Jinarc

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
Jinarc 30 mg tablets 
Jinarc 45 mg tablets 
Jinarc 60 mg tablets 
Jinarc 90 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Jinarc 15 mg tablets 
 
Each tablet contains 15 mg of tolvaptan. 
 
Excipient(s) with known effect 
Each 15 mg tablet contains approximately 35 mg lactose (as monohydrate). 
 
Jinarc 30 mg tablets 
 
Each tablet contains 30 mg of tolvaptan. 
 
Excipient(s) with known effect 
Each 30 mg tablet contains approximately 70 mg lactose (as monohydrate). 
 
Jinarc 45 mg tablets 
 
Each tablet contains 45 mg of tolvaptan. 
 
Excipient(s) with known effect 
Each 45 mg tablet contains approximately 12 mg lactose (as monohydrate). 
 
Jinarc 60 mg tablets 
 
Each tablet contains 60 mg of tolvaptan. 
 
Excipient(s) with known effect 
Each 60 mg tablet contains approximately 16 mg lactose (as monohydrate). 
 
Jinarc 90 mg tablets 
 
Each tablet contains 90 mg of tolvaptan. 
 
Excipient(s) with known effect 
Each 90 mg tablet contains approximately 24 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 



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3. PHARMACEUTICAL FORM 
 
Tablet 
 
Jinarc 15 mg tablets 
 
Blue, triangular (major axis: 6.58 mm, minor axis: 6.20 mm), shallow-convex, debossed with 
“OTSUKA” and “15” on one side. 
 
Jinarc 30 mg tablets 
 
Blue, round (diameter: 8 mm), shallow-convex, debossed with “OTSUKA” and “30” on one side. 
 
Jinarc 45 mg tablets 
 
Blue, square (6.8 mm on a side, major axis 8.2 mm), shallow-convex, debossed with “OTSUKA” and 
“45” on one side 
 
Jinarc 60 mg tablets 
 
Blue, modified rectangular (major axis 9.9 mm, minor axis 5.6 mm), shallow-convex, debossed with 
“OTSUKA” and “60” on one side 
 
Jinarc 90 mg tablets 
 
Blue, pentagonal (major axis 9.7 mm, minor axis 9.5 mm), shallow-convex, debossed with “OTSUKA” 
and “90” on one side 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Jinarc is indicated to slow the progression of cyst development and renal insufficiency of autosomal 
dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) stage 1 to 4 
at initiation of treatment with evidence of rapidly progressing disease (see section 5.1). 
 
4.2 Posology and method of administration 
 
Tolvaptan treatment must be initiated and monitored under the supervision of physicians with expertise 
in managing ADPKD and a full understanding of the risks of tolvaptan therapy including hepatic 
toxicity and monitoring requirements (see section 4.4). 
 
Posology 
 
Jinarc is to be administered twice daily in split dose regimens of 45 mg + 15 mg, 60 mg + 30 mg or 
90 mg + 30 mg. The morning dose is to be taken at least 30 minutes before the morning meal. The 
second daily dose can be taken with or without food. According to these split dose regimens the total 
daily doses are 60 mg, 90 mg, or 120 mg. 
 
Dose titration 
The initial dose is 60 mg tolvaptan per day as a split-dose regimen of 45 mg + 15 mg (45 mg taken upon 
waking and prior the morning meal and 15 mg taken 8 hours later). The initial dose is to be titrated 
upward to a split-dose regimen of 90 mg tolvaptan (60 mg + 30 mg) per day and then to a target split-
dose regimen of 120 mg tolvaptan (90 mg + 30 mg) per day, if tolerated, with at least weekly intervals 
between titrations. Dose titration has to be performed cautiously to ensure that high doses are not poorly 



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tolerated through overly rapid up-titration. Patients may down-titrate to lower doses based on 
tolerability. Patients have to be maintained on the highest tolerable tolvaptan dose. 
 
The aim of dose titration is to block activity of vasopressin at the renal V2 receptor as completely and 
constantly as possible, while maintaining acceptable fluid balance (see section 4.4). 
 
Measurements of urine osmolality are recommended to monitor the adequacy of vasopressin inhibition. 
Periodic monitoring of plasma osmolality or serum sodium (to calculate plasma osmolarity) and/or body 
weight should be considered to monitor the risk of dehydration secondary to the aquaretic effects of 
tolvaptan in case of patient’s insufficient water intake. 
 
The safety and efficacy of Jinarc in CKD stage 5 have not been explored and therefore tolvaptan 
treatment should be discontinued if renal insufficiency progresses to CKD stage 5 (see section 4.4). 
 
Therapy must be interrupted if the ability to drink or the accessibility to water is limited (see 
section 4.4). 
 
Tolvaptan must not be taken with grapefruit juice (see section 4.5). Patients must be instructed to drink 
sufficient amounts of water or other aqueous fluids (see section 4.4). 
 
Dose adjustment for patients taking strong CYP3A inhibitors 
In patients taking strong CYP3A inhibitors (see section 4.5), tolvaptan doses have to be reduced as 
follows: 
 
Tolvaptan daily split-dose Reduced dose (once daily) 
90 mg + 30 mg 30 mg (further reduction to 15 mg if 30 mg are not well tolerated) 
60 mg + 30 mg 30 mg (further reduction to 15 mg if 30 mg are not well tolerated) 
45 mg + 15 mg 15 mg 
 
Dose adjustment for patients taking moderate CYP3A inhibitors 
In patients taking moderate CYP3A inhibitors, tolvaptan doses have to be reduced as follows: 
 
Tolvaptan daily split-dose Reduced split-dose 
90 mg + 30 mg 45 mg + 15 mg 
60 mg + 30 mg 30 mg + 15 mg 
45 mg + 15 mg 15 mg + 15 mg 
 
Further reductions have to be considered if patients cannot tolerate the reduced tolvaptan doses. 
 
Special populations 
 
Elderly population 
Increasing age has no effect on tolvaptan plasma concentrations. Limited data on the safety and 
effectiveness of tolvaptan in ADPKD patients aged over 55 are available (see section 5.1). 
 
Renal impairment 
Tolvaptan is contraindicated in anuric patients (see section 4.3). 
 
Dose adjustment is not required in patients with renal impairment. 
 
No clinical trials in subjects with indices of glomerular filtration rate < 10 mL/min or in patients 
undergoing dialysis have been conducted. The risk of hepatic damage in patients with severely reduced 
renal function (i.e. estimated glomerular filtration rate [eGFR] < 20) may be increased; these patients 
should be carefully monitored for hepatic toxicity. Data for patients in CKD early stage 4 are more 
limited than for patients in stage 1, 2 or 3 (see section 5.1). No data are available for patients with CKD 
late stage 4 (eGFR < 25 mL/min/1.73 m2) and stage 5. Tolvaptan treatment should be discontinued if 
renal insufficiency progresses to CKD stage 5 (see section 4.4). 



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Hepatic impairment 
In patients with severe hepatic impairment the benefits and risks of treatment with Jinarc must be 
evaluated carefully. Patients must be managed carefully and liver enzymes must be monitored regularly 
(see section 4.4). 
 
Jinarc is contraindicated in patients with elevated liver enzymes and/or signs or symptoms of liver 
injury prior to initiation of treatment that meet the requirements for permanent discontinuation of 
tolvaptan (see sections 4.3 and 4.4). 
 
No dose adjustment is needed in patients with mild or moderate hepatic impairment (Child-Pugh classes 
A and B). 
 
Paediatric population 
The safety and efficacy of tolvaptan in children and adolescents has not yet been established. No data 
are available. Tolvaptan is not recommended in the paediatric age group. 
 
Method of administration 
 
Oral use. 
Tablets must be swallowed without chewing and with a glass of water. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to 

benzazepine or benzazepine derivatives (see section 4.4) 
• Elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment 

that meet the requirements for permanent discontinuation of tolvaptan (see section 4.4) 
• Anuria 
• Volume depletion 
• Hypernatraemia 
• Patients who cannot perceive or respond to thirst 
• Pregnancy (see section 4.6) 
• Breast-feeding (see section 4.6) 
 
4.4 Special warnings and precautions for use 
 
Idiosyncratic hepatic toxicity 
 
Tolvaptan has been associated with idiosyncratic elevations of blood alanine and aspartate 
aminotransferases (ALT and AST) with infrequent cases of concomitant elevations in bilirubin-total 
(BT). 
 
