another prokinetic agent that is not available in the U.S. for human use but is used in other countries. It is sometimes available through compounding pharmacies for certain indications. It carries cardiac risks, so its use is also monitored carefully.
- Proton Pump Inhibitors (PPIs): Medications like omeprazole (Prilosec®), lansoprazole (Prevacid®), and esomeprazole (Nexium®) are highly effective at reducing stomach acid and are standard first-line treatments for GERD.
- H2 Blockers: These reduce the amount of acid produced by the stomach and include medications like famotidine (Pepcid®) and cimetidine (Tagamet®).
- Erythromycin: An antibiotic that can be used in low doses for its prokinetic effects, particularly in diabetic gastroparesis.
Comparison of Treatment Options
| Feature | Propulsid (Cisapride) | Metoclopramide (Reglan®) | PPIs (e.g., Prilosec®) / H2 Blockers (e.g., Pepcid®) |
|---|---|---|---|
| Mechanism of Action | Serotonin 5-HT4 agonist, increases GI motility | Dopamine receptor antagonist, increases GI motility | Reduce stomach acid production |
| Primary Uses | Gastroparesis, severe GERD | Gastroparesis | GERD, heartburn, ulcers |
| Availability (Human) | Limited access program concluded; unavailable | Widely available via prescription | Widely available, including OTC options |
| Key Risks/Side Effects | Severe cardiac arrhythmias (QT prolongation) | Neurological side effects (tardive dyskinesia), anxiety, depression | Headache, diarrhea, long-term risks (e.g., nutrient deficiencies) |
| Drug Interactions | Significant interactions, especially with CYP3A4 inhibitors | Interactions exist, but generally safer profile than cisapride | Fewer severe interactions; generally very safe |
Current Availability for Veterinary Use
While can you still get Propulsid for human use is a common query, it is important to note its continued use in veterinary medicine. Veterinarians may prescribe compounded cisapride for conditions such as megacolon in cats and GI stasis in rabbits, as the cardiac risks are not as prevalent in these animals. This compounded form is not an option for human use and does not contradict the recall for human applications.
Conclusion: Prioritizing Patient Safety
The voluntary withdrawal of Propulsid from the retail market was a necessary action to protect patients from a significant and potentially fatal side effect. While the medication was effective for some, its cardiac risks, particularly when combined with other drugs or health conditions, were deemed unacceptable. The conclusion of the limited access program in 2025 further solidifies its non-availability for human patients today. For those seeking treatment for GI motility disorders, numerous safer and more widely available alternatives exist. The most prudent course of action is to consult with a healthcare professional to discuss modern treatment plans that address symptoms while prioritizing patient safety. For additional information on drug safety, the FDA's website is an authoritative source. (e.g. FDA Drug Safety Information )
