Can Reglan (metoclopramide) cause Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Metoclopramide (Reglan) and SIADH

Metoclopramide (Reglan) is not specifically identified as a cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in the current clinical guidelines. While many medications are known to cause SIADH, the most recent and comprehensive guidelines do not list metoclopramide among them 1.

Medications Known to Cause SIADH

According to the latest guidelines, several medication classes are recognized as potential causes of SIADH:

• Antipsychotics (including prochlorperazine)
• Antidepressants (particularly SSRIs and venlafaxine)
• Antiepileptics (carbamazepine)
• Antineoplastic agents
• Diuretics
• Chlorpropamide

Metoclopramide, while sharing some properties with prochlorperazine (both being dopamine antagonists used for nausea), is not specifically mentioned in the SIADH guidelines 1.

Clinical Considerations

When evaluating potential drug-induced SIADH, clinicians should:

• Look for diagnostic criteria of SIADH:

  • Hyponatremia (serum sodium <134 mEq/L)
  • Hypoosmolality (plasma osmolality <275 mOsm/kg)
  • Inappropriately high urine osmolality (>500 mOsm/kg)
  • Inappropriately high urinary sodium concentration (>20 mEq/L)
  • Clinical euvolemia with normal renal, adrenal, and thyroid function 1

• Consider risk factors that increase susceptibility to drug-induced SIADH:

  • Advanced age
  • Female gender
  • Low body weight
  • Concomitant use of other medications that can cause SIADH
  • Lower baseline serum sodium concentration 2

Management Approach

If SIADH is suspected in a patient taking metoclopramide:

1. Evaluate for other more common medication causes of SIADH
2. Consider discontinuation of suspected causative medications if clinically appropriate
3. Implement fluid restriction (1,000-1,500 mL/day)
4. Ensure adequate oral salt intake
5. Monitor serum sodium levels closely 1

Important Caveats

• The severity of SIADH symptoms correlates with the degree of hyponatremia:

  • Mild (126-135 mEq/L): Often asymptomatic or subtle symptoms
  • Moderate (120-125 mEq/L): Weakness, headache, dizziness, nausea
  • Severe (<120 mEq/L): Confusion, seizures, coma, potentially death 1

• Correction of serum sodium should not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1

• Elderly patients are at higher risk for drug-induced SIADH and should be monitored more closely when starting medications with known SIADH associations 3

While metoclopramide is not specifically identified as a cause of SIADH in current guidelines, clinicians should remain vigilant about monitoring for hyponatremia in patients taking any medication that affects central neurotransmission, particularly in high-risk populations such as the elderly.