In post-marketing experience with tolvaptan in ADPKD, acute liver failure requiring liver 
transplantation has been reported. 
 
In a double-blind, placebo-controlled trial in patients with ADPKD, the period of onset of hepatocellular 
injury (by ALT elevations > 3 × ULN) was within 3 to 14 months after initiating treatment and these 
increases were reversible, with ALT returning to < 3 × ULN within 1 to 4 months. While these 
concomitant elevations were reversible with prompt discontinuation of tolvaptan, they represent a 
potential for significant liver injury. Similar changes with other medicinal products have been associated 
with the potential to cause irreversible and potentially life-threatening liver injury (see section 4.8). 
 
Prescribing physicians must comply fully with the safety measures required below. 
 
To mitigate the risk of significant and/or irreversible liver injury, blood testing for hepatic transaminases 
and bilirubin is required prior to initiation of Jinarc, continuing monthly for 18 months and at regular 



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3-monthly intervals thereafter. Concurrent monitoring for symptoms that may indicate liver injury (such 
as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, dark 
urine or jaundice) is recommended. 
 
If a patient shows abnormal ALT, AST or BT levels prior to initiation of treatment which fulfil the 
criteria for permanent discontinuation (see below), the use of tolvaptan is contraindicated (see 
section 4.3). In case of abnormal baseline levels below the limits for permanent discontinuation 
treatment can only be initiated if the potential benefits of treatment outweigh the potential risks and liver 
function testing must continue at increased time frequency. The advice of a hepatologist is 
recommended. 
 
During the first 18 months of treatment, Jinarc can only be supplied to patients whose physician has 
determined that liver function supports continued therapy. 
 
At the onset of symptoms or signs consistent with hepatic injury or if clinically significant abnormal 
ALT or AST increases are detected during treatment, Jinarc administration must be immediately 
interrupted and repeat tests including ALT, AST, BT and alkaline phosphatase (AP) must be obtained as 
soon as possible (ideally within 48 hours to 72 hours). Testing must continue at increased time 
frequency until symptoms/signs/laboratory abnormalities stabilise or resolve, at which point Jinarc may 
be re-initiated. 
 
Current clinical practice suggests that Jinarc therapy is to be interrupted upon confirmation of sustained 
or increasing transaminase levels and permanently discontinued if significant increases and/or clinical 
symptoms of hepatic injury persist. 
 
Recommended guidelines for permanent discontinuation include: 
• ALT or AST > 8-times ULN 
• ALT or AST > 5-times ULN for more than 2 weeks 
• ALT or AST > 3-times ULN and (BT > 2-times ULN or International Normalised Ratio 

[INR] > 1.5) 
• ALT or AST > 3-times ULN with persistent symptoms of hepatic injury noted above. 
 
If ALT and AST levels remain below 3-times the ULN, Jinarc therapy may be cautiously re-started, 
with frequent monitoring at the same or lower doses, as transaminase levels appear to stabilise during 
continued therapy in some patients. 
 
Access to water 
 
Tolvaptan may cause adverse reactions related to water loss such as thirst, polyuria, nocturia, and 
pollakiuria (see section 4.8). Therefore, patients must have access to water (or other aqueous fluids) and 
be able to drink sufficient amounts of these fluids (see section 4.2). Patients have to be instructed to 
drink water or other aqueous fluids at the first sign of thirst in order to avoid excessive thirst or 
dehydration. 
 
Additionally, patients have to drink 1 to 2 glasses of fluid before bedtime regardless of perceived thirst 
and replenish fluids overnight with each episode of nocturia. 
 
Dehydration 
 
Volume status must be monitored in patients taking tolvaptan because treatment with tolvaptan may 
result in severe dehydration which constitutes a risk factor for renal dysfunction. Accurate monitoring of 
body weight is recommended. A progressive reduction in body weight could be an early sign of 
progressive dehydration. If dehydration becomes evident, take appropriate action, which may include 
the need to interrupt or reduce the dose of tolvaptan and increase fluid intake. Special care must be 
taken in patients having diseases that impair appropriate fluid intake or who are at an increased risk of 
water loss e.g. in case of vomiting or diarrhoea. 
 



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Urinary outflow obstruction 
 
Urinary output must be secured. Patients with partial obstruction of urinary outflow, for example 
patients with prostatic hypertrophy or impairment of micturition, have an increased risk of developing 
acute retention. 
 
Fluid and electrolyte balance 
 
Fluid and electrolyte status must be monitored in all patients. Administration of tolvaptan induces 
copious aquaresis and may cause dehydration and increases in serum sodium (see section 4.8) and is 
contraindicated in hypernatraemic patients (see section 4.3). Therefore, serum creatinine, electrolytes 
and symptoms of electrolyte imbalances (e.g. dizziness, fainting, palpitations, confusion, weakness, gait 
instability, hyper-reflexia, seizures, coma) have to be assessed prior to and after starting tolvaptan to 
monitor for dehydration. 
 
During long-term treatment, electrolytes have to be monitored at least every three months. 
 
Serum sodium abnormalities 
 
Pre-treatment sodium abnormalities (hyponatraemia or hypernatraemia) must be corrected prior to 
initiation with tolvaptan therapy. 
 
Anaphylaxis 
 
In post-marketing experience, anaphylaxis (including anaphylactic shock and rash generalised) has been 
reported very rarely following administration of tolvaptan. This type of reaction occurred after the first 
administration of tolvaptan. Patients have to be carefully monitored during treatment. Patients with 
known hypersensitivity reactions to benzazepines or benzazepine derivatives (e.g. benazepril, 
conivaptan, fenoldopam mesylate or mirtazapine) may be at risk for hypersensitivity reaction to 
tolvaptan (see section 4.3). 
 
If an anaphylactic reaction or other serious allergic reactions occur, administration of tolvaptan must be 
discontinued immediately and appropriate therapy initiated. Since hypersensitivity is a contraindication 
(see section 4.3) treatment must never be restarted after an anaphylactic reaction or other serious allergic 
reactions. 
 
Diabetes mellitus 
 
Diabetic patients with an elevated glucose concentration (e.g. in excess of 300 mg/dL) may present with 
pseudo-hyponatraemia. This condition must be excluded prior and during treatment with tolvaptan. 
 
Tolvaptan may cause hyperglycaemia (see section 4.8). Therefore, diabetic patients treated with 
tolvaptan must be managed cautiously. In particular this applies to patients with inadequately controlled 
type II diabetes. 
 
Uric acid increases 
 
Decreased uric acid clearance by the kidney is a known effect of tolvaptan. In a double-blind, 
placebo-controlled trial of patients with ADPKD, potentially clinically significant increased uric acid 
(greater than 10 mg/dL) was reported at a higher rate in tolvaptan-patients (6.2 %) compared to 
placebo-treated patients (1.7 %). Adverse reactions of gout were reported more frequently in 
tolvaptan-treated patients (28/961, 2.9 %) than in patients receiving placebo (7/483, 1.4 %). In addition, 
increased use of allopurinol and other medicinal products used to manage gout were observed in the 
double-blind, placebo-controlled trial. Effects on serum uric acid are attributable to the reversible renal 
hemodynamic changes that occur in response to tolvaptan effects on urine osmolality and may be 
clinically relevant. However, events of increased uric acid and/or gout were not serious and did not 
cause discontinuation of therapy in the double-blind, placebo-controlled trial. Uric acid concentrations 



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are to be evaluated prior to initiation of Jinarc therapy, and as indicated during treatment based on 
symptoms. 
 
Effect of tolvaptan on glomerular filtration rate (GFR) 
 
A reversible reduction in GFR has been observed in ADPKD trials at the initiation of tolvaptan 
treatment. 
 
Chronic Kidney Disease 
 
The safety and efficacy of Jinarc in CKD late stage 4 (eGFR< 25 mL/min/1.73 m2) and stage 5 have not 
been explored. Tolvaptan treatment should be discontinued if renal insufficiency progresses to CKD 
stage 5. 
 
Lactose 
 
Jinarc contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, 
total lactase deficiency or glucose-galactose malabsorption should not take this medicinal prodcut. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effect of other medicinal products on the pharmacokinetics of tolvaptan 
 
CYP3A inhibitors 
Concomitant use of medicinal products that are moderate CYP3A inhibitors (e.g. amprenavir, 
aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, 
fluconazole, fosamprenavir, imatinib, verapamil) or strong CYP3A inhibitors (e.g. itraconazole, 
ketoconazole, ritonavir, clarithromycin) increase tolvaptan exposure. 
 
