Usage
- Cisapride + Methylpolysiloxane is prescribed for the relief of symptoms related to gastroesophageal reflux disease (GERD), such as heartburn, acid reflux, bloating, and abdominal discomfort. It is sometimes used to treat constipation.
- Pharmacological Classification: Gastroprokinetic (Cisapride) and antiflatulent (Methylpolysiloxane).
- Mechanism of Action: Cisapride increases acetylcholine release in the myenteric plexus of the gastrointestinal tract, stimulating gut motility. Methylpolysiloxane works by reducing the surface tension of gas bubbles, allowing them to combine and be expelled more easily.
Alternate Names
- Various brand names exist, including Cisa MPS, Mogit MPS, Syspride MPS, Gastropen MPS, and Ezamps, depending on the region and manufacturer. Cisapride is often unavailable due to safety concerns and is subject to restrictions in many places.
How It Works
- Pharmacodynamics: Cisapride enhances gastrointestinal motility by increasing the release of acetylcholine. Methylpolysiloxane reduces gas formation in the digestive tract.
- Pharmacokinetics: Cisapride is metabolized by the liver, mainly via the CYP3A4 enzyme system. Methylpolysiloxane is not systemically absorbed.
- Mode of Action: Cisapride acts on the myenteric plexus to facilitate acetylcholine release. Methylpolysiloxane works physically by decreasing the surface tension of gas bubbles.
- Elimination Pathways: Cisapride is primarily eliminated through hepatic metabolism, while methylpolysiloxane is expelled from the body through the digestive tract.
Dosage
Due to safety concerns related to Cisapride, its availability is restricted, making the following dosage information primarily of historical relevance:
Standard Dosage
Adults:
- Historically, 5-10 mg orally every 6 hours, taken 15 minutes before meals and at bedtime. Dosages could be increased to 20 mg in some cases. Methylpolysiloxane dosage depends on the specific formulation.
Children:
- Historical pediatric dosing: 0.15-0.3 mg/kg/dose orally every 6-8 hours, not exceeding 10 mg/dose. Pediatric usage is discouraged due to safety risks.
Special Cases:
Due to the restricted nature of Cisapride, dosing recommendations for the following special cases are not readily available:
- Elderly Patients: Requires careful consideration due to potential age-related changes in organ function.
- Patients with Renal Impairment: Dose modifications are necessary, depending on the severity of renal function.
- Patients with Hepatic Dysfunction: Careful use and possible dose adjustments are crucial because the liver metabolizes Cisapride.
- Patients with Comorbid Conditions: Dosage adjustments and careful use may be necessary.
Clinical Use Cases
Dosing guidelines for specific clinical settings like intubation, surgical procedures, or ICU usage are not readily available, especially given the limited availability and safety concerns surrounding Cisapride.
Dosage Adjustments
Dose adjustments for renal/hepatic impairment, metabolic disorders, or genetic polymorphisms should be individualized based on the patient’s specific factors. Cisapride requires very careful consideration in these situations.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Headache
- Abdominal cramps
- Constipation
- Rhinitis
- Increased incidence of viral infections
Rare but Serious Side Effects:
- Prolonged QT interval
- Torsades de pointes
- Ventricular tachycardia
- Ventricular fibrillation
- Cardiac arrest
Long-Term Effects:
Data on the long-term effects of this drug combination are limited, particularly given the restricted usage of Cisapride.
Adverse Drug Reactions (ADR):
Serious cardiac arrhythmias (as noted above) constitute clinically significant ADRs requiring immediate medical intervention.
Contraindications
- Hypersensitivity
- QT prolongation
- History of cardiac arrhythmias
- Concomitant use of CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics)
- Hypokalemia
- Hypomagnesemia
- Renal insufficiency
- Significant hepatic dysfunction
- Gastrointestinal hemorrhage, mechanical bowel obstruction, bowel perforation
- Persistent vomiting
Drug Interactions
- Cisapride has numerous drug interactions, particularly with CYP3A4 inhibitors, which can elevate the risk of severe cardiac arrhythmias. It also interacts with drugs that prolong the QT interval.
- Alcohol can increase drowsiness when combined with this medication.
