Tenapanor

Warning

H373 (100%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P260, P319, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

When given orally, tenapanor has minimal systemic absorption and has not been associated with elevations in serum enzymes or bilirubin or with instances of clinically apparent liver injury. Since approval and general availability of tenapanor, there have been no published reports of liver injury attributed to its use.

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

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.

The majority of tenapanor's metabolism to its primary metabolite, M1, is catalyzed via CYP3A4/5. Exposure of tenapanor to hepatic CYP enzymes is likely limited due to its minimal systemic absorption, so its metabolism may be due to intestinal CYP enzyme activity. The M1 metabolite of tenapanor is a P-glycoprotein substrate and, in contrast to its parent drug, can be detected in plasma, reaching a C_max of approximately 15 ng/mL at steady state. It is not considered active against NHE3.