Co-administration of tolvaptan and ketoconazole resulted in a 440 % increase in area under 
time-concentration curve (AUC) and 248 % increase in maximum observed plasma concentration (Cmax) 
for tolvaptan. 
 
Co-administration of tolvaptan and fluconazole, a moderate CYP3A inhibitor, produced a 200 % and 
80 % increase in tolvaptan AUC and Cmax, respectively. 
 
Co-administration of tolvaptan with grapefruit juice, a moderate to strong CYP3A inhibitor, produced a 
doubling of peak tolvaptan concentrations (Cmax). 
 
Dose reduction of tolvaptan is recommended for patients while taking moderate or strong CYP3A 
inhibitors (see section 4.2). Patients taking moderate or strong CYP3A inhibitors must be managed 
cautiously, in particular if the inhibitors are taken more frequently than once a day. 
 
CYP3A inducers 
Concomitant use of medicinal products that are potent CYP3A inducers (e.g. rifampicin) will decrease 
tolvaptan exposure and efficacy. Co-administration of tolvaptan with rifampicin reduces Cmax and AUC 
for tolvaptan by about 85 %. Therefore, concomitant administration of tolvaptan with potent CYP3A 
inducers (e.g. rifampicin, rifabutin, rifapentin, phenytoin, carbamazepine, and St. John’s Wort) is to be 
avoided. 
 
Co-administration with medicinal products that increase serum sodium concentration 
There is no experience from controlled clinical trials with concomitant use of tolvaptan and hypertonic 
sodium chloride solution, oral sodium formulations, and medicinal products that increase serum sodium 
concentration. Medicinal products with high sodium content such as effervescent analgesic preparations 
and certain sodium containing treatments for dyspepsia may also increase serum sodium concentration. 
Concomitant use of tolvaptan with medicinal products that increase serum sodium concentration may 



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result in a higher risk for developing hypernatraemia (see section 4.4) and is therefore not 
recommended. 
 
Diuretics 
Tolvaptan has not been extensively studied in ADPKD in combination with diuretics. While there does 
not appear to be a synergistic or additive effect of concomitant use of tolvaptan with loop and thiazide 
diuretics, each class of agent has the potential to lead to severe dehydration, which constitutes a risk 
factor for renal dysfunction. If dehydration or renal dysfunction becomes evident, appropriate action 
must be taken which may include the need to interrupt or reduce doses of tolvaptan and/or diuretics and 
increased fluid intake. Other potential causes of renal dysfunction or dehydration must be evaluated and 
addressed. 
 
Effect of tolvaptan on the pharmacokinetics of other products 
 
CYP3A substrates 
In healthy subjects, tolvaptan, a CYP3A substrate, had no effect on the plasma concentrations of some 
other CYP3A substrates (e.g. warfarin or amiodarone). Tolvaptan increased plasma levels of lovastatin 
by 1.3-to 1.5-fold. Even though this increase has no clinical relevance, it indicates tolvaptan can 
potentially increase exposure to CYP3A4 substrates. 
 
Transporter substrates 
In-vitro studies indicate that tolvaptan is a substrate and competitive inhibitor of P-glycoprotein (P-gp). 
In vitro studies indicate that tolvaptan or its oxobutyric metabolite may have the potential to inhibit 
OATP1B1, OATP1B3, OAT3, BCRP and OCT1 transporters. Steady state digoxin concentrations were 
increased (1.3-fold in maximum observed plasma concentration [Cmax] and 1.2-fold in area under the 
plasma concentration-time curve over the dosing interval [AUCτ]) when co-administered with multiple 
once daily 60 mg doses of tolvaptan. Patients receiving digoxin or other narrow therapeutic P-gp 
substrates (e.g. dabigatran) must therefore be managed cautiously and evaluated for excessive effects 
when treated with tolvaptan. Statins commonly used in the tolvaptan phase 3 pivotal trial (e.g. 
rosuvastatin and pitavastatin) are OATP1B1 or OATP1B3 substrates, however no difference in adverse 
events profile was observed during the phase 3 pivotal trial for tolvaptan in ADPKD. If OATP1B1 and 
OATP1B3 substrates (e.g. statins such as rosuvastatin and pitavastatin), OAT3 substrates (e.g. 
methotrexate, ciprofloxacin), BCRP substrates (e.g. sulfasalazine) or OCT1 substrates (e.g. metformin) 
are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive 
effects of these medicinal products. 
 
Diuretics or non-diuretic anti-hypertensive medicinal product(s) 
Standing blood pressure was not routinely measured in ADPKD trials. Therefore, a risk of 
orthostatic/postural hypotension due to a pharmacodynamic interaction with tolvaptan cannot be 
excluded. 
 
Co-administration with vasopressin analogues 
In addition to its renal aquaretic effect, tolvaptan is capable of blocking vascular vasopressin V2 
receptors involved in the release of coagulation factors (e.g. von Willebrand factor) from endothelial 
cells. Therefore, the effect of vasopressin analogues such as desmopressin may be attenuated in patients 
using such analogues to prevent or control bleeding when co-administered with tolvaptan. It is not 
recommended to administer Jinarc with vasopressin analogues. 
 
Smoking and alcohol 
Data related to smoking or alcohol history in ADPKD trials are too limited to determine possible 
interactions of smoking or alcohol with efficacy and safety of ADPKD treatment with tolvaptan. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of tolvaptan in pregnant women. Studies in animals 
have shown reproductive toxicity (see section 5.3). Jinarc is not recommended in women of 
childbearing potential not using contraception. 
 
Jinarc is contraindicated during pregnancy (see section 4.3). 
 
Breast-feeding 
 
It is unknown whether tolvaptan is excreted in human breast milk. Studies in rats have shown excretion 
of tolvaptan in milk. A risk for the newborns/infants cannot be excluded. Jinarc is contraindicated 
during breast-feeding (see section 4.3). 
 
Fertility 
 
Studies in animals showed effects on fertility (see section 5.3). The potential risk for humans is 
unknown. 
 
4.7 Effects on ability to drive and use machines 
 
Jinarc has minor influence on the ability to drive or use machines. When driving vehicles or using 
machines it has to be taken into account that occasionally dizziness, asthenia or fatigue may occur. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The pharmacodynamically predictable and most commonly reported adverse reactions are thirst, 
polyuria, nocturia, and pollakiuria occurring in approximately 55 %, 38 %, 29 % and 23 % of patients, 
respectively. Furthermore, tolvaptan has been associated with idiosyncratic elevations of blood alanine 
aminotransferase (ALT; 4.4 %) and aspartate aminotransferases (AST; 3,1 %) with infrequent cases of 
concomitant elevations in bilirubin-total (BT; 0,2 %). 
 
Tabulated list of adverse reactions 
 
The incidences of the adverse drug reactions (ADRs) associated with tolvaptan therapy are tabulated 
below. The table is based on adverse reactions reported during clinical trials and/or post-marketing use. 
 
All ADRs are listed by system organ class and frequency; very common (≥ 1/10), common (≥ 1/100 to 
< 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and 
not known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they are 
derived from spontaneous reports. Consequently, the frequency of these adverse reactions is qualified as 
"not known". 
 
 Very common Common Uncommon Not known 
Immune system 
disorders 

   Anaphylactic 
shock, 
Generalised rash 

Metabolism and 
nutrition 
disorders 

Polydipsia Dehydration, 
Hypernatraemia, 
Decreased appetite, 

  



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Hyperuricaemia, 
Hyperglycaemia, 
Gout 

Psychiatric 
disorders 

 Insomnia   

Nervous system 
disorders 

Headache, 
Dizziness 

   

Cardiac 
disorders 

 Palpitations   

Respiratory, 
thoracic and 
mediastinal 
disorders 
 

 Dyspnoea   

Gastrointestinal 
disorders 

Diarrhoea, 
Dry mouth 

Abdominal pain, 
Abdominal distension, 
Constipation, 
Dyspepsia, 
Gastroesophageal reflux 
disease 

  

Hepatobiliary 
disorders 

 Abnormal hepatic function  Acute hepatic 
failure1 

Skin and 
subcutaneous 
tissue disorders 
 

 Rash, 
Pruritus 

  

Musculoskeletal 
and connective 
tissue disorders 
 

 Muscle spasms   

Renal and 
urinary 
disorders 

Nocturia, 
Pollakiuria, 
Polyuria 

   

General 
disorders and 
administration 
site conditions 
 

Fatigue, 
Thirst 
 

Asthenia   

Investigations  Alanine aminotransferase 
increased, 
Aspartate aminotransferase 
increased, 
Weight decreased 

Bilirubin 
increased 

 

1 observed in post-marketing with tolvaptan in ADPKD. Liver transplantation was necessary. 
 
