Can hydroxychloroquine cause hyponatremia?: Separating Fact from Anecdote

October 9, 2025 •

3 min read

While hyponatremia (low serum sodium) is the most common electrolyte abnormality in hospitalized patients, the link to hydroxychloroquine is not well-established. The existing medical literature does not identify hyponatremia as a common side effect of hydroxychloroquine, and a causal link is often not definitively proven in specific cases.

Quick Summary

Despite some case reports of low sodium levels in patients taking hydroxychloroquine, a direct causal relationship is not established in the medical literature. Hyponatremia in these cases is often attributed to underlying conditions like severe infections rather than the medication itself. Other electrolyte imbalances, especially hypokalemia during toxicity, are better-documented risks. Healthcare providers should investigate all potential causes.

Key Points

No Direct Causal Link: No established evidence suggests that therapeutic doses of hydroxychloroquine directly cause hyponatremia.
Case Report Nuance: Isolated reports of low sodium in patients on hydroxychloroquine are often complicated by co-existing severe illnesses, such as viral infections, which are the more likely cause of SIADH and hyponatremia.
Hypokalemia and Overdose: In contrast to hyponatremia, hypokalemia (low potassium) is a known and serious risk associated with hydroxychloroquine toxicity or overdose.
Risk of Hypoglycemia: Hydroxychloroquine can cause hypoglycemia (low blood sugar), which presents with some symptoms that can overlap with hyponatremia.
Underlying Conditions: Patients with autoimmune diseases treated with hydroxychloroquine, especially those with pre-existing kidney disease, are at risk for electrolyte imbalances from their underlying condition, not necessarily the medication.
Comprehensive Evaluation Needed: Any occurrence of hyponatremia in a patient taking hydroxychloroquine requires a full medical evaluation to determine the true cause, rather than immediately attributing it to the drug.

Understanding Hyponatremia

Hyponatremia is a medical condition defined by low levels of sodium in the blood. This electrolyte is vital for regulating water balance, nerve impulses, and muscle function. When blood sodium drops below 135 mmol/L, a range of symptoms, from mild to severe, can occur.

Symptoms of hyponatremia can include:

Headache
Nausea and vomiting
Fatigue and weakness
Confusion
Seizures
Coma

Diagnosing the cause of hyponatremia is often complex as it can stem from various issues, such as kidney, heart, and liver problems, hormonal imbalances, and certain medications.

Hydroxychloroquine's Known Electrolyte Effects

Hydroxychloroquine is a DMARD used for conditions like rheumatoid arthritis and systemic lupus erythematosus. Hyponatremia is generally not listed among its common side effects in standard drug information.

Instead, hypokalemia (low potassium) is the electrolyte disturbance most often associated with hydroxychloroquine, particularly in cases of overdose or toxicity. Severe hypokalemia and cardiotoxicity are significant concerns in overdose situations. While there's no reported evidence of hydroxychloroquine causing SIADH, other medications like certain antidepressants and anticancer drugs are known to induce SIADH and subsequent hyponatremia through specific mechanisms.

Hydroxychloroquine is also known to cause hypoglycemia (low blood sugar). The symptoms of hypoglycemia, such as dizziness, confusion, and weakness, can resemble those of hyponatremia, potentially complicating diagnosis.

The Hyponatremia-Hydroxychloroquine Connection: Scrutinizing the Evidence

The link between hydroxychloroquine and hyponatremia is primarily based on isolated case reports, not extensive clinical studies. One such report involved a COVID-19 patient who developed hyponatremia while receiving multiple treatments, including hydroxychloroquine. The authors of that report suggested that the viral infection itself, rather than hydroxychloroquine, was the likely cause of SIADH and hyponatremia, noting a lack of reported evidence connecting hydroxychloroquine or favipiravir to SIADH.

This highlights the importance of distinguishing between association and causation. In complex medical situations, especially with severe illnesses like COVID-19, numerous factors can contribute to symptoms, making it difficult to attribute an electrolyte imbalance solely to one medication without clear evidence.

Potential Mechanisms and Explanations

While hydroxychloroquine may not directly cause hyponatremia, other factors in patients taking the medication could be responsible:

Underlying Disease: Autoimmune diseases such as SLE, for which hydroxychloroquine is prescribed, can cause kidney disease, leading to electrolyte imbalances.
Interactions with Other Medications: Patients on hydroxychloroquine often take other drugs known to cause hyponatremia, such as certain diuretics or SSRIs.
Renal Issues: Although generally considered safe for kidneys at therapeutic doses, rare cases of renal phospholipidosis have been reported with long-term HCQ use. Severe kidney problems can result in electrolyte imbalances, including hyponatremia, though this is uncommon.

Hydroxychloroquine: Confirmed vs. Unconfirmed Effects on Electrolytes


Feature	HCQ's Confirmed Effects	HCQ's Unconfirmed/Rarely Reported Effects
Effect on Sodium (Hyponatremia)	No direct evidence of causation at therapeutic doses.	Rare association in case reports, often linked to underlying disease or other drugs.
Effect on Potassium (Hypokalemia)	Known risk in overdose or toxicity situations.	Not a typical issue at standard therapeutic doses.
Effect on Glucose (Hypoglycemia)	Documented risk, can cause confusion and weakness.	An important side effect to monitor, especially in patients with diabetes.
Electrolyte Focus	Monitoring is recommended for pre-existing low potassium or magnesium due to cardiac risk.	Focus is on other electrolyte imbalances, not typically sodium.

Conclusion

Based on the available evidence, hydroxychloroquine does not appear to cause hyponatremia as a typical or direct side effect. Case reports of low sodium in patients on the medication are often attributed to other factors like severe underlying illness (e.g., viral infections causing SIADH) or concurrent medications known to cause electrolyte disturbances. Hypokalemia and cardiac issues are the primary concerns in overdose situations. When evaluating electrolyte abnormalities, healthcare providers should consider the entire clinical picture, including the patient's underlying condition, other medications, and kidney function, before attributing hyponatremia solely to hydroxychloroquine. Regular monitoring is recommended for patients on long-term therapy or with pre-existing kidney issues. MedlinePlus is an authoritative source for general drug information.

This article is for informational purposes only and should not be considered medical advice. Always consult with a healthcare professional regarding your specific health condition and medication.

Frequently Asked Questions

No, hyponatremia is not listed as a common or typical side effect of hydroxychloroquine based on the available medical information and clinical reports.

Hyponatremia is low blood sodium, while hypokalemia is low blood potassium. While hyponatremia is not linked to hydroxychloroquine, hypokalemia is a known risk in cases of acute toxicity or overdose.

If you experience symptoms like persistent headache, nausea, fatigue, or confusion, you should contact your doctor immediately. These symptoms warrant medical evaluation, but they should not be automatically assumed to be caused by your medication.

Yes. The autoimmune diseases treated by hydroxychloroquine, as well as concurrent infections or other medications, can cause electrolyte abnormalities or other symptoms that might be mistaken for drug side effects.

At therapeutic doses, hydroxychloroquine is generally safe for kidney function, though dose adjustments may be needed for patients with existing severe kidney disease. Long-term use can rarely cause a specific kidney condition called renal phospholipidosis.

Patients on hydroxychloroquine should be monitored for hypoglycemia (low blood sugar), which is a more established metabolic side effect. Pre-existing low magnesium or potassium can also increase cardiac risk.

During the pandemic, some patients with severe COVID-19 developed SIADH and hyponatremia. Since some of these patients were also treated with various medications, including hydroxychloroquine, it was present in some cases of hyponatremia. However, studies concluded the virus was the more likely cause, not the hydroxychloroquine.