TOLAVAT 15MG TABLETS

Indications

• Hyponatremia associated with heart failure
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Polycystic kidney disease for slowing renal function decline

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric populations.

Adults: Refer to the BNF for specific dosing information, as it varies based on clinical condition and patient response.

Mechanism of action

Tolvaptan acts as a selective antagonist of the vasopressin V2 receptors located in the renal collecting ducts. By blocking these receptors, tolvaptan inhibits the action of vasopressin (also known as antidiuretic hormone), leading to increased aquaporin-2 channel insertion in the renal tubules, which promotes water reabsorption. This ultimately results in increased urine output (aquaresis) and a reduction in water retention.

Pharmacodynamics

Tolvaptan increases the excretion of free water without significantly affecting the excretion of electrolytes. This selective action on the renal collecting ducts helps to correct diluted plasma sodium levels seen in hyponatremia. The onset of action typically occurs within 2 to 8 hours, with a peak effect seen within 12 to 24 hours. Its diuretic effects are dose-dependent and can lead to significant changes in fluid balance.

Pharmacokinetics

Tolvaptan is well absorbed following oral administration, with peak plasma concentrations occurring approximately 4 hours after dosing. It has a bioavailability of about 56%. The drug is extensively metabolized in the liver, primarily by cytochrome P450 3A4, and has a half-life of approximately 12 hours. It is excreted mainly in the urine as metabolites, with only a small percentage of unchanged drug found in urine.

Contra-indications

• Hypersensitivity to tolvaptan or any of its components
• Anuria
• Severe liver impairment

Adverse effects

• Thirst
• Dry mouth
• Nausea
• Diarrhea
• Increased urination
• Hypernatremia
• Hepatotoxicity

Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) may increase tolvaptan levels
• CYP3A4 inducers (e.g., rifampicin, carbamazepine) may decrease tolvaptan levels
• Diuretics may enhance the diuretic effect of tolvaptan

Precautions

• Monitor serum sodium levels regularly
• Assess liver function before initiation and during treatment
• Caution in patients with volume depletion or hypotension
• Not recommended for use in patients with a history of significant liver disease

Pregnancy

Tolvaptan is not recommended during pregnancy due to potential risks to the fetus. Data on its use in pregnant women are limited.

Breast-feeding

It is not known whether tolvaptan is excreted in human milk. Caution should be exercised when administering tolvaptan to nursing mothers.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Tablets: 15 mg, 30 mg, 60 mg