MECHANISM OF ACTION

MECHANISM OF ACTION

The FIRST-IN-CLASS Phosphate Absorption Inhibitor (PAI)

XPHOZAH provides a non-binder mechanism of action that blocks phosphate absorption through the paracellular pathway1

XPHOZAH is minimally absorbed and works via local inhibition of the sodium/hydrogen exchanger 3 (NHE3) in the GI tract to specifically block paracellular phosphate absorption.1

Play VideoXPHOZAH mechanism of action

A different approach that blocks, not binds, phosphate1

Blocking mechanism and duration of action enable XPHOZAH to be dosed as one 30 mg pill BID.1

About NHE3 INHIBITION

XPHOZAH has a different mechanism of action that specifically blocks paracellular phosphate absorption in the GI tract via local inhibition of NHE31

Graphic of XPHOZAH Mechanism of Action
Graphic of XPHOZAH Mechanism of Action
By inhibiting NHE3, XPHOZAH
  1. Reduces sodium absorption, resulting in a modest intracellular proton retention.2,3
  2. Modest intracellular proton retention is proposed to induce a conformational change in claudin proteins* present in tight junctions.2-4
  3. Conformational change in tight junctions* specifically blocks the absorption of phosphate through the paracellular pathway.1,2,4

*Based on in vitro models and the relevance to humans is not known.4

GI = gastrointestinal; NHE3 = sodium/hydrogen exchanger 3.

RELATED LINKS

REFERENCES

1.

XPHOZAH® (tenapanor) full Prescribing Information. Waltham, MA: Ardelyx, Inc.; 2023.

2.

Kovesdy CP, Adebiyi A, Rosenbaum D, Jacobs JW, Quarles LD. Novel treatments from inhibition of the intestinal sodium-hydrogen exchanger 3. Int J Nephrol Renovasc Dis. 2021;14:411-420.

3.

Block GA, Bleyer AJ, Silva AL, et al. Safety and efficacy of tenapanor for long-term serum phosphate control in maintenance dialysis: a 52-week randomized phase 3 trial (PHREEDOM). Kidney360. 2021;2(10):1600-1610.

4.

King AJ, Siegel M, He Y, et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med. 2018;10(456):eaam6474.

Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

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