JYNARQUE tolvaptan 15 mg Tablet, 30-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Vasopressin V2 Receptor Antagonist class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Tolvaptan (Jynarque) is used to slow the worsening of kidney function in certain patients with autosomal dominant polycystic kidney disease (ADPKD; a certain type of inherited kidney disease). Tolvaptan (Jynarque) is in a class of medications called vasopressin V2 receptor antagonists. It works by increasing the amount of water released from the body as urine and decreases the growth of cysts in the kidneys. Removing fluid from the body and slowing the growth of cysts helps to slow the worsening of kidney function. Tolvaptan is also available as a tablet (Samsca) to treat low blood levels of s...
Read the full MedlinePlus article ↗- This is a safety requirement — not just a formality. When tolvaptan raises your blood sodium levels, it has to happen gradually. If sodium goes up too fast, it can cause a rare but...
- Why do I have to start this medication in a hospital?
- Tolvaptan can cause liver damage — and with Jynarque, which is used long-term for kidney disease, that risk needs to be watched carefully. Liver blood tests check for signs of inju...
- Why do I need regular liver blood tests if I'm on Jynarque?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tolvaptan — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 4AQJ3LG584
A synthetic blue dye combined with aluminum to create a stable colorant. It's used in medicines and supplements to add blue color or create specific shades for product identification and appearance.
-
UNII 9XZ8H6N6OH
A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 2165RE0K14
A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
7 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $386.55 | $11,596.55 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tolvaptan 15 mg 72205-0130-11 | Novadoz | 10 tablets | $14.612 | AB1 | Availability likely | — |
| Tolvaptan 15 mg 49884-0768-54 | Endo | 10 tablets | $14.612 | AB1 | Availability likely | — |
| tolvaptan 15 mg 60505-4317-00 | Apotex | 10 tablets | $14.612 | AB1 | Availability likely | — |
| Jynarque 15 mgthis 59148-0082-13 | Otsuka | 30 tablets | — | AB | FDA listed | — |
| Tolvaptan 15 mg 70748-0238-06 | Lupin | 30 tablets | — | AB2 | FDA listed | — |
| Tolvaptan 15 mg 31722-0868-01 | Camber | 100 tablets | — | AB1 | FDA listed | — |
| Tolvaptan 15 mg 67877-0635-01 | Ascend | 100 tablets | — | AB1 | FDA listed | — |
| Samsca 15 mg 59148-0020-50 | Otsuka | 10 tablets | — | AB1 | FDA listed | — |
| Tolvaptan 15 mg 72603-0932-01 | Northstar | 10 tablets | — | AB1 | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10905694 ↗ | Drug product | — | Apr 7, 2030 |
| US 8501730 ↗ | Drug substance | — | Sep 1, 2026 |
| US 8501730 ↗ | Drug substance | — | Sep 1, 2026 |
| US 8501730 ↗ | Drug substance | — | Sep 1, 2026 |
| US 10905694 ↗ | Drug product | — | Apr 7, 2030 |
| US 8501730 ↗ | Drug substance | — | Sep 1, 2026 |
| US 8501730 ↗ | Drug substance | — | Sep 1, 2026 |
| US 10905694 ↗ | Drug product | — | Apr 7, 2030 |
| US 10905694 ↗ | Drug product | — | Apr 7, 2030 |
| US 10905694 ↗ | Drug product | — | Apr 7, 2030 |
Is there a generic version of JYNARQUE 15 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 59148-0082-13 You're viewing this | 1 BOTTLE in 1 CARTON (59148-082-13) / 30 TABLET in 1 BOTTLE | 2018-04-23 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF SERIOUS LIVER INJURY JYNARQUE (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported [see Warnings and Precautions (5.1) ] . 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 [see Warnings and Precautions (5.1) ] .
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 is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tolvaptan for ADPKD Shared System REMS [see Warnings and Precautions (5.2) ] . WARNING: RISK OF SERIOUS LIVER INJURY See full prescribing information for complete boxed warning .
