Samsca (Tolvaptan) – Oral


Always start or restart therapy with Samsca in a hospital and monitor serum sodium to avoid a rapid increase in sodium levels. 

Too rapid correction of hyponatremia, such as greater than 12 milliequivalents per liter per 24 hours (mEq/L/24 hours), may lead to osmotic demyelination (severe nerve damage caused by quick increases in sodium levels), resulting in: 

  • Dysarthria (weakness of speech muscle)
  • Mutism (an absence of speech while conversing)
  • Dysphagia (swallowing difficulties)
  • Lethargy (lack of energy)
  • Affective (emotional) changes
  • Spastic quadriparesis (muscles that are stiff, tight, or unable to move freely)
  • Seizures
  • Coma and death

In susceptible patients with severe malnutrition, alcoholism, or advanced liver disease, slower correction rates may be advisable.

The Food and Drug Administration (FDA) has taken back the approval, and Samsca is not for use for autosomal dominant polycystic kidney disease (ADPKD)

Because of the risk of hepatotoxicity (kidney toxicity), Samsca should not be used for ADPKD outside the FDA-approved Risk Evaluation and Mitigation Strategy (REMS) program.

What Is Samsca?

Samsca contains the active drug tolvaptan, which belongs to the vasopressin receptor antagonist class. It is a prescription drug used to treat hyponatremia (low sodium levels). It is usually started in a hospital setting.

Samsca binds to vasopressin receptors and blocks vasopressin. This causes water to be released from the body as urine without impacting sodium and potassium levels. This is in contrast to traditional diuretics (water pills).

Drug Facts

Generic Name: Tolvaptan

Brand Name(s): Samsca

Drug Availability: Prescription

Therapeutic Classification: Vasopressin receptor antagonists

Available Generically: Yes (tolvaptan 15-milligram tablets)

Controlled Substance: No

Administration Route: Oral

Active Ingredient: Tolvaptan

Dosage Form(s): Tablets

What Is Samsca Used For?

Samsca was approved for use in the United States in May 2009 for the treatment of hypervolemic and euvolemic hyponatremia in patients with:

  • Heart failure
  • Syndrome of inappropriate antidiuretic hormone (SIADH), where high hormone levels make the body retain fluid.

Limitations of Use:

Samsca should not be used:

  • For more than 30 consecutive days, mainly due to increased liver enzyme levels and risk of liver toxicity.
  • In patients requiring intervention, raise sodium levels quickly to prevent or treat severe neurological symptoms

Hyponatremia affects about 1 in 5 of all hospitalized patients. It can cause cognitive and motor impairment; however, severe hyponatremia is associated with morbidity (increased disease) and mortality (death) in some instances.

How to Take Samsca

Read the directions on the prescription label carefully, and ask your pharmacist any questions you have or if you do not understand any part of the directions.

At the beginning of your treatment, Samsca will be given at a regularly scheduled time in the hospital under the close observation of a healthcare professional. Take Samsca in the following ways:

  • Samsca is available on prescription as a tablet to take by mouth.
  • It is usually taken once a day for no longer than 30 days.
  • You can take Samsca with or without food.
  • When taking Samsca home after being discharged, you should take it daily. 
  • Take your dose exactly as directed.
  • Do not take more, less, or more often than prescribed by your healthcare provider.
  • Do not take grapefruit juice or eat it when taking Samsca.
  • Drink plenty of water or fluids.

Your healthcare provider may start you on a low dose of Samsca and gradually increase the dose, but you will take it not more than once every 24 hours.

Talk to your healthcare provider after you stop taking Samsca. You will probably need to limit your fluid intake, and your healthcare provider will monitor you closely for changes in your serum sodium and volume.


Store Samsca tablets in the original container at room temperature. Keep it away from heat and moisture. Keep your medications out of the reach of children and pets, ideally locked in a cabinet or closet.

