Reviewed on 3/9/2022

What Is Tolvaptan and How Does It Work?

Tolvaptan is a prescription medication used for the treatment of hyponatremia and polycystic kidney disease.

  • Tolvaptan is available under the following different brand names: Samsca, Jynarque

What Are Dosages of Tolvaptan?

Adult dosage

Tablet (Samsca)

  • 15mg
  • 30mg

Tablet (Jynarque)

  • 15mg
  • 30mg
  • 45mg
  • 60mg
  • 90mg


Adult dosage

  • Initial: 15 mg orally once daily
  • Maintenance: May increase to 30 mg once daily after at least 24 hr to achieve the optimal serum sodium level; not to exceed 60 mg/day
  • Not to exceed 30 days of treatment

Polycystic Kidney Disease

Jynarque only

Adult dosage

  • Initial: 45 mg orally taken on waking and 15 mg taken 8 hours later (i.e., 60 mg/day)

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Are Side Effects Associated with Using Tolvaptan?

Common side effects of Tolvaptan include:

  • dry mouth,
  • increased thirst or urination,
  • hunger,
  • fruity breath odor,
  • constipation, and
  • weakness
  • thirst and drinking more fluid than normal
  • making large amounts of urine, urinating often, and urinating at night

Serious side effects of Tolvaptan include:

  • hives,
  • difficulty breathing,
  • swelling of the face, lips, tongue, or throat,
  • severe dizziness,
  • problems with speech or muscle control,
  • trouble swallowing,
  • trouble moving the arms and legs,
  • confusion,
  • mood changes,
  • seizure,
  • weakness,
  • lightheadedness,
  • right-sided upper stomach pain,
  • vomiting,
  • loss of appetite,
  • fever,
  • itching,
  • yellowing of the skin or eyes,
  • feeling unwell,
  • feeling very thirsty or hot,
  • little or no urine,
  • heavy sweating,
  • dizziness,
  • fainting,
  • weight loss,
  • irregular heartbeat, and
  • feel confused or weak.

Rare side effects of Tolvaptan include:

  • none 
This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Tolvaptan?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Tolvaptan has severe interactions with the following drug:
  • Tolvaptan has serious interactions with at least 98 other drugs.
  • Tolvaptan has moderate interactions with at least 193 other drugs.
  • Tolvaptan has minor interactions with the following drugs:

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

What Are Warnings and Precautions for Tolvaptan?


  • Concomitant use of strong CYP3A inhibitors
  • Hypersensitivity (e.g., anaphylactic shock, generalized rash)
  • Anuria
  • The inability of the patient to sense or appropriately respond to thirst
  • Hypovolemic hyponatremia
  • Samsca
    • Use in patients with ADPKD outside of FDA-approved REMS (see Black Box Warnings)
    • Urgent need to raise serum sodium acutely
  • Jynarque
    • History, signs, or symptoms of significant liver impairment or injury; this contraindication does not apply to uncomplicated polycystic liver disease
    • Uncorrected abnormal blood sodium concentrations
    • Uncorrected urinary outflow obstruction

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Tolvaptan?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Tolvaptan?”


  • Hypernatremia, hypovolemia, and/or dehydration may occur; encourage patient to drink whenever thirsty
  • Patients with partial obstruction of the urinary outflow, patients with prostatic hypertrophy or impairment of micturition, have an increased risk of developing acute retention
  • Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported; discontinue if laboratory abnormalities or signs or symptoms of liver injury are evident (see Black Box Warnings); limit the duration of therapy to 30 days; avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover from liver injury may be impaired
  • In patients who develop medically significant signs or symptoms of hypovolemia, interrupt or discontinue therapy and provide supportive care with careful management of vital signs, fluid balance, and electrolytes; fluid restriction during therapy may increase the risk of dehydration and hypovolemia; patients receiving therapy should continue ingestion of fluid in response to thirst
  • Osmotic demyelination syndrome
    • Osmotic demyelination syndrome is a risk associated with too-rapid correction of hyponatremia (see Black Box Warnings)
    • In susceptible patients, including those with severe malnutrition, alcoholism, or advanced liver disease, slower rates of correction may be advisable
    • In patients who develop too rapid a rise in serum sodium, discontinue or interrupt treatment and consider administration of hypotonic fluid; fluid restriction during the first 24 hr of therapy may increase the likelihood of overly-rapid correction of serum sodium, and should generally be avoided; co-administration of diuretics also increases the risk of too rapid correction of serum sodium; such patients should undergo close monitoring of serum sodium
    • Patients with symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice should discontinue treatment
  • Drug interaction overview
    • Hypertonic saline: Concomitant use not recommended
    • Diuretics: Increases risk for dehydration
    • P-p inhibitors: Monitor; dose reduction may be required
    • Drugs that increase serum potassium: Tolvaptan may have additive hyperkalemic effects if coadministered
    • P-GP substrates: Tolvaptan may increase AUC and Cmax of P-GP substrates
    • OATP1B1/3 and OAT3 substrates: Avoid concomitant use; tolvaptan may increase plasma concentrations of these substrates
    • BCRP substrates: Avoid concomitant use; tolvaptan is an inhibitor of BCRP
    • V2-receptor agonists: Avoid concomitant use; tolvaptan, a V2-antagonist, interferes with V2-agonist activity (eg, desmopressin [dDAVP])
    • CYP3A
    • Tolvaptan is a substrate of CYP3A
    • CYP3A inhibitors can lead to a marked increase in tolvaptan concentrations
    • Coadministration with strong CY3A inhibitors: Contraindicated
    • Coadministration with moderate CYP3A inhibitors: Avoid (Samsca); modify dose (Jynarque)
    • Coadministration with CYP3A inducers: Monitor; dosage increase may be required

Pregnancy and Lactation

  • Available data are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes
  • Lactation
    • Data are not available on the presence of tolvaptan in human milk, the effects on the breastfed infant, or the effects on milk production
    • Tolvaptan is present in rat milk
    • Because of the potential for serious adverse reactions, including liver toxicity, electrolyte abnormalities (e.g., hypernatremia), hypotension, and volume depletion in breastfed infants, advise women not to breastfeed during treatment
Medscape. Tolvaptan.

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