Description of selected adverse reactions 
 
Laboratory results 
Elevation (> 3 × upper limit of normal [ULN]) of ALT was observed in 4.4 % (42/958) of patients on 
tolvaptan and 1.0 % (5/484) of patients on placebo, while elevation (> 3 × ULN) of AST was observed 
in 3.1 % (30/958) of patients on tolvaptan and 0.8 % (4/484) patients on placebo in a double-blind, 
placebo-controlled trial in patients with ADPKD. Two (2/957, 0.2 %) of these tolvaptan treated-patients, 
as well as a third patient from an extension open label trial, exhibited increases in hepatic enzymes 
(> 3 × ULN) with concomitant elevations in BT (> 2 × ULN). 
 
Reporting of suspected adverse reactions 



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Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
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 2,000 mg/kg (maximum 
feasible dose). A single oral dose of 2,000 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 tolvaptan overdose, assessment of vital signs, electrolyte concentrations, ECG 
and fluid status is recommended. Appropriate replacement of water and/or electrolytes must continue 
until aquaresis abates. Dialysis may not be effective in removing tolvaptan because of its high binding 
affinity for human plasma protein (> 98 %). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Diuretics, vasopressin antagonists, ATC code: C03XA01. 
 
Mechanism of action 
 
Tolvaptan is a vasopressin antagonist that specifically blocks the binding of arginine vasopressin (AVP) 
at the V2 receptors of the distal portions of the nephron. Tolvaptan affinity for the human V2 receptor is 
1.8 times that of native AVP. 
 
Pharmacodynamic effects 
 
The pharmacodynamic effects of tolvaptan have been determined in healthy subjects and subjects with 
ADPKD across CKD stages 1 to 4. Effects on free water clearance and urine volume are evident across 
all CKD stages with smaller absolute effects observed at later stages, consistent with the declining 
number of fully functioning nephrons. Acute reductions in mean total kidney volume were also 
observed following 3 weeks of therapy in all CKD stages, ranging from -4.6 % for CKD stage 1 to -
1.9 % for CKD stage 4. 
 
Clinical efficacy and safety 
 
The primary focus of the clinical program for development of tolvaptan tablets for the treatment of 
ADPKD is a single pivotal, multi-national, phase 3, randomised, placebo-controlled trial in which the 
long-term safety and efficacy of oral split dose tolvaptan regimens (titrated between 60 mg/day and 
120 mg/day) were compared with placebo in 1,445 adult subjects with ADPKD. 
 
In total, 14 clinical trials involving tolvaptan have been completed worldwide in support of the ADPKD 
indication, including 8 trials in the US, 1 in the Netherlands, 3 in Japan, 1 in Korea, and the 
multinational phase 3 pivotal trial. 
 
The phase 3 pivotal trial (TEMPO 3:4, 156-04-251) included subjects from 129 centres in the Americas, 
Japan, Europe and other countries. The primary objective of this trial was to evaluate the long-term 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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efficacy of tolvaptan in ADPKD through rate of total kidney volume (TKV) change (normalised as 
percentage; %) for tolvaptan-treated compared with placebo-treated subjects. In this trial a total of 1,445 
adult patients (age 18 years to 50 years) with evidence of rapidly-progressing, early ADPKD (meeting 
modified Ravine criteria, TKV ≥ 750 mL, estimated creatinine clearance ≥ 60 mL/min) were 
randomised 2:1 to treatment with tolvaptan or placebo. Patients were treated for up to 3 years. 
 
Tolvaptan (n = 961) and placebo (n = 484) groups were well matched in terms of gender with an 
average age of 39 years. The inclusion criteria identified patients who at baseline had evidence of early 
disease progression. At baseline, patients had average estimated glomerular filtration rate (eGFR) of 
82 mL/min/1.73 m2 (Chronic Kidney Disease-Epidemiology Collaboration; CKD-EPI) with 79 % 
having hypertension and a mean TKV of 1,692 mL (height adjusted 972 mL/m). Approximately 35 % of 
subjects were CKD stage 1, 48 % CKD stage 2, and 17 % CKD stage 3 (eGFRCKD-EPI). While these 
criteria were useful in enriching the study population with patients who were rapidly progressing, 
subgroup analyses based on stratification criteria (age, TKV, GFR, Albuminuria, Hypertension) 
indicated the presence of such risk factors at younger ages predicts more rapid disease progression. 
 
The results of the primary endpoint, the rate of change in TKV for subjects randomised to tolvaptan 
(normalised as percentage, %) to the rate of change for subjects on placebo, were highly statistically 
significant. The rate of TKV increase over 3 years was significantly less for tolvaptan-treated subjects 
than for subjects receiving placebo: 2.80 % per year versus 5.51 % per year, respectively (ratio of 
geometric mean 0.974; 95 % CI 0.969 to 0.980; p < 0.0001). 
 
Pre-specified secondary endpoints were tested sequentially. The key secondary composite endpoint 
(ADPKD progression) was time to multiple clinical progression events of: 
1) worsening kidney function (defined as a persistent [reproduced over at least 2 weeks] 25 % 

reduction in reciprocal serum creatinine during treatment [from end of titration to last on-
medicinal product visit]) 

2) medically significant kidney pain (defined as requiring prescribed leave, last-resort analgesics, 
narcotic and anti-nociceptive, radiologic or surgical interventions) 

3) worsening hypertension 
4) worsening albuminuria 
 
The relative rate of ADPKD-related events was decreased by 13.5 % in tolvaptan-treated patients, 
(hazard ratio, 0.87; 95 % CI, 0.78 to 0.97; p = 0.0095). 
 
The result of the key secondary composite endpoint is primarily attributed to effects on worsening 
kidney function and medically significant kidney pain. The renal function events were 61.4 % less likely 
for tolvaptan compared with placebo (hazard ratio, 0.39; 95 % CI, 0.26 to 0.57; nominal p < 0.0001), 
while renal pain events were 35.8 % less likely in tolvaptan-treated patients (hazard ratio, 0.64; 95 % 
CI, 0.47 to 0.89; nominal p = 0.007). In contrast, there was no effect of tolvaptan on either progression 
of hypertension or albuminuria. 
 
TEMPO 4:4 is an open-label extension study that included 871 subjects that completed TEMPO 
3:4 from 106 centres across 13 countries. This trial evaluated the effects of tolvaptan on safety, TKV 
and eGFR in subjects receiving active treatment for 5 years (early-treated), compared with subjects 
treated with placebo for 3 years, then switched to active treatment for 2 years (delayed-treated). 
 
The primary end point for TKV did not distinguish a difference in change (−1.7 %) over the 5-year 
treatment between early- and delayed-treated subjects at the pre-specified threshold of statistical 
significance (p = 0.3580). Both groups’ TKV growth trajectory was slowed, relative to placebo in the 
first 3 years, suggesting both early- and delayed- tolvaptan treated subjects benefitted to a similar 
degree. 
 
A secondary endpoint testing the persistence of positive effects on renal function indicated that the 
preservation of eGFR observed by the end of the TEMPO 3:4 pivotal trial (3.01 to 3.34 mL/min/1.73 m2 
at follow-up visits 1 and 2) could be preserved during open-label treatment. This difference was 
maintained in the pre-specified mixed effect model repeat measurement (MMRM) analysis 



14 

(3.15 mL/min/1.73 m2, 95 %CI 1.462 to 4.836, p = 0.0003) and with sensitivity analyses where baseline 
eGFR data were carried forward (2.64 mL/min/1.73 m2, 95 % CI 0.672 to 4.603, p = 0.0086). These 
data suggest that tolvaptan can slow the rate of renal function decline, and that these benefits persist 
over the duration of therapy. 
 
Longer term data are not currently available to show whether long-term therapy with tolvaptan 
continues to slow the rate of renal function decline and affect clinical outcomes of ADPKD, including 
delay in the onset of end-stage renal disease. 
 
Genotyping for PKD1 and PKD2 genes was conducted in a majority of patients entering the open-label 
extension study (TEMPO 4:4) but the results are not yet known. 
 
Following an additional 2 years of tolvaptan treatment, resulting in a total of 5 years on tolvaptan 
therapy no new safety signals were identified. 
 
