Does Invega Cause Hypercalcemia?
No, Invega (paliperidone) does not cause hypercalcemia based on available evidence. The provided guidelines and research focus exclusively on hypercalcemia caused by other medications—specifically thiazide diuretics, vitamin D preparations, calcium supplements, lithium, and certain newer agents like patiromer and tirzepatide—but antipsychotic medications including paliperidone are not mentioned as causes of hypercalcemia 1, 2, 3, 4, 5.
Established Medication-Related Causes of Hypercalcemia
The evidence clearly identifies specific drug classes that cause hypercalcemia through distinct mechanisms:
Medications That Increase Calcium Reabsorption
- Thiazide diuretics are well-documented causes of hypercalcemia by reducing urinary calcium excretion and increasing renal tubular calcium reabsorption 2, 3, 5
- Severe cases reaching calcium levels as high as 19.8 mg/dL have been reported with thiazides 3
Medications That Increase Calcium Absorption or Mobilization
- Vitamin D preparations (vitamin D2, D3, and active forms like calcitriol) cause hypercalcemia through increased gastrointestinal calcium absorption and bone resorption 2, 4
- Vitamin A intoxication increases bone resorption 2, 4
- Calcium supplements, particularly when combined with thiazides, can precipitate hypercalcemia 3
- Lithium is recognized as a less common medication cause 3, 4
Newer Agents With Hypercalcemia Risk
- Patiromer (a potassium binder) exchanges calcium for potassium in the colon and has rare reported cases of hypercalcemia, though this may be underreported 6
- Tirzepatide (GIP/GLP-1 agonist) has emerging case reports of severe hypercalcemia when combined with chronic thiazide use 5
Why Paliperidone Is Not Implicated
The comprehensive guidelines on drug-induced hypercalcemia 6 extensively list medications causing various electrolyte disturbances, particularly hyperkalemia (elevated potassium), but do not include antipsychotic medications as causes of hypercalcemia. The focus is on RAAS inhibitors, diuretics, NSAIDs, and other specific drug classes 6.
Clinical Caveat
If hypercalcemia develops in a patient taking Invega, investigate alternative causes including primary hyperparathyroidism (the most common cause accounting for 45% of cases), malignancy (45% of cases), vitamin D excess, thiazide diuretics, immobilization, or other medications the patient may be taking concurrently 1, 4. The hypercalcemia is not attributable to the paliperidone itself based on current evidence.