If you plan to travel with Samsca, become familiar with your final destination's regulations. In general, be sure to make a copy of your Samsca prescription. If possible, keep your medication in its original container from your pharmacy with your name on the label. Ask your pharmacist or healthcare provider if you have any questions about traveling with your medicine.

Discard all unused and expired drugs, but do not pour them down the drain or toilet. Ask your pharmacist or medical provider about the best ways to dispose of this medicine. And check out drug take-back programs in your area.

Off-Label Uses

Ask your healthcare provider about any other uses of this drug.

How Long Does Samsca Take to Work?

Samsca starts working within two to four hours after taking a dose. The drug reaches its peak effects within two to eight hours after administration. The drug's ability to work in the body is not affected by food. 

What Are the Side Effects of Samsca?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other symptoms, contact your pharmacist or healthcare provider. You may report side effects to the Food and Drug Administration (FDA) at or 800-FDA-1088.

Common Side Effects

Some common side effects of Samsca are:

This may not be a complete list of side effects. Call your healthcare provider if your symptoms do not improve or if your condition worsens.

Severe Side Effects

Contact your healthcare provider if you have any signs of a severe reaction. Call 911 if your symptoms feel life-threatening.

People with severe liver disease may have an increased risk of bleeding from the stomach or intestines with symptoms:

  • Black/bloody stools
  • Vomit containing blood

A severe allergic reaction includes symptoms such as:

  • Rashes
  • Itching or swelling of the face, tongue, and throat
  • Severe dizziness
  • Trouble breathing

Long-Term Side Effects

Samsca should not be taken for more than 30 days. Long-term use may cause serious (possibly fatal) liver disease with symptoms such as:

  • Continued nausea or vomiting
  • Loss of appetite
  • Stomach or abdominal pain on the right side
  • Yellowing eyes and skin
  • Dark urine

Report Side Effects

Samsca may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Samsca Should I Take?

Your healthcare provider will determine and administer the initial dosage of Samsca for you in the hospital.

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For hyponatremia:
      • Adults—At first, 15 milligrams (mg) once a day. Your doctor will adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
      • Children—Use and dose must be determined by your doctor.
    • For slowing kidney function decline in patients who are at risk of autosomal dominant polycystic kidney disease (ADPKD):
      • Adults—At first, 60 milligrams (mg) per day (45 mg upon waking, then 15 mg taken 8 hours after). Your doctor will adjust your dose as needed and tolerated.
      • Children—Use and dose must be determined by your doctor.


The following modifications (changes) should be kept in mind when using Samsca:

Pregnancy: In nonhuman studies, fetal harm was observed in animal subjects at 1,000 milligrams per kilogram (mg/kg). Not enough is known about the safety and effectiveness of Samsca in pregnant humans and their fetuses. Discuss with your healthcare provider if you are or plan to become pregnant, and weigh the benefits and risks of taking Samsca during your pregnancy.

Breastfeeding: The effect of Samsca or its metabolites in human milk, its effects on the breastfed infant, or milk production are unknown. Do not breastfeed during treatment with Samsca due to the potential risk of severe adverse reactions, including electrolyte abnormalities, hypotension (low blood pressure), and volume depletion (fluid loss) in breastfed infants.

Adults over 65: Of the total hyponatremic subjects treated with Samsca in clinical studies, 42% were 65 years old and over, while 19% were 75 years old and over. No overall differences in the safety or effectiveness of this drug were observed in geriatric patients, but there can be exceptions in some individuals.

Children: The safety and effectiveness of Samsca in children have not been established.

Other modifications: Moderate and severe hepatic impairment does not affect exposure to tolvaptan. Avoid the use of Samsca in patients with underlying liver disease. No dose adjustment is necessary based on renal function. 

Administration modifications: Do not eat grapefruit or drink grapefruit juice while taking Samsca.

Missed Dose

If you accidentally forget your Samsca dose, take it as soon as you remember. If it's already close to your next scheduled dose, however, then skip the missed dose and take the following dose at your next scheduled dosing time. Don't try to double up to make up for the missed dose.

