Is Quviviq (Daridorexant) associated with polydipsia?

Daridorexant (Quviviq) and Polydipsia

Daridorexant (Quviviq) has not been associated with polydipsia in clinical studies or post-marketing surveillance, and there is no evidence suggesting it causes excessive thirst or fluid intake.

Mechanism of Action and Safety Profile

Daridorexant is a dual orexin receptor antagonist (DORA) approved for the treatment of insomnia. It works by antagonizing orexin receptors, thereby reducing the wake drive and promoting sleep 1. Unlike some other medications that may cause polydipsia as a side effect, the clinical trials and safety data for daridorexant do not indicate polydipsia as a reported adverse effect.

The most common adverse events associated with daridorexant include:

• Somnolence
• Fatigue
• Dizziness

These adverse events occurred at only slightly greater frequency with daridorexant than with placebo, and most were mild in severity 1. Notably, the incidence of adverse events was not dose-dependent, suggesting a favorable safety profile.

Medications Known to Cause Polydipsia

Several medications and conditions are known to cause polydipsia, but daridorexant is not among them. Medications commonly associated with polydipsia include:

1. Antipsychotics: Particularly typical antipsychotics have been associated with worsening polydipsic behavior in schizophrenic patients 2

2. Certain antidiabetic medications: Some medications used for diabetes management can cause polydipsia as a side effect or due to underlying hyperglycemia 3

3. Lithium: Can cause nephrogenic diabetes insipidus leading to polydipsia 4

Conditions Associated with Polydipsia

Polydipsia can be a symptom of several underlying conditions:

• Diabetes mellitus: Characterized by polyuria, polydipsia, and polyphagia 3
• Diabetes insipidus: Central or nephrogenic forms leading to excessive urination and compensatory thirst 4
• Primary polydipsia: Pathologically high levels of water intake not related to homeostatic regulation 5
• Psychiatric disorders: Particularly in chronic schizophrenia patients 2

Pharmacokinetics in Special Populations

Daridorexant has been studied in patients with renal impairment, and its pharmacokinetics are not significantly affected by renal function. A study evaluating daridorexant in patients with severe renal function impairment found:

• Maximum plasma concentrations (Cmax) were virtually unchanged
• Time to reach Cmax was similar
• Half-life was comparable to control subjects
• Overall exposure was only slightly higher in patients with severe renal impairment 6

Based on these findings, no dose adjustment is necessary for patients with renal impairment 6.

Clinical Implications

When considering daridorexant for insomnia treatment:

• Monitor for the common side effects (somnolence, fatigue, dizziness)
• No special monitoring for polydipsia is required based on current evidence
• If a patient develops polydipsia while taking daridorexant, consider other causes such as:
  • Undiagnosed diabetes mellitus (check for hyperglycemia)
  • Diabetes insipidus
  • Medication interactions
  • Primary psychiatric causes

Conclusion

Based on the available evidence, daridorexant (Quviviq) has not been associated with polydipsia. The medication has demonstrated a favorable safety profile in clinical trials, with most adverse events being mild and occurring at rates similar to placebo 1, 7. If a patient develops symptoms of polydipsia while taking daridorexant, clinicians should investigate other potential causes rather than assuming it is a medication side effect.