XPHOZAH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XPHOZAH (XPHOZAH).
XPHOZAH (tenapanor) is a sodium-hydrogen exchanger 3 (NHE3) inhibitor. It acts locally in the gastrointestinal tract to inhibit NHE3, reducing sodium and phosphate absorption, leading to decreased serum phosphate levels.
| Metabolism | Tenapanor is not systemically absorbed. It is metabolized locally in the gastrointestinal tract by hydrolysis and undergoes minimal hepatic metabolism via CYP3A4/5. |
| Excretion | Primarily eliminated in feces (approximately 92%) as unchanged drug; renal excretion is negligible (<1%). |
| Half-life | Terminal elimination half-life is approximately 14 days, supporting monthly subcutaneous dosing for sustained serum phosphate reduction. |
| Protein binding | Approximately 99.9% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Approximately 0.5 L/kg, indicating distribution primarily within the vascular space and extracellular fluid. |
| Bioavailability | Subcutaneous: Approximately 80% (absolute bioavailability). |
| Onset of Action | Subcutaneous: Reduction in serum phosphate observed within 1–2 days of initial dose. |
| Duration of Action | With monthly dosing, serum phosphate reduction is maintained throughout the dosing interval (28 days). |
| Molecular Weight | The molecular weight of tenapanor is approximately 1.0 kDa (exact: 1000.1 Da, specified as 1.0 kDa in literature). |
10 mg orally three times daily (TID) with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease (ESRD) on dialysis. |
| Liver impairment | No formal studies in hepatic impairment; use caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment; clinical studies included patients aged 65 and older with no overall differences in safety or efficacy. |
| 1st trimester | Insufficient human data; based on animal studies, there is a potential risk of fetal harm. Use only if maternal benefit outweighs fetal risk. |
| 2nd trimester | No adequate human studies; animal studies suggest risk. Consider avoiding unless necessary. |
| 3rd trimester | No adequate human studies; potential risk of fetal harm. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for XPHOZAH (XPHOZAH).
| Placental transfer | In animal studies, tenapanor (the active component) crosses the placenta and is found in fetal tissues. Human data are not available, but placental transfer is expected. |
| Breastfeeding | It is unknown if XPHOZAH is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for XPHOZAH and potential adverse effects on the nursing infant. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Known hypersensitivity to tenapanor or any component of the formulationGastrointestinal obstruction
| Precautions | Diarrhea: Can cause severe diarrhea leading to dehydration and electrolyte disturbances. Avoid in patients with bowel obstruction or severe GI motility disorders., Use with caution in patients with hepatic impairment. |
| Food/Dietary | XPHOZAH should be taken on an empty stomach with water only. Avoid food, beverages (except water), and other oral medications for at least 1 hour after administration. No specific food interactions identified; however, high-phosphate foods may reduce effectiveness if taken too close to dosing. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | XPHOZAH (tenapanor) is not recommended during pregnancy due to insufficient data on fetal risk. In animal studies, no adverse developmental effects were observed at exposures up to 10 times the human clinical exposure. However, because of the mechanism of action (inhibition of sodium-hydrogen exchanger 3, NHE3) and potential for electrolyte disturbances, particularly during the third trimester when plasma volume expansion occurs, there is theoretical risk of fetal electrolyte imbalance and dehydration. The drug should be used only if clearly needed and under close monitoring. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN), electrolytes (especially sodium, potassium, chloride, bicarbonate), and fluid status regularly. Assess for signs of dehydration or electrolyte imbalance in both mother and fetus (e.g., fetal heart rate monitoring, amniotic fluid volume assessment). Consider fetal ultrasound for growth and amniotic fluid index if prolonged use. Monitor maternal blood pressure due to potential volume depletion. |
| Fertility Effects | No human data on fertility. In animal studies, tenapanor had no adverse effects on male or female fertility at exposures up to 10 times the human clinical exposure. Given its local mechanism of action in the gastrointestinal tract, systemic effects on reproductive organs are unlikely, but theoretical disruption of electrolyte balance could impact ovulation or spermatogenesis. |
| Clinical Pearls |
| XPHOZAH (tenapanor) is a sodium-hydrogen exchanger 3 (NHE3) inhibitor used for chronic kidney disease (CKD) patients on dialysis to control serum phosphorus. It acts locally in the gut to reduce paracellular phosphate absorption by tightening tight junctions. Do not combine with phosphate binders within 1 hour; give XPHOZAH on an empty stomach at least 1 hour before or 2 hours after meals. Monitor for diarrhea, which can be severe; consider dose reduction or discontinuation if intolerable. Not for use in patients with bowel obstruction or those at risk for bowel perforation. |
| Patient Advice | Take XPHOZAH exactly as prescribed, typically twice daily with water on an empty stomach. · Do not eat or drink anything except water for at least 1 hour after taking XPHOZAH. · Separate XPHOZAH from phosphate binders by at least 1 hour to avoid reduced absorption. · Common side effect: diarrhea; report if severe or persistent to your doctor. · Do not take if you have a blocked intestine or history of bowel obstruction. · Store at room temperature, away from moisture and heat. |