Generic Name and Formulations:
Tolvaptan 15mg, 30mg; tabs.
Otsuka America Pharmaceutical, Inc.
Indications for SAMSCA:
Clinically significant euvolemic and hypervolemic hyponatremia (serum sodium <125mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and syndrome of inappropriate antidiuretic hormone (SIADH). Limitations of use: not for urgent serum sodium correction to prevent or treat serious neurological symptoms.
Initiate and re-initiate only in a hospital. Initially 15mg once daily, may increase dose after ≥24hrs to 30mg once daily, then to max 60mg once daily as needed to raise serum sodium. Max therapy: 30 days duration. Avoid fluid restriction during the first 24hrs of therapy; resume fluid restriction after drug discontinuation.
Autosomal dominant polycystic kidney disease (ADPKD). Urgent need to raise serum sodium acutely. Inability of patient to sense or appropriately respond to thirst. Hypovolemic hyponatremia. Concomitant strong CYP3A inhibitors (eg, clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin). Anuric patients.
Initiate and re-initiate in a hospital and monitor serum sodium.
Do not use for ADPKD outside of FDA-approved REMS; risk of serious and potentially fatal liver injury. Risk of osmotic demyelination syndrome; discontinue or interrupt therapy if too rapid a rise in serum sodium occurs (eg, >12mEq/L/24hrs). Severe malnutrition, alcoholism, or advanced liver disease: slower rates of correction advisable. Patients with SIADH or low baseline serum sodium concentrations. Avoid in patients with underlying liver disease, including cirrhosis; discontinue if symptoms of liver injury develop. Severe renal impairment (CrCl<10mL/min): not recommended. Monitor frequently for changes in serum sodium, volume and neurologic status during initiation and titration. Monitor serum potassium in patients with K+ >5mEq/L or on drugs known to increase potassium. Pregnancy (Cat.C). Nursing mothers: not recommended.
Selective vasopressin V2-receptor antagonist.
See Contraindications. Potentiated by CYP3A inhibitors, grapefruit juice; avoid moderate CYP3A inhibitors (eg, erythromycin, fluconazole, aprepitant, diltiazem, verapamil). Antagonized by CYP3A inducers (eg, rifampin, rifabutin, rifapentin, barbiturates, phenytoin, carbamazepine, St. John's wort); avoid; if given, may need to increase tolvaptan dose. Concomitant P-gp inhibitors (eg, cyclosporine); consider reducing tolvaptan dose. May potentiate digoxin. Concomitant hypertonic saline or V2 agonist (desmopressin): not recommended. Concomitant diuretics increases the risk of too rapid correction of sodium; monitor serum sodium closely.
Thirst, dry mouth, asthenia, constipation, pollakiuria, polyuria, hyperglycemia; osmotic demyelination syndrome, liver injury, hypovolemia (discontinue or interrupt if significant), hyperkalemia.