- Interactions may occur with commonly prescribed medications, OTC drugs and supplements, as well as certain food and lifestyle factors.
Pregnancy and Breastfeeding
Cisapride is generally contraindicated in pregnancy and breastfeeding due to potential adverse effects on the developing fetus and newborn.
Drug Profile Summary
- Mechanism of Action: Cisapride enhances acetylcholine release, stimulating gastrointestinal motility. Methylpolysiloxane reduces gas bubbles in the digestive tract.
- Side Effects: Common: Diarrhea, nausea, headache. Serious: Cardiac arrhythmias (QT prolongation, torsades de pointes, ventricular fibrillation).
- Contraindications: Hypersensitivity, QT prolongation, history of cardiac arrhythmias, concomitant use of CYP3A4 inhibitors, renal/hepatic dysfunction.
- Drug Interactions: Numerous drug interactions, especially with CYP3A4 inhibitors and drugs that prolong the QT interval.
- Pregnancy & Breastfeeding: Generally contraindicated.
- Dosage: Historically, adults: 5–10 mg orally every 6 hours. Children: 0.15-0.3 mg/kg/dose orally every 6-8 hours. (Usage is often restricted due to safety concerns.)
- Monitoring Parameters: ECG (QT interval), serum electrolytes.
Popular Combinations
Due to the significant safety concerns surrounding Cisapride, information about common drug combinations involving this medication is not typically presented. Its usage is generally avoided or restricted.
Precautions
- General Precautions: Assess for allergies, existing medical conditions, and organ dysfunction.
- Specific Populations: For pregnant women, breastfeeding mothers, children, and the elderly, the risks and potential safety concerns associated with Cisapride need careful consideration. Its use in these populations is often discouraged or contraindicated.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cisapride + Methylpolysiloxane?
A: Due to safety concerns, Cisapride is generally unavailable or restricted. Historically, the adult dosage was 5-10 mg every 6 hours, 15 minutes before meals and at bedtime, potentially increased to 20 mg. Methylpolysiloxane dosage varies depending on the formulation.
Q2: What are the major side effects of Cisapride?
A: The most serious side effects are cardiac arrhythmias, including QT prolongation, torsades de pointes, ventricular tachycardia, and ventricular fibrillation. More common side effects include diarrhea, nausea, headache, and abdominal discomfort.
Q3: What are the contraindications for using Cisapride?
A: Cisapride is contraindicated in patients with a history of cardiac arrhythmias, QT prolongation, concomitant use of CYP3A4 inhibitors, hypokalemia, hypomagnesemia, renal insufficiency, and hepatic dysfunction.
Q4: Can Cisapride be used during pregnancy or breastfeeding?
A: Cisapride is generally contraindicated during pregnancy and breastfeeding due to potential risks to the fetus or neonate.
Q5: How does Cisapride work to alleviate GERD symptoms?
A: Cisapride works by increasing acetylcholine release in the myenteric plexus, stimulating gastrointestinal motility and helping to move food through the digestive system more efficiently, reducing reflux.
Q6: What drugs interact with Cisapride?
A: Cisapride has many significant drug interactions, especially with CYP3A4 inhibitors (like some antifungals and antibiotics), which can increase the risk of cardiac arrhythmias. It also interacts with drugs that prolong the QT interval.
Q7: What precautions should be taken when prescribing Cisapride?
A: Before starting Cisapride, assess the patient for any pre-existing medical conditions, organ dysfunction, electrolyte imbalances, and concomitant medications. ECG monitoring is essential due to the risk of cardiac arrhythmias.
Q8: Is Cisapride readily available for prescription?
A: Cisapride is largely unavailable or restricted due to safety concerns related to cardiac events. Its usage is carefully controlled and often avoided in favor of safer alternatives.
Q9: What is the role of Methylpolysiloxane in this combination?
A: Methylpolysiloxane acts as an antiflatulent. It reduces gas and bloating by decreasing the surface tension of gas bubbles in the digestive tract, aiding in their coalescence and expulsion.
Q10: How should Cisapride + Methylpolysiloxane be administered?
A: It is typically administered orally, usually 15 minutes before meals, although its usage is often restricted due to Cisapride’s safety profile. Consult available historical information or specific guidelines if considering its use under restricted access programs.
