Jinarc (Tolvaptan)
Vasopressin V2-receptor antagonist for slowing the progression of autosomal dominant polycystic kidney disease (ADPKD)
Jinarc (tolvaptan) is a prescription medicine used to slow the progression of cyst development and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). It works by blocking vasopressin, a hormone that drives cyst growth in polycystic kidneys. Jinarc is indicated for adults with CKD stages 1 to 4 who show evidence of rapidly progressive disease. This guide covers indications, dosage, side effects, liver monitoring requirements, drug interactions, and practical advice for patients taking tolvaptan.
Quick Facts About Jinarc
Key Takeaways About Jinarc
- Slows ADPKD progression: Clinical trials (TEMPO 3:4, REPRISE) demonstrated that tolvaptan significantly reduces the rate of kidney volume growth and eGFR decline in patients with rapidly progressing ADPKD
- Split-dose regimen: Jinarc is taken twice daily – a higher dose in the morning and a lower dose 8 hours later – starting at 45 mg + 15 mg and titrated up to 90 mg + 30 mg
- Mandatory liver monitoring: Monthly blood tests for liver enzymes are required because tolvaptan can cause hepatotoxicity, including rare cases of acute liver failure
- Significant water intake needed: Jinarc causes large volumes of dilute urine (aquaresis), so patients must drink adequate water throughout the day and night to prevent dehydration
- Avoid grapefruit juice and strong CYP3A4 inhibitors: These can dangerously increase tolvaptan blood levels, raising the risk of side effects including liver damage
What Is Jinarc and What Is It Used For?
Jinarc (tolvaptan) is a vasopressin V2-receptor antagonist prescribed to slow the progression of cyst development and renal insufficiency in adults with autosomal dominant polycystic kidney disease (ADPKD) at CKD stages 1 to 4 with evidence of rapidly progressing disease.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney disorders, affecting approximately 1 in 400 to 1 in 1,000 people worldwide. The condition is characterised by the progressive growth of fluid-filled cysts in both kidneys, which gradually enlarge and compress surrounding healthy tissue. Over time, this relentless cyst expansion leads to deterioration of kidney function and, in roughly half of all patients, eventual kidney failure requiring dialysis or transplantation by the age of 60.
The hormone vasopressin (also called antidiuretic hormone or ADH) plays a central role in ADPKD. In healthy kidneys, vasopressin acts on V2 receptors in the collecting ducts to regulate water balance. In polycystic kidneys, however, vasopressin-driven signalling through cyclic AMP (cAMP) directly promotes the proliferation of cyst-lining epithelial cells and the secretion of fluid into cysts. This makes the vasopressin–cAMP pathway a critical therapeutic target.
Jinarc contains the active substance tolvaptan, which selectively blocks vasopressin V2 receptors. By interrupting this signalling pathway, tolvaptan reduces intracellular cAMP levels in cyst cells, thereby slowing the rate of cyst growth, fluid secretion into cysts, and overall kidney enlargement. In the landmark TEMPO 3:4 trial involving 1,445 patients, tolvaptan reduced the annual increase in total kidney volume by 49% compared to placebo over 3 years. The subsequent REPRISE trial confirmed that tolvaptan also slows the rate of kidney function decline (measured by estimated glomerular filtration rate, eGFR) in patients with later-stage CKD (stages 2–5).
Jinarc is specifically indicated for the treatment of ADPKD in adults with CKD stages 1 to 4 at initiation of treatment who have evidence of rapidly progressive disease. Your prescribing specialist will assess factors such as kidney size, rate of kidney growth, rate of eGFR decline, and genetic analysis to determine whether your disease is progressing rapidly enough to warrant treatment with tolvaptan.
What Should You Know Before Taking Jinarc?
Jinarc must not be used during pregnancy or breastfeeding, in patients who cannot perceive thirst, those with hypernatraemia, severe dehydration, anuria, or liver enzyme elevations that preclude treatment. Monthly liver function monitoring is mandatory throughout treatment.