JYNARQUE (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported ( 5.1 ) Measure transaminases and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then continuing monthly for the first 18 months and every 3 months thereafter ( 5.1 ) JYNARQUE is available only through a restricted distribution program called the Tolvaptan for ADPKD Shared System REMS ( 5.2 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE JYNARQUE is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). JYNARQUE is a selective vasopressin V 2 -receptor antagonist indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD) ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended dosage ( 2.1 ) Initial Dosage Titration Step Target Dosage 1st Dose 45 mg 1st Dose 60 mg 1st Dose 90 mg 2nd Dose (8 hours later) 15 mg 2nd Dose (8 hours later) 30 mg 2nd Dose (8 hours later) 30 mg Total Daily Dose 60 mg Total Daily Dose 90 mg Total Daily Dose 120 mg Dose adjustment is recommended for patients taking moderate CYP3A inhibitors ( 2.4 , 5.4 , 7.1 )
2.1Recommended Dosage The initial dosage for JYNARQUE is 60 mg orally per day as 45 mg taken on waking and 15 mg taken 8 hours later. Titrate to 60 mg plus 30 mg then to 90 mg plus 30 mg per day if tolerated with at least weekly intervals between titrations. Patients may down-titrate based on tolerability. Encourage patients to drink enough water to avoid thirst or dehydration.
2.2Monitoring To mitigate the risk of significant or irreversible liver injury, perform blood testing for ALT, AST and bilirubin prior to initiation of JYNARQUE, at 2 and 4 weeks after initiation, monthly for 18 months and every 3 months thereafter . Monitor for concurrent symptoms that may indicate liver injury [see Warnings and Precautions (5.1) ] .
2.3Missed Doses If a dose of JYNARQUE is not taken at the scheduled time, take the next dose at its scheduled time.
2.4Co-Administration with CYP3A Inhibitors CYP3A Inhibitors Concomitant use of strong CYP3A inhibitors is contraindicated [see Contraindications (4) and Warnings and Precautions (5.4) ] . In patients taking concomitant moderate CYP3A inhibitors, reduce the dose of JYNARQUE per Table 1. Consider further reductions if patients cannot tolerate the reduced dose [see Warnings and Precautions (5.4) and Drug Interactions (7.1) ] .
Interrupt JYNARQUE temporarily for short term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available. Table 1: Dose adjustment for patients taking moderate CYP3A inhibitors Standard Morning and Afternoon Dose (mg) Dose (mg) with Moderate CYP3A Inhibitors 90 mg and 30 mg 45 mg and 15 mg 60 mg and 30 mg 30 mg and 15 mg 45 mg and 15 mg 15 mg and 15 mg
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS JYNARQUE (tolvaptan) is supplied as non-scored, blue, shallow-convex, immediate release tablets, debossed with "OTSUKA" and the tablet strength (mg) on one side as follows: Strength Shape 15 mg triangular 30 mg round 45 mg square 60 mg rectangular 90 mg pentagonal Tablets: 15 mg, 30 mg, 45 mg, 60 mg and 90 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS JYNARQUE is contraindicated in patients: With a history, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease [see Warnings and Precautions (5.1) ] Taking strong CYP3A inhibitors With uncorrected abnormal blood sodium concentrations [see Warnings and Precautions (5.3) ] Unable to sense or respond to thirst [see Warnings and Precautions (5.3) ] Hypovolemia [see Warnings and Precautions (5.3) ] Hypersensitivity (e.g., anaphylaxis, rash) to tolvaptan or any component of the product [see Adverse Reactions (6) ] Uncorrected urinary outflow obstruction Anuria History of signs or symptoms of significant liver impairment or injury, does not include uncomplicated polycystic liver disease ( 4 ) Concomitant use of strong CYP3A inhibitors is contraindicated ( 4 ) Uncorrected abnormal blood sodium concentrations ( 4 , 5.3 ) Unable to sense or respond to thirst ( 4 ) Hypovolemia ( 4 ) Hypersensitivity to tolvaptan or any of its components ( 4 ) Uncorrected urinary outflow obstruction ( 4 ) Anuria ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypernatremia, dehydration and hypovolemia: May require intervention ( 5.3 )
5.1Serious Liver Injury JYNARQUE can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported in the post-marketing ADPKD experience. Discontinuation in response to laboratory abnormalities or signs or symptoms of liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) can reduce the risk of severe hepatotoxicity.
