Can Keppra (levetiracetam) cause hypercalcemia?

Levetiracetam (Keppra) and Hypercalcemia

Levetiracetam (Keppra) is not known to cause elevated calcium levels or hypercalcemia based on available evidence. The medication has a favorable side effect profile compared to many other antiepileptic drugs and does not typically affect calcium metabolism.

Levetiracetam's Pharmacological Profile

Levetiracetam has a unique mechanism of action that involves:

• Binding to synaptic vesicle protein 2A (SV2A)
• Inhibiting calcium release from intraneuronal stores
• Opposing negative modulators of GABA and glycine-gated currents
• Inhibiting N-type calcium channels 1, 2

Unlike many other antiepileptic medications, levetiracetam:

• Has minimal metabolism (primarily hydrolysis of the acetamide group)
• Is primarily eliminated renally
• Lacks cytochrome P450 enzyme-inducing potential
• Has minimal drug-drug interactions 1, 2

Evidence Regarding Calcium Metabolism

Research specifically examining levetiracetam's effects on calcium metabolism shows:

• A prospective study in children with epilepsy found no significant changes in calcium levels, bone metabolism markers, or bone mineral density during 12 months of levetiracetam treatment 3
• This contrasts with oxcarbazepine, which in the same study was shown to decrease calcium levels and increase parathyroid hormone levels after 6-12 months of treatment 3

Known Side Effects of Levetiracetam

Common adverse effects of levetiracetam include:

• Somnolence
• Irritability
• Dizziness
• Nausea
• Behavioral effects 1, 2, 4

Notably, levetiracetam:

• Does not cause weight gain
• Does not typically cause cognitive impairment
• Does not induce clinically significant electrolyte disturbances 1, 2

Medications Known to Affect Calcium Levels

For context, medications that are known to potentially cause hypercalcemia include:

1. Patiromer (a potassium-binding agent) - exchanges calcium for potassium in the colon and has been reported to cause hypercalcemia in rare cases 5
2. Thiazide diuretics - can cause hypercalcemia by decreasing urinary calcium excretion
3. Lithium - can cause hyperparathyroidism
4. Vitamin D analogs - can increase calcium absorption

Clinical Implications

If a patient on levetiracetam presents with hypercalcemia:

• Consider other causes of hypercalcemia (primary hyperparathyroidism, malignancy, etc.)
• Review all medications for potential calcium-affecting agents
• Evaluate for conditions like multiple myeloma, which can cause hypercalcemia through excessive bone resorption 5
• Consider that the hypercalcemia is likely unrelated to levetiracetam therapy

Conclusion

Based on the available evidence, levetiracetam does not cause hypercalcemia. If a patient on levetiracetam develops elevated calcium levels, clinicians should investigate other potential causes rather than attributing it to the medication.