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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XPHOZAH (XPHOZAH).
| Breastfeeding | It is unknown whether tenapanor or its metabolites are excreted in human milk. In lactating rats, drug-related material was present in milk at concentrations similar to maternal plasma, giving an estimated milk-to-plasma ratio of approximately 1. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for XPHOZAH and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition. Caution is advised. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Patients with known or suspected mechanical gastrointestinal 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."] |
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| 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. |