In a 3-year placebo-controlled trial and its open-label extension (in which patients' liver tests were monitored every 4 months), evidence of serious hepatocellular injury (elevations of hepatic transaminases of at least 3 times the upper limit of normal [ULN] combined with elevated bilirubin at least 2 times the ULN) occurred in 0.2% (3/1487) of tolvaptan-treated patients compared to none of the placebo-treated patients. To reduce the risk of significant or irreversible liver injury, assess ALT, AST and bilirubin prior to initiation of JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.
At the onset of signs or symptoms consistent with hepatic injury or if ALT, AST, or bilirubin increase to >2 times ULN, immediately discontinue JYNARQUE, obtain repeat tests as soon as possible (within 48 to 72 hours), and continue testing as appropriate. If laboratory abnormalities stabilize or resolve, JYNARQUE may be reinitiated with increased frequency of monitoring as long as ALT and AST remain below 3 times the ULN. Do not restart JYNARQUE in patients who experience signs or symptoms consistent with hepatic injury or whose ALT or AST ever exceeds 3 times the ULN during treatment with tolvaptan, unless there is another explanation for liver injury and the injury has resolved.
In patients with a stable, low baseline AST or ALT, an increase above 2 times baseline, even if less than 2 times the ULN, may indicate early liver injury. Such elevations may warrant treatment suspension and prompt (48 to 72 hours) re-evaluation of liver test trends prior to reinitiating therapy with more frequent monitoring.
5.2Tolvaptan for ADPKD Shared System REMS JYNARQUE is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tolvaptan for ADPKD Shared System REMS, because of the risks of liver injury [see Warnings and Precautions (5.1) ] . Notable requirements of the Tolvaptan for ADPKD Shared System REMS include the following: Prescribers must be certified by enrolling in the REMS program. Prescribers must inform patients receiving JYNARQUE about the risk of hepatotoxicity associated with its use and how to recognize the signs and symptoms of hepatotoxicity and the appropriate actions to take if it occurs.
Patients must enroll in the REMS program and comply with ongoing monitoring requirements. Pharmacies must be certified by enrolling in the REMS program and must only dispense to patients who are authorized to receive JYNARQUE. Further information, including a list of qualified pharmacies/distributors, is available at www.TolvaptanADPKDSharedREMS.com or by telephone at 1-866-244-9446.
5.3Hypernatremia, Dehydration and Hypovolemia JYNARQUE increases free water clearance and, as a result, may cause dehydration, hypovolemia and hypernatremia. Therefore, ensure abnormalities in sodium concentrations are corrected prior to initiation of therapy. Instruct patients to drink water when thirsty, and throughout the day and night if awake.
Monitor for weight loss, tachycardia and hypotension because they may signal dehydration. In the two double-blind, placebo-controlled trials of patients with ADPKD, hypernatremia (defined as any serum sodium concentration >150 mEq/L) was observed in 4.0% versus 0.6% and 1.4% versus 0% of tolvaptan-treated versus placebo-treated patients, res…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Serious Liver Injury [see Boxed Warning and Warnings and Precautions (5.1) ] Hypernatremia, Dehydration and Hypovolemia [see Warnings and Precautions (5.3) ] Drug Interactions with Inhibitors of CYP3A [see Warnings and Precautions (5.4) ] Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. JYNARQUE has been studied in over 3000 patients with ADPKD. Long-term, placebo-controlled safety information of JYNARQUE in ADPKD is principally derived from two trials where 1,413 subjects received tolvaptan and 1,098 received placebo for at least 12 months across both studies.
TEMPO 3:4: A Phase 3, Double-Blind, Placebo-Controlled, Randomized Trial in Early, Rapidly-Progressing ADPKD The TEMPO 3:4 (NCT00428948) trial employed a two-arm, 2:1 randomization to tolvaptan or placebo, titrated to a maximally-tolerated total daily dose of 60 to 120 mg. A total of 961 subjects with rapidly progressing ADPKD were randomized to JYNARQUE. Of these, 742 (77%) subjects who were treated with JYNARQUE remained on treatment for at least 3 years.
The average daily dose in these subjects was 96 mg daily. Adverse events that led to discontinuation were reported for 15.4% (148/961) of subjects in the JYNARQUE group and 5.0% (24/483) of subjects in the placebo group. Aquaretic effects were the most common reasons for discontinuation of JYNARQUE.
