Usage
Prucalopride is prescribed for the symptomatic treatment of chronic idiopathic constipation (CIC) in adults, specifically when laxatives have failed to provide adequate relief. It’s classified as a selective, high-affinity 5-HT4 receptor agonist, falling under the pharmacological classification of a gastroprokinetic agent. Prucalopride works by stimulating peristaltic movements in the colon, thereby facilitating bowel movements.
Alternate Names
While “Prucalopride” is the generic name, brand names include Resolor and Motegrity.
How It Works
Pharmacodynamics: Prucalopride selectively activates 5-HT4 receptors in the gut, leading to increased acetylcholine release. This stimulates colonic motility and propulsive contractions, aiding in the passage of stool.
Pharmacokinetics:
- Absorption: Prucalopride is readily absorbed after oral administration, reaching peak plasma concentrations within 2-3 hours. Food does not significantly affect its absorption.
- Metabolism: Primarily metabolized via CYP450 enzymes, particularly CYP3A4, with minor contributions from CYP2D6 and CYP1A2.
- Elimination: Elimination is primarily through renal excretion (approximately 60% as unchanged drug) and to a lesser extent through fecal excretion. The elimination half-life is approximately 24 hours.
Mode of Action: Prucalopride’s primary mode of action is at the 5-HT4 receptors in the enteric nervous system. Stimulation of these receptors initiates a cascade of events, including increased acetylcholine release, which increases gut motility.
Receptor Binding: Prucalopride has high affinity and selectivity for 5-HT4 receptors, minimizing off-target effects.
Elimination Pathways: Prucalopride is eliminated via both renal and hepatic routes. Renal excretion is the primary route, with about 60% of the dose excreted as unchanged drug. The remainder is metabolized by CYP enzymes, primarily CYP3A4, and excreted in feces.
Dosage
Standard Dosage
Adults:
The standard dose is 2 mg once daily, taken with or without food.
Children:
Prucalopride is not recommended for use in children and adolescents younger than 18 years.
Special Cases:
- Elderly Patients (over 65 years): The initial recommended dose is 1 mg once daily. This can be increased to 2 mg once daily if needed.
- Patients with Renal Impairment: For severe renal impairment (GFR < 30 mL/min/1.73 m2), the recommended dose is 1 mg once daily. No dose adjustment is needed for mild to moderate renal impairment.
- Patients with Hepatic Dysfunction: For severe hepatic impairment (Child-Pugh Class C), the initial dose is 1 mg once daily. It may be increased to 2 mg if required and tolerated. No dose adjustment is necessary for mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Dosage adjustment may be required in patients with specific comorbid conditions. It is crucial to consider potential drug interactions and individual patient factors.
Clinical Use Cases
Prucalopride is not indicated for the clinical use cases mentioned (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations). Its sole indication is for chronic idiopathic constipation in adults who have not found relief with other laxatives.
Dosage Adjustments
Dose modifications might be necessary based on factors like renal or hepatic impairment, age, and individual response to therapy. Regular monitoring of patient response and potential side effects is recommended.
Side Effects
Common Side Effects:
Headache, nausea, abdominal pain, and diarrhea. These typically occur at the start of treatment and subside within a few days.
Rare but Serious Side Effects:
Palpitations, tachycardia, and allergic reactions.
Long-Term Effects:
Limited data are available on the long-term effects of prucalopride.
Adverse Drug Reactions (ADR):
Severe allergic reactions, though rare, warrant immediate medical attention.
Contraindications
Absolute contraindications include hypersensitivity to prucalopride, renal impairment requiring dialysis, intestinal perforation or obstruction, obstructive ileus, and severe inflammatory conditions of the intestinal tract (e.g., Crohn’s disease, ulcerative colitis, toxic megacolon).
Drug Interactions
Concomitant use of CYP3A4 inhibitors may increase plasma levels of prucalopride, and dose adjustment might be necessary. Ketoconazole, a potent CYP3A4 inhibitor, significantly increased prucalopride exposure, warranting a dose reduction to 1 mg in case of co-administration. Prucalopride may enhance the effects of other prokinetic drugs, such as metoclopramide, and caution should be exercised when combining such medications.
Pregnancy and Breastfeeding
Prucalopride is not recommended during pregnancy. While data on human breast milk are limited, breastfeeding is not recommended during treatment.
Drug Profile Summary
- Mechanism of Action: 5-HT4 receptor agonist stimulating colonic motility.
- Side Effects: Headache, nausea, abdominal pain, diarrhea.
- Contraindications: Hypersensitivity, renal impairment requiring dialysis, bowel obstruction, intestinal perforation.
- Drug Interactions: CYP3A4 inhibitors (e.g., ketoconazole), other prokinetic agents (e.g., metoclopramide).
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 2 mg once daily (1 mg for elderly or severe hepatic/renal impairment).
- Monitoring Parameters: Bowel movement frequency, side effects.
Popular Combinations
Prucalopride is typically used as monotherapy. Combination with other laxatives might be considered for short-term relief if prucalopride alone is insufficient, but it is not a standard practice.
Precautions
Standard precautions apply, including pre-screening for allergies and relevant medical conditions. Close monitoring of patients with renal or hepatic impairment is recommended. Lifestyle considerations include advising patients to maintain adequate hydration.
FAQs
Q1: What is the recommended dosage for Prucalopride?
A: Adults: 2 mg once daily. Elderly (over 65) or patients with severe renal or hepatic impairment: 1 mg once daily. Children: Not recommended.
Q2: How does Prucalopride work?
A: It’s a 5-HT4 receptor agonist, stimulating colonic motility.
Q3: What are the common side effects?
A: Headache, nausea, abdominal pain, diarrhea.
Q4: Is Prucalopride safe during pregnancy?
A: No, it is not recommended during pregnancy.
Q5: Can Prucalopride be taken with other laxatives?
A: Combining with other laxatives is generally not recommended for long-term use, but may be considered short-term by a physician if prucalopride alone is ineffective.
Q6: What if a patient misses a dose?
A: Take the missed dose as soon as remembered. If it’s close to the next dose, skip the missed dose and resume the regular schedule.
Q7: How long does it take for Prucalopride to work?
A: Some patients experience effects within a few hours, but it may take several days or even weeks for regular bowel movements to establish.
Q8: What should patients with renal impairment do?
A: Those with severe renal impairment should take a reduced dose (1 mg daily).
Q9: What are the key contraindications?
A: Renal impairment requiring dialysis, intestinal obstruction or perforation, hypersensitivity.
Q10: Are there any specific dietary restrictions with Prucalopride?
A: No specific dietary restrictions are associated with Prucalopride. Maintaining adequate hydration is generally recommended for overall health and bowel function.
