Jynarque (tolvaptan)
An approved treatment for Polycystic Kidney Disease.
Drug facts
The same compound appears under different names depending on the context. Here is how to identify Tolvaptan wherever you encounter it, plus the key facts at a glance.
- Generic name
- Tolvaptan
- Brand name
- Jynarque
- Drug class
- Vasopressin V2-receptor antagonist
- Manufacturer
- Otsuka America Pharmaceutical (Otsuka Pharmaceutical Co., Ltd.)
- How it's taken
- Oral tablets twice a day, on waking and 8 hours later
A twice-daily pill and the first FDA-approved treatment to slow the loss of kidney function in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD), approved in April 2018.
- Jynarque carries a boxed warning for serious liver injury and is available only through a safety program with regular liver blood tests.
- Generic tolvaptan for ADPKD is also approved, and Lupin launched the first in May 2025.
- Jynarque is not approved for the recessive form of PKD (ARPKD) or for children.
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Where Tolvaptan fits
Tolvaptan, sold as Jynarque and as generics, is the only medicine FDA-approved to slow kidney function decline in ADPKD[1][3].
- Blood pressure control is the base of ADPKD care, and KDIGO 2025 recommends an ACE inhibitor or ARB as the first blood pressure medicine, with a home target of 110/75 mmHg or lower for adults 18 to 49 with early-stage kidney disease, if tolerated[14].
- KDIGO 2025 recommends offering tolvaptan to adults with an eGFR of 25 or more who are at risk of rapid progression, judged by kidney imaging (Mayo class 1C to 1E) or a past eGFR decline of 3 or more points a year[14].
- Tolvaptan's 2 main trials compared it with placebo, and no trial has compared it head to head with another treatment[1].
- A question to bring to a nephrologist is whether imaging or past eGFR results show a risk of rapid progression, and how the twice-daily doses, extra urination and monthly liver tests would fit daily life.
How Tolvaptan works
Vasopressin is a hormone that tells the kidneys to hold on to water. When it binds the V2 receptor in the kidney, it raises a cell signal called cAMP, and in ADPKD that signal helps cysts grow and fill with fluid. Tolvaptan blocks the V2 receptor and lowers cAMP[1]. In human ADPKD cyst cells grown in the lab, tolvaptan slowed cyst growth and fluid secretion into cysts, and in animal models lower cAMP went with slower growth of total kidney volume and fewer new cysts[1].
Blocking vasopressin also makes the kidneys pass much more water: with the 90mg and 30mg doses, people with good kidney function made about 4 more liters of urine a day, for about 7 liters in total[1]. Kidney filtration (GFR) drops by about 6-10% during treatment, and the label says that change reverses when tolvaptan is stopped[1].
Side effects and safety
- Serious liver injury. ALT above 3 times normal in 4.9% on tolvaptan against 1.1% on placebo in the first 18 months; serious liver injury in 0.2% (3 of 1,487). The label stops tolvaptan when liver tests rise above 2 times normal or liver symptoms appear.
- REMS safety program. Prescribers and pharmacies must be certified, and patients must enroll and keep up with the liver test schedule.
- High blood sodium, dehydration and low blood volume. Hypernatremia in 4.0% against 0.6% and 1.4% against 0% in the 2 trials; dehydration or low blood volume in 2.1% against 0.7% and 2.3% against 0.4%. Weight loss, a fast heartbeat and low blood pressure can signal dehydration.
- CYP3A medicine interactions. Strong CYP3A inhibitors such as ketoconazole raise tolvaptan levels (5.4 times the exposure with ketoconazole) and cannot be combined with it; moderate CYP3A inhibitors need a lower dose; grapefruit juice and strong CYP3A inducers are avoided.
- Desmopressin. Tolvaptan blocks the effect of desmopressin (dDAVP), and the label says to avoid combining them.
- Pregnancy and breastfeeding. Human data are too limited to judge the risk; rabbit studies showed fetal harm at doses toxic to the mother, and the label advises against breastfeeding.