These included pollakiuria, polyuria, or nocturia in 63 (6.6%) subjects treated with JYNARQUE compared to 1 subject (0.2%) treated with placebo. Table 2 lists the adverse reactions that occurred in at least 3% of ADPKD subjects treated with JYNARQUE and at least 1.5% more than on placebo. Table 2: TEMPO 3:4, Treatment Emergent Adverse Reactions in ≥3% of JYNARQUE Treated Subjects with Risk Difference ≥1.5%, Randomized Period Adverse Reaction Tolvaptan (N=961) Placebo (N=483) Number of Subjects Proportion (%) 100× (Number of subjects with an adverse event/N) Annualized Rate 100× (Number of subjects with an adverse event/Total subject years of drug exposure) Number of Subjects Proportion (%) Annualized Rate Increased urination Increased urination includes micturition urgency, nocturia, pollakiuria, polyuria 668 69.5 28.6 135 28.0
10.3Thirst Thirst includes polydipsia and thirst 612 63.7 26.2 113 23.4
8.7Dry mouth 154 16.0 6.6 60 12.4
4.6Fatigue 131 13.6 5.6 47 9.7
3.6Diarrhea 128 13.3 5.5 53 11.0
4.1Dizziness 109 11.3 4.7 42 8.7
3.2Dyspepsia 76 7.9 3.3 16 3.3
1.2Decreased appetite 69 7.2 3.0 5 1.0
0.4Abdominal distension 47 4.9 2.0 16 3.3
1.2Dry skin 47 4.9 2.0 8 1.7
0.6Rash 40 4.2 1.7 9 1.9
0.7Hyperuricemia 37 3.9 1.6 9 1.9
0.7Palpitations 34 3.5 1.5 6 1.2
0.5REPRISE: A Phase 3, Randomized-Withdrawal, Placebo-Controlled, Double-Blind, Trial in Late Stage 2 to Early Stage 4 ADPKD The REPRISE (NCT02160145) trial employed a 5-week single-blind titration and run-in period for JYNARQUE prior to the randomized double-blind period. During the JYNARQUE titration and run-in period, 126 (8.4%) of the 1496 subjects discontinued the study, 52 (3.5%) were due to aquaretic effects and 10 (0.7%) were due to liver test findings. Because of this run-in design, the adverse reaction rates observed during the randomized period are not described.
Liver Injury In the two double-blind, placebo-controlled trials, ALT elevations >3 times ULN were observed at a…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Avoid concomitant use with: Strong CYP3A Inducers ( 7.1 ) V 2 -Receptor Agonists ( 7.2 )
7.1CYP3A Inhibitors and Inducers CYP3A Inhibitors Tolvaptan's AUC was 5.4 times as large and Cmax was 3.5 times as large after co-administration of tolvaptan and 200 mg ketoconazole [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3) ] . Larger doses of the strong CYP3A inhibitor would be expected to produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A inhibitors is contraindicated [see Contraindications (4) ].
Dose reduction of JYNARQUE is recommended for patients while taking moderate CYP3A inhibitors [see Dosage and Administration (2.4) ]. Patients should avoid grapefruit juice beverages while taking JYNARQUE. Strong CYP3A Inducers Co-administration of JYNARQUE with strong CYP3A inducers reduces exposure to JYNARQUE [see Clinical Pharmacology (12.3) ].
Avoid concomitant use of JYNARQUE with strong CYP3A inducers [see Dosage and Administration (2.4) ].
7.2V 2 -Receptor Agonist As a V 2 -receptor antagonist, tolvaptan will interfere with the V 2 -agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V 2 -agonist.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm ( 8.1 ) Lactation: Breastfeeding not recommended ( 8.2 )
8.1Pregnancy Risk Summary Available data with JYNARQUE use in pregnant women are insufficient to determine if there is a drug associated risk of adverse developmental outcomes. In embryo-fetal development studies, pregnant rats and rabbits received oral tolvaptan during organogenesis. At maternally non-toxic doses, tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 4- and 1-times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 90/30 mg.
However, effects on embryo-fetal development occurred in both species at maternally toxic doses. In rats, reduced fetal weights and delayed fetal ossification occurred at 17 times the human exposure. In rabbits, increased abortions, embryo-fetal death, fetal microphthalmia, open eyelids, cleft palate, brachymelia and skeletal malformations occurred at approximately 3 times the human exposure (see Data ).
