Tenapanor and Enalapril: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Enalapril
Tenapanor
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced enalapril and enalapril active metabolite (enalaprilat) exposure, reduced efficacy of enalapril
Interaction Deep Dive
Coadministration of tenapanor (an inhibitor of intestinal uptake transporter, OATP2B1 with drugs which are substrates of OATP2B1 like enalapril may have reduced exposures of enalapril. Monitor for signs related to loss of efficacy and adjust the dose of concomitantly administered drug as needed. In a clinical study, when enalapril was coadministered with tenapanor (30 mg twice daily for five days), the Cmax of enalapril and its active metabolite, enalaprilat, decreased by approximately 70% and AUC decreased by 50 to 65% compared to when enalapril was administered alone. However, the decrease in enalaprilat’s exposure with tenapanor may be offset by the inherently higher exposures observed in patients with CKD on dialysis due to its reduced renal clearance. Therefore, a lower starting dose of enalapril, which is otherwise recommended in patients with CKD on dialysis is not required when enalapril is coadministered with tenapanor1.
Why it happens (mechanism)
Inhibition of OATP2B1-mediated oral absorption of enalapril
Literature reports
1 report — tap to read
a) In a clinical study, when 20 mg single dose enalapril was coadministered with tenapanor (30 mg twice daily for five days) at steady state, the mean AUC and Cmax of enalapril was decreased by 64% and 69%, respectively, in healthy subjects. The mean AUC and Cmax of enalaprilat was decreased by 52% and 68%, respectively, in healthy subjects 1.
Common questions
Can I take Tenapanor and Enalapril together?
Reduced enalapril and enalapril active metabolite (enalaprilat) exposure, reduced efficacy of enalapril Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tenapanor and Enalapril interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Tenapanor or Enalapril need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: XPHOZAH(R) oral film coated tablets, tenapanor oral film coated tablets. Ardelyx Inc (per FDA), Waltham, MA, 2023. DailyMed
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