- ALT, AST and bilirubin before starting, at 2 and 4 weeks, monthly for 18 months, then every 3 months
- Liver symptoms such as fatigue, nausea, right upper belly pain, dark urine or yellow skin
- Blood sodium, corrected before starting
- Weight loss, fast heartbeat and low blood pressure as signs of dehydration
Jynarque carries a boxed warning: it can cause serious and potentially fatal liver injury, and acute liver failure needing a liver transplant has been reported since approval[1]. In the 2 placebo-controlled trials, ALT rose above 3 times the upper limit of normal in 4.9% of people on tolvaptan against 1.1% on placebo within the first 18 months, and these rises usually went away 1 to 4 months after stopping.
Serious liver injury, with high liver enzymes plus high bilirubin, occurred in 0.2% (3 of 1,487) of tolvaptan-treated patients in TEMPO 3:4 and its extension and in no placebo patients[1]. Because tolvaptan makes the body lose water, the label also warns about high blood sodium (hypernatremia, in 4.0% against 0.6% in one trial and 1.4% against 0% in the other) and dehydration or low blood volume (2.1% against 0.7% and 2.3% against 0.4%)[1].
In TEMPO 3:4, the most common side effects were more urination (69.5% against 28.0% on placebo), thirst (63.7% against 23.4%), dry mouth (16.0% against 12.4%), fatigue (13.6% against 9.7%), diarrhea (13.3% against 11.0%) and dizziness (11.3% against 8.7%), and 15.4% of people stopped tolvaptan because of a side effect against 5.0% on placebo, most often because of the extra urination[1].
Since approval, anaphylaxis and raised creatine phosphokinase have also been reported[1]. The label says the risk in pregnancy is not known from human data, reports harm to the fetus in rabbits at doses toxic to the mother, and advises against breastfeeding during treatment[1].
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Tolvaptan
Jynarque is taken twice a day as a split dose: a larger dose on waking and a smaller dose 8 hours later[1]. The starting dose is 45mg on waking plus 15mg 8 hours later (60mg a day). If tolerated, the dose goes up to 60mg plus 30mg, then to 90mg plus 30mg (120mg a day), with at least a week between steps, and it can be lowered for tolerability[1].
A missed dose is skipped and the next dose taken at its usual time. The label asks prescribers to encourage enough water to avoid thirst or dehydration, and the Medication Guide tells patients to drink water when thirsty and through the day and night when awake[1]. People taking a moderate CYP3A inhibitor get a lower dose, for example 45mg plus 15mg in place of 90mg plus 30mg[1].
Tablets come in 15mg, 30mg, 45mg, 60mg and 90mg, sold in 7-day blister cards that pair the morning and afternoon doses, and in 30-tablet bottles of 15mg and 30mg[1].
Availability and cost
Generic versions may be available at a lower cost. Ask your pharmacist.
A daily pill taken for years. The label gives no price. Otsuka's copay program covers eligible commercially insured patients, and generic tolvaptan for ADPKD has been sold since Lupin's May 2025 launch.
Help paying for Jynarque
With private insurance, the drugmaker's copay card can lower what you pay for Jynarque. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE. Pick your insurance below to see which offers fit you.
- Copay help
Eligible commercially insured patients may pay as little as $0 per 28-day supply of Jynarque, with a monthly maximum based on typical insurance reimbursement and an annual maximum equal to the Affordable Care Act out-of-pocket limit ($10,600 for 2026). Patients must be 18 or older and live in the US or Puerto Rico. Not valid with Medicare Part D, Medicaid, Medigap, VA, DOD or TRICARE, or with maximizer or accumulator programs. Massachusetts residents are excluded from May 13, 2025, and California residents from August 13, 2025, unless they completed step therapy or prior authorization or no lower-cost generic is available on their plan.
For: private insurance · source - Insurance and case manager help
Otsuka Patient Support nurses answer questions about product access and reimbursement and connect patients to local treatment sites.