Advise pregnant women of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2 to 4% and 15 to 20% of clinically recognized pregnancies, respectively. Data Animal Data Oral administration of tolvaptan during the period of organogenesis in Sprague-Dawley rats produced no evidence of teratogenesis at doses up to 100 mg/kg/day. Lower body weights and delayed ossification were seen at 1000 mg/kg, which is approximately 17 times the human exposure at the 90/30 mg dose (AUC 24h 6570 h∙ng/mL).
The fetal effects are likely secondary to maternal toxicity (decreased food intake and low body weights). In a prenatal and postnatal study in rats, tolvaptan had no effect on physical development, reflex function, learning ability or reproductive performance at doses up to 1000 mg/kg/day. In New Zealand White rabbits, placental transfer was demonstrated with C max values in the yolk sac fluid approximating 22.7% of the value in maternal rabbit serum.
In embryo-fetal studies, teratogenicity (microphthalmia, embryo-fetal mortality, cleft palate, brachymelia and fused phalanx) was evident in rabbits at 1000 mg/kg (approximately 3 times the exposure at the 90/30 mg dose). Body weights and food consumption were lower in dams at all doses, equivalent to 0.6 to 3 times the human exposure at the 90/30 mg dose.
8.2Lactation Risk Summary There are no data 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. When a drug is present in animal milk, it is possible that the drug will be present in human milk, but relative levels may vary (see Data ) .
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 with JYNARQUE. Data In lactating rats administration of radiolabeled tolvaptan, lacteal radioactivity concentrations reached the highest level at 8 hours after administration and then decreased gradually with time with a half-life of 27.3 hours. The level of activity in milk ranged from 1.5- to 15.8-fold those in blood over the period of 72 hours post-dose.
In a prenatal and postnatal study in rats, maternal toxicity was noted at 100 mg/kg/day or higher (≥4.4 times the human exposure at the 90/30 mg dose). Increased perinatal death and decreased body weight of the offspring were observed during the lactation period and after weaning at approximately 17.3 times the human exposure at the 90/30 mg dose.
8.4 Pediatric Use Safety and effectiveness of JYNARQUE in pediatric patients have not…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data with JYNARQUE use in pregnant women are insufficient to determine if there is a drug associated risk of adverse developmental outcomes. In embryo-fetal development studies, pregnant rats and rabbits received oral tolvaptan during organogenesis. At maternally non-toxic doses, tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 4- and 1-times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 90/30 mg.
However, effects on embryo-fetal development occurred in both species at maternally toxic doses. In rats, reduced fetal weights and delayed fetal ossification occurred at 17 times the human exposure. In rabbits, increased abortions, embryo-fetal death, fetal microphthalmia, open eyelids, cleft palate, brachymelia and skeletal malformations occurred at approximately 3 times the human exposure (see Data ).
Advise pregnant women of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2 to 4% and 15 to 20% of clinically recognized pregnancies, respectively. Data Animal Data Oral administration of tolvaptan during the period of organogenesis in Sprague-Dawley rats produced no evidence of teratogenesis at doses up to 100 mg/kg/day. Lower body weights and delayed ossification were seen at 1000 mg/kg, which is approximately 17 times the human exposure at the 90/30 mg dose (AUC 24h 6570 h∙ng/mL).
The fetal effects are likely secondary to maternal toxicity (decreased food intake and low body weights). In a prenatal and postnatal study in rats, tolvaptan had no effect on physical development, reflex function, learning ability or reproductive performance at doses up to 1000 mg/kg/day. In New Zealand White rabbits, placental transfer was demonstrated with C max values in the yolk sac fluid approximating 22.7% of the value in maternal rabbit serum.
In embryo-fetal studies, teratogenicity (microphthalmia, embryo-fetal mortality, cleft palate, brachymelia and fused phalanx) was evident in rabbits at 1000 mg/kg (approximately 3 times the exposure at the 90/30 mg dose). Body weights and food consumption were lower in dams at all doses, equivalent to 0.6 to 3 times the human exposure at the 90/30 mg dose.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of JYNARQUE in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of tolvaptan did not include sufficient numbers of subjects aged 65 years old and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE Single oral doses up to 480 mg (4 times the maximum recommended daily dose) and multiple doses up to 300 mg once daily for 5 days have been well tolerated in trials in healthy subjects. There is no specific antidote for tolvaptan intoxication. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: a rise in serum sodium concentration, polyuria, thirst, and dehydration/hypovolemia.
