Tolvaptan
Pronunciation: tol-VAP-tan.
- Generic name
- tolvaptan
- Drug class
- Vasopressin V2-receptor antagonist (aquaretic)
- Form
- Tablet (multiple strengths: 7.5 mg, 15 mg, 30 mg, 45 mg, 60 mg, 90 mg depending on brand/indication)
- Route
- Oral
- Legal status
- Prescription-only, specialist-initiated
Availability and supply rules vary by country
Trade names by country: United States · United Kingdom · Canada · Australia · New Zealand
Australia: Samsca (7), Jinarc (7) · Full directory
Boxed warning: Serious liver injury, and risk of dangerous neurological injury from too-rapid sodium correction
Tolvaptan carries a boxed warning (the US FDA's strongest safety warning) with two parts that apply depending on which product and indication is used. For the ADPKD indication (Jynarque in the US; Jinarc elsewhere): tolvaptan can cause serious and potentially fatal liver injury, and acute liver failure requiring liver transplantation has been reported. Liver blood tests (ALT, AST, and bilirubin) must be measured before starting treatment, at 2 and 4 weeks after starting, then monthly for the first 18 months, and every 3 months after that. This product is available only through a restricted distribution program (a Risk Evaluation and Mitigation Strategy, REMS) because of this liver injury risk. For the hyponatraemia indication (Samsca): treatment must be started, and restarted, only in a hospital where blood sodium levels can be monitored closely, because correcting a low sodium level too quickly (for example, more than 12 mEq/L in 24 hours) can cause a serious and potentially fatal brain injury called osmotic demyelination syndrome, with symptoms including slurred speech, inability to speak, difficulty swallowing, severe tiredness, mood or behaviour changes, stiffness and loss of movement in the limbs, seizures, coma, and death. Samsca must not be used for ADPKD outside of the approved REMS program, because of the same liver injury risk described above. (1) (2)
What tolvaptan is and how it works
Tolvaptan is a prescription medicine that blocks the action of vasopressin (a hormone that helps the kidneys hold on to water), causing the kidneys to pass more water into the urine. It is used for two very different purposes: raising a dangerously low blood sodium level (as Samsca), or slowing kidney decline in autosomal dominant polycystic kidney disease (as Jynarque/Jinarc). (2) (1)
Because of a genuine risk of serious liver injury, and -- for the sodium-correcting use -- a genuine risk of serious brain injury if sodium is corrected too fast, tolvaptan is only started under close medical supervision, with regular blood tests. Never take tolvaptan without this monitoring in place, and never adjust your own dose.
Mechanism of action: how tolvaptan works
Tolvaptan is a selective arginine vasopressin V2-receptor antagonist. Blocking V2 receptors in the kidney's collecting ducts reduces water reabsorption, producing an aquaresis (electrolyte-sparing water loss) that raises serum sodium in hyponatraemia, and is thought to slow cyst growth and kidney function decline in ADPKD via reduced cyclic AMP signalling in kidney tubule cells. (1) (2)
What tolvaptan is used for
Low blood sodium (hyponatraemia)
Used to raise blood sodium levels that are low because of conditions such as SIADH (syndrome of inappropriate antidiuretic hormone secretion), heart failure, or other causes of clinically significant hyponatraemia, when fluid restriction alone is not enough. (2) (4)
Autosomal dominant polycystic kidney disease (ADPKD)
Used to slow the decline in kidney function (and, outside the US, to slow cyst development) in adults with ADPKD who have evidence of rapidly progressing disease. (1) (3)
Before taking tolvaptan
Do not take / not appropriate for
- Do not take tolvaptan if you have a known serious allergic reaction to it or to benzazepine-related medicines. (all countries) (4) (3)
- Do not take tolvaptan if you cannot sense or respond to thirst, or if you are unable to drink enough water to replace what you lose. (all countries) (2) (1)
- Do not take tolvaptan (for the ADPKD indication) if you have current liver injury, abnormal liver blood tests, or a history of significant liver problems (aside from uncomplicated polycystic liver disease). (all countries) (1) (3)
- Do not take tolvaptan if you produce no urine (anuria), or have uncorrected low blood volume or an uncorrected blockage in your urinary tract. (all countries) (2) (1)
- Do not combine tolvaptan with strong CYP3A inhibitor medicines or grapefruit juice. (all countries) (4) (3)
Tell your clinician about
- Any history of liver problems, or if you have ever had abnormal liver blood tests.