The official page does not say who qualifies. Ask the program. · source
Good to know: Phone hours are not published. The copay page links uninsured patients to otsukapatientassistance.com, whose terms could not be read (403), and no free-drug terms are published on jynarque.com. Generic tolvaptan for ADPKD is sold by Lupin since May 2025.
Access and eligibility
Adults at risk of rapidly progressing autosomal dominant PKD (ADPKD)[1]. The label does not cover the recessive form (ARPKD), and safety and effectiveness in children have not been established. TEMPO 3:4 enrolled adults under 51 with an estimated creatinine clearance of 60 or more and total kidney volume of 750mL or more; REPRISE enrolled adults 18 to 65 with an eGFR of 25 to 65 (25 to 44 with a fast decline for ages 56 to 65). The label rules out people with significant liver disease other than uncomplicated polycystic liver disease, people taking strong CYP3A inhibitors, and people with uncorrected blood sodium problems, low blood volume, no sense of thirst, a blocked urinary outflow or no urine output[1].
Source: JYNARQUE Copay Assistance
Access program details are provided for informational purposes and may vary based on insurance coverage, geographic location, and individual circumstances. Confirm current eligibility directly with the manufacturer or your specialty pharmacy.
Clinical trial results
TEMPO 3:4 (NCT00428948) randomly assigned 1,445 adults with earlier-stage, rapidly progressing ADPKD (estimated creatinine clearance of 60 or more, total kidney volume of 750mL or more and age under 51) to tolvaptan or placebo for 3 years[1][12]. Kidney growth was slower on tolvaptan (p<0.0001), with most of the difference built up in the first year, and the gap in kidney size was not kept once both groups took tolvaptan in the extension[1].
Kidney function fell 1.0 point (mL/min/1.73m2) a year more slowly on tolvaptan. Worsening kidney function events affected 4.6% of people on tolvaptan against 12.8% on placebo, and kidney pain events 9.9% against 16.2%, while tolvaptan had no effect on worsening high blood pressure or rising albumin in the urine[1]. REPRISE (NCT02160145) tested later-stage disease, an eGFR of 25 to 65, in 1,370 adults who first showed they could tolerate 1 of the 2 highest doses (60mg plus 30mg or 90mg plus 30mg)[1][13].
Over 12 months, eGFR fell 2.3 points a year on tolvaptan against 3.6 on placebo, a difference of 1.3 points a year (p<0.0001)[1]. Few Black or African American patients took part in either trial[1].
Development history
Otsuka's first application for tolvaptan in ADPKD received a complete response letter from the FDA in 2013, and Otsuka ran an additional Phase 3 trial, REPRISE, to address it, according to Otsuka's May 21, 2017 release[4][13]. The FDA approved Jynarque on April 23, 2018 under NDA 204441, with priority review[2], and Otsuka announced the approval the next day as the first treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD[3].
Tolvaptan had been sold since 2009 as Samsca, a separate product for low blood sodium[5]. The FDA approved the first generic tolvaptan for ADPKD, from Lupin, on April 23, 2025, and Lupin announced its launch on May 13, 2025[7][11]. Generics from Apotex, Alkem (sold by Ascend Laboratories) and Teva were approved between November 2025 and July 2026[8][9][10]. The label updated in September 2026 reports the current safety and dosing information[1].
Explore Polycystic Kidney Disease trials
Common questions about Tolvaptan
▸What is Tolvaptan (Jynarque)?
A twice-daily pill and the first FDA-approved treatment to slow the loss of kidney function in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD), approved in April 2018. Jynarque carries a boxed warning for serious liver injury and is available only through a safety program with regular liver blood tests. Generic tolvaptan for ADPKD is also approved, and Lupin launched the first in May 2025. Jynarque is not approved for the recessive form of PKD (ARPKD) or for children.
▸How does Tolvaptan work?
