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Pronunciation: tol-VAP-tan
Class: Vasopressin receptor antagonist

Trade Names

- Tablets 15 mg
- Tablets 30 mg


Antagonist of the arginine vasopressin V 2 receptor, thereby antagonizing the effect of vasopressin and causing an increase in urine water excretion that results in an increase in free water Cl, a decrease in urine osmolality, and a resulting increase in serum sodium concentrations.

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AUC increases in proportion with the dose. At least 40% of the dose is absorbed as parent drug or metabolites. T max is between 2 and 4 h.


Vd is about 3 L/kg. Protein binding is 99%.


Metabolized mainly by CYP3A and is a substrate and inhibitor of P-glycoprotein (P-gp).


Elimination is by nonrenal routes. Cl is about 4 mL/min/kg and the terminal half-life is about 12 h.


2 to 4 h.


4 to 8 h.


24 h.

Special Populations

Renal Function Impairment

Tolvaptan has not been evaluated in patients with CrCl less than 10 mL/min or in patients undergoing dialysis; contraindicated in patients with anuria.

Hepatic Function Impairment

Vd is increased and Cl is decreased in patients with severe hepatic function impairment; however, these changes do not appear to be clinically important.


Vd is increased and Cl is decreased in patients with CHF; however, these changes do not appear to be clinically important.

Indications and Usage

Treatment of clinically important hypervolemic and euvolemic hyponatremia (serum sodium less than 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and SIADH.


Urgent need to increase serum sodium acutely; inability of the patient to sense or appropriately respond to thirst; hypovolemic hyponatremia; coadministration of strong CYP3A inhibitors; anuria.

Dosage and Administration


PO 15 mg once daily without regard to meals. Increase the dosage to 30 mg once daily, after at least 24 h, to a maximum of 60 mg once daily, as needed to achieve the desired serum sodium level.

General Advice

  • Avoid fluid restrictions during the first 24 h of therapy.
  • Patients can continue ingestion of fluid in response to thirst.
  • May be taken without regard to meals.
  • Following discontinuation, patients should resume fluid restriction.


Store at 59° to 86°F.

Drug Interactions

CYP3A inducers (eg, barbiturates [eg, phenobarbital], carbamazepine, phenytoin, rifamycins [eg, rifampin], St. John's wort)

Tolvaptan plasma concentrations may be reduced, decreasing the efficacy.

CYP3A inhibitors (eg, aprepitant, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, verapamil)

Tolvaptan exposure may be increased; tolvaptan is contraindicated in patients receiving strong CYP3A inhibitors; avoid use with moderate CYP3A inhibitors.


Exposure to digoxin may be increased.

Drugs that increase serum potassium (eg, ACE inhibitors [eg, captopril], angiotensin receptor blockers [eg, candesartan], potassium-sparing diuretics [eg, spironolactone])

Coadministration may increase the hyperkalemic effects of both agents.

Hypertonic solutions

Coadministration is not recommended.


Exposure to lovastatin and its active metabolite may be increased; however, the change is not expected to be clinically important.

P-gp inhibitors (eg, cyclosporine)

Dose of tolvaptan may need to be reduced.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Deep vein thrombosis, disseminated intravascular coagulation, intracardiac thrombus, ventricular fibrillation (less than 2%).


Nausea (21%); asthenia (9%); cerebrovascular accident (less than 2%).


Dry mouth (13%); constipation (7%); anorexia (4%); ischemic colitis (less than 2%).


Pollakiuria or polyuria (11%); urethral hemorrhage, vaginal hemorrhage (less than 2%).


Hyperglycemia (6%); anorexia (4%); diabetic ketoacidosis (less than 2%).


Pulmonary embolism, respiratory failure (less than 2%).


Thirst (16%); pyrexia (4%); prolonged PT, rhabdomyolysis (less than 2%).




Initiate and reinitiate treatment only in patients in a hospital where serum sodium can be monitored.

Rapid correction of hyponatremia

Too rapid correction of hyponatremia (eg, more than 12 mEq/L in 24 hours) can cause osmotic demyelination resulting in affective changes, dysarthria, dysphagia, lethargy, mutism, seizures, and spastic quadriparesis, coma and death. In susceptible patients, including those with advanced liver disease, alcoholism, or severe malnutrition, slower rates of correction may be advisable.


During initiation and titration of the treatment, frequently monitor for changes in serum electrolytes, volume, vital signs, and neurologic status. Following discontinuation, monitor patients for changes in serum sodium and volume status. Monitor serum potassium levels after initiation of treatment in patients with a serum potassium greater than 5 mEq/L and in patients receiving drugs that increase serum potassium levels.


Category C .




Safety and efficacy not established.

Renal Function

Dosage adjustment is not needed in patients with mild to severe renal function impairment (CrCl 10 to 79 mL/min). Tolvaptan has not been evaluated in patients with CrCl less than 10 mL/min or in patients undergoing dialysis. No benefit is expected in anuric patients.

Hepatic Function

Dosage adjustment is not needed.

Special Risk Patients

Patients with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium.


No dosage adjustment is needed.


Can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted. Interruption or discontinuation of therapy may be needed if significant hypovalemia develops.

GI bleeding

Use in cirrhotic patients only if the need to treat outweighs the risk.


Can occur.



Dehydration/hypovolemia, increase in serum sodium concentration, polyuria, thirst.

Patient Information

  • Review the tolvaptan Medication Guide with every patient.
  • Advise patients to continue ingestion of fluid in response to thirst and that they should have water available at all times.
  • Advise patients to resume fluid restriction following discontinuation of tolvaptan.
  • Advise patients to inform health care provider if they are taking strong (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, saquinavir, telithromycin) or moderate (eg, aprepitant, dilatiazem, erythromycin, fluconazole, verapamil) CYP3A inhibitors or P-gp inhibitors (eg, cyclosporine).
  • Advise patients to immediately contact their health care provider if they experience confusion, drowsiness, mood changes, trouble speaking, trouble swallowing or feeling like food or liquid is stuck while swallowing, or other new symptoms.
  • Advise patients not to drink grapefruit juice while taking tolvaptan.
  • Advise patient to notify health care provider immediately if they experience an illness such as nausea, vomiting, or diarrhea that may keep them from drinking water.
  • Instruct patients to call health care provider immediately if they take too much tolvaptan.
  • Advise women not to breast-feed while taking tolvaptan.
  • Advise patients to notify health care provider immediately if they vomit bright red blood, vomit dark blood clots or material that looks like coffee-grounds, if their stools are black or look like tar, if they pass blood or a stool mixed with blood, or if their stool is bright red or contains maroon-colored blood.

Copyright © 2009 Wolters Kluwer Health.