No mortality was observed in rats or dogs following single oral doses of 2000 mg/kg (maximum feasible dose). A single oral dose of 2000 mg/kg was lethal in mice, and symptoms of toxicity in affected mice included decreased locomotor activity, staggering gait, tremor and hypothermia. In patients with suspected JYNARQUE overdosage, assessment of vital signs, electrolyte concentrations, ECG and fluid status is recommended.
Continue replacement of water and electrolytes until aquaresis abates. Dialysis may not be effective in removing JYNARQUE because of its high binding affinity for human plasma protein (>98%).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Tolvaptan is a selective vasopressin V 2 -receptor antagonist with an affinity for the V 2 -receptor that is 1.8 times that of native arginine vasopressin (AVP). Tolvaptan affinity for the V 2 -receptor is 29 times that for the V 1a -receptor. Decreased binding of vasopressin to the V 2 -receptor in the kidney lowers adenylate cyclase activity resulting in a decrease in intracellular adenosine 3′, 5′-cyclic monophosphate (cAMP) concentrations.
Decreased cAMP concentrations prevent aquaporin 2 containing vesicles from fusing with the plasma membrane, which in turn causes an increase in urine water excretion, an increase in free water clearance (aquaresis) and a decrease in urine osmolality. In human ADPKD cyst epithelial cells, tolvaptan inhibited AVP-stimulated in vitro cyst growth and chloride-dependent fluid secretion into cysts. In animal models, decreased cAMP concentrations were associated with decreases in the rate of growth of total kidney volume and the rate of formation and enlargement of kidney cysts.
Tolvaptan metabolites have no or weak antagonist activity for human V 2 -receptors compared with tolvaptan.
12.2Pharmacodynamics In healthy subjects or patients with eGFRs as low as 10 mL/min/1.73m 2 receiving a single dose of tolvaptan, the onset of the aquaretic effects occurs within 1 to 2 hours post-dose. In healthy subjects, single doses of 60 mg and 90 mg produce a peak effect of about a 9 mL/min increase in urine excretion rate is observed between 4 and 8 hours post-dose. Higher doses of tolvaptan do not increase the peak effect in urine excretion rate but sustain the effect for a longer period of time.
Urine excretion rate returns to baseline within 24 hours following the maximum recommended 90 mg dose of tolvaptan. Changes in free water clearance mirror the changes in urine excretion rate. Increased free water clearance causes an increase in serum sodium concentration unless fluid intake is increased to match urine output.
Increases in urine excretion rate and free water clearance are positively correlated with baseline glomerular filtration rate with increases in both values observed in patients with creatinine clearance as low as 15 mL/min. With the recommended split-dose regimens, tolvaptan inhibits vasopressin from binding to the V 2 -receptor in the kidney for the entire day, as indicated by increased urine output and decreased urine osmolality. Following a 90/30 mg split-dose regimen in patients with eGFR >60 mL/min/1.73 m 2 , the change in mean daily urine volume was about 4 L for a mean total daily volume of about 7 L.
In patients with eGFR <30 mL/min/1.73 m 2 , the mean change in daily urine volume was about 2 L for a total daily urine volume of about 5 L. Plasma concentrations of native AVP may increase (avg. 2 to 9 pg/mL) with tolvaptan treatment and return to baseline levels when treatment is stopped.
During tolvaptan treatment, small changes in renal function are expected and the changes are independent of baseline renal function. Glomerular filtration rate is decreased about 6% to 10% and uric acid clearance is decreased about 20% to 25%. Percent changes in renal plasma flow are highly correlated to percent changes in GFR.
These changes are reversed upon discontinuation of tolvaptan. Cardiac Electrophysiology No prolongation of the QT interval was observed with tolvaptan following multiple doses of 300 mg/day for 5 days.
12.3Pharmacokinetics In healthy subjects, the pharmacokinetics of tolvaptan after single doses of up to 480 mg and multiple doses up to 300 mg once daily have been studied. In ADPKD patients, single doses up to 120 mg and multiple split-doses up to 90/30 mg have been studied. Absorption In healthy subjects, peak concentrations of tolvaptan are observed between 2 and 4 hours post-dose.