- Any history of very low blood sodium, alcohol use disorder, severe malnutrition, or advanced liver disease -- these change how carefully your sodium correction needs to be paced.
- All other medicines, especially anything affecting liver enzymes (CYP3A), diuretics, or other treatments for low sodium.
- Whether you are pregnant, plan to become pregnant, or are breastfeeding.
- Whether you have reliable access to water and can reliably tell when you are thirsty.
How to take tolvaptan
- For the hyponatraemia (Samsca) use: treatment is started, and restarted if ever stopped, only in a hospital, so your blood sodium and fluid status can be checked closely as your dose is adjusted.
- For the ADPKD (Jynarque/Jinarc) use: taken as two doses each day, a larger one in the morning and a smaller one in the afternoon, on an individualised schedule set and adjusted by your clinician.
- Do not change your dose or stop taking tolvaptan without your clinician's guidance -- both the timing and the dose matter for safety.
- Avoid grapefruit and grapefruit juice, which can raise tolvaptan levels in your body.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6) (7) (8)
Missed dose
Contact your prescriber or care team for guidance if you miss a dose. Do not double up or adjust your next dose on your own, since correct timing is part of how this medicine is kept safe.
Overdose
Seek urgent medical attention if you think you have taken too much tolvaptan, or if you develop severe thirst, dizziness, fainting, a very fast heartbeat, or any new neurological symptoms such as slurred speech, confusion, or weakness. (2)
Side effects
Side effects and their urgency vary; report severe, persistent, or concerning symptoms.
Thirst and increased urination (including at night).
What to notice: Thirst and increased urination (including at night).
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (3) (4)
Dry mouth.
What to notice: Dry mouth.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (2) (1)
Headache and dizziness.
What to notice: Headache and dizziness.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (3)
Fatigue and diarrhoea.
What to notice: Fatigue and diarrhoea.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1) (3)
Raised blood sugar (with Samsca use).
What to notice: Raised blood sugar (with Samsca use).
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (2)
Serious warnings
Signs of serious liver injury — boxed_warning
Symptoms: Unusual tiredness, loss of appetite, discomfort in the upper right side of the abdomen, dark urine, or yellowing of the skin or eyes (jaundice).
Action: Contact your clinician immediately and have liver blood tests checked -- tolvaptan can cause serious, potentially fatal liver injury, including liver failure requiring a transplant. Do not restart tolvaptan after such signs without your clinician's explicit direction. (1) (2)
Signs of too-rapid sodium correction (osmotic demyelination syndrome) — boxed_warning
Symptoms: Slurred speech, inability to speak, difficulty swallowing, severe drowsiness, sudden mood or behaviour changes, stiffness or loss of movement in the arms or legs, or seizures.
Action: Seek emergency medical help immediately. This is why hyponatraemia treatment with tolvaptan must start, and restart, only in a hospital where sodium levels can be checked frequently and correction paced safely. (2)
Signs of dehydration or excessive fluid loss — high caution
Symptoms: Dizziness, fainting, a fast heartbeat, low blood pressure, or reduced urination despite feeling very thirsty.
Action: Contact your clinician promptly -- tolvaptan increases water loss through urine, and dehydration needs prompt assessment, especially if you cannot drink enough to keep up. (2) (3)
Signs of a serious allergic reaction — emergency
Symptoms: Swelling of the face, lips, tongue, or throat; difficulty breathing; widespread rash or hives.
