TENAPANOR Drug Interactions: What You Need to Know

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 ).

Sodium Polystyrene

Sulfonate (SPS): Separate administration by at least three hours ( 7.2 ).

7.1 OATP2B1 Substrates Tenapanor is an inhibitor of intestinal uptake transporter, OATP2B1 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Drugs which are substrates of OATP2B1 may have reduced exposures when concomitantly taken with XPHOZAH. Monitor for signs related to loss of efficacy and adjust the dose of concomitantly administered drug as needed. Enalapril is a substrate of OATP2B1. When enalapril was coadministered with XPHOZAH (30 mg twice daily for five days), the peak exposure (C max ) of enalapril and its active metabolite, enalaprilat, decreased by approximately 70% and total systemic exposures (AUC) decreased by 50 to 65% compared to when enalapril was administered alone <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . However, the decrease in enalaprilat&apos;s exposure with XPHOZAH may be offset by the inherently higher exposures observed in patients with CKD on dialysis due to its reduced renal clearance. Therefore, a lower starting dose of enalapril, which is otherwise recommended in patients with CKD on dialysis is not required when enalapril is coadministered with XPHOZAH.

7.2 Sodium Polystyrene Sulfonate Separate administration of XPHOZAH and sodium polystyrene sulfonate (SPS) by at least 3 hours. SPS binds to many commonly prescribed oral medicines.

XPHOZAH is contraindicated in patients under 6 years of age because of the risk of diarrhea and serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.5) ]. XPHOZAH is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Pediatric patients under 6 years of age ( 4 ). Patients with known or suspected mechanical gastrointestinal obstruction ( 4 ).

AND PRECAUTIONS Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate patient. ( 5.2 )

5.1 Risk of Serious Dehydration in Pediatric Patients IBSRELA is contraindicated in patients below 6 years of age. The safety and effectiveness of IBSRELA 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 IBSRELA 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 IBSRELA in patients 6 years to less than 12 years of age <span class="opacity-50 text-xs">[see Contraindications (4) , Warnings and Precautions (5.2) , Use in Specific Populations (8.4) ]</span> .

5.2 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 IBSRELA-treated patients <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . If severe diarrhea occurs, suspend dosing and rehydrate patient.