tenapanor

Action and Spectrum

Actions and spectrum: 

tenapanor is a medication used for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. It works as a sodium-hydrogen exchanger 3 (NHE3) inhibitor, which inhibits the absorption of sodium in the intestines, resulting in an increase of water in the stool and promoting bowel movements. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Diarrhea (15-16%)  

1-10% 

Abdominal distension (2-3%) 

Severe diarrhea (2.5%) 

Rectal bleeding (<2%) 

Flatulence (3%) 

Dizziness (2%) 

Abnormal GI sounds (<2%) 

Black Box Warning

Contraindication / Caution

Contraindication/Caution 

Contraindication 

tenapanor is contraindicated in individuals with a known history of hypersensitivity to the drug. Additionally, it should not be used in patients with severe renal impairment (GFR < 30 mL/min/1.73 m²) or end-stage renal disease.  

Caution 

• Gastrointestinal side effects: tenapanor can cause diarrhea, nausea, and abdominal pain, especially during the first weeks of treatment. Patients should be advised to stay hydrated and to contact their healthcare provider if these symptoms persist. 
• Hypovolemia: tenapanor can decrease fluid volume in the body, leading to hypovolemia, which can result in low blood pressure and dehydration. Patients should be monitored for signs of hypovolemia, especially those who are elderly or have kidney problems. 
• Electrolyte imbalances: tenapanor can alter the levels of electrolytes in the body, particularly sodium and potassium. Patients should have their electrolyte levels monitored periodically, especially if they have underlying kidney disease. 
• Use in pregnancy and lactation: The safety of tenapanor during pregnancy and lactation has not been established, and its use in these populations is not recommended. 
• Drug interactions: tenapanor may interact with other medications that affect the gastrointestinal tract, including laxatives, antidiarrheal agents, and drugs that alter gastric pH. Patients should inform their healthcare provider of all medications they are taking before starting tenapanor. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category C 

Lactation: safety and efficacy are not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology 

tenapanor is a small molecule that acts as an inhibitor of the sodium-proton exchanger NHE3 in the gastrointestinal tract. It works by reducing the absorption of sodium and phosphate from the small intestine, thereby decreasing the amount of phosphate that is available for absorption in the proximal tubules of the kidney. This results in a reduction of serum phosphorus levels. Additionally, tenapanor may reduce the absorption of other nutrients and minerals, such as magnesium, calcium and iron.  

Pharmacodynamics 

tenapanor is a small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), a protein that is expressed on the surface of epithelial cells in the gastrointestinal tract. By inhibiting NHE3, tenapanor reduces the absorption of sodium in the gut, leading to an increase in the delivery of sodium to the colon. This increase in sodium delivery to the colon results in an increase in water content in the lumen of the colon, leading to a softening of the stool and an increase in bowel movements. tenapanor also reduces the absorption of phosphate in the gut, leading to a decrease in serum phosphate levels.  

Pharmacokinetics 

tenapanor is a minimally absorbed drug, and only small amounts are absorbed following oral administration. After oral administration, the drug reaches peak plasma concentration within 2 hours. The plasma protein binding of tenapanor and its metabolite, M1, is approximately 99% and 96%, respectively.

tenapanor is metabolized by carboxylesterase 1 and 2 and does not undergo cytochrome P450 metabolism. The primary route of elimination is through feces, with approximately 85% of the administered dose excreted in feces as unchanged tenapanor. The half-life of tenapanor is approximately 13 hours. 

Adminstartion

Administration 

tenapanor is available as an oral tablet and should be taken by mouth with or without food. The recommended starting dose is 12.5 mg twice daily, and it should be titrated up or down based on the patient’s response and tolerability. The tablets should be administered whole and not crushed or chewed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tenapanor 

Pronounced: (ten-A-pa-nor)  

Why do we use tenapanor? 

tenapanor is a prescription medication that is used to treat bowel problems such as chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). It works by inhibiting the NHE3 transporter in the gastrointestinal tract, which reduces the absorption of sodium and increases the secretion of chloride and bicarbonate, thereby increasing the water content and softening the stool. This can help to relieve constipation and improve bowel movements in people with these conditions.