Introduction
Xphozah (tenapanor) is a novel first-in-class medication approved by the FDA for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis. It represents a unique therapeutic approach to hyperphosphatemia management through its localized action in the gastrointestinal tract.
Mechanism of Action
Xphozah is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) located in the gastrointestinal tract. By inhibiting NHE3, tenapanor reduces sodium absorption, which increases water content in the intestinal lumen and accelerates intestinal transit time. This mechanism decreases gastrointestinal phosphate absorption through paracellular pathways, resulting in reduced serum phosphate levels without systemic phosphate binding.
Indications
Xphozah is indicated for the reduction of serum phosphorus in adults with chronic kidney disease on dialysis, in combination with phosphate binder therapy or as monotherapy in patients intolerant of phosphate binders.
Dosage and Administration
Recommended dosage: 30 mg taken orally twice daily, approximately before the morning and evening meals. Administration:- Swallow tablets whole; do not crush or chew
- Take approximately 30 minutes before meals
- Missed dose: Take as soon as remembered unless close to next scheduled dose
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Geriatric patients: No dosage adjustment required
Pharmacokinetics
Absorption: Minimal systemic absorption with mean peak plasma concentration (Cmax) of 0.88 ng/mL Distribution: Primarily confined to gastrointestinal tract with minimal tissue distribution Metabolism: Not significantly metabolized Elimination: Primarily excreted unchanged in feces (>99%) Half-life: Approximately 1 hour (based on limited systemic exposure)Contraindications
- Known hypersensitivity to tenapanor or any component of the formulation
- Patients with known or suspected mechanical gastrointestinal obstruction
Warnings and Precautions
Gastrointestinal Effects: May cause diarrhea and other gastrointestinal symptoms. In clinical trials, 43-53% of patients experienced diarrhea, which was severe in 3-5% of cases. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Pregnancy and Lactation: No human data available. Use during pregnancy only if potential benefit justifies potential risk. Monitoring: Regular assessment of serum phosphorus levels and gastrointestinal tolerance recommended.Drug Interactions
Minimal systemic drug interactions expected due to negligible systemic absorption. However, potential interactions may occur with:- Other medications that affect gastrointestinal motility
- Medications with narrow therapeutic windows that require specific gastrointestinal pH for absorption
- Phosphate binders (concomitant administration may affect efficacy)
Adverse Effects
Most common adverse reactions (≥10%):- Diarrhea (43-53%)
- Abdominal pain (9-15%)
- Flatulence (6-12%)
- Nausea (5-10%)
- Severe diarrhea requiring medical intervention (3-5%)
- Dehydration secondary to diarrhea
Monitoring Parameters
- Serum phosphorus levels (monthly initially, then as clinically indicated)
- Signs and symptoms of diarrhea and dehydration
- Electrolyte levels, particularly in patients experiencing significant diarrhea
- Body weight and fluid status
- Adherence to medication regimen
Patient Education
- Take Xphozah 30 minutes before morning and evening meals
- Swallow tablets whole; do not crush or chew
- Maintain prescribed dietary phosphate restrictions
- Report severe or persistent diarrhea to healthcare provider
- Stay adequately hydrated, especially if experiencing diarrhea
- Inform all healthcare providers about all medications being taken
- Do not stop taking without consulting healthcare provider
- Store at room temperature (20-25°C/68-77°F)
References
1. FDA prescribing information for Xphozah (tenapanor). October 2023. 2. Block GA, et al. Efficacy and Safety of Tenapanor for Hyperphosphatemia in Patients on Dialysis. J Am Soc Nephrol. 2021;32(4):791-803. 3. Rosenbaum DP, et al. Tenapanor: A First-in-Class NHE3 Inhibitor for Hyperphosphatemia. Clin Pharmacol Drug Dev. 2021;10(11):1273-1285. 4. ClinicalTrials.gov: Phase 3 studies of tenapanor in CKD patients on dialysis (NCT03427125, NCT03435893). 5. Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD.