Can IBSRELA (tenapanor) cause hyponatremia?

IBSRELA (Tenapanor) and Hyponatremia Risk

IBSRELA (tenapanor) does not cause hyponatremia; in fact, it may reduce intestinal sodium absorption, which could theoretically lead to hypernatremia rather than hyponatremia.

Mechanism of Action and Sodium Effects

• Tenapanor is a first-in-class sodium hydrogen exchanger 3 (NHE3) inhibitor that acts locally in the gut with minimal systemic absorption 1
• It functions by reducing intestinal sodium absorption, which leads to increased sodium excretion in stool and decreased urinary sodium excretion 1, 2
• In clinical studies, tenapanor treatment resulted in higher mean stool sodium content compared to placebo, accompanied by lower urinary sodium content 2

Systemic Exposure and Safety Profile

• Tenapanor has minimal systemic availability - 98.5% of 895 plasma samples in clinical trials had concentrations below the quantification limit (0.5 ng/ml) 1
• The most common adverse effect is diarrhea, which was reported in clinical trials but rarely led to discontinuation 3
• No clinically relevant changes in serum electrolytes, including sodium levels, were observed in clinical trials 1

Hyponatremia Context in Medical Practice

• Hyponatremia (low serum sodium) is a common concern in certain patient populations, particularly those with cirrhosis and ascites 4
• Severe hyponatremia (serum sodium <130 mmol/L) is a predisposing factor for hepatic encephalopathy in patients with cirrhosis 4
• Medications that can cause hyponatremia include:
  • Proton pump inhibitors (PPIs), which can increase hyponatremia risk through multiple mechanisms 4
  • Diuretics, particularly loop diuretics, which can lead to potassium and sodium depletion 4

Theoretical Considerations for Tenapanor

• Based on its mechanism of action (reducing intestinal sodium absorption), tenapanor would theoretically be more likely to cause hypernatremia rather than hyponatremia if it were to affect serum sodium levels 1, 2
• Unlike vaptans (V2-receptor antagonists) which are specifically used to treat hyponatremia by enhancing solute-free water excretion 4, tenapanor's mechanism does not directly affect water balance in this manner

Clinical Applications of Tenapanor

• Tenapanor (IBSRELA) is FDA-approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults 5
• It is also being investigated for hyperphosphatemia in patients with chronic kidney disease on dialysis 6, 3
• Clinical trials have shown that tenapanor not only affects sodium absorption but also reduces phosphate absorption from the gut 2

Monitoring Recommendations

• While specific monitoring for hyponatremia with tenapanor is not indicated based on current evidence, general monitoring of electrolytes may be prudent when starting any new medication that affects gastrointestinal function 1
• For patients with pre-existing conditions that predispose to electrolyte abnormalities, routine electrolyte monitoring may be considered as part of standard care 4