Contraindications
There are several important situations in which Jinarc must not be taken. Before starting treatment, your doctor will carefully assess whether any of these apply to you. Do not take Jinarc if you:
- Are allergic to tolvaptan or any of the other ingredients in the tablet (including lactose monohydrate, maize starch, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, and indigo carmine aluminium lake E132)
- Are allergic to benzazepine or benzazepine derivatives such as benazepril, conivaptan, fenoldopam mesylate, or mirtazapine
- Have been told that you have elevated liver enzymes in your blood that prevent treatment with tolvaptan
- Have anuria (your kidneys are not producing any urine)
- Have a condition associated with very low blood volume (hypovolaemia), such as severe dehydration or major bleeding
- Have a condition that causes elevated blood sodium (hypernatraemia)
- Cannot perceive or respond to thirst – this is critical because tolvaptan increases urine output dramatically and you must be able to drink in response to thirst to avoid dangerous dehydration
- Are pregnant
- Are breastfeeding
Warnings and Precautions
Talk to your doctor before taking Jinarc if any of the following apply to you. Your doctor may need to adjust your dose or monitor you more closely:
- You have or have had a liver disease
- You cannot drink enough water or must restrict your fluid intake for any medical reason
- You have difficulty urinating (for example, due to an enlarged prostate)
- You have abnormally high or low blood sodium levels
- You have diabetes mellitus
- You have been told you have elevated uric acid levels (which may have caused gout attacks)
- You have advanced kidney disease
Jinarc can cause potentially serious liver injury. Contact your doctor immediately if you experience any of the following symptoms:
- Nausea or vomiting
- Fever
- Unusual fatigue or tiredness
- Loss of appetite
- Abdominal (stomach) pain
- Dark-coloured urine
- Jaundice (yellowing of the skin or whites of the eyes)
- Itching of the skin
- Flu-like syndrome (joint and muscle pain with fever)
Your doctor will perform monthly blood tests to check your liver function throughout your treatment with Jinarc. Do not miss these appointments.
Drinking Enough Water
Jinarc works by blocking the hormone vasopressin, which normally tells your kidneys to conserve water. As a result, your kidneys will produce significantly more urine than usual – patients on tolvaptan typically produce 6 to 9 litres of urine per day. This water loss can lead to dehydration if you do not drink enough to compensate.
It is essential that you have constant access to water and drink whenever you feel thirsty. Before going to bed, drink 1–2 glasses of water even if you are not thirsty, and drink again if you wake during the night to urinate. You must take special care during hot weather, exercise, or if you have vomiting or diarrhoea, as these increase the risk of dehydration. Because of the increased urine output, always ensure you have access to a toilet.
Pregnancy and Breastfeeding
Jinarc must not be used during pregnancy. Animal studies have shown adverse effects on the developing foetus, and the potential risk to human pregnancies is unknown but cannot be excluded. Women of childbearing potential must use reliable contraception during the entire course of treatment. If you become pregnant or suspect you may be pregnant while taking Jinarc, stop the medication immediately and contact your doctor.
Breastfeeding is contraindicated during Jinarc treatment. Tolvaptan has been detected in animal milk, and it is unknown whether it passes into human breast milk. Given the potential for serious adverse reactions in the nursing infant, a decision must be made whether to discontinue breastfeeding or to discontinue the drug.
Children and Adolescents
Jinarc is not recommended for use in children and adolescents under 18 years of age because its safety and efficacy have not been studied in this age group. ADPKD rarely requires pharmacological intervention in the paediatric population, and clinical trials to date have focused exclusively on adults.
Driving and Using Machines
Some patients experience dizziness, weakness, or fatigue while taking Jinarc. If you notice any of these effects, do not drive, operate heavy machinery, or use tools until the symptoms have resolved. The large volume of urine produced may also cause practical difficulties during long journeys.
Lactose Content
Jinarc tablets contain lactose monohydrate as an excipient. If you have been told by your doctor that you have an intolerance to certain sugars, consult your doctor before taking this medicine.
How Does Jinarc Interact with Other Drugs?
Jinarc has significant interactions with CYP3A4 inhibitors (which increase tolvaptan levels), CYP3A4 inducers (which decrease tolvaptan levels), and P-glycoprotein substrates (whose levels may increase). Grapefruit juice must be avoided entirely. Tell your doctor about all medications you take.
Tolvaptan is metabolised primarily by the cytochrome P450 enzyme CYP3A4 and is also a substrate and inhibitor of P-glycoprotein (P-gp). Many commonly used medications can affect how tolvaptan works in your body, and tolvaptan itself can alter the blood levels of other drugs. It is critical that you inform your doctor, pharmacist, or specialist about every medicine you are taking, including prescription drugs, over-the-counter medications, and herbal supplements.