Vasopressin is a hormone that tells the kidneys to hold on to water. When it binds the V2 receptor in the kidney, it raises a cell signal called cAMP, and in ADPKD that signal helps cysts grow and fill with fluid. Tolvaptan blocks the V2 receptor and lowers cAMP[1]. In human ADPKD cyst cells grown in the lab, tolvaptan slowed cyst growth and fluid secretion into cysts, and in animal models lower cAMP went with slower growth of total kidney volume and fewer new cysts[1]. Blocking vasopressin also makes the kidneys pass much more water: with the 90mg and 30mg doses, people with good kidney function made about 4 more liters of urine a day, for about 7 liters in total[1]. Kidney filtration (GFR) drops by about 6-10% during treatment, and the label says that change reverses when tolvaptan is stopped[1].
▸What are the side effects of Tolvaptan?
Jynarque carries a boxed warning: it can cause serious and potentially fatal liver injury, and acute liver failure needing a liver transplant has been reported since approval[1]. In the 2 placebo-controlled trials, ALT rose above 3 times the upper limit of normal in 4.9% of people on tolvaptan against 1.1% on placebo within the first 18 months, and these rises usually went away 1 to 4 months after stopping. Serious liver injury, with high liver enzymes plus high bilirubin, occurred in 0.2% (3 of 1,487) of tolvaptan-treated patients in TEMPO 3:4 and its extension and in no placebo patients[1]. Because tolvaptan makes the body lose water, the label also warns about high blood sodium (hypernatremia, in 4.0% against 0.6% in one trial and 1.4% against 0% in the other) and dehydration or low blood volume (2.1% against 0.7% and 2.3% against 0.4%)[1]. In TEMPO 3:4, the most common side effects were more urination (69.5% against 28.0% on placebo), thirst (63.7% against 23.4%), dry mouth (16.0% against 12.4%), fatigue (13.6% against 9.7%), diarrhea (13.3% against 11.0%) and dizziness (11.3% against 8.7%), and 15.4% of people stopped tolvaptan because of a side effect against 5.0% on placebo, most often because of the extra urination[1]. Since approval, anaphylaxis and raised creatine phosphokinase have also been reported[1]. The label says the risk in pregnancy is not known from human data, reports harm to the fetus in rabbits at doses toxic to the mother, and advises against breastfeeding during treatment[1].
▸How is Tolvaptan taken?
Jynarque is taken twice a day as a split dose: a larger dose on waking and a smaller dose 8 hours later[1]. The starting dose is 45mg on waking plus 15mg 8 hours later (60mg a day). If tolerated, the dose goes up to 60mg plus 30mg, then to 90mg plus 30mg (120mg a day), with at least a week between steps, and it can be lowered for tolerability[1]. A missed dose is skipped and the next dose taken at its usual time. The label asks prescribers to encourage enough water to avoid thirst or dehydration, and the Medication Guide tells patients to drink water when thirsty and through the day and night when awake[1]. People taking a moderate CYP3A inhibitor get a lower dose, for example 45mg plus 15mg in place of 90mg plus 30mg[1]. Tablets come in 15mg, 30mg, 45mg, 60mg and 90mg, sold in 7-day blister cards that pair the morning and afternoon doses, and in 30-tablet bottles of 15mg and 30mg[1].
▸Is Tolvaptan FDA approved?
Yes, Tolvaptan (Jynarque) is FDA approved (2018) for the treatment of Polycystic Kidney Disease.
▸How often do you need liver blood tests on Jynarque?
Before starting, at 2 weeks and 4 weeks, then every month for the first 18 months and every 3 months after that, according to the boxed warning[1].
Tests: ALT, AST and bilirubin.
Why: tolvaptan can cause serious and potentially fatal liver injury, and acute liver failure needing a transplant has been reported.
REMS: patients enroll in the Tolvaptan for ADPKD Shared System REMS, which requires them to keep up with the monitoring, and only certified pharmacies can dispense it.
If tests rise: the label stops tolvaptan when ALT, AST or bilirubin rise above 2 times normal or liver symptoms appear, with repeat tests within 48 to 72 hours.
