Plecanatide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Trulance: 3 mg

Pharmacology

Mechanism of Action

Plecanatide and its active metabolite bind and agonize guanylate cyclase-C on the luminal surface of intestinal epithelium. Intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentrations are subsequently increased resulting in chloride and bicarbonate secretion into the intestinal lumen. Intestinal fluid increases and GI transit time is accelerated.

Pharmacokinetics/Pharmacodynamics

Absorption

Minimal systemic availability; plasma concentrations are not measurable when used at recommended doses

Distribution

Minimal tissue distribution is expected given immeasurable plasma concentrations when used at recommended doses.

Metabolism

Metabolized within GI tract to active metabolite; parent drug and metabolite undergo proteolytic degradation within the intestinal lumen to smaller peptides and amino acids.

Use: Labeled Indications

Chronic idiopathic constipation: Treatment of chronic idiopathic constipation (CIC) in adults

Irritable bowel syndrome with constipation: Treatment of irritable bowel syndrome with constipation (IBS-C) in adults

Contraindications

Pediatric patients <6 years; mechanical gastrointestinal obstruction (known or suspected).

Dosage and Administration

Dosing: Adult

Chronic idiopathic constipation (CIC): Oral: 3 mg once daily

Irritable bowel syndrome with constipation (IBS-C): Oral: 3 mg once daily

Dosing: Geriatric

Refer to adult dosing; use with caution.

Administration

Administer with or without food. Swallow tablet whole.

For patients with swallowing difficulties, tablets can be crushed and administered orally either in applesauce or with water or administered with water via a nasogastric or gastric feeding tube. Mixing crushed tablets in other soft foods or in other liquids has not been tested.

Administration in applesauce: Crush tablet to a powder and mix with 1 teaspoonful (5 mL) of room temperature applesauce. Swallow entire mixture immediately. Do not store mixture for later use.

Administration in water: Combine tablet and ~30 mL of room temperature water into a cup and mix by gently swirling for at least 10 seconds; the tablet will fall apart in the water. Swallow the entire contents of the mixture immediately. If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 10 seconds, and swallow immediately. Do not store mixture for later use.

Administration via a nasogastric or gastric feeding tube: Combine tablet and 30 mL of room temperature water into a cup and mix by gently swirling for at least 15 seconds; the tablet will fall apart in the water. Flush the nasogastric or gastric feeding tube with 30 mL of water using an appropriate syringe. Draw up the mixture using the syringe and immediately administer via the nasogastric or gastric feeding tube. If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 15 seconds, and using the same syringe, administer via the nasogastric or gastric feeding tube. Using the same or a fresh syringe, flush the nasogastric or gastric feeding tube with at least 10 mL of water after administration. Do not store mixture for later use.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not subdivide or repackage; protect from moisture.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

1% to 10%:

Central nervous system: Dizziness (1% to <2%)

Gastrointestinal: Diarrhea (4% to 5%), abdominal distension (<2%), abdominal tenderness (<2%), flatulence (<2%), nausea (1% to <2%), severe diarrhea (≤1%)

Genitourinary: Urinary tract infection (1% to <2%)

Hepatic: Increased serum ALT (<2%), increased serum AST (<2%)

Respiratory: Sinusitis (<2%), upper respiratory tract infection (<2%), nasopharyngitis (1% to <2%)

Warnings/Precautions

Concerns related to adverse effects:

• Diarrhea: May cause diarrhea; may occur within the first month of treatment (severe diarrhea may occur within the first 3 days of treatment). Consider discontinuation of therapy and rehydration if severe diarrhea occurs.

Special populations:

• Pediatric patients: [US Boxed Warning]: Use is contraindicated in pediatric patients <6 years. Avoid use in pediatric patients 6 to 17 years of age. In studies in young juvenile mice, administration of a single oral dose of plecanatide caused deaths due to dehydration. The safety and effectiveness of plecanatide has not been established in patients <18 years.

Monitoring Parameters

Frequency of straining during bowel movements; spontaneous bowel movement quality and frequency

Pregnancy

Pregnancy Considerations

Plecanatide and its metabolite are not measurable in plasma when used at recommended doses. Maternal use is not expected to result in fetal exposure.

Patient Education

What is this drug used for?

• It is used to treat constipation.
• It is used to treat irritable bowel syndrome.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe or persistent diarrhea
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.