The phase 3, multi-centre, international, randomised-withdrawal, placebo-controlled, double-blind trial 
156-13-210 compared the efficacy and safety of tolvaptan (45 mg/day to 120 mg/day) to placebo in 
patients able to tolerate tolvaptan during a five-week titration and run-in period on tolvaptan. The trial 
utilised a randomised withdrawal design, to enrich for patients that were able to tolerate tolvaptan for a 
5-week, single-blind pre-randomisation period consisting of a 2-week titration period and 3-week run-in 
period. The design was used to minimise the impact of early discontinuation and missing data on trial 
endpoints. 
 
A total of 1,370 patients (age 18 years to 65 years) with CKD with an eGFR between 25 and 
65 mL/min/1.73 m2 if younger than age 56 years; or eGFR between 25 and 44 mL/min/1.73 m2, plus 
eGFR decline >2.0 mL/min/1.73 m2/year if between age 56 years to 65 years were randomised to either 
tolvaptan (n = 683) or placebo (n = 687) and were treated for a period of 12 months. 
 
For subjects randomised, the baseline, average eGFR was 41 mL/min/1.73 m2 (CKD-EPI) and historical 
TKV, available in 318 (23 %) of subjects, averaged 2,026 mL. Approximately 5 %, 75 % and 20 % had 
an eGFR 60 mL/min/1.73 m2 or greater (CKD stage 2), or less than 60 and greater than 
30 mL/min/1.73 m2 (CKD stage 3) or less than 30 but greater than 15 mL/min/1.73 m2 (CKD stage 4), 
respectively. The CKD stage 3 can be subdivided further to stage 3a 30 %, (eGFR 45 mL/min/1.73 m2 
to less than 60 mL/min/1.73 m2) and stage 3b 45 %, (eGFR between 30 and 45 mL/min/1.73 m2). 
 
The primary endpoint of the trial was the change in eGFR from pre-treatment baseline levels to post-
treatment assessment. In patients treated with tolvaptan the reduction in eGFR was significantly less 
than in patients treated with placebo (p < 0.0001). The treatment difference in eGFR change observed in 
this trial is 1.27 mL/min/1.73 m2, representing a 35 % reduction in the LS means of change in eGFR of -
2.34 mL/min/1.73 m2 in tolvaptan group relative to a -3.61 mL/min/1.73 m2 in placebo group observed 
over the course of one year. The key secondary endpoint was a comparison of the efficacy of tolvaptan 
treatment versus placebo in reducing the decline of annualised eGFR slope across all measured time 
points in the trial. These data also showed significant benefit from tolvaptan versus placebo 
(p < 0.0001). 
 
Subgroup analysis of the primary and secondary endpoints by CKD stage found similar, consistent 
treatment effects relative to placebo for subjects in stages 2, 3a, 3b and early stage 4 (eGFR 25 to 
29 mL/min/1.73 m2) at baseline. 
 
A pre-specified subgroup analysis suggested that tolvaptan had less of an effect in patients older than 
55 years of age, a small subgroup with a notably slower rate of eGFR decline. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
tolvaptan in one or more subsets of the paediatric population in polycystic kidney disease (see 
section 4.2 for information on paediatric use). 



15 

 
5.2 Pharmacokinetic properties 
 
Absorption 
 
After oral administration, tolvaptan is rapidly absorbed with peak plasma concentrations occurring 
about 2 hours after dosing. The absolute bioavailability of tolvaptan is about 56 %. Co-administration of 
tolvaptan with a high-fat meal increased peak concentrations of tolvaptan up to 2-fold but left AUC 
unchanged. Even though the clinical relevance of this finding is not known, the morning dose should be 
taken under fasted conditions to minimise the unnecessary risk of increasing the maximal exposure (see 
section 4.2). 
 
Distribution 
 
Following single oral doses of ≥ 300 mg, peak plasma concentrations appear to plateau, possibly due to 
saturation of absorption. Tolvaptan binds reversibly (98 %) to plasma proteins. 
 
Biotransformation 
 
Tolvaptan is extensively metabolised in the liver almost exclusively by CYP3A. Tolvaptan is a weak 
CYP3A4 substrate and does not appear to have any inhibitory activity. In vitro studies indicated that 
tolvaptan has no inhibitory activity for CYP3A. Fourteen metabolites have been identified in plasma, 
urine and faeces; all but one were also metabolised by CYP3A. Only the oxobutyric acid metabolite is 
present at greater than 10 % of total plasma radioactivity; all others are present at lower concentrations 
than tolvaptan. Tolvaptan metabolites have little to no contribution to the pharmacological effect of 
tolvaptan; all metabolites have no or weak antagonist activity for human V2 receptors when compared 
with tolvaptan. The terminal elimination half-life is about 8 hours and steady-state concentrations of 
tolvaptan are obtained after the first dose. 
 
Elimination 
 
Less than 1 % of intact active substance is excreted unchanged in the urine. Radio labelled tolvaptan 
experiments showed that 40 % of the radioactivity was recovered in the urine and 59 % was recovered 
in the faeces, where unchanged tolvaptan accounted for 32 % of radioactivity. Tolvaptan is only a minor 
component in plasma (3 %). 
 
Linearity/non-linearity 
 
Following single oral doses, Cmax values show less than dose proportional increases from 30 mg to 
240 mg and then a plateau at doses from 240 mg to 480 mg. AUC increases linearly. 
 
Following multiple once daily dosing of 300 mg, tolvaptan exposure was only increased 6.4-fold when 
compared to a 30 mg dose. For split-dose regimens of 30 mg/day, 60 mg/day and 120 mg/day in 
ADPKD patients, tolvaptan exposure (AUC) increases linearly. 
 
Pharmacokinetics in special populations 
 
Age 
Clearance of tolvaptan is not significantly affected by age. 
 
Hepatic impairment 
The effect of mildly or moderately impaired hepatic function (Child-Pugh classes A and B) on the 
pharmacokinetics of tolvaptan was investigated in 87 patients with liver disease of various origins. No 
clinically significant changes have been seen in clearance for doses ranging from 5 mg to 60 mg. Very 
limited information is available in patients with severe hepatic impairment (Child-Pugh class C). 
 



16 

In a population pharmacokinetic analysis in patients with hepatic oedema, AUC of tolvaptan in severely 
(Child-Pugh class C) and mildly or moderately (Child-Pugh classes A and B) hepatic impaired patients 
were 3.1-times and 2.3-times higher than that in healthy subjects. 
 
Renal impairment 
In a population pharmacokinetic analysis for patients with ADPKD, tolvaptan concentrations were 
increased, compared to healthy subjects, as renal function decreased below eGFR of 
60 mL/min/1.73 m2. An eGFRCKD-EPI decrease from 72.2 to 9.79 (mL/min/1.73 m2) was associated with 
a 32 % reduction in total body clearance. 
 
5.3 Preclinical safety data 
 
Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential. Teratogenicity was noted 
in rabbits given 1,000 mg/kg/day (7.5 times the exposure from the 120 mg/day human dose on an AUC 
basis). No teratogenic effects were seen in rabbits at 300 mg/kg/day (about 1.25 to 2.65 times the 
exposure in humans at the 120 mg/day dose, based on AUC). In a peri- and post-natal study in rats, 
delayed ossification and reduced pup bodyweight were seen at the high dose of 1,000 mg/kg/day. 
 
Two fertility studies in rats showed effects on the parental generation (decreased food consumption and 
body weight gain, salivation), but tolvaptan did not affect reproductive performance in males and there 
were no effects on the foetuses. In females, abnormal oestrus cycles were seen in both studies. 
The no observed adverse effect level (NOAEL) for effects on reproduction in females (100 mg/kg/day) 
was about 8-times the maximum human recommended dose of 120 mg/day on a mg/m2 basis. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Maize starch 
Hydroxypropylcellulose 
Lactose monohydrate 
Magnesium stearate 
Microcrystalline cellulose 
Indigo carmine aluminium lake 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light and moisture. 
 
