What oral tablet is recommended for treating chronic eu‑osmolar or hyper‑osmolar hyponatraemia in an adult patient (e.g., syndrome of inappropriate antidiuretic hormone secretion, heart‑failure‑related dilutional hyponatraemia, or cirrhosis‑related hyponatraemia)?

Oral Tablet for Chronic Hyponatraemia

Tolvaptan is the only FDA-approved oral tablet specifically indicated for treating clinically significant hypervolemic and euvolemic hyponatraemia (serum sodium <125 mEq/L or symptomatic hyponatraemia resistant to fluid restriction) in conditions such as SIADH, heart failure, and cirrhosis. 1

FDA-Approved Indication and Dosing

Tolvaptan (a selective vasopressin V2-receptor antagonist) is initiated at 15 mg once daily, titrated after at least 24 hours to 30 mg daily, and may be increased to a maximum of 60 mg daily as needed to achieve target sodium levels. 1

• Initiation and re-initiation must occur in a hospital setting where serum sodium can be monitored closely, as too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome. 1
• Treatment duration should not exceed 30 days to minimize hepatotoxicity risk. 1
• During the first 24 hours of therapy, avoid fluid restriction and allow patients to drink in response to thirst. 1

Mechanism and Clinical Efficacy

Tolvaptan promotes aquaresis (electrolyte-sparing water excretion) by blocking arginine vasopressin binding to V2 receptors in the renal collecting ducts, thereby increasing free water clearance without sodium loss. 2

• The SALT trials demonstrated that tolvaptan rapidly and effectively resolved hyponatraemia in hypervolemic (heart failure, cirrhosis) and euvolemic (SIADH) settings. 3
• Tolvaptan significantly increased serum sodium levels compared to placebo, with effects seen as early as 8 hours after the first dose. 4
• In controlled trials, 7% of tolvaptan-treated subjects with sodium <130 mEq/L had an increase >8 mEq/L at approximately 8 hours, and 2% had an increase >12 mEq/L at 24 hours. 1

Specific Population Considerations

Heart Failure

For heart failure patients with persistent severe hyponatraemia despite water restriction and maximization of guideline-directed medical therapy, tolvaptan may be considered for short-term use. 5, 4

• Fluid restriction to 1–1.5 L/day remains first-line therapy for sodium <125 mmol/L in hypervolemic hyponatraemia. 4
• Tolvaptan should only be added after optimizing ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists. 4

Cirrhosis

In cirrhotic patients, tolvaptan should be used with extreme caution and only after failure of fluid restriction and albumin infusion, due to increased risk of gastrointestinal bleeding (10% vs. 2% placebo) and hepatotoxicity. 4, 3

• Correction rates must be limited to 4–6 mmol/L per day (maximum 8 mmol/L in 24 hours) in cirrhotic patients due to exceptionally high risk of osmotic demyelination syndrome. 4
• Albumin infusion (8 g/L of ascites removed) should be tried before tolvaptan. 4
• Monthly monitoring of liver function tests (ALT, AST, bilirubin) is required, as 4.4% of patients developed ALT >3× upper limit of normal. 4

SIADH

For euvolemic hyponatraemia due to SIADH, tolvaptan is indicated when fluid restriction (<1 L/day) and oral sodium supplementation fail to adequately correct sodium levels. 4, 1

• Tolvaptan starting dose of 15 mg once daily can be titrated based on serum sodium response. 4
• Close monitoring is required to prevent overly rapid correction (>8 mmol/L/day). 4

Absolute Contraindications

Tolvaptan is contraindicated in patients who are unable to sense or respond to thirst, those with hypovolemic hyponatraemia, anuric patients, and those taking strong CYP3A inhibitors. 1

• Patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS are contraindicated due to hepatotoxicity risk. 1
• Hypersensitivity reactions (anaphylactic shock, generalized rash) are contraindications. 1

Critical Monitoring Requirements

Serum sodium must be checked every 2 hours during the first 8 hours after the initial dose, then every 4–6 hours while on therapy to ensure safe correction rates. 4

• Daily weights and fluid balance should be tracked meticulously. 4
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2–7 days after rapid correction. 4
• Monitor for side effects including thirst, dry mouth, and increased urination. 4

Alternative Oral Therapies (Less Preferred)

While urea and oral sodium chloride tablets can be used for SIADH, they have significant limitations compared to tolvaptan. 6

• Urea (40 g in 100–150 mL normal saline every 8 hours) is effective but has poor palatability and gastric intolerance. 6
• Oral sodium chloride (100 mEq three times daily) can be added to fluid restriction for SIADH but requires careful monitoring. 4
• Demeclocycline and lithium are less commonly used due to side effects and lack of FDA approval for this indication. 4

Common Pitfalls to Avoid

• Never use tolvaptan as first-line therapy before exhausting fluid restriction and standard measures. 4
• Never extend tolvaptan treatment beyond 30 days due to hepatotoxicity risk. 1
• Never apply fluid restriction during the first 24 hours of tolvaptan therapy, as this increases the risk of overly rapid sodium correction. 1, 3
• Never use tolvaptan in patients requiring urgent intervention to raise serum sodium acutely (e.g., severe symptomatic hyponatraemia with seizures or coma)—these patients require hypertonic saline. 1
• Never correct chronic hyponatraemia faster than 8 mmol/L in 24 hours, as this causes osmotic demyelination syndrome. 4, 1