Plecanatide

Plecanatide is a Guanylate Cyclase-C (GC-C) Agonist belonging to Gastrointestinal agent/ Drug for Constipation.

Plecanatide is a laxative used to treat chronic idiopathic constipation and IBS with constipation.

Plecanatide is minimally absorbed with negligible systemic availability following oral administration. Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, the volume of distribution cannot be calculated. Plecanatide is metabolized in the GI tract to an active metabolite by loss of the terminal leucine moiety. Both plecanatide and the metabolite are proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids. Plecanatide exhibits little to no binding to human serum albumin or human α-1-acid glycoprotein.

Plecanatide shows side effects like stomach bloating or tenderness, gas, mild diarrhea, nausea, dizziness.

Plecanatide is available in the form of Oral tablets.

Plecanatide is available in India, US, Spain, Canada, China, UK, France, Italy, and Russia.

Plecanatide belongs to the Gastrointestinal agent/ Drug for Constipation acts as a Guanylate Cyclase-C (GC-C) Agonist.

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. In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency. In an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain. The mechanism has not been studied.

The Data of Onset and duration of action of Plecanatide is not clinically established.

Plecanatide is available in the form of Oral tablets.

Plecanatide tablets is taken orally, usually once daily.

Plecanatide is a laxative used to treat chronic idiopathic constipation and IBS with constipation.

Plecanatide is a Guanylate Cyclase-C (GC-C) Agonist belonging to Gastrointestinal agent/ Drug for Constipation.

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.

Plecanatide is approved for use in the following clinical indications

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation

• Chronic idiopathic constipation

Oral: 3 mg once daily.

• Irritable bowel syndrome with constipation

Oral: 3 mg once daily.

Plecanatide is available in various strengths as 3mg.

Plecanatide is available in the form of Oral tablet.

Plecanatide is contraindicated in patients with

• Patients less than 6 years of age due to the risk of serious dehydration.
• Patients with known or suspected mechanical gastrointestinal obstruction.

• Risk of Serious Dehydration in Pediatric Patients

plecanatide is contraindicated in patients less than 6 years of age. The safety and effectiveness of plecanatide in patients less than 18 years of age have not been established. In young juvenile mice (human age equivalent of approximately 1 month to less than 2 years), plecanatide 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 hours, apparently due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences. Avoid the use of plecanatide in patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in younger mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of plecanatide in patients 6 years to less than 18 years of age.

• Diarrhea

Diarrhea was the most common adverse reaction in the two placebo-controlled clinical trials. Severe diarrhea was reported in 0.6% of patients. If severe diarrhea occurs, suspend dosing, and rehydrate the patient.

There is no information regarding the presence of plecanatide in human milk, or its effects on milk production or the breastfed infant. No lactation studies in animals have been conducted. Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration. It is unknown whether the negligible systemic absorption of plecanatide by adults will result in clinically relevant exposure to breastfed infants. Exposure to plecanatide in breastfed infants has the potential for serious adverse effects. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for plecanatide and any potential adverse effects on the breastfed infant from plecanatide or from the underlying maternal condition.

Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug. The available data on plecanatide use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of plecanatide in mice and rabbits during organogenesis at doses much higher than the recommended human dosage. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

• Common

Abdominal distension, abdominal tenderness, diarrhea, flatulence, nausea, Urinary tract infection, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Dizziness, Nasopharyngitis, sinusitis, upper respiratory tract infection.

• Rare

Pruritus, skin rash, urticaria, vomiting.

The common side effects of Plecanatide include the following

• Common side effects

Stomach bloating or tenderness, gas, mild diarrhea, nausea, dizziness.

• Rare side effects

Severe diarrhea.

• Pregnancy

Pregnancy Category

Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug. The available data on plecanatide use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of plecanatide in mice and rabbits during organogenesis at doses much higher than the recommended human dosage. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

• Nursing Mothers

There is no information regarding the presence of plecanatide in human milk, or its effects on milk production or the breastfed infant. No lactation studies in animals have been conducted. Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration. It is unknown whether the negligible systemic absorption of plecanatide by adults will result in clinically relevant exposure to breastfed infants. Exposure to plecanatide in breastfed infants has the potential for serious adverse effects. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for plecanatide and any potential adverse effects on the breastfed infant from plecanatide or from the underlying maternal condition.

• Pediatric Use

Plecanatide is contraindicated in pediatric patients less than 6 years of age. Avoid use of plecanatide in patients 6 years to less than 18 years of age. The safety and effectiveness of plecanatide in patients less than 18 years of age have not been established.

• Geriatric Use

Clinical studies of plecanatide did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from patients 18 years to less than 65 years of age. Of 2601 subjects in clinical trials of plecanatide, 273 (10%) were 65 years of age and over, and 47 (2%) were 75 years and over. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pharmacodynamic

Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of 9 mg (3 times the recommended dose). In clinical studies, Plecanatide was administered with or without food.

Pharmacokinetics

• Absorption

Plecanatide is minimally absorbed with negligible systemic availability following oral administration. Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg.

• Distribution

Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, the volume of distribution can not be calculated.

• Metabolism and Excretion

Plecanatide is metabolized in the GI tract to an active metabolite by loss of the terminal leucine moiety. Both plecanatide and the metabolite are proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids. Plecanatide exhibits little to no binding to human serum albumin or human α-1-acid glycoprotein.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208745lbl.pdf
• https://www.uptodate.com/contents/plecanatide-drug-information?search=plecanatide&source=panel_search_result&selectedTitle=1~7&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://go.drugbank.com/drugs/DB13170
• https://www.rxlist.com/trulance-drug.htm#clinpharm
• https://www.drugs.com/dosage/plecanatide.html
• https://medlineplus.gov/druginfo/meds/a617020.html