plecanatide (Rx)

1-10%

Diarrhea 5%

Frequency Not Defined

Sinusitis

Upper respiratory tract infection

Abdominal distension

Flatulence

Abdominal tenderness

Increased ALT and AST

Postmarketing Reports

Hypersensitivity Reactions: skin itching, hives, rash

Vomiting

Contraindications

Children <6 yr (also see Black Box Warnings and Cautions)

Known or suspected mechanical gastrointestinal obstruction

Cautions

Diarrhea may occur; however, severe diarrhea is infrequent; if severe diarrhea occurs, suspend dosing and rehydrate the patient

Risk of serious dehydration in pediatric patients

• Contraindicated in children aged <6 yr
• In young juvenile mice (human age equivalent of ~1 month to <2 yr), the drug increased fluid secretion into the intestines as a consequence of stimulation of guanylate cyclase-C (GC-C), resulting in mortality in some mice within the first 24 hr, apparently owing to dehydration
• Because of increased intestinal expression of GC-C, patients aged <6 yr may be more likely than older children to develop severe diarrhea and its potentially serious consequences
• Safety and efficacy have not been established in children aged <18 yr
• Also see Contraindications and Black Box Warnings

Pregnancy

Data are insufficient to assess drug-associated risks for major birth defects and miscarriage in humans

Plecanatide and its active metabolite are negligibly absorbed systemically, and maternal use is not expected to result in fetal exposure to the drug

Lactation

Unknown if distributed in human breast milk

Plecanatide and its active metabolite are negligibly absorbed systemically, and maternal use is not expected to result in fetal exposure to the drug

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Guanylate cyclase C (GC-C) agonist

Plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of intestinal epithelial cells; GC-C activation leads to increased cyclic guanosine monophosphate (cGMP), which, in turn, stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit

Absorption

Negligible systemic absorption

Distribution

Expected to have minimal tissue distribution

Metabolism

Metabolized into small peptides proteolytically in GI tract

Elimination

No human studies have been conducted

Oral Preparation

For patients with swallowing difficulties, tablets can be crushed and administered PO either in applesauce or with water, or administered via a feeding tube

Administration in applesauce

• In a clean container, crush the tablet to a powder and mix with 1 teaspoonful of room temperature applesauce
• Consume the entire mixture immediately; do not store the mixture for later use

Administration in water

• Place the tablet in a clean cup
• Pour ~30 mL of room temperature water into the cup
• Mix by gently swirling the tablet and water mixture for at least 10 seconds
• 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 the mixture for later use

Administration via a nasogastric or gastric feeding tube

• Place the tablet in a clean cup with 30 mL of room temperature water
• Mix by gently swirling the tablet and water mixture for at least 15 seconds
• 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; do not reserve for future use
• 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

Oral Administration

May take with or without food

Swallow tablet whole for each dose

For patients with swallowing difficulties, tablets can be crushed and administered PO either in applesauce or with water, or administered via a feeding tube (see Oral Preparation)

Missed dose

• If a dose is missed, skip the missed dose and take the next dose at the regular time
• Do not take 2 doses at the same time

Storage

Store at room temperature, 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Store in a dry place

Protect from moisture