Can Carboplatin Cause Hyponatremia?
Yes, carboplatin can cause hyponatremia, though it occurs much less frequently than with cisplatin. The FDA drug label documents electrolyte abnormalities including hyponatremia (abnormally decreased serum sodium in 29% of patients, 47% in pretreated ovarian cancer patients), though these were rarely symptomatic 1. Case reports confirm carboplatin-induced hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH) mechanism 2.
Incidence and Clinical Significance
- Carboplatin is significantly less likely to cause hyponatremia than cisplatin, which is well-recognized for causing hyponatremia through renal salt wasting 2, 3
- The FDA label reports abnormally decreased serum sodium in 29% of patients overall (47% in pretreated ovarian cancer patients), though most cases were mild and asymptomatic 1
- Only rare case reports exist of clinically significant carboplatin-induced hyponatremia requiring intervention, with just three cases documented in the literature prior to 2012 2
Mechanism of Hyponatremia
Carboplatin can cause hyponatremia through two distinct mechanisms:
- SIADH (more common): Inappropriate ADH secretion leading to water retention and dilutional hyponatremia 2, 3
- Renal salt wasting syndrome (RSWS): Direct renal sodium loss with dehydration and high urinary sodium excretion 4, 3
The mechanism differs from cisplatin, which primarily causes renal salt wasting 2, 3.
Risk Factors and Timing
Key risk factors include:
- Female gender - women are at higher risk for drug-induced hyponatremia 5
- Lung cancer patients - particularly small cell lung cancer (SCLC) where hyponatremia is common regardless of chemotherapy 5, 6
- Prior cisplatin exposure - patients previously treated with emetogenic agents, especially cisplatin, may be more susceptible 1
- Elderly patients (>65 years) - require closer sodium monitoring when on multiple medications 7
Onset typically occurs within 3-10 days of carboplatin administration 5, 4.
Clinical Monitoring Recommendations
Before each carboplatin cycle:
- Check baseline serum sodium, particularly in high-risk patients (women, elderly, lung cancer, prior cisplatin exposure) 5
- Monitor electrolytes throughout therapy as recommended by the FDA label 1
During treatment:
- If hyponatremia develops, obtain serum and urine osmolality, urine sodium, and assess volume status to distinguish SIADH from RSWS 8, 4
- For SIADH: urine sodium >20-40 mmol/L with inappropriately concentrated urine (>300 mOsm/kg) in euvolemic patient 8
- For RSWS: evidence of dehydration with high urinary sodium excretion 4
Management Approach
For SIADH mechanism:
- Fluid restriction to 1 L/day for mild-moderate cases 8
- For severe symptomatic hyponatremia (<120 mmol/L with neurological symptoms): 3% hypertonic saline with target correction of 6 mmol/L over 6 hours, not exceeding 8 mmol/L in 24 hours 8
For RSWS mechanism:
- Volume expansion with isotonic or hypertonic saline (opposite of SIADH treatment) 4
- Consider switching from cisplatin to carboplatin if RSWS occurred with cisplatin, as one case report showed no recurrence with carboplatin 4
For subsequent cycles:
- If severe hyponatremia occurred, consider alternative platinum agent or increased monitoring 2, 4
- One case series showed successful rechallenge with docetaxel-trastuzumab after carboplatin-induced hyponatremia, confirming carboplatin as the causative agent 2
Common Pitfalls
- Assuming all platinum-induced hyponatremia is SIADH - carboplatin can also cause RSWS, which requires opposite treatment (volume expansion vs. fluid restriction) 4
- Overlooking mild hyponatremia - even sodium 130-135 mmol/L increases fall risk and mortality 8
- Failing to distinguish from tumor-related hyponatremia - particularly in SCLC where paraneoplastic SIADH is common independent of chemotherapy 6
- Not monitoring electrolytes routinely - the FDA label notes electrolyte supplementation was not routinely administered, and abnormalities were rarely symptomatic, but monitoring is still essential 1