Drugs That Increase the Effect of Jinarc
CYP3A4 inhibitors slow the breakdown of tolvaptan in the body, causing blood levels to rise and potentially increasing the risk of side effects, including liver toxicity. If you must take any of these medications, your doctor may prescribe a lower dose of Jinarc (possibly 30 mg or 15 mg once daily).
| Drug | Therapeutic Use | Interaction Mechanism | Clinical Advice |
|---|---|---|---|
| Ketoconazole | Antifungal | Strong CYP3A4 inhibitor; may increase tolvaptan exposure up to 5-fold | Contraindicated with Jinarc. Do not use together. |
| Itraconazole, Fluconazole | Antifungal agents | Moderate to strong CYP3A4 inhibition | Dose reduction of Jinarc required. Close monitoring. |
| Clarithromycin, Erythromycin | Macrolide antibiotics | Moderate CYP3A4 inhibition | Dose reduction of Jinarc may be needed. |
| Verapamil, Diltiazem | Heart disease, hypertension | Moderate CYP3A4 inhibition | Dose reduction of Jinarc may be needed. |
| Amprenavir, Atazanavir, Darunavir/Ritonavir, Fosamprenavir | HIV/AIDS antiretrovirals | Strong CYP3A4 inhibition | Dose reduction of Jinarc required. Specialist supervision. |
| Aprepitant | Antiemetic (chemotherapy nausea) | Moderate CYP3A4 inhibition | Dose adjustment may be required. |
| Crizotinib, Imatinib | Cancer treatment | CYP3A4 inhibition | Close monitoring; dose adjustment may be needed. |
| Ciprofloxacin | Antibiotic | Moderate CYP3A4 inhibition | Dose adjustment may be required. |
| Grapefruit juice | Dietary | Strong CYP3A4 inhibition in the gut wall | Avoid entirely during Jinarc treatment. |
Drugs That Decrease the Effect of Jinarc
CYP3A4 inducers accelerate the breakdown of tolvaptan, potentially reducing its blood levels to subtherapeutic concentrations and making the treatment less effective or ineffective.
| Drug | Therapeutic Use | Clinical Advice |
|---|---|---|
| Rifampicin, Rifabutin, Rifapentin | Tuberculosis treatment | May significantly reduce tolvaptan efficacy. Avoid co-administration if possible. |
| Phenytoin, Carbamazepine | Epilepsy treatment | May significantly reduce tolvaptan efficacy. Discuss alternatives with your neurologist. |
| St John’s wort (Hypericum perforatum) | Herbal remedy for mild depression and anxiety | Avoid during Jinarc treatment. Use alternative antidepressant if needed. |
Drugs Whose Effect May Be Increased by Jinarc
Tolvaptan inhibits P-glycoprotein and certain other drug transporters, which can raise the blood levels of some medications. Inform your doctor if you take any of the following:
- Digoxin (used for irregular heartbeat and heart failure) – tolvaptan can increase digoxin blood levels. Your doctor may need to monitor digoxin levels and adjust the dose.
- Dabigatran (blood thinner) – tolvaptan may increase dabigatran exposure, raising the bleeding risk.
- Sulfasalazine (used for inflammatory bowel disease or rheumatoid arthritis) – tolvaptan may increase sulfasalazine blood levels.
- Metformin (used for type 2 diabetes) – tolvaptan may increase metformin exposure.
Drugs Whose Effect May Be Decreased by Jinarc
- Vasopressin analogues such as desmopressin (used to increase clotting factors, control urine output, or treat bedwetting) – tolvaptan directly opposes the action of vasopressin and its analogues, reducing their effectiveness.
Other Important Interactions
- Diuretics (water pills) – when taken together with Jinarc, they may increase the risk of dehydration and kidney problems due to excessive fluid loss. Close monitoring is required.
- Antihypertensive medications (blood pressure medicines) – combination with Jinarc may increase the risk of postural hypotension (dizziness when standing up). Rise slowly from sitting or lying positions.
- Medicines that increase blood sodium or contain large amounts of salt (such as effervescent tablets or antacids) – these may enhance Jinarc’s effect on sodium levels, potentially leading to hypernatraemia.
What Is the Correct Dosage of Jinarc?
Jinarc is taken as a split dose: a higher dose in the morning (at least 30 minutes before breakfast) and a lower dose 8 hours later. Treatment starts at 45 mg + 15 mg daily and may be titrated up to 90 mg + 30 mg. Only specialist physicians experienced in ADPKD management should prescribe Jinarc.
Jinarc can only be prescribed by doctors with specialist knowledge of ADPKD management. Always take this medicine exactly as your doctor has instructed. If you are unsure, consult your doctor or pharmacist.
Adults – Split Dose Regimen
The daily dose of Jinarc is divided into two doses taken at specific times. The higher dose is taken in the morning when you wake up, at least 30 minutes before breakfast. The lower dose is taken 8 hours after the morning dose. Swallow the tablets whole with a glass of water – do not chew them.
