Can Pramipexole (Dopamine Agonist) cause hyponatremia (low sodium levels)?

Pramipexole and Hyponatremia

Yes, pramipexole can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). Multiple case reports have documented this association, showing that pramipexole can lead to clinically significant hyponatremia that resolves upon dose reduction or discontinuation of the medication 1, 2, 3.

Mechanism and Evidence

• Pramipexole, a dopamine agonist used in Parkinson's disease and restless legs syndrome, can enhance antidiuretic hormone (ADH/vasopressin) secretion through activation of dopamine receptors, particularly D4 receptors, in the supraoptic nucleus 1, 2
• Case reports demonstrate significantly elevated ADH levels (up to 5 times the upper normal limit) in patients taking pramipexole who developed hyponatremia 2, 3
• Pramipexole has a higher selectivity for D4 receptors compared to other dopamine agonists (D4:D2 ratio of 13 for pramipexole versus 0.44 for pergolide and 0.017 for cabergoline), which may explain its stronger association with SIADH 2

Clinical Presentation

• Patients may present with:
  • Asthenia (weakness) 1
  • Delirium or altered mental status 1, 3
  • Worsening of parkinsonian symptoms 1
  • Laboratory findings consistent with SIADH: hyponatremia, low serum osmolarity, inappropriate urine hyperosmolarity, and elevated urine sodium concentration 2, 3

Risk Factors

• Elderly patients appear to be at higher risk, with case reports involving patients aged 60-85 years 1, 2, 3
• Dose escalation of pramipexole may trigger the development of hyponatremia 1
• The American Geriatrics Society Beers Criteria® identifies tramadol and other medications as causing hyponatremia or SIADH in older adults, and while pramipexole is not specifically listed, the documented cases suggest similar caution is warranted 4

Management

• Monitor serum sodium levels in patients receiving pramipexole, especially during dose escalation periods 1
• If hyponatremia develops, consider dose reduction or discontinuation of pramipexole 2, 3
• After pramipexole withdrawal, symptoms typically resolve and sodium levels return to normal 1
• For patients with severe hyponatremia who require continued dopaminergic therapy, consider switching to a dopamine agonist with lower D4 receptor affinity 2

Differential Diagnosis

• Rule out other causes of hyponatremia such as:
  • Heart failure (which can cause dilutional hyponatremia) 4
  • Liver cirrhosis 3
  • Hypotonic dehydration 3
  • Malignancy-associated SIADH 3
  • Other medications known to cause hyponatremia 4

Clinical Implications

• When initiating pramipexole (typical starting dose 0.125 mg at bedtime for RLS or Parkinson's disease), be aware of the potential for hyponatremia 4, 5
• Patients experiencing unexplained neurological deterioration, confusion, or delirium while on pramipexole should have their sodium levels checked 1, 3
• The risk of adverse effects including hallucinations appears to be higher with pramipexole compared to some other dopamine agonists when each is compared to placebo 6

In conclusion, clinicians should maintain vigilance for hyponatremia in patients taking pramipexole, particularly during dose adjustments and in elderly patients. Prompt recognition and management can prevent serious complications associated with hyponatremia.