Symptoms to report: fatigue, loss of appetite, nausea, right upper belly discomfort, vomiting, fever, rash, itching, dark urine or yellow skin.
More information: TolvaptanADPKDSharedREMS.com or 1-866-244-9446.
Source: Jynarque prescribing information, September 2026.
▸Is Jynarque the same as Samsca?
Both contain tolvaptan, but they are separate products with different uses, doses and warnings[1][6].
Jynarque: approved to slow kidney function decline in adults at risk of rapidly progressing ADPKD, taken twice a day for the long term with a REMS and regular liver tests.
Samsca: approved for low blood sodium (hyponatremia), including in heart failure and SIADH, started in a hospital and given once a day for no more than 30 days.
Boxed warning: Samsca's label says tolvaptan should not be used for ADPKD outside the FDA-approved REMS because of the liver risk.
Generics: the FDA rates the ADPKD generics as equivalent to Jynarque (code AB2) and the low-sodium generics as equivalent to Samsca (code AB1)[7].
Source: Jynarque prescribing information, September 2026; Samsca prescribing information, May 2026; Drugs@FDA.
▸Is there a generic version of Jynarque?
Yes. The FDA has approved generic tolvaptan for ADPKD from Lupin, Apotex, Alkem and Teva, rated as equivalent to Jynarque[7].
First launch: Lupin announced on May 13, 2025 that it had launched tolvaptan tablets in 15mg, 30mg, 45mg, 60mg and 90mg strengths[11].
Approvals: Lupin April 2025, Apotex November 2025, Alkem April 2026 (sold by Ascend Laboratories) and Teva July 2026.
Same rules: generic tolvaptan for ADPKD is part of the same Tolvaptan for ADPKD Shared System REMS, with the same liver test schedule.
Not interchangeable with: generics of Samsca, which treat low blood sodium.
Source: Drugs@FDA; Lupin press release, May 13, 2025.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Otsuka America Pharmaceutical via DailyMed · 2026-09-30. JYNARQUE- tolvaptan kit JYNARQUE- tolvaptan tablet. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3febc0a1-9e5a-4ce0-843d-210f21d862c4
- FDA · 2018-04-23. JYNARQUE approval history, NDA 204441. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=204441
- Otsuka · 2018-04-24. Otsuka's JYNARQUE™ (tolvaptan) Approved by U.S. FDA as the First Treatment to Slow Kidney Function Decline in Adults at Risk of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease (ADPKD). https://www.otsuka-us.com/discover/articles-1188
- Otsuka · 2017-05-21. Otsuka Announces Results of Phase 3 Data on Tolvaptan Under Development for ADPKD in U.S.. https://www.otsuka-us.com/discover/articles-1029
- FDA · 2009-05-19. SAMSCA approval history, NDA 022275. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022275
- Otsuka America Pharmaceutical via DailyMed · 2026-05-07. SAMSCA (tolvaptan) tablets, for oral use: prescribing information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566
- FDA. Tolvaptan approval history, ANDA 216063 (Lupin). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=216063
- FDA. Tolvaptan approval history, ANDA 218381 (Apotex). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218381
- FDA. Tolvaptan approval history, ANDA 220147 (Alkem). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220147
- FDA. Tolvaptan approval history, ANDA 216933 (Teva). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=216933
- Lupin · 2025-05-13. Lupin Launches Tolvaptan Tablets in the U.S. with 180-Day Exclusivity. https://lupin.com/US/media/lupin-launches-tolvaptan-tablets-in-the-u-s-with-180-day-exclusivity
- ClinicalTrials.gov. Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD). https://clinicaltrials.gov/study/NCT00428948
- ClinicalTrials.gov. Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease. https://clinicaltrials.gov/study/NCT02160145
- Kidney International · 2025-02. KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). https://pubmed.ncbi.nlm.nih.gov/39848759/
- Otsuka America Pharmaceutical. JYNARQUE Copay Assistance. https://www.jynarque.com/copay-assistance.html