Jinarc Dose Titration Schedule
| Titration Step | Morning Dose | Evening Dose (8 h later) | Total Daily Dose |
|---|---|---|---|
| Step 1 (Starting dose) | 45 mg | 15 mg | 60 mg |
| Step 2 | 60 mg | 30 mg | 90 mg |
| Step 3 (Maximum dose) | 90 mg | 30 mg | 120 mg |
Your doctor will check how well you tolerate each dose level before increasing. You should always take the highest tolerable dose combination that your doctor prescribes. If you are also taking CYP3A4 inhibitors, your doctor may prescribe a reduced dose of 30 mg or 15 mg once daily in the morning.
Children and Adolescents
Jinarc is not approved for use in children or adolescents under 18 years of age. No clinical data are available for this age group.
Elderly Patients
No specific dose adjustment is required for elderly patients. However, older patients may be more susceptible to dehydration and electrolyte disturbances, and careful monitoring of hydration status and renal function is recommended.
Missed Dose
If you forget to take a dose, take it as soon as you remember on the same day. If you do not take your tablets during one day, take your normal dose the next day. Do not take a double dose to make up for a missed dose. Taking the higher dose late in the day may cause more frequent nighttime urination.
Overdose
If you have taken more tablets than prescribed, drink plenty of water immediately and contact your doctor or go to the nearest hospital emergency department. Bring the medicine packaging with you so that medical staff can see what you have taken. Symptoms of overdose may include excessive water loss, dehydration, and electrolyte disturbances (high blood sodium).
If you stop taking Jinarc, the cysts in your kidneys may resume growing at the same rate as before treatment. Only discontinue this medicine if your doctor tells you to do so or if you experience side effects requiring urgent medical care.
What Are the Side Effects of Jinarc?
The most common side effects of Jinarc are related to its mechanism of action: excessive thirst, frequent urination, dry mouth, and nocturia (nighttime urination). These affect more than 1 in 10 patients. Liver injury is a serious but less common side effect that requires monthly monitoring.
Like all medicines, Jinarc can cause side effects, although not everyone experiences them. The side effects listed below are organised by how frequently they occur. Because tolvaptan blocks vasopressin’s water-retaining action on the kidneys, the aquaretic effects (increased urination and thirst) are expected pharmacological consequences rather than true adverse reactions, but they can be significant in daily life.
Very Common Side Effects
- Thirst (requiring you to drink large amounts of water)
- Headache
- Dizziness
- Diarrhoea
- Dry mouth
- Increased urgency to urinate, need to urinate at night (nocturia), or more frequent urination (pollakiuria)
- Fatigue
Common Side Effects
- Dehydration
- High levels of sodium, uric acid, and blood sugar
- Decreased appetite
- Altered taste
- Gout
- Insomnia (difficulty sleeping)
- Fainting (syncope)
- Palpitations (awareness of heartbeat)
- Shortness of breath (dyspnoea)
- Abdominal pain, bloating, or stomach discomfort
- Constipation
- Heartburn (gastro-oesophageal reflux)
- Abnormal liver function test results
- Dry skin
- Rash
- Itching (pruritus)
- Urticaria (hives)
- Joint pain (arthralgia)
- Muscle spasms
- Muscle pain (myalgia)
- General weakness (asthenia)
- Elevated liver enzymes in blood tests
- Weight loss
- Weight gain
Uncommon Side Effects
- Increased bilirubin levels (a substance that can cause yellowing of the skin or eyes)
Not Known Frequency
- Allergic reactions (swelling of face, lips, or tongue; widespread rash; severe wheezing or shortness of breath)
- Generalised rash
- Acute liver failure (potentially life-threatening)
- Increased creatine phosphokinase levels (a marker of muscle and heart function)
- Difficulty urinating
- Swelling of the face, lips, or tongue, itching, widespread rash, or severe wheezing/shortness of breath (signs of an allergic reaction)
- Nausea, vomiting, fever, fatigue, loss of appetite, abdominal pain, dark urine, or yellowing of skin/eyes (signs of liver injury)
Stop taking Jinarc and contact your doctor or go to the nearest emergency department immediately.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorised is important for ongoing safety surveillance. Healthcare professionals and patients are encouraged to report adverse reactions to their national regulatory authority (e.g., the EMA in the EU, the FDA MedWatch programme in the United States, or the MHRA Yellow Card Scheme in the United Kingdom).
How Should You Store Jinarc?
