Usage
Plecanatide is prescribed for the treatment of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C) in adults. It is classified as a guanylate cyclase-C agonist. This drug acts locally in the gastrointestinal tract to increase intestinal fluid secretion and accelerate transit, thereby facilitating bowel movements.
Alternate Names
The generic name is plecanatide. It is marketed under the brand name Trulance.
How It Works
Pharmacodynamics: Plecanatide is a guanylate cyclase-C agonist. It binds to guanylate cyclase-C receptors on the luminal surface of intestinal epithelial cells. This binding increases intracellular cyclic guanosine monophosphate (cGMP) levels, leading to chloride and bicarbonate secretion into the intestinal lumen. The increased fluid secretion softens the stool and accelerates intestinal transit time, promoting bowel movements.
Pharmacokinetics: Plecanatide and its active metabolite are minimally absorbed systemically following oral administration, with negligible plasma concentrations. The drug primarily acts locally in the gut. Elimination pathways are not fully characterized due to the minimal systemic absorption.
Dosage
Standard Dosage
Adults:
The standard dose for both CIC and IBS-C is 3 mg orally once daily. The maximum recommended dosage is 3 mg per day.
Children:
Plecanatide is contraindicated in children younger than 6 years of age due to the risk of serious dehydration. Use is not recommended in patients aged 6 to 17 years.
Special Cases:
- Elderly Patients: Clinical trials did not include a sufficient number of elderly patients. Use with caution, as the elderly may be more susceptible to adverse effects like dehydration. No specific dose adjustments are recommended.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Use with caution in patients with conditions that predispose to dehydration.
Clinical Use Cases
Plecanatide is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is limited to chronic constipation management.
Dosage Adjustments
No dosage adjustments are needed for renal or hepatic impairment.
Side Effects
Common Side Effects:
Diarrhea is the most common side effect. Other common side effects include:
- Upper respiratory tract infection
- Sinusitis
- Abdominal distension
- Flatulence
- Abdominal tenderness
Rare but Serious Side Effects:
- Severe diarrhea with dehydration (can be life-threatening, particularly in children under 6)
Long-Term Effects:
Long-term effects have not been fully characterized due to the limited duration of clinical trials.
Adverse Drug Reactions (ADR):
Severe diarrhea requiring medical attention.
Contraindications
- Children under 6 years of age.
- Known or suspected mechanical gastrointestinal obstruction.
- Hypersensitivity to plecanatide or any of its components.
Drug Interactions
No clinically significant drug interactions have been reported with plecanatide. In vitro studies suggest that plecanatide and its metabolite do not interact with cytochrome P450 enzymes or P-glycoprotein transporters.
Pregnancy and Breastfeeding
-
Pregnancy: Data are insufficient to assess the risk of birth defects or miscarriage. Plecanatide is minimally absorbed systemically, so fetal exposure is expected to be negligible. Animal studies did not show adverse developmental effects.
-
Breastfeeding: It is unknown if plecanatide is present in human milk. Due to minimal systemic absorption, infant exposure is anticipated to be low. The benefits of breastfeeding should be weighed against the potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Guanylate cyclase-C agonist, increasing intestinal fluid and motility.
- Side Effects: Diarrhea (most common), upper respiratory infection, sinusitis, abdominal distension, flatulence.
- Contraindications: Age <6 years, bowel obstruction, hypersensitivity.
- Drug Interactions: None reported.
- Pregnancy & Breastfeeding: Insufficient data in humans; minimal absorption suggests low risk.
- Dosage: 3 mg orally once daily.
- Monitoring Parameters: Monitor bowel movements and signs of dehydration (especially if diarrhea occurs).
Popular Combinations
Plecanatide is typically used as monotherapy. There are no established popular drug combinations.
Precautions
- General Precautions: Assess for history of bowel obstruction. Monitor for severe diarrhea.
- Specific Populations: See above.
- Lifestyle Considerations: No specific lifestyle considerations.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Plecanatide?
A: The standard adult dose is 3 mg orally once a day for both CIC and IBS-C.
Q2: How does Plecanatide work?
A: It acts locally on guanylate cyclase-C receptors in the gut, increasing fluid secretion and promoting bowel movements.
Q3: Is Plecanatide safe for children?
A: Plecanatide is contraindicated in children younger than 6 years old and not recommended for use in those aged 6 to 17.
Q4: Are there any drug interactions with Plecanatide?
A: No clinically significant drug interactions have been reported.
Q5: Can Plecanatide be used during pregnancy?
A: Data are limited. Consult with a healthcare provider to assess the risks and benefits.
Q6: What is the most common side effect of Plecanatide?
A: Diarrhea.
Q7: What should I do if a patient experiences severe diarrhea while taking Plecanatide?
A: Discontinue the medication and initiate rehydration therapy.
Q8: Can Plecanatide be used in patients with renal impairment?
A: Yes, no dose adjustment is needed.
Q9: Can Plecanatide be used in patients with hepatic impairment?
A: Yes, no dose adjustment is needed.
