Drug Guide

Generic Name

Tolvaptan

Brand Names Samsca, Jynarque

Classification

Therapeutic: Vasopressin V2-receptor antagonist for fluid regulation in hyponatremia and autosomal dominant polycystic kidney disease

Pharmacological: Selective vasopressin V2-receptor antagonist

FDA Approved Indications

Hyponatremia (especially SIADH)
Autosomal dominant polycystic kidney disease (ADPKD)

Mechanism of Action

Tolvaptan selectively blocks V2 receptors in the renal collecting ducts, leading to aquaresis (excretion of free water) without electrolyte loss, thereby increasing serum sodium levels.

Dosage and Administration

Adult: Typically 15 mg once daily, titrate up to 30 or 60 mg based on response and tolerability.

Pediatric: Not approved for pediatric use.

Geriatric: Use caution; start at lowest dose and titrate slowly due to potential for increased sensitivity and adverse effects.

Renal Impairment: Adjust dose based on renal function; avoid in severe renal impairment.

Hepatic Impairment: Use caution; lower starting doses and close monitoring recommended.

Pharmacokinetics

Absorption: Rapidly absorbed after oral administration.

Distribution: Widely distributed; volume of distribution approximately 150 liters.

Metabolism: Metabolized primarily by CYP3A4 enzymes.

Excretion: Excreted mainly via feces; renal excretion minimal.

Half Life: Approximately 12 hours.

Contraindications

Hypovolemic hyponatremia
Anuria
Concurrent use of strong CYP3A4 inhibitors
Liver failure or disease

Precautions

Monitor serum sodium closely to prevent overly rapid correction of hyponatremia, which can lead to osmotic demyelination syndrome.
Use with caution in patients with hepatic impairment and in elderly patients due to increased adverse effect risk.

Adverse Reactions - Common

Thirst (Common)
Dry mouth (Common)
Polyuria (Common)
Weakness (Common)

Adverse Reactions - Serious

Osmotic demyelination syndrome (ODS) due to rapid serum sodium correction (Rare but serious)
Hepatotoxicity (jaundice, elevated liver enzymes) (Reported in rare cases)

Drug-Drug Interactions

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase tolaptan levels and risk of adverse effects.
Other medications that affect serum sodium levels.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Assessment: Monitor serum sodium, liver function tests, and renal function regularly.

Diagnoses:

Imbalanced fluid volume related to fluid shifts or medication effects.
Risk for electrolyte imbalance.

Implementation: Administer exactly as prescribed, with careful titration.

Evaluation: Assess for normalization of serum sodium and monitor for adverse effects.

Patient/Family Teaching

Take medication exactly as prescribed.
Report symptoms of high or low serum sodium (e.g., confusion, headache, weakness).
Avoid rapid changes in fluid intake without medical advice.
Inform about potential hepatotoxicity and importance of liver function monitoring.

Special Considerations

Black Box Warnings:

Severe hepatic injury observed with tolvaptan use, especially in ADPKD.
Rapid correction of serum sodium can lead to osmotic demyelination syndrome.

Genetic Factors: No specific genetic markers identified, but CYP3A4 metabolizer status may affect drug levels.

Lab Test Interference: None significant.

Overdose Management

Signs/Symptoms: Severe hyponatremia, dehydration, hypotension, changes in mental status.

Treatment: Discontinue medication, implement fluid restrictions, administer hypertonic saline if severe hyponatremia persists, and provide supportive care.

Storage and Handling

Storage: Store at room temperature, away from moisture and sunlight.

Stability: Stable for the duration of the expiration date on the package.