Try to find ways to help yourself remember to routinely take your medication.

Overdose: What Happens If I Take Too Much Samsca?

In case of an overdose, you need to be treated in a hospital. Assessment of vital signs, electrocardiogram (ECG or EKG), electrolyte imbalance and fluid status is required. If you're experiencing an overdose or life-threatening symptoms, seek immediate medical attention.

What Happens If I Overdose on Samsca?

If you think you or someone else may have overdosed on Samsca, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Samsca, call 911 immediately.


Drug Content Provided and Reviewed by IBM Micromedex®

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to decide if you should continue to use it. Blood tests may be needed to check for unwanted effects.

You should not use tolvaptan together with clarithromycin (Biaxin®), indinavir (Crixivan®), itraconazole (Sporanox®), ketoconazole (Nizoral®), nefazodone (Serzone®), nelfinavir (Viracept®), ritonavir (Norvir®), saquinavir (Fortovase®, Invirase®), or telithromycin (Ketek®). Using these medicines together may increase risk for more serious side effects.

Check with your doctor right away if you have drowsiness, confusion, mood changes, muscle weakness in the arms or legs, seizures (convulsions), or trouble with speaking, swallowing, or controlling body movements. These may be symptoms of a serious and rare condition called osmotic demyelination syndrome (ODS). This may occur if the sodium blood level rises too fast.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Certain medicines or illnesses, such as vomiting or diarrhea, may cause you to lose too much body water (dehydration). If you think you are dehydrated, tell your doctor right away. Always have water available to drink if you are thirsty, unless your doctor tells you otherwise.

Ask your doctor first before you use any medicine or salt substitutes that contain potassium.

You should not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit or grapefruit juice may increase the effects of tolvaptan in your body.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

What Are Reasons I Shouldn’t Take Samsca?

Contraindications for Samsca (reasons not to use it) includes the following conditions:

  • Long-term use in autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS
  • Inability by the patient to sense or respond to thirst
  • Hypovolemic hyponatremia (a decrease in total body water with a more significant drop in total body sodium)
  • Taking strong CYP3A inhibitor drugs such as antifungals ketoconazole, itraconazole, human immunodeficiency virus (HIV) drugs ritonavir, indinavir, nelfinavir, saquinavir, and antibiotics clarithromycin)
  • Anuria (loss of urine production)
  • Hypersensitivity to tolvaptan or any other ingredient of the product

What Other Medications Interact With Samsca?

Use caution when taking Samsca with the following medications:

Strong and Moderate CYP3A Inhibitors

Use of Samsca with potent and moderate CYP3A inhibitors is contraindicated. Larger doses of the potent CYP3A inhibitor would increase the tolvaptan exposure. Some examples of these drugs include:

  • Sporanox (itraconazole)
  • Biaxin XL (clarithromycin)
  • Viracept (nelfinavir)
  • Norvir (ritonavir)

It would be best to avoid grapefruit juice, beverages, or eating grapefruit while taking Samsca.

Strong CYP3A Inducers

Co-administered Samsca with strong CYP3A inducers can reduce exposure to Samsca. Some examples of these drugs are:

Angiotensin Receptor Blockers (ARBs), Angiotensin-Converting Enzyme (ACE) Inhibitors, and Potassium Sparing Diuretics

Although specific interaction studies were not performed, in clinical studies, hyperkalemia (too much potassium) adverse reactions were approximately 1% to 2% higher when Samsca was administered with ARBs, ACE inhibitors, and potassium-sparing diuretics. Some examples of these drugs include:

V2-Receptor Agonist

Samsca may interfere with the V2-agonist activity of dDAVP (desmopressin). Avoid concomitant use of Samsca with a V2-agonist.

Talk with your pharmacist or healthcare provider to get more detailed information about medication interactions with Samsca.

And be sure to inform your healthcare provider of all other medicines you take or plan to take, including over-the-counter (OTC), nonprescription products, vitamins, herbs, or plant-based medicines.

What Medications Are Similar?

Vasopressin receptor antagonists (Vaptans) are a new group of nonpeptide drugs used in the clinical management of hyponatremia. Some vaptans other than Samsca (tolvaptan) are:

  • Vaprisol (conivaptan)
  • Satavaptan

They produce aquaresis by acting on vasopressin V2 receptors and thus increase salt-free water excretion.

Frequently Asked Questions

  • What is Samsca used for?

    Samsca (tolvaptan) is indicated to treat symptoms of hypervolemic and euvolemic hyponatremia (low levels of sodium in the blood) in patients with heart failure and syndrome of inappropriate antidiuretic hormone (SIADH). 

  • How does Samsca work?

    Samsca (tolvaptan) belongs to the class of vasopressin V2 receptor antagonists. It improves urine flow without causing the body to lose too much sodium as you urinate. 

  • How to start taking Samsca?

    Start and restart (initiate and reinitiate) the therapy with Samsca in the hospital, where blood sodium levels can be monitored closely. After you are told to take it at home, take it at the same time each day as prescribed.

  • What are the common side effects of Samsca?

    Common side effects of Samsca are:

    • Thirst
    • Dry mouth
    • Constipation
    • Increased blood sugar
    • Increased urination
    • Weakness

    Call your healthcare provider if any symptom gets worse or do not go away.

  • How long does Samsca take to work?

    Samsca starts working within two to four hours of taking and reaches its peak plasma concentration with two to eight hours.

  • How long should I take Samsca?

    Samsca is not for long-term use. Do not take this medicine for more than 30 days to avoid the risk of liver problems, including life-threatening liver failure.

How Can I Stay Healthy While Taking Samsca?

Samsca is used to treat hyponatremia. It is one of the most common electrolyte abnormalities in patients admitted to the hospital. Nausea, seizures, and coma accompany the decrease in sodium levels. Hyponatremia is commonly associated with SIADH, excessive hydration during exercise, cirrhosis, heart failure, and certain drugs. 

Low sodium levels may cause increased fatigue and myalgia and impair quality of life. Samsca is an effective therapeutic option in such patients. Identifying hyponatremia and initiating early treatment will improve quality of life and may prevent lethal outcomes.

Never take Samsca for more than 30 days in a row. When taking Samsca at home, please don't stop taking it and then reinitiate it on your own. Always reinitiate in a hospital for close monitoring. Follow the recommendations regarding fluid intake and regular checkups to get maximum benefits from the drug and avoid side effects.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Narayen G, Mandal SN. Vasopressin receptor antagonists and their role in clinical medicine. Indian J Endocrinol Metab. 2012;16(2):183-191. doi:10.4103/2230-8210.93734

  2. Rangarajan B, Binoy V, Hingmire SS, Noronha V. Tolvaptan. South Asian J Cancer. 2014;3(3):182-184. doi:10.4103/2278-330X.136811

  3. The U.S. Food and Drug Administration. Samsca label.

  4. The U.S Food and Drug Administration. Samsca label.

  5. O’Donoghue D, Trehan A. SIADH and hyponatraemia: foreword. NDT Plus. 2009;2(Suppl 3):iii1-iii4. doi:10.1093/ndtplus/sfp152

  6. Reilly T, Chavez B. Tolvaptan (Samsca) for hyponatremia: is it worth its salt? P T. 2009;34(10):543-547.

  7. The U.S. Food and Drug Administration. Samsca label.

  8. Blair HA. Tolvaptan: a review in autosomal dominant polycystic kidney disease. Drugs. 2019;79(3):303-313. doi:10.1007/s40265-019-1056-1.

  9. Aditya S, Rattan A. Vaptans: A new option in the management of hyponatremia. Int J Appl Basic Med Res. 2012;2(2):77-83. doi:10.4103/2229-516X.106347