Peak concentrations increase less than dose proportionally with doses greater than 240 mg. The absolute bioavailability of tolvaptan decreases with…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Tolvaptan is a selective vasopressin V 2 -receptor antagonist with an affinity for the V 2 -receptor that is 1.8 times that of native arginine vasopressin (AVP). Tolvaptan affinity for the V 2 -receptor is 29 times that for the V 1a -receptor. Decreased binding of vasopressin to the V 2 -receptor in the kidney lowers adenylate cyclase activity resulting in a decrease in intracellular adenosine 3′, 5′-cyclic monophosphate (cAMP) concentrations.
Decreased cAMP concentrations prevent aquaporin 2 containing vesicles from fusing with the plasma membrane, which in turn causes an increase in urine water excretion, an increase in free water clearance (aquaresis) and a decrease in urine osmolality. In human ADPKD cyst epithelial cells, tolvaptan inhibited AVP-stimulated in vitro cyst growth and chloride-dependent fluid secretion into cysts. In animal models, decreased cAMP concentrations were associated with decreases in the rate of growth of total kidney volume and the rate of formation and enlargement of kidney cysts.
Tolvaptan metabolites have no or weak antagonist activity for human V 2 -receptors compared with tolvaptan.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied All JYNARQUE (tolvaptan) tablets are non-scored, blue, shallow-convex, debossed with "OTSUKA" and the tablet strength (mg) on one side and supplied as follows: 15 mg tablets are triangular, 30 mg tablets are round, 45 mg tablets are square, 60 mg tablets are rectangular, and 90 mg tablets are pentagonal. Morning and Afternoon Doses NDC 7‑Day Blister Card (Containing 14 Tablets) 28‑Day Carton (4 Blister Cards Containing a Total of 56 Tablets) 15 mg and 15 mg 59148-079-07 59148-079-28 30 mg and 15 mg 59148-080-07 59148-080-28 45 mg and 15 mg 59148-087-07 59148-087-28 60 mg and 30 mg 59148-088-07 59148-088-28 90 mg and 30 mg 59148-089-07 59148-089-28 30 Count Bottles NDC 15 mg 59148-082-13 30 mg 59148-083-13 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP controlled Room Temperature].
📦 Storage and Handling ▾
Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION JYNARQUE contains tolvaptan, a selective vasopressin V2-receptor antagonist in immediate release tablets for oral administration available in 15 mg, 30 mg, 45 mg, 60 mg and 90 mg strengths. Tolvaptan is (±)-4'-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1 H -1-benzazepin-1-yl) carbonyl]- o -tolu- m -toluidide. The empirical formula is C 26 H 25 ClN 2 O 3 .
Molecular weight is 448.94. The chemical structure is: Inactive ingredients include corn starch, hydroxypropyl cellulose, lactose monohydrate, low-substituted hydroxypropyl cellulose, magnesium stearate and microcrystalline cellulose and FD&C Blue No. 2 Aluminum Lake as colorant.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION As part of patient counseling, healthcare providers must review the JYNARQUE Medication Guide with every patient [see Medication Guide ]. Serious Liver Injury Advise patients that blood testing is required before starting JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly during the first 18 months of therapy and every 3 months thereafter as a requirement to reduce the risk of serious liver injury [see Boxed Warning and Warnings and Precautions (5.1) ]. Advise patients to immediately stop taking JYNARQUE and notify their healthcare provider if they have symptoms or signs (e.g., abnormal transaminase elevations) of hepatic injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort or tenderness, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) [see Warnings and Precautions (5.1) ].
Tolvaptan for ADPKD Shared System REMS Advise patients that JYNARQUE is only available through a restricted program called the Tolvaptan for ADPKD Shared System REMS [see Warnings and Precautions (5.2) ]. Inform the patient of the following notable requirement: Patients must enroll in the program and comply with ongoing monitoring requirements [see Warnings and Precautions (5.2) ] Advise patients that JYNARQUE is only available only through restricted distribution from certified specialty pharmacies participating in the Tolvaptan for ADPKD Shared System REMS.