6.5 Nature and contents of container 
 
Jinarc 15 mg tablets 
 
7 or 28 tablets in PVC/aluminium foil blister 
 
Jinarc 30 mg tablets 
 



17 

7 or 28 tablets in PVC/aluminium foil blister 
 
Jinarc 15 mg tablets + Jinarc 45 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister with 7 × 15 mg and 7 × 45 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters with 7 × 15 mg and 7 × 45 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters with 7 × 15 mg and 7 × 45 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister in wallet card with 7 × 15 mg and 7 × 45 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters in wallet card with 7 × 15 mg and 7 × 45 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters in wallet card with 7 × 15 mg and 7 × 45 mg tablets 
 
Jinarc 30 mg tablets + Jinarc 60 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister with 7 × 30 mg and 7 × 60 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters with 7 × 30 mg and 7 × 60 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters with 7 × 30 mg and 7 × 60 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister in wallet card with 7 × 30 mg and 7 × 60 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters in wallet card with 7 × 30 mg and 7 × 60 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters in wallet card with 7 × 30 mg and 7 × 60 mg tablets 
 
Jinarc 30 mg tablets + Jinarc 90 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister with 7 × 30 mg and 7 × 90 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters with 7 × 30 mg and 7 × 90 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters with 7 × 30 mg and 7 × 90 mg tablets 
 
14 tablets in 1 PVC/aluminium foil blister in wallet card with 7 × 30 mg and 7 × 90 mg tablets 
28 tablets in 2 PVC/aluminium foil blisters in wallet card with 7 × 30 mg and 7 × 90 mg tablets 
56 tablets in 4 PVC/aluminium foil blisters in wallet card with 7 × 30 mg and 7 × 90 mg tablets 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Jinarc 15 mg tablets 
 
EU/1/15/1000/001-002 (blister) 
 
Jinarc 30 mg tablets 
 
EU/1/15/1000/003-004 (blister) 



18 

 
Jinarc 15 mg tablets + Jinarc 45 mg tablets 
 
EU/1/15/1000/005-007 (blister) 
EU/1/15/1000/014-016 (blister in wallet card) 
 
Jinarc 30 mg tablets + Jinarc 60 mg tablets 
 
EU/1/15/1000/008-010 (blister) 
EU/1/15/1000/017-019 (blister in wallet card) 
 
Jinarc 30 mg tablets + Jinarc 90 mg tablets 
 
EU/1/15/1000/011-013 (blister) 
EU/1/15/1000/020-022 (blister in wallet card) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 27 May 2015 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 

http://www.ema.europa.eu/


19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



20 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
AndersonBrecon (UK) Limited 
Units 2-7, Wye Valley Business Park, Brecon Road, Hay-on-Wye 
Hereford - HR3 5PG 
United Kingdom 
 
Almac Pharma Services Limited 
Almac House, 20 Seagoe Industrial Estate 
Craigavon - BT63 5QD 
United Kingdom 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate, Dundalk, 
Co. Louth - A91 P9KD 
Ireland 
 
Millmount Healthcare Limited 
Block-7, City North Business Campus, Stamullen, 
Co. Meath, K32 YD60 
Ireland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 
interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and 
any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



21 

 
• Additional risk minimisation measures 
 
Prior to launch of Jinarc in each Member State the Marketing Authorisation Holder must agree the 
content and format of the educational programme, including communication media and distribution 
modalities with each National Competent Authority. The MAH must ensure that all healthcare 
professionals and patients/carers who are expected to prescribe and/or use JINARC have access to/are 
provided with the following educational package 
• Physician educational material 
• Patient information pack 
 
The educational programme is aimed at ensuring awareness about the potential risk of hepatotoxicity 
and providing guidance on how to manage this risk and the importance of pregnancy prevention prior to 
the initiation and during the treatment with Jinarc. 
 
The physician educational material should contain: 
• The Summary of product Characteristics 
• Healthcare professionals training material 
 
The healthcare professional training material shall contain the following key elements 
• the risk of hepatotoxicity associated with the use of Jinarc 
• the importance of pregnancy prevention, before and during treatment with Jinarc 
 
The patient information pack should contain: 
• The Patient information leaflet 
• Patient/Carer educational material 
• A Patient Alert Card 
 
The Patient/Carer educational material shall contain the following key messages: 
• the risk of hepatotoxicity associated with the use of Jinarc 
• the importance of pregnancy prevention, before and during treatment with Jinarc 
 
The Patient Alert Card shall contain the following key messages: 
• Signs or symptoms of liver toxicity and severe dehydration 
• Advice if such symptoms occur 
 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
A non-interventional post-authorisation safety study (PASS) to investigate the risks 
of: 
• Hepatotoxicity  
associated with the use of Jinarc. 
 
In addition the study should also provide information on 
• Pregnancy outcomes, in patients treated with Jinarc 
• Patterns of medicinal product utilisation, especially with regards to off-label 

use and use in patients over 50 years old 
• ADRs associated with long term use of Jinarc 
 
Final study report should be submitted by: Q1 2026 
 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 15 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
7 tablets 
28 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 



25 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/001 (7 tablets) 
EU/1/15/1000/002 (28 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



26 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 30 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
7 tablets 
28 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 



28 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/003 (7 tablets) 
EU/1/15/1000/004 (28 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



29 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
Jinarc 45 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 15 mg tablet contains 15 mg tolvaptan. 
Each 45 mg tablet contains 45 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 15 mg tablets and 7 × 45 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 15 mg tablets and 14 × 45 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 15 mg tablets and 28 × 45 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



31 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/005 (14 tablets; 7 × 15 mg + 7 × 45 mg) 
EU/1/15/1000/006 (28 tablets; 14 × 15 mg + 14 × 45 mg) 
EU/1/15/1000/007 (56 tablets; 28 × 15 mg + 28 × 45 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 15 mg 
Jinarc 45 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



32 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
Jinarc 45 mg tablets 
 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (blisters in wallet card) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
Jinarc 45 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 15 mg tablet contains 15 mg tolvaptan. 
Each 45 mg tablet contains 45 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 15 mg tablets and 7 × 45 mg tablets in card packaging 
 
Each pack of 28 tablets contains: 
14 × 15 mg tablets and 14 × 45 mg tablets in card packaging 
 
Each pack of 56 tablets contains: 
28 × 15 mg tablets and 28 × 45 mg tablets in card packaging 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



35 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/014 (14 tablets; 7 × 15 mg + 7 × 45 mg) 
EU/1/15/1000/015 (28 tablets; 14 × 15 mg + 14 × 45 mg) 
EU/1/15/1000/016 (56 tablets; 28 × 15 mg + 28 × 45 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 15 mg 
Jinarc 45 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



36 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
WALLET CARD 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 15 mg tablets 
Jinarc 45 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 15 mg tablet contains 15 mg tolvaptan. 
Each 45 mg tablet contains 45 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 15 mg tablets and 7 × 45 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 15 mg tablets and 14 × 45 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 15 mg tablets and 28 × 45 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



38 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/014 (14 tablets; 7 × 15 mg + 7 × 45 mg) 
EU/1/15/1000/015 (28 tablets; 14 × 15 mg + 14 × 45 mg) 
EU/1/15/1000/016 (56 tablets; 28 × 15 mg + 28 × 45 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 15 mg 
Jinarc 45 mg 
 



39 

 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 60 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 60 mg tablet contains 60 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 60 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 60 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 60 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



41 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/008 (14 tablets; 7 × 30 mg + 7 × 60 mg) 
EU/1/15/1000/009 (28 tablets; 14 × 30 mg + 14 × 60 mg) 
EU/1/15/1000/010 (56 tablets; 28 × 30 mg + 28 × 60 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 60 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



42 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



43 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 60 mg tablets 
 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (blisters in wallet card) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 60 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 60 mg tablet contains 60 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 60 mg tablets in card packaging 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 60 mg tablets in card packaging 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 60 mg tablets in card packaging 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



45 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/017 (14 tablets; 7 × 30 mg + 7 × 60 mg) 
EU/1/15/1000/018 (28 tablets; 14 × 30 mg + 14 × 60 mg) 
EU/1/15/1000/019 (56 tablets; 28 × 30 mg + 28 × 60 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 60 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



46 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



47 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
WALLET CARD 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 60 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 60 mg tablet contains 60 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 60 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 60 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 60 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



48 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/017 (14 tablets; 7 × 30 mg + 7 × 60 mg) 
EU/1/15/1000/018 (28 tablets; 14 × 30 mg + 14 × 60 mg) 
EU/1/15/1000/019 (56 tablets; 28 × 30 mg + 28 × 60 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 60 mg 
 



49 

 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



50 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 90 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 90 mg tablet contains 90 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 90 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 90 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 90 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



