Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
India, US, UK, Canada, China and Japan
Tenapanor is a Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitor belonging to Gastrointestinal agent.
Tenapanor is an NHE3 inhibitor indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C).
Tenapanor undergoes very minimal systemic absorption following oral administration. During clinical trials, plasma concentrations were below the limit of quantitation (i.e. less than 0.5 ng/mL) in the majority of samples from healthy subjects. Plasma protein binding of tenapanor and its major metabolite, M1, is approximately 99% and 97%. Tenapanor is metabolized primarily by CYP3A4/5 and low levels of its major metabolite, M1, are detected in plasma. The Cmax of M1 is approximately 13 ng/mL after single dose of tenapanor 50 mg and 15 ng/mL at steady state following repeated dosing of tenapanor 50 mg twice daily in healthy subjects.
Tenapanor shows side effects like Dizziness, gas, stomach bloating or tenderness, mild diarrhea.
Tenapanor is available in the form of Oral Tablet.
Tenapanor is available in India, US, UK, Canada, China and Japan.
Tenapanor belongs to the Gastrointestinal agent acts as a Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitor.
Tenapanor is a locally acting small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), an antiporter expressed on the apical surface of enterocytes in the small intestine and colon which is involved in sodium-fluid homeostasis. By inhibiting this antiporter Tenapanor causes retention of sodium within the lumen of the intestine; this results in an osmotic gradient that draws water into the lumen and softens stool consistency.
The Data of Onset and duration of action of Tenapanor is not clinically established.
Tenapanor is available in the form of Oral Tablet.
Tenapanor tablet is taken orally, usually twice daily.
Tenapanor is an NHE3 inhibitor indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C).
Tenapanor is a Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitor belonging to Gastrointestinal agent.
Tenapanor is a sodium/hydrogen exchanger 3 inhibitor, which acts locally to reduce sodium absorption from the small intestine and colon. Reduced sodium absorption results in increased intestinal lumen water secretion, accelerating intestinal transit time, and softening stool consistency. Tenapanor also decreases intestinal permeability and visceral hypersensitivity in animal models, which may reduce abdominal pain.
Tenapanor is approved for use in the following clinical indications
- Irritable bowel syndrome with constipation
Tenapanor is an NHE3 inhibitor indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C).
• Irritable bowel syndrome with constipation
Oral: 50 mg twice daily.
Tenapanor is available in 50 mg strength.
Tenapanor is available in the form of Oral Tablet.
Tenapanor 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
tenapanor is contraindicated in patients below 6 years of age. The safety and effectiveness of tenapanor in patients less than 18 years of age have not been established. In young juvenile rats (less than 1 week old; approximate human age equivalent of less than 2 years of age), decreased body weight and deaths occurred, presumed to be due to dehydration, following oral administration of tenapanor. There are no data available in older juvenile rats (human age equivalent 2 years to less than 12 years). Avoid the use of tenapanor in patients 6 years to less than 12 years of age. Although there are no data in older juvenile rats, given the deaths in younger rats and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of tenapanor in patients 6 years to less than 12 years of age.
- Diarrhea
Diarrhea was the most common adverse reaction in two randomized, double-blind, placebo-controlled trials of IBS-C. Severe diarrhea was reported in 2.5% of tenapanor-treated patients. If severe diarrhea occurs, suspend dosing and rehydrate patient.
Breast Feeding Warning
There are no data available on the presence of tenapanor in either human or animal milk, its effects on milk production or its effects on the breastfed infant. Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration. The minimal systemic absorption of tenapanor will not result in a clinically relevant exposure to breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tenapanor and any potential adverse effects on the breastfed infant from tenapanor or from the underlying maternal condition.
Pregnancy Warning
Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration. Therefore, maternal use is not expected to result in fetal exposure to the drug. The available data on tenapanor exposure from a small number of pregnant women have not identified any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In reproduction studies with tenapanor in pregnant rats and rabbits, no adverse fetal effects were observed in rats at 0.1 times the maximum recommended human dose and in rabbits at doses up to 8.8 times the maximum recommended human dose (based on body surface area). 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
• Diarrhea, Abdominal distension, abnormal bowel sounds, flatulence, Rectal hemorrhage, Dizziness.
The common side effects of Tenapanor include the following
Common side effects
• Dizziness, gas, stomach bloating or tenderness, mild diarrhea.
Rare side effects
• Severe diarrhea.
- Pregnancy
Pregnancy Category
Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration. Therefore, maternal use is not expected to result in fetal exposure to the drug. The available data on tenapanor exposure from a small number of pregnant women have not identified any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In reproduction studies with tenapanor in pregnant rats and rabbits, no adverse fetal effects were observed in rats at 0.1 times the maximum recommended human dose and in rabbits at doses up to 8.8 times the maximum recommended human dose (based on body surface area). 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 are no data available on the presence of tenapanor in either human or animal milk, its effects on milk production or its effects on the breastfed infant. Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration. The minimal systemic absorption of tenapanor will not result in a clinically relevant exposure to breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tenapanor and any potential adverse effects on the breastfed infant from tenapanor or from the underlying maternal condition.
- Pediatric Use
tenapanor is contraindicated in patients less than 6 years of age. Avoid tenapanor in patients 6 years to less than 12 years of age. The safety and effectiveness of tenapanor in patients less than 18 years of age have not been established.
- Geriatric Use
Of the 1203 patients in placebo-controlled clinical trials of tenapanor, 100 (8%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdose of tenapanor may result in gastrointestinal adverse effects such as diarrhea because of exaggerated pharmacology with a risk for dehydration if diarrhea is severe or prolonged.
- Pharmacodynamic
Through the inhibition of dietary sodium absorption tenapanor causes an increase in water secretion into the intestines, thereby decreasing transit time and softening stool consistency.
- Pharmacokinetics
Absorption
Tenapanor undergoes very minimal systemic absorption following oral administration. During clinical trials, plasma concentrations were below the limit of quantitation (i.e. less than 0.5 ng/mL) in the majority of samples from healthy subjects
Distribution
Plasma protein binding of tenapanor and its major metabolite, M1, is approximately 99% and 97%.
Metabolism and Excretion
Tenapanor is metabolized primarily by CYP3A4/5 and low levels of its major metabolite, M1, are detected in plasma. The Cmax of M1 is approximately 13 ng/mL after single dose of tenapanor 50 mg and 15 ng/mL at steady state following repeated dosing of tenapanor 50 mg twice daily in healthy subjects.
1. Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 12-week, placebo-controlled phase 3 trial (T3MPO-1). The American Journal of Gastroenterology. 2020 Feb;115(2):281.
2. Spencer AG, Labonte ED, Rosenbaum DP, Plato CF, Carreras CW, Leadbetter MR, Kozuka K, Kohler J, Koo-McCoy S, He L, Bell N. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Science translational medicine. 2014 Mar 12;6(227):227ra36-.
3. King AJ, Siegel M, He Y, Nie B, Wang J, Koo-McCoy S, Minassian NA, Jafri Q, Pan D, Kohler J, Kumaraswamy P. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Science translational medicine. 2018 Aug 29;10(456):eaam6474
- https://www.uptodate.com/contents/tenapanor-drug-information?search=Tenapanor&source=panel_search_result&selectedTitle=1~5&usage_type=panel&kp_tab=drug_general&display_rank=1
- https://www.rxlist.com/ibsrela-drug.htm#side_effects
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211801s000lbl.pdf
- https://go.drugbank.com/drugs/DB11761
- https://www.drugs.com/mtm/tenapanor.html
- https://medlineplus.gov/druginfo/meds/a622060.html