Action: Seek emergency medical help immediately. (4)
Interactions
- Strong CYP3A inhibitor medicines (such as ketoconazole, certain macrolide antibiotics, and diltiazem) can raise tolvaptan levels several-fold and generally must not be combined with it, or require significant dose reduction under close supervision. (4) (3)
- Grapefruit and grapefruit juice increase tolvaptan levels and should be avoided. (4)
- Strong CYP3A inducers (such as rifampicin or carbamazepine) can reduce how well tolvaptan works and should generally be avoided. (3)
- Other treatments for low blood sodium, and medicines that affect potassium (such as ACE inhibitors, ARBs, or potassium-sparing diuretics), may need closer monitoring alongside tolvaptan. (2)
Pregnancy, breastfeeding, kidney/liver function, age
Pregnancy
Tolvaptan is contraindicated or not recommended in pregnancy across the sources reviewed, based on animal studies showing reproductive toxicity; discuss family planning with your clinician before starting. (1) (2) (3) (4) (5) (6) (7) (8)
Breastfeeding
Not recommended -- tolvaptan passed into milk in animal studies, and breastfeeding is generally advised against during treatment. (1) (2) (3) (4) (5) (6) (7) (8)
Children
Not established for routine use in children in the sources reviewed for this dossier; any paediatric use would be under specialist care. (1) (2) (3) (4) (5) (6) (7) (8)
Elderly
No specific dose adjustment based on age alone is described in the sources reviewed, but dehydration and sodium-correction risks may need closer attention in older adults. (1) (2) (3) (4) (5) (6) (7) (8)
Hepatic_impairment
Contraindicated in significant current or past liver impairment/injury for the ADPKD indication (aside from uncomplicated polycystic liver disease); underlying liver disease needs caution for the hyponatraemia indication too, given the shared hepatotoxicity risk. (1) (2) (3) (4) (5) (6) (7) (8)
Renal_impairment
Used specifically in the context of chronic kidney disease for the ADPKD indication; dosing and monitoring are individualised to kidney function and stage. (1) (2) (3) (4) (5) (6) (7) (8)
Source_ids
US-DAILYMED-JYNARQUE-2026,US-DAILYMED-SAMSCA-2026,UK-EMC-JINARC-2026 (1) (2) (3) (4) (5) (6) (7) (8)
Monitoring
Before starting
- Baseline liver function tests (ALT, AST, bilirubin)
- Baseline serum sodium and volume status
- Kidney function and CKD stage (for ADPKD use)
- Review of other medicines for CYP3A interactions
During treatment
- Liver function tests: before treatment, at 2 and 4 weeks after starting, then monthly for the first 18 months, then every 3 months (ADPKD/Jynarque schedule).
- Serum sodium checked within hours of starting or restarting treatment for hyponatraemia, then at frequent intervals until stable, in a hospital setting.
- Ongoing assessment for signs of liver injury, dehydration, and (for the hyponatraemia indication) neurological symptoms.
Storage
Store tablets in their original packaging at room temperature, protected from light and moisture, out of reach of children.
Professional information
Clinician-facing context only, sourced from the current US FDA prescribing information for both Samsca and Jynarque; verify against the current full label before prescribing.
United States / United Kingdom / European Union / Canada / Australia / New Zealand
Indication: Hyponatraemia (Samsca)
Dose summary: 15 mg once daily initial (7.5 mg in higher-risk patients), titrated at intervals of at least 24 hours to a maximum of 60 mg once daily; hospital initiation/re-initiation only; not usually continued beyond 30 days.
Renal context: Not the primary indication for this brand; caution with volume status and electrolyte monitoring regardless of renal function. (2) (4)
United States / United Kingdom / European Union / Canada / Australia / New Zealand
Indication: ADPKD (Jynarque/Jinarc)
Dose summary: Split AM/PM dosing, titrated from 45+15 mg to 60+30 mg to 90+30 mg daily as tolerated; dose reduced ~50% with moderate CYP3A inhibitors; the prescriber reassesses ongoing suitability if CKD progresses to stage 5.