51 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/011 (14 tablets; 7 × 30 mg + 7 × 90 mg) 
EU/1/15/1000/012 (28 tablets; 14 × 30 mg + 14 × 90 mg) 
EU/1/15/1000/013 (56 tablets; 28 × 30 mg + 28 × 90 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 90 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



52 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



53 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 90 mg tablets 
 
tolvaptan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 



54 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (blisters in wallet card) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 90 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 90 mg tablet contains 90 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 90 mg tablets in card packaging 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 90 mg tablets in card packaging 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 90 mg tablets in card packaging 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



55 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light and moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/020 (14 tablets; 7 × 30 mg + 7 × 90 mg) 
EU/1/15/1000/021 (28 tablets; 14 × 30 mg + 14 × 90 mg) 
EU/1/15/1000/022 (56 tablets; 28 × 30 mg + 28 × 90 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 90 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



56 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



57 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
WALLET CARD 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jinarc 30 mg tablets 
Jinarc 90 mg tablets 
 
tolvaptan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 30 mg tablet contains 30 mg tolvaptan. 
Each 90 mg tablet contains 90 mg tolvaptan. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet 
 
Each pack of 14 tablets contains: 
7 × 30 mg tablets and 7 × 90 mg tablets 
 
Each pack of 28 tablets contains: 
14 × 30 mg tablets and 14 × 90 mg tablets 
 
Each pack of 56 tablets contains: 
28 × 30 mg tablets and 28 × 90 mg tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Do not chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



58 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1000/020 (14 tablets; 7 × 30 mg + 7 × 90 mg) 
EU/1/15/1000/021 (28 tablets; 14 × 30 mg + 14 × 90 mg) 
EU/1/15/1000/022 (56 tablets; 28 × 30 mg + 28 × 90 mg) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
Mon. 
Tue. 
Wed. 
Thu. 
Fri. 
Sat. 
Sun. 
 
 
16. INFORMATION IN BRAILLE 
 
Jinarc 30 mg 
Jinarc 90 mg 
 



59 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



60 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



61 

Package leaflet: Information for the patient 
 

Jinarc 15 mg tablets 
Jinarc 30 mg tablets 
Jinarc 45 mg tablets 
Jinarc 60 mg tablets 
Jinarc 90 mg tablets 

 
Tolvaptan 

 
This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Jinarc is and what it is used for 
2. What you need to know before you take Jinarc 
3. How to take Jinarc 
4. Possible side effects 
5. How to store Jinarc 
6. Contents of the pack and other information 
 
 
1. What Jinarc is and what it is used for 
 
Jinarc contains the active substance tolvaptan which blocks the effect of vasopressin, a hormone 
involved in the formation of cysts in the kidneys of ADPKD patients. By blocking the effect of 
vasopressin, Jinarc slows the development of kidney cysts in patients with ADPKD, reduces symptoms 
of the disease and increases urine production. 
 
Jinarc is a medicine used to treat a disease called “autosomal dominant polycystic kidney disease” 
(ADPKD). This disease causes growth of fluid-filled cysts in the kidneys, which put pressure on 
surrounding tissues and reduce kidney function, possibly leading to kidney failure. Jinarc is used to treat 
ADPKD in adults with chronic kidney disease (CKD) stages 1 to 4 with evidence of rapidly progressing 
disease. 
 
 
2. What you need to know before you take Jinarc 
 
Do not take Jinarc 
• if you are allergic to tolvaptan or any of the other ingredients of this medicine (listed in section 6) 

or if you are allergic to benzazepine or benzazepine derivatives (e.g. benazepril, conivaptan, 
fenoldopam mesylate or mirtazapine) 

• if you have been told that you have raised levels of liver enzymes in your blood which do not 
allow treatment with tolvaptan 

• if your kidneys do not work (no urine production) 
• if you have a condition which is associated with a very low blood volume (e.g. severe 

dehydration or bleeding) 



62 

• if you have a condition which increases the sodium in your blood 
• if you do not realise when you are thirsty 
• if you are pregnant 
• if you are breastfeeding. 
 
Warnings and precautions 
Talk to your doctor before taking Jinarc 
• if you suffer from liver disease. 
• if you cannot drink enough water (see “drinking enough water” below) or if you have to restrict 

your fluid intake. 
• if you have difficulties urinating (e.g. have an enlarged prostate). 
• if you suffer from too high or too low blood sodium. 
• if you had an allergic reaction in the past to benzazepine, tolvaptan or other benzazepine 

derivatives (e.g. benazepril, conivaptan, fenoldopam mesylate or mirtazapine), or to any of the 
other ingredients of this medicine (listed in section 6). 

• if you have diabetes. 
• if you have been told you have high levels of a chemical called uric acid in your blood (which 

may have caused attacks of gout). 
• if you have advanced kidney disease. 
 
This medicine may cause your liver to not work properly. Therefore, please inform your doctor 
immediately if you have signs that could indicate potential liver problems such as: 
• nausea 
• vomiting 
• fever 
• tiredness 
• loss of appetite 
• pain in the abdomen 
• dark urine 
• jaundice (yellowing of skin or eyes) 
• itching of your skin 
• flu-like syndrome (joint and muscle pain with fever) 
 
During treatment with this medicine, your doctor will arrange monthly blood tests to check for 
changes in your liver function. 
 
Drinking enough water 
 
This medicine causes water loss because it increases your urine production. This water loss may result 
in side effects such as dry mouth and thirst or even more severe side effects like kidney problems (see 
section 4). It is therefore important that you have access to water and that you are able to drink sufficient 
amounts when you feel thirsty. Before bed-time you must drink 1 or 2 glasses of water even if you do 
not feel thirsty and you must also drink water after you urinate at night. Special care must be taken if 
you have a disease that reduces appropriate fluid intake or if you are at an increased risk of water loss 
e.g. in case of vomiting or diarrhoea. Due to the increased urine production, it is also important that you 
always have access to a toilet. 
 
Children and adolescents 
Do not give this medicine to children and adolescents (under age of 18 years) because it has not been 
studied in these age groups. 
 
Other medicines and Jinarc 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, 
including medicines obtained without a prescription. 
 
The following medicines may increase the effect of Jinarc: 
• amprenavir, atazanavir, darunavir/ritonavir and fosamprenavir (used to treat HIV/AIDS), 



63 

• aprepitant (used to avoid nausea and vomiting in chemotherapy), 
• crizotinib and imatinib (used to treat cancer), 
• ketoconazole, fluconazole or itraconazole (used to treat fungal infections), 
• macrolide antibiotics like erythromycin or clarithromycin, 
• verapamil (used to treat heart diseases and high blood pressure), 
• diltiazem (used to treat high blood pressure and chest pain). 
 
The following medicines may lower the effect of Jinarc: 
• phenytoin or carbamazepine (used to treat epilepsy), 
• rifampicin, rifabutin or rifapentin (used to treat tuberculosis), 
• St. John’s Wort (a traditional herbal medicinal product for the relief of slightly low mood and 

mild anxiety). 
 
Jinarc may increase the effect of the following medicines: 
• digoxin (used to treat irregular heart beat and heart failure), 
• dabigatran (used to thin the blood), 
• rosuvastatin or pitavastatin (used to lower blood cholesterol), 
• methotrexate (used to treat cancer, arthritis), 
• ciprofloxacin (an antibiotic), 
• sulfasalazine (used to treat inflammatory bowel disease or rheumatoid arthritis), 
• metformin (used to treat diabetes). 
 
Jinarc may lower the effect of the following medicines: 
• vasopressin analogues such as desmopressin (used to increase blood clotting factors or to control 

urine output or bedwetting). 
 
These medicines can affect or be affected by Jinarc: 
• diuretics (used to influence the production of urine). Taken with Jinarc these may increase the 

risk of side effects due to water loss or may cause kidney problems. 
• diuretics or other medicines for the treatment of high blood pressure. Taken with Jinarc these may 

increase the risk of low blood pressure when you stand up from sitting or lying down. 
• medicines which increase the level of sodium in your blood or which contain large amounts of 

salt (e.g. tablets that dissolve in water and indigestion remedies). These may increase the effect of 
Jinarc. There is a risk that this may lead to too much sodium in your blood. 

 
It may still be alright for you to take these medicines and Jinarc together. Your doctor will be able to 
decide what is suitable for you. 
 
Jinarc with food and drink 
Do not drink grapefruit juice when taking this medicine. 
 
