Overview
11 DESCRIPTION IBSRELA (tenapanor) tablets contain tenapanor hydrochloride as an active ingredient. Tenapanor hydrochloride is a sodium/hydrogen exchanger 3 (NHE3) inhibitor for oral use. The chemical name for tenapanor hydrochloride is 12,15-Dioxa-2,7,9-triazaheptadecanamide, 17-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]-N-[2-[2-[2-[[[3-[(4S)-6,8-d...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tenapanor is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.
Indications
- 1 INDICATIONS AND USAGE IBSRELA is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults. IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults. ( 1 )
Common Doses
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of IBSRELA in adults is 50 mg orally twice daily. The recommended dosage in adults is 50 mg, orally twice daily. ( 2 ) Take immediately prior to breakfast or the first meal of the day and immediately prior to dinner. ( 2 ) Administration Instructions Take IBSRELA immediately prior to breakfast or the first meal of the day and immediately prior to dinner [see Clinical Pharmacology (12.2) ] . 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.
Black Box Warning
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS IBSRELA is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile rats administration of tenapanor caused deaths presumed to be due to dehydration [see Contraindications (4) , Use in Specific Populations (8.4) ]. Avoid use of IBSRELA in patients 6 years to less than 12 years of age [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. The safety and effectiveness of IBSRELA have not been established in patients less than 18 years of age [see Use in Specific Populations (8.
Contraindications
- 4 CONTRAINDICATIONS IBSRELA is contraindicated in: Patients less than 6 years of age due to the risk of serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. Patients with known or suspected mechanical gastrointestinal obstruction . Pediatric patients less than 6 years of age. ( 4 , 5.1 , 8.4 ) Patients with known or suspected mechanical gastrointestinal obstruction. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (≥2%) are diarrhea, abdominal distension, flatulence and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ardelyx at 1-844-427-7352 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS OATP2B1 Substrates: Potential for reduced exposure of the concomitant drug (e.g., enalapril). Monitor for signs related to loss of efficacy and adjust the dosage of the concomitantly administered drug as needed. ( 7.1 ) 7.1 OATP2B1 Substrates Tenapanor is an inhibitor of intestinal uptake transporter, OATP2B1 [see Clinical Pharmacology (12.3) ] . Drugs which are substrates of OATP2B1 may have reduced exposures when concomitantly taken with IBSRELA. Monitor for signs related to loss of efficacy and adjust the dosage of concomitantly administered drug as needed.