Tolvaptan is a selective vasopressin V2 receptor antagonist used for the treatment of specific types of hyponatremia.

I. Indications

1. Target Population for Treatment

(1) Tolvaptan is indicated for clinically significant hypervolemic or euvolemic hyponatremia.

(2) This includes serum sodium below 125 mEq/L, or less severe hyponatremia that is symptomatic and has failed fluid restriction therapy.

(3) Common underlying causes include heart failure, syndrome of inappropriate antidiuretic hormone (SIADH), and cirrhosis.

2. Non-applicable Situations

This drug is not indicated for patients who require emergent elevation of serum sodium to prevent or treat severe neurological symptoms.

II. Contraindications and Prohibited Foods

1. Absolute Contraindications in Populations

Tolvaptan is contraindicated in the following patients: those with autosomal dominant polycystic kidney disease (except under FDA-approved REMS program); patients who cannot sense or respond to thirst; patients with hypovolemic hyponatremia; patients with anuria; and those with hypersensitivity to tolvaptan or any of its components.

2. Contraindications Related to Drug Interactions

(1) Coadministration with strong CYP3A inhibitors is prohibited, e.g., ketoconazole, clarithromycin, ritonavir, etc.

(2) These drugs significantly increase tolvaptan plasma concentrations, raising the risk of adverse reactions.

3. Prohibited Foods

(1) Patients should avoid consuming grapefruit juice while taking tolvaptan.

(2) Grapefruit juice inhibits the CYP3A metabolic enzyme, leading to a 60% to 90% increase in tolvaptan plasma concentration, thereby increasing the risk of toxicity.

III. Use in Special Populations

1. Use During Pregnancy

Advise women of childbearing potential of the potential risk to the fetus. If pregnant or planning to become pregnant, they should inform their doctor promptly.

2. Use During Breastfeeding

Due to the potential for serious adverse reactions (e.g., hypernatremia, hypotension, hypovolemia) in breastfed infants, women are advised not to breastfeed while taking this medication.

3. Use in Children

Use in individuals under 18 years of age is currently not recommended.

4. Use in the Elderly

Age does not significantly affect tolvaptan plasma concentrations.

5. Use in Patients with Hepatic Impairment

(1) Mild-to-moderate and severe hepatic impairment have no clinically significant effect on tolvaptan exposure.

(2) However, given the potentially impaired recovery capacity following liver injury, use in patients with underlying liver disease (including cirrhosis) should be avoided.

(3) Limit treatment duration to 30 days to reduce the risk of liver injury.

6. Use in Patients with Renal Impairment

(1) Dose adjustment based on renal function is not necessary.

(2) However, for patients with creatinine clearance below 10 mL/min, clinical trial data are lacking, and the drug’s effect on raising serum sodium may be lost; therefore, use is not recommended.

(3) Tolvaptan is contraindicated in patients with anuria.