Pregnancy and breast-feeding 
Do not take this medicine if you are pregnant or breast-feeding. 
Women of childbearing age must use reliable contraceptive measures during use of this medicine. 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Some people may feel dizzy, weak or tired after being given Jinarc. If this happens to you, do not drive 
or use any tools or machines. 
 
Jinarc contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 



64 

3. How to take Jinarc 
 
Jinarc can only be prescribed by doctors who are specialised in the treatment of ADPKD. Always take 
this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not 
sure. 
 
Dose 
 
The daily amount of Jinarc is split into two doses, one bigger than the other. The higher dose should be 
taken in the morning when you wake up, at least 30 minutes before the morning meal. The lower dose is 
taken 8 hours later. 
 
The dose combinations are: 
45 mg + 15 mg 
60 mg + 30 mg 
90 mg + 30 mg 
 
Your treatment will normally start with a dose of 45 mg in the morning and 15 mg 8 hours later. Your 
doctor may gradually increase your dose up to a maximum combination of 90 mg on waking and 30 mg 
after 8 hours. To find the best dose your doctor will regularly check how well you are tolerating a 
prescribed dose. You should always take the highest tolerable dose combination prescribed by your 
doctor. 
 
If you take other medicines, which can increase the effects of Jinarc you may receive lower doses. In 
this case your doctor may prescribe you Jinarc tablets with 30 mg or 15 mg tolvaptan which have to be 
taken once a day in the morning. 
 
Method of administration 
 
Swallow the tablets without chewing, with a glass of water. 
The morning dose is to be taken at least 30 minutes before the morning meal. The second daily dose can 
be taken with or without food. 
 
If you take more Jinarc than you should 
If you have taken more tablets than your prescribed dose, drink plenty of water and contact your 
doctor or your local hospital immediately. Remember to take the medicine pack with you so that it is 
clear what you have taken. If you take the higher dose very late in the day you may have to go to the 
toilet at night more frequently. 
 
If you forget to take Jinarc 
If you forget to take your medicine, you should take the dose as soon as you remember on the same day. 
If you do not take your tablets on one day, take your normal dose on the next day. DO NOT take a 
double dose to make up for forgotten individual doses. 
 
If you stop taking Jinarc 
If you stop taking this medicine your kidney cysts may grow as fast as they did before you started 
treatment with Jinarc. Therefore, you should only stop taking this medicine if you notice side effects 
requiring urgent medical attention (see section 4) or if your doctor tells you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects: 



65 

 
If you notice any of the following side effects, you may need urgent medical attention. Stop taking 
Jinarc and immediately contact a doctor or go to the nearest hospital if you: 
• find it difficult to urinate. 
• experience swelling of the face, lips or tongue, itching, generalised rash, or severe wheezing or 

breathlessness (symptoms of an allergic reaction). 
 
Jinarc may cause your liver not to work properly. 
Consult your doctor if symptoms of nausea, vomiting, fever, tiredness, loss of appetite, pain in the 
abdomen, dark urine, jaundice (yellowing of skin or eyes), itching of your skin or joint and muscle pain 
with fever occur. 
 
Other side effects: 
 
Very common (may affect more than 1 in 10 people) 
• thirst (requiring excessive drinking of water) 
• headache 
• dizziness 
• diarrhoea 
• dry mouth 
• increased need to urinate, to urinate at night, or to urinate more frequently 
• fatigue 
 
Common (may affect up to 1 in 10 people) 
• dehydration 
• high levels of sodium, uric acid and blood sugar 
• decreased appetite 
• gout 
• difficulty sleeping 
• heart pounding 
• shortness of breath 
• belly pain 
• full or bloated or uncomfortable feeling in the stomach 
• constipation 
• heartburn 
• liver function abnormal 
• rash 
• itching 
• muscle spasms 
• general weakness 
• raised levels of liver enzymes in the blood 
• weight loss 
 
Uncommon (may affect up to 1 in 100 people) 
• increase of bilirubin (a substance that can cause yellowing of skin or eyes) in the blood 
 
Not known (frequency cannot be estimated from the available data) 
• allergic reactions (see above) 
• generalised rash 
• acute liver failure (ALF) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


66 

 
5. How to store Jinarc 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated on the carton, wallet card and the blister 
after EXP. The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from light and moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Jinarc contains 
 
• The active substance is tolvaptan. 

Each Jinarc 15 mg tablet contains 15 mg tolvaptan. 
Each Jinarc 30 mg tablet contains 30 mg tolvaptan. 
Each Jinarc 45 mg tablet contains 45 mg tolvaptan. 
Each Jinarc 60 mg tablet contains 60 mg tolvaptan. 
Each Jinarc 90 mg tablet contains 90 mg tolvaptan. 

 
• The other ingredients are lactose monohydrate (see section 2), maize starch, microcrystalline 

cellulose, hydroxypropylcellulose, magnesium stearate, indigo carmine aluminium lake. 
 
What Jinarc looks like and contents of the pack 
 
The different strengths of Jinarc tablets have different shapes and embossing: 
15 mg tablet: blue, triangular, debossed with “OTSUKA” and “15” on one side. 
30 mg tablet: blue, round, debossed with “OTSUKA” and “30” on one side. 
45 mg tablet: blue, square, debossed with “OTSUKA” and “45” on one side 
60 mg tablet: blue, modified rectangular, debossed with “OTSUKA” and “60” on one side 
90 mg tablet: blue, pentagonal, debossed with “OTSUKA” and “90” on one side 
 
Your medicine is supplied in the following pack sizes: 
 
Jinarc 15 mg tablets: packs containing 7 tablets or 28 tablets 
 
Jinarc 30 mg tablets: packs containing 7 tablets or 28 tablets 
 
Jinarc 45 mg tablets + Jinarc 15 mg tablets: packs (blisters with or without wallet card) containing 
14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength), 
28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength) or 
56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength). 
 
Jinarc 60 mg tablets + Jinarc 30 mg tablets: packs (blisters with or without wallet card) containing 
14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength), 
28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength) or 
56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength). 
 
Jinarc 90 mg tablets + Jinarc 30 mg tablets: packs (blisters with or without wallet card) containing 
14 tablets (7 tablets of the higher strength + 7 tablets of the lower strength), 
28 tablets (14 tablets of the higher strength + 14 tablets of the lower strength) or 
56 tablets (28 tablets of the higher strength + 28 tablets of the lower strength). 



67 

 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
Manufacturer 
 
AndersonBrecon (UK) Limited 
Units 2-7, Wye Valley Business Park, Brecon Road, Hay-on-Wye 
Hereford - HR3 5PG 
United Kingdom 
 
Almac Pharma Services Limited 
Almac House, 20 Seagoe Industrial Estate 
Craigavon - BT63 5QD 
United Kingdom 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate, Dundalk, 
Co. Louth - A91 P9KD 
Ireland 
 
Millmount Healthcare Limited 
Block-7, City North Business Campus, Stamullen,  
Co. Meath, K32 YD60 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tél/Tel: +31 (0) 20 85 46 555 

Lietuva 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

България 
Otsuka Pharmaceutical Netherlands B.V. 
Teл: +31 (0) 20 85 46 555 

Luxembourg/Luxemburg 
Otsuka Pharmaceutical Netherlands B.V. 
Tél/Tel: +31 (0) 20 85 46 555 
 

Česká republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Magyarország 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Malta 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Deutschland 
Otsuka Pharma GmbH 
Tel: +49 (0) 69 1700 860 
 

Nederland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 



68 

Eesti 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Ελλάδα 
Otsuka Pharmaceutical Netherlands B.V. 
Thλ: +31 (0) 20 85 46 555 
 

Österreich 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

España 
Otsuka Pharmaceutical S.A 
Tel: +34 (0) 93 208 1020 
 

Polska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

France 
Otsuka Pharmaceutical France SAS 
Tél: +33 (0) 1 47 08 00 00 
 

Portugal 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Hrvatska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

România 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ireland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Slovenija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Ísland 
Otsuka Pharma Scandinavia AB 
Sími: +46 (0) 8 545 286 60 
 

Slovenská republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 (0) 2 0063 2710 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Puh/Tel: +46 (0) 8 545 286 60 
 

Κύπρος 
Otsuka Pharmaceutical Netherlands B.V. 
Thλ: +31 (0) 20 85 46 555 

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46 (0) 8 545 286 60 
 

Latvija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd. 
Tel: +44 (0) 203 747 5300 
 

 
This leaflet was last revised in MM/YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET