Can Compazine (prochlorperazine) cause Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Can Compazine (Prochlorperazine) Cause SIADH?

Yes, Compazine (prochlorperazine) can cause Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) as it belongs to the antipsychotic medication class, which is known to be associated with SIADH.

Mechanism and Risk

Prochlorperazine, like other antipsychotic medications, can lead to SIADH through:

• Non-osmotic hypersecretion of vasopressin (ADH)
• Alteration in normal ADH regulation
• Enhanced proximal nephron sodium reabsorption

The Annals of Oncology clinical practice guidelines specifically mention that antipsychotics are among the medications that can cause confusion associated with SIADH 1. This medication-induced SIADH is typically idiosyncratic and often resolves after withdrawal of the offending medication.

Diagnostic Criteria for SIADH

When suspecting SIADH caused by Compazine, look for:

• 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 2

Management of Drug-Induced SIADH

If SIADH is suspected due to Compazine use:

1. Discontinue the medication if clinically appropriate 1

   • The Annals of Oncology guidelines specifically recommend "medication or therapy withdrawal in patients with delirium related to anticancer treatments" and similar approach for medication-induced SIADH 1

2. Institute fluid restriction (typically 1,000-1,500 mL/day) 1, 2

3. Ensure adequate oral salt intake 1

4. Monitor serum sodium levels closely

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

Special Considerations

• Elderly patients are at higher risk for developing drug-induced SIADH 3
• Concomitant use of other medications that can cause SIADH (such as SSRIs, carbamazepine, diuretics) increases the risk 3, 4
• Patients with malnutrition, alcoholism, or advanced liver disease may require slower rates of sodium correction 2

Severity Classification

The severity of SIADH symptoms depends on the degree of hyponatremia:

• Mild (126-135 mEq/L): Often asymptomatic or subtle symptoms
• Moderate (120-125 mEq/L): Weakness, gait instability, headache, dizziness
• Severe (<120 mEq/L): Confusion, delirium, lethargy, seizures, potential coma 2

For severe symptomatic hyponatremia, more aggressive intervention may be required, including hypertonic saline administration under close monitoring 1.

Drug-induced SIADH typically resolves following discontinuation of the offending agent, but careful monitoring is essential during correction of hyponatremia 3.