Novel Mechanisms for Phosphorus Lowering – Tenapanor

This is a continuation of my previous post which summarizes a presentation I attended at the National Kidney Foundation Spring Clinical Meeting.

Session Information: Phosphorus Management: Walking the Tightrope

Speakers: Christine Corbett, Joanna Hudson, Kathleen Hill Gallant, Kristal Higgins

How is phosphorus absorbed in the gut?

In the gut, phosphorus is absorbed through the Na-H Exchanger 3 via the paracellular pathway. The Na-H Exchanger 3 exchanges sodium and protein and impacts the permeability of phosphorus. 

Tenapanor blocks phosphorus absorption by acting on the Na-H Exchanger.  This process will lead to more sodium in the intestinal space which can result in diarrhea.

What trials have been conducted on tenapanor that led to approval?

1. Phreedom Trial – done in PD and HD.  At the end of the treatment period there was a greater decrease in phosphorus than those on placebo. The most common side effect was diarrhea.
2. Amplify Trial – in patients on dialysis with hyperphosphatemia, Tenapanor was added to other phosphorus binders. In 4 weeks, there was a bigger reduction in phosphorus and more people achieved phosphorus targets compared to those on placebo.
3. Normalize Trial – Tenapanor alone or in combination with other PO4 binders helped more patients achieve serum phosphorus targets.  Tenapanor group also helped reduce total number of pills.
4. Optimize Trial – Patients who were not taking any other PO4 binders were studied in this trial. 63% of people achieved phosphorus target.  The patient experience survey had patients reporting easier management of serum phosphorus levels.

How is Tenapanor dosed?

30mg twice daily before the morning and evening meals.  Do not take before dialysis because we don’t want them to have any BMs during dialysis. Also plan to stop other laxatives, if they are taking any.