What drugs contribute to hyponatremia?

From the Guidelines

Drugs that can contribute to hyponatremia include diuretics, antidepressants, antipsychotics, anticonvulsants, and certain pain medications, as well as antidiabetic drugs, chemotherapy agents, and drugs that stimulate antidiuretic hormone release or enhance its effect. According to the most recent and highest quality study, 1, treatment of hyponatremia in cirrhotic ascites depends on etiology, chronicity, severity, and urgency. The study highlights the importance of correcting hyponatremia in patients with cirrhosis and ascites, and notes that vasopressin receptor antagonists, such as tolvaptan, can be effective in improving serum sodium concentration in hypervolemic, hyponatremic states.

Some key points to consider when evaluating the risk of hyponatremia in patients taking certain medications include:

• The type of medication and its mechanism of action
• The patient's age, kidney function, and overall health status
• The presence of other medications that can affect sodium levels
• The severity and chronicity of the hyponatremia

In terms of specific medications, the following can contribute to hyponatremia:

• Diuretics, such as thiazides and loop diuretics, which can increase sodium excretion by the kidneys
• Antidepressants, such as selective serotonin reuptake inhibitors, which can increase water retention through antidiuretic hormone effects
• Antipsychotics, such as haloperidol and olanzapine, which can increase water retention through antidiuretic hormone effects
• Anticonvulsants, such as carbamazepine and valproate, which can increase water retention through antidiuretic hormone effects
• Certain pain medications, such as NSAIDs and opioids, which can increase water retention through antidiuretic hormone effects

It's worth noting that the risk of hyponatremia is higher in elderly patients, those with kidney disease, and patients taking multiple medications that can affect sodium levels. Symptoms of medication-induced hyponatremia can range from mild to severe, depending on how quickly and severely sodium levels drop.

From the FDA Drug Label

Hyponatremia has been reported during treatment with SNRIs and SSRIs, including fluoxetine. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia can occur as a result of treatment with carbamazepine. In many cases, the hyponatremia appears to be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH)

The following drugs contribute to hyponatremia:

• Fluoxetine (2)
• Carbamazepine (3)

Key points:

• Elderly patients may be at greater risk of developing hyponatremia with these drugs.
• Patients taking diuretics or who are otherwise volume depleted may be at greater risk.
• Discontinuation of the drug should be considered in patients with symptomatic hyponatremia.

From the Research

Drugs Contributing to Hyponatremia

The following drugs have been associated with hyponatremia:

• Thiazide diuretics: These drugs can cause hyponatremia by impairing urinary dilution, renal loss of sodium and potassium, stimulation of antidiuretic hormone (ADH), and perhaps from a dipsogenic effect 4, 5, 6.
• Selective serotonin reuptake inhibitors (SSRIs): SSRIs can cause hyponatremia through the syndrome of inappropriate ADH release 7, 5.
• Antipsychotics: Certain antipsychotics, such as haloperidol, may induce hyponatremia by intrarenal mechanisms for aquaporin-2 (AQP2) upregulation, compatible with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) 8.
• Anticonvulsants: Some anticonvulsants, like carbamazepine, may also induce hyponatremia by similar mechanisms 8.
• Cyclophosphamide: This anticancer chemotherapeutic agent can cause hyponatremia by inducing SIADH or NSIAD 8.
• Vincristine and ifosfamide: These drugs are associated with sustained plasma AVP levels and can cause SIADH 8.
• Desmopressin: Although used to treat diabetes insipidus, desmopressin can induce hyponatremia when prescribed for nocturnal polyuria in older patients due to its selective binding to vasopressin V2 receptor (V2R) 8.
• Oxytocin: As a V2R agonist, oxytocin can produce hyponatremia when used to induce labor or abortion 8.

Patient Risk Factors

Certain patient factors can increase the risk of developing hyponatremia when taking these drugs, including:

• Advanced age 7
• Female gender 7, 6
• Low weight 7
• Sodium levels in the lower limits 7
• Excess water intake 4, 6
• Hypokalemia 4, 6