What medications can cause hypercalcaemia?

Drug Causes of Hypercalcaemia

Multiple medications can cause hypercalcaemia through various mechanisms, with the most common being vitamin D analogs, thiazide diuretics, calcium supplements, and lithium. 1

Common Medication Causes of Hypercalcaemia

Medications Decreasing Calcium Excretion

• Thiazide diuretics: Enhance renal proximal calcium reabsorption, potentially converting asymptomatic normocalcemic or intermittently hypercalcemic hyperparathyroidism into classic hypercalcemic hyperparathyroidism 2, 3
• Lithium: Primarily causes hypercalcaemia through drug-induced hyperparathyroidism 2
• Calcineurin inhibitors (cyclosporine, tacrolimus): Decrease renal calcium excretion 4

Medications Increasing Calcium Absorption/Release

• Vitamin D supplements and analogs: Increase intestinal calcium absorption, renal calcium reabsorption, and bone resorption 2, 5
  • 1α-hydroxylated vitamin D analogs (calcitriol, alfacalcidol)
  • Topical vitamin D analogs (tacalcitol, calcipotriol) when absorbed through damaged skin 5
• Calcium supplements: Direct increase in calcium load 4, 5
• Recombinant human PTH: Can cause transient hypercalcaemia due to overtreatment, particularly during acute illness 2

Other Medications

• Potassium-sparing diuretics (spironolactone, triamterene, amiloride): Can affect calcium homeostasis 4
• NSAIDs: May reduce renal calcium excretion 4
• Sacubitril/valsartan: Can affect electrolyte balance 4
• Stored blood products: May contain elevated calcium levels 4
• Vitamin A: Excessive intake can increase bone resorption 5

Less Common Medication Causes

• Amino acids (aminocaproic acid, arginine, lysine) 4
• Penicillin G (in high doses) 4
• Pentamidine 4
• Digitalis 4
• Heparin (with prolonged use) 4
• Trimethoprim-sulfamethoxazole 4

Herbal/Dietary Supplements Associated with Hypercalcaemia

• Alfalfa 4
• Dandelion 4
• Dried toad skin 4
• Hawthorne berry 4
• Horsetail 4
• Lily of the valley 4
• Milkweed 4
• Nettle 4
• Noni juice 4
• Siberian ginseng 4

Monitoring and Management

Monitoring Recommendations

• Regular calcium monitoring every 1-2 weeks initially, then monthly after stabilization 1
• Monitor renal function before each treatment with medications that can affect calcium levels 1
• Check serum calcium, phosphate, magnesium, and electrolytes regularly in patients on high-risk medications 1

Management of Drug-Induced Hypercalcaemia

1. Discontinue the offending medication when possible
2. Hydration: Aggressive IV fluid resuscitation with normal saline (200-300 mL/hour initially) 1
3. Bisphosphonates: For severe cases (zoledronic acid 4 mg IV over 15 minutes) 1
4. Loop diuretics: Only after adequate hydration to enhance calcium excretion 1
5. Denosumab: For refractory cases or in patients with severe renal impairment 1

Clinical Pearls and Pitfalls

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia in hypercalcaemia 1
• Failing to correct calcium for albumin when interpreting levels 1
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcaemia 1
• Failing to monitor for hypocalcaemia after treatment 1

Risk Factors for Drug-Induced Hypercalcaemia

• Pre-existing renal impairment
• Advanced age
• Concomitant use of multiple medications affecting calcium homeostasis
• Underlying primary hyperparathyroidism (especially with thiazide diuretics) 3
• Dehydration
• Immobilization

Remember that severe hypercalcaemia (>14 mg/dL) is a medical emergency requiring prompt treatment to prevent complications such as cardiac arrhythmias, renal failure, and altered mental status 6.