Renal context: Indicated specifically for CKD stage 1-4 ADPKD patients with evidence of rapidly progressing disease; discontinuation considered at stage 5 (kidney failure). (1) (3)
Hepatic guidance
Contraindicated in current/prior significant liver impairment for the ADPKD indication; hepatotoxicity is a shared, boxed-warning-level risk across both indications, requiring scheduled liver function monitoring.
Overdose note
No specific antidote; manage with supportive care, monitoring of fluid/electrolyte status, and close attention to neurological status if used for sodium correction. (1) (2)
Frequently asked questions
Is tolvaptan available in the US, UK, Europe, Canada, Australia, and New Zealand?
Yes. It is authorised in all of these regions, sold as Samsca everywhere for low blood sodium, and as Jynarque (United States) or Jinarc (European Union, United Kingdom, Canada, Australia, New Zealand) for slowing kidney decline in autosomal dominant polycystic kidney disease. (2) (1) (3) (4) (5) (6) (7) (8)
Why does treatment for low sodium have to start in a hospital?
Because correcting a low blood sodium level too quickly with tolvaptan can cause a serious, potentially fatal brain injury (osmotic demyelination syndrome). Starting and restarting treatment in a hospital allows blood sodium to be checked frequently so the rate of correction can be kept safe. (2)
Why do I need regular liver blood tests on tolvaptan?
Tolvaptan carries a boxed warning for serious, potentially fatal liver injury, including rare cases of liver failure needing a transplant. Regular liver blood tests (before starting, at 2 and 4 weeks, then monthly for 18 months, then every 3 months for the ADPKD indication) are required to catch early signs of liver injury. (1)
What is the mechanism of action of tolvaptan?
Tolvaptan is a selective arginine vasopressin V2-receptor antagonist. Blocking V2 receptors in the kidney's collecting ducts reduces water reabsorption, producing an aquaresis (electrolyte-sparing water loss) that raises serum sodium in hyponatraemia, and is thought to slow cyst growth and kidney function decline in ADPKD via reduced cyclic AMP signalling in kidney tubule cells. (1) (2)
References
- JYNARQUE (tolvaptan) tablets for oral use -- full prescribing informationU.S. Food and Drug Administration / DailyMed (NIH), full prescribing information, Otsuka America Pharmaceutical, Inc. · United States · accessed 2026-07-30 · source 1
- SAMSCA (tolvaptan) tablets for oral use -- full prescribing informationU.S. Food and Drug Administration / DailyMed (NIH), full prescribing information, Otsuka America Pharmaceutical, Inc. · United States · accessed 2026-07-30 · source 2
- Jinarc 30 mg and 60 mg tablets -- Summary of Product Characteristicselectronic medicines compendium (emc), United Kingdom -- Otsuka Pharmaceuticals (UK) Ltd · United Kingdom · accessed 2026-07-30 · source 3
- Samsca 15 mg tablets -- Summary of Product Characteristicselectronic medicines compendium (emc), United Kingdom -- Otsuka Pharmaceuticals (UK) Ltd · United Kingdom · accessed 2026-07-30 · source 4
- Samsca (tolvaptan) and Jinarc (tolvaptan) -- EPAR medicine overviewsEuropean Medicines Agency (EMA) -- EPARs for Samsca and Jinarc · European Union · accessed 2026-07-30 · source 5
- JINARC (tolvaptan) and SAMSCA (tolvaptan) Product MonographsHealth Canada product monographs, Otsuka Canada Pharmaceutical Inc. · Canada · accessed 2026-07-30 · source 6
- SAMSCA tolvaptan 15 mg and 30 mg tablet blister pack -- ARTG entries 176602 / 176601Therapeutic Goods Administration (TGA), Australia · Australia · accessed 2026-07-30 · source 7
- JINARC New Zealand Data SheetMedsafe (New Zealand regulator) · New Zealand · accessed 2026-07-30 · source 8
Brand names by country
Single-ingredient tolvaptan names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- JYNARQUE30 mg, 15 mg · otsuka america pharmaceutical, inc.
- SAMSCA15 mg, 30 mg · otsuka america pharmaceutical, inc.
United Kingdom
Canada
- SAMSCA