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

Prochlorperazine (Compazine) and SIADH

Yes, Compazine (prochlorperazine) can cause Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). Antipsychotics, including prochlorperazine, are among the medications documented to cause SIADH according to clinical practice guidelines 1.

Mechanism and Risk Factors

Prochlorperazine, like other antipsychotics, can lead to SIADH through:

• Increased release of antidiuretic hormone (ADH) from the posterior pituitary
• Altered sensitivity of hypothalamic osmoreceptors to serum osmolality
• Enhanced renal tubular sensitivity to circulating ADH

Risk factors that increase the likelihood of developing SIADH with prochlorperazine include:

• Advanced age 2
• Concomitant use of other medications that can cause SIADH
• Excessive fluid intake
• Underlying conditions that limit free water excretion

Clinical Presentation

The severity of SIADH symptoms depends on the degree of hyponatremia and how rapidly it develops:

• Mild hyponatremia (126-135 mEq/L): Often asymptomatic or subtle symptoms including nausea, muscle cramps, headache 1
• Moderate hyponatremia (120-125 mEq/L): Weakness, gait instability, headache, dizziness, nausea, vomiting 1
• Severe hyponatremia (<120 mEq/L): Confusion, delirium, lethargy, seizures, coma, and potentially death if untreated 1

Diagnostic Criteria for SIADH

When suspecting prochlorperazine-induced SIADH, look for:

1. Hyponatremia (serum sodium <134 mEq/L)
2. Hypoosmolality (plasma osmolality <275 mOsm/kg)
3. Inappropriately high urine osmolality (>500 mOsm/kg) relative to serum osmolality
4. Inappropriately high urinary sodium concentration (>20 mEq/L)
5. Clinical euvolemia and normal renal, adrenal, and thyroid function 1

Management of Prochlorperazine-Induced SIADH

The management approach should follow these steps:

1. Discontinue prochlorperazine if clinically appropriate 1
2. Implement fluid restriction (1,000-1,500 mL/day) 1
3. Ensure adequate oral salt intake 1
4. Monitor serum sodium levels closely 1

For symptomatic or severe hyponatremia:

• Administer hypertonic saline (3% sodium chloride) with close monitoring
• Consider intravenous furosemide to enhance free water excretion 3
• Ensure correction rate does not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1

Important Considerations

• Drug-induced SIADH usually resolves following discontinuation of the offending agent 2
• Patients with malnutrition, alcoholism, or advanced liver disease may require slower rates of sodium correction 1
• Consider alternative antiemetics that have lower risk of causing SIADH if antiemetic therapy is still needed

Monitoring and Follow-up

• Regular monitoring of serum sodium levels until normalization
• Careful attention to the rate and extent of correction of hyponatremia 2
• Consider water loading test after resolution to confirm the causative role of prochlorperazine 4

While SIADH is a well-documented adverse effect of various psychotropic medications, including antipsychotics like prochlorperazine 2, 4, prompt recognition and appropriate management typically lead to complete resolution of the condition.