Generic
Tolvaptan
2 brands available in the market
At a glance
Tolvaptan is indicated for hypervolemic or euvolemic hyponatremia and autosomal dominant polycystic kidney disease. It is a selective vasopressin V2-receptor antagonist.
Description
Tolvaptan is a selective vasopressin V2-receptor antagonist. Its affinity for V2-receptors is 29 times greater than for V1a-receptors. It antagonizes vasopressin, causing aquaresis, decreased urine osmolality, and increased serum sodium concentrations.
Indications
- Hypervolemic or euvolemic hyponatremia
- Autosomal dominant polycystic kidney disease (ADPKD)
Therapeutic class
Selective vasopressin V2-receptor antagonist
Pharmacological class
Vasopressin V2-receptor antagonist
Pharmacology
Tolvaptan antagonizes vasopressin at V2-receptors, increasing free water clearance (aquaresis), decreasing urine osmolality, and increasing serum sodium concentrations. Urinary excretion of sodium and potassium and plasma potassium concentrations are not significantly changed.
Mechanism of action
Antagonizes vasopressin V2-receptors, increasing aquaresis and serum sodium.
Dosage
Adult Dose (Oral):
- Hyponatremia: Initial 15 mg once daily; increase to 30 mg once daily, then 60 mg once daily as needed; do not use for more than 30 days
- ADPKD: Initial 60 mg/day (45 mg upon wakening + 15 mg 8 hours later); titrate to 90 mg/day, then 120 mg/day
Administration
- May be taken with or without food
- Take as directed by your doctor
Missed dose
If you miss a dose, take it as soon as possible; if almost time for next dose, skip it; do not double the dose.
Side effects
Common Side Effects:
- Thirst
- Dry mouth
- Weakness
- Constipation
- Making large amounts of urine and urinating often
- Increased blood sugar levels
Precautions & warnings
- Too rapid correction of serum sodium can cause serious neurologic sequelae
- Risk of hepatotoxicity; do not use for more than 30 days
- Maintain adequate hydration
- Contraindicated in pregnancy
Contraindications
- Hypersensitivity to active substance or excipients
- Anuria
- Volume depletion
- Hypovolemic hyponatremia
- Hypernatremia
- Patients who cannot perceive thirst
- Pregnancy
- Breast-feeding
Drug interactions
- Strong CYP3A inhibitors: increased tolvaptan concentrations; do not use together
- Moderate CYP3A inhibitors: avoid concomitant use
- CYP3A inducers (rifampin, rifabutin, phenytoin, carbamazepine): reduced plasma concentration and effectiveness
- P-gp inhibitors (cyclosporine): dose reduction may be needed
Food interactions
Alcohol consumption should be cautioned.
Use in pregnancy
Use in Pregnancy: Contraindicated; animal studies show reproductive toxicity; do not use during pregnancy.
Pregnancy Category: C — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; contraindicated.
Pediatric use
Safety and effectiveness not established in pediatric patients
Geriatric use
No overall differences in safety or effectiveness observed between elderly and younger patients
Renal / hepatic impairment
Renal Impairment: No dose adjustment necessary; not recommended in CrCl<10 ml/min
Hepatic Impairment: Moderate and severe: no clinically relevant effect on exposure; avoid in underlying liver disease
Overdose effects
Symptoms: Rise in serum sodium, polyuria, thirst, dehydration/hypovolemia.
Treatment: Assess vital signs, electrolytes, ECG, fluid status; replace water and electrolytes.
Storage conditions
Store below 25°C in a dry place, protected from light; keep out of reach of children.