Tenapanor

Uses

Tenapanor is an NHE3 inhibitor indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C).

Tenapanor is indicated for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in adults. It is also currently being investigated as a treatment for hyperphosphatemia in chronic kidney disease patients undergoing dialysis (NCT02081534 and NCT02675998).

Tenapanor is also used to associated treatment for these conditions: Constipation-predominant Irritable Bowel Syndrome (IBS-C)

How Tenapanor works

Tenapanor is a locally-acting small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), an antiporter expressed on the apical surface of enterocytes in the small intestine and colon which is involved in sodium-fluid homeostasis. By inhibiting this antiporter tenapanor causes retention of sodium within the lumen of the intestine - this results in an osmotic gradient that draws water into the lumen and softens stool consistency.

There is some evidence that tenapanor can inhibit the uptake of dietary phosphorus in the gastrointestinal tract, though the exact mechanism of this activity has yet to be elucidated.

Toxicity

Symptoms of overdose are likely to be consistent with tenapanor's adverse effect profile, and may therefore include gastrointestinal effects such as diarrhea. Dehydration may occur depending on duration and severity of diarrhea. No specific management strategies have been proposed in cases of overdose.

Food Interaction

• Take before a meal. Tenapanor should be administered immediately prior to the first meal of the day and immediately prior to dinner.

[Moderate] ADJUST DOSING INTERVAL: Administration of tenapanor immediately before a meal may enhance its effectiveness.

In clinical trials, administration of tenapanor 5 to 10 minutes before a meal increased the 24-hour stool sodium excretion compared to taking tenapanor in the fed or fasting state.

The resulting higher levels of sodium in the intestine and colon cause an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.

MANAGEMENT: The manufacturer recommends administering tenapanor immediately prior to breakfast or the first meal of the day and immediately prior to dinner.

Elimination Route

Tenapanor undergoes very minimal systemic absorption following oral administration. During clinical trials, plasma concentrations were below the limit of quantitation (i.e. less than 0.5 ng/mL) in the majority of samples from healthy subjects - for this reason, typical pharmacokinetic values related to absorption such as AUC and C_max were unable to be ascertained.

The effects of tenapanor are greatest when administered 5 to 10 minutes before meals.

Half Life

Tenapanor's FDA label states that its half-life could not be determined during clinical trials due to its minimal systemic absorption resulting in plasma concentrations below the limit of quantitation (i.e. less than 0.5 ng/mL).

Elimination Route

Following administration of a radio labeled dose of tenapanor, 70% of the radioactivity was excreted in the feces within 120 hours of administration and 79% within 240 hours. Approximately 65% of the total dose is excreted as unchanged parent drug within 144 hours of administration. Only 9% of the administered dose was found in the urine, existing primarily as metabolites. Tenapanor's M1 metabolite is excreted unchanged in the urine and accounts for approximately 1.5% of the total dose within 144 hours of administration.

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