What medications can cause or exacerbate hyponatremia (low sodium levels)?

From the Guidelines

Medications such as diuretics, antidepressants, antipsychotics, antiepileptic drugs, chemotherapy agents, NSAIDs, proton pump inhibitors, and ACE inhibitors/ARBs can cause or worsen hyponatremia, and it is crucial to monitor sodium levels when starting these medications, especially in high-risk patients. Several medications can cause or worsen hyponatremia, including:

• Diuretics, particularly thiazides and loop diuretics, which increase sodium excretion in urine 1
• Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), which can cause syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Antipsychotics, such as haloperidol and risperidone, which may also trigger SIADH
• Antiepileptic drugs, notably carbamazepine, oxcarbazepine, and sodium valproate, which can reduce sodium levels
• Certain chemotherapy agents, such as cyclophosphamide and vincristine
• NSAIDs, including ibuprofen and naproxen
• Proton pump inhibitors, such as omeprazole and pantoprazole
• ACE inhibitors/ARBs, including lisinopril and losartan These medications affect sodium balance through various mechanisms, including increased water retention, enhanced sodium excretion, or stimulation of ADH release, as noted in the management of hyponatremia in patients with cirrhosis 1. It is essential to be aware of these potential causes of hyponatremia, especially in elderly patients, those with kidney disease, heart failure, or liver disease, who are particularly susceptible to medication-induced hyponatremia. The treatment of hyponatremia involves addressing the underlying cause, and in some cases, using medications such as vaptans, which have been shown to be effective in improving serum sodium concentration in patients with hypervolemic hyponatremia 1.

From the FDA Drug Label

Hyponatremia — Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Prozac. Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including Trazodone Hydrochloride Tablets.

The medications that can cause or worsen hyponatremia are:

• SSRIs (Selective Serotonin Reuptake Inhibitors), such as fluoxetine 2
• SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), such as trazodone 3

From the Research

Medications that Can Cause or Worsen Hyponatremia

• Thiazide diuretics: These medications 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.
• Selective serotonin reuptake inhibitors (SSRIs): SSRIs can cause hyponatremia through the syndrome of inappropriate ADH release 6, 4.
• Combination of thiazide diuretics and SSRIs: The concurrent use of thiazide diuretics and SSRIs is associated with an increased risk of hyponatremia in older populations 7, 4.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and tricyclic antidepressants: These medications can also increase the risk of thiazide-associated hyponatremia when taken concurrently with thiazide diuretics 8.

Patient Risk Factors

• Older age: Elderly patients are more susceptible to hyponatremia induced by thiazide diuretics and SSRIs 7, 8, 5.
• Female sex: Women, especially elderly women, seem to be at increased risk for thiazide-induced hyponatremia and SSRI-induced hyponatremia 8, 4.
• Reduced body mass: Patients with lower body mass are more prone to thiazide-induced hyponatremia 5.
• Concurrent use of other medications: The use of other medications that impair water excretion can increase the risk of hyponatremia when taken with thiazide diuretics or SSRIs 8, 5.