Store Jinarc in the original packaging, protected from light and moisture, at room temperature. Keep out of the reach and sight of children. Do not use after the expiry date printed on the packaging.
Proper storage of Jinarc is important to maintain the medicine’s effectiveness and safety throughout its shelf life. Follow these guidelines:
- Keep out of reach and sight of children at all times
- Store in the original packaging to protect from light and moisture
- No special temperature storage requirements – store at room temperature
- Do not use after the expiry date printed on the carton, wallet, and blister after “EXP.” The expiry date refers to the last day of the stated month
- Do not dispose of medicines in wastewater or household waste. Return unused medicines to a pharmacy for safe disposal to protect the environment
What Does Jinarc Contain?
The active ingredient is tolvaptan, available in five strengths (15 mg, 30 mg, 45 mg, 60 mg, and 90 mg). Each strength has a unique tablet shape for easy identification. All tablets are blue and marked with “OTSUKA” and the strength number.
Active Ingredient
Each tablet contains the specified amount of tolvaptan as the active substance:
- Jinarc 15 mg tablet – 15 mg tolvaptan
- Jinarc 30 mg tablet – 30 mg tolvaptan
- Jinarc 45 mg tablet – 45 mg tolvaptan
- Jinarc 60 mg tablet – 60 mg tolvaptan
- Jinarc 90 mg tablet – 90 mg tolvaptan
Other Ingredients (Excipients)
The other ingredients are: lactose monohydrate, maize starch, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, and indigo carmine aluminium lake (E132).
Tablet Appearance
Each strength of Jinarc has a distinctive shape to help patients and healthcare professionals identify the correct tablets:
| Strength | Shape | Colour | Imprint |
|---|---|---|---|
| 15 mg | Triangular | Blue | OTSUKA and 15 |
| 30 mg | Round | Blue | OTSUKA and 30 |
| 45 mg | Square | Blue | OTSUKA and 45 |
| 60 mg | Modified rectangular | Blue | OTSUKA and 60 |
| 90 mg | Pentagonal (5-sided) | Blue | OTSUKA and 90 |
Pack Sizes
Jinarc is available as combination packs containing a higher-strength morning tablet and a lower-strength evening tablet (e.g., 45 mg + 15 mg, 60 mg + 30 mg, 90 mg + 30 mg). Packs are available in blister cards with or without wallet packaging, containing 14, 28, or 56 tablets. Single-strength packs of 15 mg and 30 mg (7 or 28 tablets) are also available for dose-reduction regimens. Not all pack sizes may be marketed in every country.
Manufacturer
Jinarc is manufactured by Millmount Healthcare Limited, Block-7, City North Business Campus, Stamullen, Co. Meath, Ireland, and is marketed by Otsuka Pharmaceutical Netherlands B.V., Amsterdam, Netherlands.
Frequently Asked Questions About Jinarc
Medical References and Sources
- European Medicines Agency (EMA). Jinarc (tolvaptan) – Summary of Product Characteristics (SmPC). EPAR last updated 2024. Available at: ema.europa.eu/en/medicines/human/EPAR/jinarc
- Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407–2418. doi:10.1056/NEJMoa1205511 (TEMPO 3:4 trial)
- Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med. 2017;377(20):1930–1942. doi:10.1056/NEJMoa1710030 (REPRISE trial)
- Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2024.
- Gansevoort RT, Arici M, Benzing T, et al. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant. 2016;31(3):337–348. doi:10.1093/ndt/gfv456
- U.S. Food and Drug Administration (FDA). Jynarque (tolvaptan) – Prescribing Information. Available at: accessdata.fda.gov
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Geneva: World Health Organization; 2023.
- Chebib FT, Torres VE. Autosomal dominant polycystic kidney disease: core curriculum 2016. Am J Kidney Dis. 2016;67(5):792–810. doi:10.1053/j.ajkd.2015.07.037
- Devuyst O, Chapman AB, Gansevoort RT, et al. Urine osmolality, response to tolvaptan, and outcome in autosomal dominant polycystic kidney disease: results from the TEMPO 3:4 trial. J Am Soc Nephrol. 2017;28(5):1592–1602. doi:10.1681/ASN.2016040448
- Blair HA. Tolvaptan: a review in autosomal dominant polycystic kidney disease. Drugs. 2019;79(3):303–313. doi:10.1007/s40265-019-1064-0
Editorial Team
This article has been written and medically reviewed by our specialist editorial team, following international clinical guidelines and evidence-based standards.
Medical Content Team
Board-certified physicians specialising in nephrology and clinical pharmacology with expertise in inherited kidney diseases and pharmacotherapy.
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