Therefore, provide patients with the telephone number and web site for information on how to obtain the product [see Warnings and Precautions (5.2) ]. Hypernatremia, Dehydration and Hypovolemia Advise patients to drink water to avoid thirst, throughout the day and night. Patients should stop taking JYNARQUE and notify their healthcare provider if they have symptoms or signs of sodium imbalance or dehydration (e.g., dizziness, fainting, weight loss, palpitations, confusion, weakness, gait instability) [see Warnings and Precautions (5.3) ].
Advise the patient that if they cannot drink enough water for any reason (no access to water, cannot sense thirst, unable to maintain hydration due to vomiting, diarrhea) they should stop taking JYNARQUE and inform their health care provider right away [see Warnings and Precautions (5.3) ] . Pregnancy Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1) ].
Lactation Advise women not to breastfeed during treatment with JYNARQUE [see Use in Specific Populations (8.2) ].
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 3/2025 MEDICATION GUIDE JYNARQUE ® (jin-AR-kew) (tolvaptan) Tablets What is the most important information I should know about JYNARQUE?
JYNARQUE can cause serious side effects, including: Serious liver problems. JYNARQUE can cause serious liver problems that can lead to the need for a liver transplant or can lead to death. Stop taking JYNARQUE and call your healthcare provider right away if you get any of the following symptoms: feeling tired loss of appetite nausea right upper stomach (abdomen) pain or tenderness vomiting fever rash itching yellowing of the skin and white part of the eye (jaundice) dark urine To help reduce your risk of liver problems, your healthcare provider will do a blood test to check your liver: before you start taking JYNARQUE at 2 weeks and 4 weeks after you start treatment with JYNARQUE then monthly for 18 months during treatment with JYNARQUE and every 3 months from then on It is important to stay under the care of your healthcare provider during treatment with JYNARQUE.
Because of the risk of serious liver problems JYNARQUE is only available through a restricted distribution program called the Tolvaptan for ADPKD Shared System REMS. Before you start treatment with JYNARQUE, you must enroll in the Tolvaptan for ADPKD Shared System REMS. Talk to your healthcare provider about how to enroll in the program.
JYNARQUE can only be dispensed by a certified pharmacy that participates in the Tolvaptan for ADPKD Shared System REMS. Your healthcare provider can give you information on how to find a certified pharmacy. What is JYNARQUE?
JYNARQUE is a prescription medicine used to slow kidney function decline in adults who are at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). It is not known if JYNARQUE is safe and effective in children. Do not take JYNARQUE if you: have a history of liver problems or have signs or symptoms of liver problems, excluding polycystic liver disease. cannot feel if you are thirsty or cannot replace fluids by drinking. have been told that the amount of sodium (salt) in your blood is too high or too low. are dehydrated. are allergic to tolvaptan or any of the ingredients in JYNARQUE.
See the end of this Medication Guide for a complete list of ingredients in JYNARQUE. are unable to urinate. Before taking JYNARQUE, tell your healthcare provider about all your medical conditions, including if you: have a history of sodium levels that are too low. are pregnant or plan to become pregnant. It is not known if tolvaptan will harm your unborn baby.
Tell your healthcare provider if you become pregnant or think that you may be pregnant. are breast-feeding or plan to breastfeed. It is not known if tolvaptan passes into your breast milk. Do not breastfeed during treatment with JYNARQUE.
Talk to your healthcare provider about the best way to feed your baby during this time. Tell your healthcare provider about all the medicines you take including prescription medicines, over-the-counter medicines, vitamins and herbal supplements. Taking JYNARQUE with certain medicines could cause you to have too much tolvaptan in your blood.
JYNARQUE should not be taken with certain medications. Your healthcare provider can tell you if it is safe to take JYNARQUE with other medicines. Do not start taking a new medicine without talking to your healthcare provider.
Keep a list of your medicines to show your healthcare provider and pharmacist. How should I take JYNARQUE? Take JYNARQUE exactly as your healthcare provider tells you to.
Take JYNARQUE orally two times each day. Take the first dose of JYNARQUE when you wake up and take the second dose 8 hours later. Be sure to drink enough water so that you will not get thirsty or become dehydrated.
If you miss a dose of JYNARQUE, take the next dose at your regular time. If you take too much JYNARQUE, call your healthcare provider or go to the nearest…