Usage
Cisapride + Simethicone is a combination medication primarily used to treat gastrointestinal discomfort and dysfunction. It combines a prokinetic agent (cisapride) with an anti-foaming agent (simethicone).
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Medical Conditions: This combination is prescribed for symptoms like bloating, fullness, abdominal discomfort, and excessive gas associated with conditions such as gastroesophageal reflux disease (GERD), gastroparesis (delayed gastric emptying), and functional dyspepsia (indigestion). In some cases, it may be used to treat intestinal pseudo-obstruction and constipation-predominant irritable bowel syndrome (IBS-C).
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Pharmacological Classification: Cisapride is a gastroprokinetic agent, and simethicone is an anti-foaming agent. Therefore, this combined medication can be classified under both drug classes.
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Mechanism of Action: Cisapride acts on serotonin 5-HT4 receptors in the gut, increasing acetylcholine release, which stimulates gut motility and coordination. Simethicone reduces the surface tension of gas bubbles, causing them to combine into larger bubbles that can be passed more easily.
Alternate Names
While the generic name is Cisapride + Simethicone, brand names vary depending on the country and manufacturer. Some examples include Cisapid Mps, and various combinations paired with regional brand names for cisapride or simethicone.
How It Works
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Pharmacodynamics: Cisapride increases the frequency and strength of esophageal contractions, accelerates gastric emptying, and increases small bowel and colonic transit. Simethicone works locally within the GI tract to reduce the surface tension of gas bubbles. It is not absorbed into the systemic circulation.
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Pharmacokinetics: Cisapride is metabolized primarily by the hepatic cytochrome P-450 3A4 enzyme system. Simethicone is not absorbed and is excreted unchanged in the feces.
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Mode of Action: Cisapride works by stimulating 5-HT4 receptors in the gut, increasing acetylcholine release and enhancing coordinated gut contractions. Simethicone acts physically to reduce the surface tension of gas bubbles.
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Elimination Pathways: Cisapride is eliminated mainly through hepatic metabolism, while simethicone is eliminated through fecal excretion.
Dosage
Standard Dosage
Adults:
Cisapride: 10 mg orally 4 times a day, 15 minutes before meals and at bedtime. The dose may be increased to 20 mg if necessary.
Simethicone: 40–125 mg orally after meals and at bedtime, as needed. The maximum daily dose is 500 mg.
Children:
Cisapride: >1 year: 0.2 to 0.3 mg/kg/dose orally 3 to 4 times a day. Maximum: 10 mg per dose.
Simethicone: Children 2–12 years: 40 mg 4 times daily, maximum daily dose of 480 mg.
Children under 2 years: 20 mg 4 times daily, maximum daily dose of 240 mg.
Special Cases:
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Elderly Patients: Dosage adjustments may be necessary depending on overall health and organ function. Due to the risk of cardiac side effects with cisapride, its use in elderly patients should be approached with caution.
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Patients with Renal Impairment: Data on cisapride dosage adjustments are not available for renal impairment. For simethicone, no adjustments are typically needed.
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Patients with Hepatic Dysfunction: Reduce the cisapride daily dosage by 50%. For simethicone, no adjustments are typically needed.
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Patients with Comorbid Conditions: Careful consideration is required for patients with cardiac conditions, electrolyte imbalances, or taking medications that prolong the QT interval due to potential drug interactions with cisapride.
Clinical Use Cases
The use of cisapride in clinical settings like intubation, surgical procedures, mechanical ventilation, and the ICU is generally avoided due to its potential for serious cardiac side effects. Simethicone can be used as needed to relieve gas and bloating.
Dosage Adjustments
Dosage adjustments are necessary for patients with hepatic dysfunction and those taking drugs that interact with cisapride, particularly CYP3A4 inhibitors.
Side Effects
Common Side Effects
- Diarrhea
- Headache
- Abdominal pain
- Nausea
- Runny nose
Rare but Serious Side Effects
- Cardiac arrhythmias (QT prolongation, torsades de pointes) with cisapride
Long-Term Effects
Data on the long-term effects of combined cisapride and simethicone use are limited due to the withdrawal of cisapride from many markets.
Adverse Drug Reactions (ADR)
Serious cardiac arrhythmias represent the most significant ADRs associated with cisapride.
Contraindications
- Hypersensitivity to cisapride or simethicone
- History of QT prolongation or cardiac arrhythmias
- Concomitant use of drugs that prolong the QT interval or inhibit CYP3A4
- Gastrointestinal obstruction, perforation, or hemorrhage
- Severe respiratory disorders
Drug Interactions
Cisapride interacts with numerous drugs, including:
- CYP3A4 inhibitors (e.g., macrolide antibiotics, azole antifungals)
- QT prolonging agents (e.g., some antipsychotics, antiarrhythmics)
Pregnancy and Breastfeeding
- Cisapride: Should generally be avoided during pregnancy due to limited safety data and the potential for cardiac effects. Limited information suggests low levels in breast milk, but caution is advised.
- Simethicone: Generally considered safe during pregnancy and breastfeeding, as it is not systemically absorbed.
Drug Profile Summary
- Mechanism of Action: Cisapride: prokinetic (5-HT4 receptor agonist). Simethicone: anti-foaming (reduces surface tension of gas bubbles).
- Side Effects: Cisapride: diarrhea, headache, abdominal pain, nausea, cardiac arrhythmias. Simethicone: generally well-tolerated, occasional constipation or nausea.
- Contraindications: Hypersensitivity, QT prolongation risk, GI obstruction, severe respiratory disorders.
- Drug Interactions: Cisapride: CYP3A4 inhibitors, QT prolonging drugs. Simethicone: Minimal interactions.
- Pregnancy & Breastfeeding: Cisapride: Avoid if possible. Simethicone: Generally safe.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Electrocardiogram (ECG) for QT interval when using cisapride.
Popular Combinations
Cisapride is less often combined with other drugs due to safety concerns. Simethicone is commonly combined with antacids.
Precautions
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cisapride + Simethicone?
A: See detailed dosage section above.
Q2: What are the primary side effects of Cisapride?
A: Common side effects include diarrhea, headache, abdominal pain, and nausea. The most concerning side effect is cardiac arrhythmias, particularly QT prolongation.
Q3: Why is Cisapride contraindicated in patients with QT prolongation?
A: Cisapride can exacerbate QT prolongation, increasing the risk of serious and potentially fatal cardiac arrhythmias like torsades de pointes.
Q4: How does Simethicone work to relieve gas?
A: Simethicone lowers the surface tension of gas bubbles in the gut, allowing them to coalesce into larger bubbles that can be eliminated more easily.
Q5: Can Cisapride + Simethicone be used during pregnancy?
A: Cisapride should generally be avoided during pregnancy due to potential cardiac risks to the fetus. Simethicone is considered safe.
Q6: What are the main drug interactions to be aware of with Cisapride?
A: Cisapride interacts with CYP3A4 inhibitors and QT prolonging medications. Co-administration should be avoided or carefully managed.
Q7: Are there any dietary restrictions while taking Cisapride + Simethicone?
A: Patients should avoid grapefruit juice, as it can inhibit CYP3A4 and increase cisapride levels. General dietary modifications to reduce gas and bloating may be helpful.
Q8: What should I do if a patient experiences an adverse reaction to Cisapride?
A: Discontinue cisapride immediately and provide supportive care as needed. If cardiac arrhythmias occur, appropriate medical intervention is required.
A: Cisapride is primarily metabolized by the hepatic cytochrome P450 3A4 enzyme system.
