ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
NHE3 Inhibitor — Intestinal Phosphate Absorption Reducer Pregnancy: Avoid — no human data. Minimal systemic absorption suggests low foetal exposure risk, but insufficient data to recommend. Not for use in pregnancy.

Tenapanor

Brand names: Xphozah

Adult dose

Dose: 30 mg twice daily (immediately before morning and evening meals)
Route: Oral
Frequency: Twice daily immediately before meals
Max: 60 mg/day
Hyperphosphataemia in adults on haemodialysis — as adjunct to phosphate binders or when phosphate binders alone are insufficient. MHRA 2023 approval (USA FDA approved 2023; conditional MHRA approval under exceptional circumstances). Must be taken immediately before meals for optimal effect. Source: MHRA SPC Xphozah; NEJM 2019.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed in paediatric hyperphosphataemia.

Dose adjustments

Renal

Primarily intended for dialysis patients (ESKD/haemodialysis). Tenapanor acts entirely in the gut — less than 1% systemic absorption. No renal dose adjustment required.

Hepatic

No dose adjustment required — minimal systemic absorption means hepatic metabolism is negligible.

Paediatric weight-based calculator

Not licensed in paediatric hyperphosphataemia.

Clinical pearls

  • Novel mechanism — NHE3 inhibition: sodium-hydrogen exchanger 3 (NHE3) in intestinal epithelium drives paracellular phosphate absorption. When NHE3 is inhibited → tight junctions become less permeable → reduced passive paracellular phosphate transport across intestinal epithelium → less phosphate absorbed, more excreted in stool. Completely different mechanism to phosphate binders (which bind phosphate in gut lumen). First drug to target the paracellular phosphate transport pathway.
  • AMPLIFY trial (NEJM 2019): tenapanor 30 mg twice daily reduced serum phosphate by 0.51 mmol/L vs placebo at 26 weeks in dialysis patients. In combination with phosphate binders, additive phosphate reduction vs binders alone without significant additional toxicity.
  • Phosphate binder burden relief: dialysis patients often take 6–12 phosphate binder tablets daily with every meal — significant pill burden affecting adherence. Tenapanor offers an alternative mechanism that reduces phosphate binder dose requirements. The combination of tenapanor + lower-dose phosphate binder achieves similar phosphate control with fewer tablets.
  • Diarrhoea management: most patients experience some diarrhoea, but severe diarrhoea (grade 3) occurs in only ~5%. Starting at 10 mg twice daily and titrating to 30 mg over 4 weeks reduces early diarrhoea. The diarrhoea often improves with continued use. Stop if persistent severe diarrhoea — dehydration risk in dialysis patients who have limited fluid clearance between sessions.
  • IBS-C vs hyperphosphataemia doses: tenapanor 50 mg twice daily is FDA-approved for IBS with constipation (different US indication). The hyperphosphataemia dose (30 mg twice daily) has less diarrhoea than the IBS-C dose. Source: BNF 90 (conditional 2023); Block et al. NEJM 2019 (AMPLIFY); MHRA SPC Xphozah.

Contraindications

  • Bowel obstruction
  • Children under 18 years
  • IBS with constipation (tenapanor causes diarrhoea — separate US indication for IBS-C at lower doses)
  • Hypersensitivity to tenapanor

Side effects

  • Diarrhoea (most common and dose-limiting — ~50% of patients; usually mild to moderate; mechanism-related to NHE3 inhibition increasing intestinal fluid secretion)
  • Abdominal pain, flatulence, abdominal distension
  • Hypophosphataemia (excessive phosphate reduction if combined with phosphate binders — monitor serum phosphate)
  • Nausea

Interactions

  • Phosphate binders (calcium carbonate, sevelamer, lanthanum): additive phosphate lowering — monitor serum phosphate to avoid hypophosphataemia
  • No significant drug-drug interactions expected (minimal systemic absorption)

Monitoring

  • Serum phosphate every 4 weeks until stable, then every 3 months (target 0.8–1.8 mmol/L)
  • Stool frequency and consistency (diarrhoea grade — reduce or stop if grade 3)
  • Body weight and hydration status (diarrhoea-related dehydration risk)
  • Calcium and PTH (part of CKD-MBD monitoring panel)

Reference: BNFc; BNF 90 (conditional approval); Block et al. NEJM 2019 (AMPLIFY trial); MHRA SPC Xphozah; KDIGO CKD-MBD Guidelines 2017. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways