Pronunciation:

tol-VAP-tan

Brand Names:

• Jynarque
• Samsca

Dosage Forms:

• Tablet

Warnings:

Samsca(R) should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too-rapid correction of hyponatremia (eg, greater than 12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death. Slower rates of correction may be advisable in susceptible patients (eg, those with severe malnutrition, alcoholism, or advanced liver disease) .Samsca(R) Not For Use For Autosomal Dominant Polycystic Kidney Disease (ADPKD): Because of the risk of hepatoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS .

Warning: Risk Of Serious Liver Injury:Jynarque(TM) (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported.Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity.Because of the risks of serious liver injury, Jynarque(TM) is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Jynarque(TM) REMS Program .

Classifications:

Therapeutic—

Endocrine-Metabolic Agent

Pharmacologic—

Vasopressin Receptor Antagonist, V2

Uses of This Medicine:

Tolvaptan is used to treat hyponatremia (low sodium in the blood) in patients with heart failure or syndrome of inappropriate antidiuretic hormone (SIADH).

Tolvaptan is also used to slow kidney function decline in adults who are at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

Sodium is a chemical that the body needs for it to function well. If you have a low sodium blood level, your body will not function normally and you may not feel well. Tolvaptan works in the kidneys to help maintain the right amount of sodium for the body.

Samsca® is available only with your doctor's prescription. Jynarque™ is available only under a restricted distribution program called the Jynarque™ REMS (Risk Evaluation and Mitigation Strategy) Program.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of tolvaptan in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tolvaptan in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving tolvaptan.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Boceprevir
• Clarithromycin
• Cobicistat
• Conivaptan
• Delavirdine
• Idelalisib
• Indinavir
• Itraconazole
• Ketoconazole
• Levoketoconazole
• Lopinavir
• Nefazodone
• Nelfinavir
• Posaconazole
• Ritonavir
• Saquinavir
• Telaprevir
• Telithromycin
• Tipranavir
• Voriconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abrocitinib
• Adagrasib
• Amobarbital
• Amprenavir
• Aprepitant
• Asciminib
• Atazanavir
• Avacopan
• Belzutifan
• Berotralstat
• Butabarbital
• Capmatinib
• Carbamazepine
• Ceritinib
• Ciprofloxacin
• Crizotinib
• Cyclosporine
• Dabrafenib
• Daridorexant
• Desmopressin
• Digoxin
• Diltiazem
• Dronedarone
• Duvelisib
• Efavirenz
• Elacestrant
• Enasidenib
• Enzalutamide
• Erdafitinib
• Erythromycin
• Fedratinib
• Fexinidazole
• Fluconazole
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Gilteritinib
• Imatinib
• Isavuconazonium Sulfate
• Ivacaftor
• Ivosidenib
• Lanreotide
• Larotrectinib
• Lasmiditan
• Lefamulin
• Lenacapavir
• Letermovir
• Lorlatinib
• Lumacaftor
• Mavacamten
• Methotrexate
• Mitapivat
• Mitotane
• Mobocertinib
• Modafinil
• Neratinib
• Netupitant
• Nevirapine
• Nilotinib
• Nirogacestat
• Octreotide
• Olutasidenib
• Omaveloxolone
• Oxcarbazepine
• Pacritinib
• Palbociclib
• Pentobarbital
• Phenobarbital
• Phenytoin
• Pioglitazone
• Pirtobrutinib
• Primidone
• Repotrectinib
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritlecitinib
• Secobarbital
• Selpercatinib
• Simeprevir
• Sotorasib
• St John's Wort
• Taurursodiol
• Tocilizumab
• Trofinetide
• Tucatinib
• Venetoclax
• Verapamil
• Vilazodone
• Vonoprazan
• Voxelotor

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcoholism, chronic or
• Cirrhosis (liver disease) or
• Liver disease, severe or
• Malnutrition (poor nutrition or undernourished condition)—May increase risk for more serious side effects.

• Anuria (not able to pass urine) or
• Bladder blockage, uncorrected or
• Hypovolemic hyponatremia (low blood sodium with low blood fluid) or
• Kidney disease, severe or
• Liver disease, severe, history of or
• Not able to sense or respond to thirst or
• Patients with sodium blood levels that must be increased right away—Should not be used in patients with these conditions.

• Dehydration or
• Hyperkalemia (high potassium in the blood) or
• Hypovolemia (low blood volume) or
• Stomach or bowel bleeding—Use with caution. May make these conditions worse.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

It is important that you take your first dose or restart your treatment with this medicine in a hospital or medical facility. This will allow your doctor to check your response to this medicine and monitor any unwanted problems that may occur.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

This medicine is not for long-term use. You should not take Samsca® for more than 30 days to lessen your risk of having liver injury.

Dosing—

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.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose of Jynarque™, skip the missed dose, and go back to your regular dosing schedule.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

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.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Blurred vision

dry mouth

flushed, dry skin

frequent urination

fruit-like breath odor

increased hunger

increased thirst

increased urination

increased volume of pale, dilute urine

nausea

stomach pain

sweating

thirst

troubled breathing

unexplained weight loss

unusual tiredness or weakness

vomiting

Less common

Anxiety

blood in the urine

bloody stools

blue lips, fingernails, or skin

bruising

chest pain

confusion

cough

coughing or vomiting blood

dark urine

dizziness or lightheadedness

fainting

fast, slow, irregular, or shallow heartbeat

fever

irregular, fast or slow, or shallow breathing

loss of consciousness

muscle cramp, spasm, pain, or stiffness

pain, redness, or swelling in the arm or leg

persistent bleeding or oozing from puncture sites, mouth, or nose

pink or red urine

rash

rectal bleeding

stomach tenderness

troubled breathing

sweating

vaginal bleeding

Incidence not known

Difficulty swallowing

general feeling of tiredness or weakness

headache

high blood pressure

hives, itching, skin rash

irritability

light-colored stools

muscle twitching

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

restlessness

seizures

stomach pain, continuing

swelling of the feet or lower legs

tightness in the chest

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Difficulty having a bowel movement

lack or loss of strength

Less common

Loss of appetite

weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.