Can hydroxychloroquine (HCQ) cause hypokalemia?

Hydroxychloroquine and Hypokalemia

Yes, hydroxychloroquine (HCQ) can cause hypokalemia, particularly in overdose situations, and this represents a potentially serious adverse effect that requires monitoring.

Mechanism and Clinical Significance

• Hydroxychloroquine-induced hypokalemia is most commonly observed in overdose situations, where it correlates with the severity of toxicity 1, 2
• Hypokalemia is considered one of the cardinal manifestations of hydroxychloroquine toxicity, along with cardiovascular effects and central nervous system depression 3, 4
• The hypokalemia appears to be due to an intracellular shift of potassium rather than total body potassium depletion 2

Risk Factors and Clinical Context

• Hypokalemia risk is heightened when hydroxychloroquine is combined with other medications that can cause electrolyte disturbances 5
• Particular caution is needed when hydroxychloroquine is used with:
  • Corticosteroids 5
  • Cisplatin and other chemotherapeutic agents 5
  • Medications causing digestive disorders 5
• Hypokalemia (potassium <3.4 mmol/L) is a modifiable risk factor that increases the risk of drug-induced QT prolongation and torsades de pointes when using hydroxychloroquine 5

Monitoring and Management

• Monitor serum potassium levels in patients taking hydroxychloroquine, especially when:

  • Starting therapy
  • Increasing doses
  • Adding other medications that may affect potassium levels
  • Patient develops symptoms of hypokalemia (muscle weakness, cardiac arrhythmias)
  • Patient has risk factors for QT prolongation 5

• In cases of hydroxychloroquine overdose:

  • Hypokalemia can be profound and develop rapidly 2, 3
  • Careful potassium repletion is essential but must be done cautiously 1
  • Rapid or excessive correction of hypokalemia can be dangerous and lead to ventricular arrhythmias 1
  • After elimination of hydroxychloroquine, extracellular transfer of excess potassium may occur, potentially causing hyperkalemia 1

Clinical Pearls and Pitfalls

• The combination of hypokalemia and QT prolongation significantly increases the risk of torsades de pointes and sudden cardiac death 5
• Hydroxychloroquine-induced hypokalemia may appear within 30 minutes of overdose ingestion 4
• In therapeutic dosing, routine monitoring of potassium levels is advisable, especially when combined with other medications that may affect potassium levels or prolong the QT interval 5
• The FDA drug label for hydroxychloroquine notes that severe hypokalemia secondary to an intracellular shift is common in severe toxicity 6

Special Populations

• In pediatric patients with hydroxychloroquine overdose, hypokalemia is a key manifestation requiring prompt recognition and careful management 3
• Elderly patients may be at higher risk due to age-related changes in renal function and concomitant medications 6
• Patients with renal or hepatic impairment may require dose adjustments of hydroxychloroquine to prevent toxicity 6

Remember that while hypokalemia is well-documented in hydroxychloroquine overdose, it can also occur at therapeutic doses, particularly when combined with other medications that affect potassium levels.