Can plecanatide (generic name) cause hyponatremia?

Plecanatide and Hyponatremia

Plecanatide does not cause hyponatremia based on the available clinical evidence. The medication's mechanism of action and safety profile do not indicate hyponatremia as a reported adverse effect.

Mechanism of Action and Risk Assessment

• Plecanatide is a pH-dependent guanylate cyclase-C (GC-C) agonist that increases cyclic guanosine monophosphate concentrations, resulting in luminal chloride and bicarbonate secretion, thereby increasing intestinal fluid and accelerating GI transit 1
• Plecanatide is a 16-amino acid peptide analog of uroguanylin that stimulates GC-C receptors primarily in the proximal small bowel, which is unique compared to other medications in its class 2
• Unlike medications known to cause hyponatremia (such as diuretics, antidepressants, and antiepileptics), plecanatide works locally in the intestine and has minimal systemic absorption 3, 4

Safety Profile from Clinical Evidence

• In comprehensive clinical trials and safety assessments, hyponatremia has not been identified as an adverse effect of plecanatide 1
• The most common adverse event associated with plecanatide is diarrhea, reported in approximately 4.3% of patients in phase 3 trials (compared to 1% with placebo), with discontinuation due to diarrhea in only 1.2% of patients 1
• Long-term safety studies of plecanatide involving 2,370 patient exposures demonstrated that treatment-emergent adverse events were primarily mild to moderate in severity, with diarrhea (7.1%) and urinary tract infection (2.2%) being the most common 5
• Serious adverse events with plecanatide were rare (0.8%) and similar to placebo rates, with no reported cases of hyponatremia 1

Clinical Considerations

• While severe diarrhea from any cause can potentially lead to electrolyte disturbances, the incidence of severe diarrhea with plecanatide is low, with diarrhea leading to discontinuation in only 3.1% of patients in long-term studies 5
• The American Gastroenterological Association and American College of Gastroenterology strongly recommend plecanatide for chronic idiopathic constipation with moderate certainty of evidence, without mentioning hyponatremia as a concern 1
• Plecanatide's pH-dependent activation primarily in the proximal small intestine limits its systemic effects, potentially contributing to its favorable safety profile regarding electrolyte disturbances 3

Monitoring and Precautions

• While specific monitoring for hyponatremia is not indicated based on clinical evidence, patients with severe diarrhea should be monitored for dehydration and electrolyte imbalances as a standard precaution 1
• Plecanatide is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction, similar to other medications in its class 1
• Patients should be counseled about the possibility of diarrhea as a side effect, though the risk appears to be lower than with some other medications used for similar indications 1, 5

Dosing Considerations

• Plecanatide is FDA-approved for chronic idiopathic constipation at a dose of 3 mg daily, which can be taken with or without food 1
• The same 3 mg daily dose is approved for irritable bowel syndrome with constipation (IBS-C) 1
• Clinical trials have also studied a 6 mg dose, which showed similar efficacy but slightly higher rates of diarrhea (4.5% vs 3.2% with the 3 mg dose) 6