Can rosuvastatin (calcium) cause hypercalcemia?

Rosuvastatin Calcium and Hypercalcemia

Rosuvastatin calcium does not typically cause hypercalcemia, but patiromer (a potassium binder that contains calcium) has been reported to cause hypercalcemia in rare cases. 1

Mechanism and Evidence

Rosuvastatin itself has not been directly linked to hypercalcemia in major clinical guidelines or research. The comprehensive review of rosuvastatin's adverse effects 2 does not mention hypercalcemia as a known side effect. Instead, the medication is associated with other well-documented statin class effects such as myopathy, liver enzyme elevations, and potential renal effects.

However, there are important considerations regarding calcium in the context of medications:

1. Patiromer-induced hypercalcemia: The Mayo Clinic Proceedings (2021) specifically notes that patiromer (a potassium binder) contains a calcium-sorbitol counterion that exchanges calcium for potassium as it passes through the colon. While rare, cases of patiromer-induced hypercalcemia have been reported 1. This is relevant for patients who might be on both rosuvastatin and patiromer.

2. Other statin-calcium interactions: There are isolated case reports of hypercalcemia with other statins:

   • A 2024 case report described calcium elevation after atorvastatin initiation in a patient with hyperparathyroidism 3
   • A 2014 case report suggested possible asymptomatic hypercalcemia with atorvastatin calcium 4

3. Rhabdomyolysis-related hypercalcemia: Severe statin-induced rhabdomyolysis can lead to hypercalcemia during recovery, as documented in a case with simvastatin 5. This represents an indirect mechanism where the statin causes muscle breakdown, which subsequently leads to calcium release.

Clinical Implications

When managing patients on rosuvastatin calcium:

• Monitor calcium levels in patients at risk for hypercalcemia, particularly those with:

  • Pre-existing hyperparathyroidism
  • Concurrent use of patiromer or other calcium-containing medications
  • Signs of rhabdomyolysis (severe muscle pain, weakness, dark urine)

• Symptoms of hypercalcemia to watch for include:

  • Gastrointestinal: nausea, vomiting, constipation, abdominal pain
  • Neurological: confusion, lethargy, impaired cognitive function
  • Musculoskeletal: muscle cramps, bone pain, weakness 6

• If hypercalcemia develops:

  1. Consider medication review and possible discontinuation of calcium-containing agents
  2. Evaluate for other causes of hypercalcemia
  3. Manage according to severity following established hypercalcemia protocols 6

Important Caveats

• The calcium salt form of rosuvastatin does not appear to contribute significant calcium to cause hypercalcemia
• Most reported cases of statin-associated hypercalcemia are isolated case reports rather than established patterns
• When hypercalcemia occurs in patients on statins, consider other common causes such as hyperparathyroidism, malignancy, or other medications

Conclusion

While rosuvastatin calcium itself is not established as a direct cause of hypercalcemia, clinicians should be aware of the potential for hypercalcemia in patients taking combination therapy with calcium-containing medications like patiromer, or in those who develop rhabdomyolysis. Regular monitoring of calcium levels may be warranted in high-risk patients.