The Voluntary Withdrawal of Propulsid (Cisapride)
Cisapride, once marketed under the brand name Propulsid, was a prokinetic agent used to treat gastrointestinal (GI) motility disorders. Its primary function was to increase muscle contractions in the GI tract, which helped relieve symptoms of conditions like nighttime heartburn from gastroesophageal reflux disease (GERD) and gastroparesis. However, reports emerged linking cisapride to life-threatening cardiac arrhythmias, including a specific type called torsades de pointes, which can be fatal.
Following consultation with the U.S. Food and Drug Administration (FDA), the manufacturer voluntarily removed the drug from the market in July 2000. The cardiac risks were exacerbated by co-administering cisapride with other medications that inhibit its metabolism via the cytochrome P-450 (CYP) 3A4 enzyme system. This led to dangerously high blood levels of cisapride and an increased risk of QT interval prolongation.
Restricted Availability for Human Patients
Even after its commercial withdrawal, access to cisapride was not completely eliminated for human use. For patients with severe, debilitating GI conditions who failed to respond to all other treatment options, a limited-access investigational program was established. This program was highly restrictive and involved strict eligibility criteria and monitoring protocols to mitigate the known cardiac risks.
To be considered for the program, a patient must be enrolled by a certified physician. The process requires extensive evaluation, and continuous monitoring is mandatory throughout treatment. The goal was to provide a last-resort option while ensuring the utmost caution and patient safety.
Requirements for the Limited-Access Program
- Patients must have a severely debilitating condition unresponsive to standard therapies.
- Enrollment must be handled by a certified physician who follows specific protocols.
- Strict cardiac and laboratory monitoring, including an electrocardiogram (ECG), is required.
- The patient must be educated on all potential drug interactions and contraindicated conditions.
Continued Veterinary Use via Compounding
While largely unavailable for general human prescription, cisapride is widely used and readily available in veterinary medicine, primarily for treating gastrointestinal issues in cats and dogs. This is typically done through compounding pharmacies.
The cardiac risks observed in humans have not been documented to the same extent in veterinary patients. For this reason, veterinarians can prescribe customized, compounded forms of the drug to address specific needs, such as feline megacolon.
Alternatives to Cisapride
Since cisapride was withdrawn, physicians have relied on alternative prokinetic and acid-suppressing therapies. The choice depends on the specific condition, patient health, and side effect profiles. Below is a comparison of some common alternatives.
| Medication | Primary Indication | Availability | Potential Cardiac Risk | Other Notable Side Effects |
|---|---|---|---|---|
| Cisapride (Limited Program) | Severe gastroparesis, GERD | Highly restricted via limited-access program for humans; compounded for veterinary use. | High; associated with QT prolongation and torsades de pointes. | Headache, diarrhea, GI discomfort. |
| Metoclopramide (Reglan®) | Gastroparesis, GERD, nausea | Widely available via prescription. | Possible, especially with high doses or drug interactions; less frequent than cisapride. | Drowsiness, anxiety, restlessness, tardive dyskinesia. |
| Domperidone | Gastroparesis, dyspepsia | Available in many countries; not in the US. Often used in veterinary medicine. | Possible QT prolongation; higher risk with IV use. | Drowsiness, dry mouth. |
| Erythromycin | Diabetic gastroparesis | Widely available; used off-label as a prokinetic agent. | Can cause QT prolongation, but less than cisapride. | Nausea, GI upset, antimicrobial resistance. |
| Prucalopride (Motegrity®) | Chronic idiopathic constipation | Prescription only. | Considered safer than cisapride regarding cardiac risk. | Headache, nausea, diarrhea. |
Lasting Regulatory Impact and Current Status
The high-profile withdrawal of cisapride served as a critical reminder of the importance of post-market surveillance and reporting drug interactions. Despite early warnings, studies showed that physicians and pharmacists continued prescribing cisapride with contraindicated medications, highlighting failures in communication and safety protocols. This case has influenced modern drug safety practices, leading to more stringent monitoring and communication strategies for high-risk medications.
Today, the answer to "is cisapride still available?" is generally no for human use, unless under the rare and strict conditions of the limited access program. However, it remains a common tool for veterinarians due to its efficacy and apparently lower cardiac risk profile in animal species. For human patients, safer and widely available alternatives have become the standard of care for treating motility disorders. For comprehensive information on cisapride and its withdrawal, see the archived label information available via the FDA.
Conclusion
In summary, the medication cisapride is no longer commercially available for general human prescription due to severe cardiac safety concerns that led to its withdrawal in 2000. A highly restricted, limited-access program still exists for specific human patients with no other options, and the drug is commonly compounded for veterinary use. This major regulatory action reshaped approaches to drug safety and emphasizes the need for continuous vigilance and awareness of medication risks. Patients with GI motility issues should consult their healthcare provider to discuss safer, modern alternatives.
