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Jinarc is a brand name for Tolvaptan. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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).
Verbatim from this product's EMA label. Tap a section to expand.
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 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.
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.
4). 4). 5). 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. 1). 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.
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.
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, Hyperuricaemia, Hyperglycaemia, Gout Psychiatric disorders Insomnia Nervous system disorders Headache, Dizziness Dysgeusia, Syncope Cardiac disorders Palpitations Respiratory, thoracic and mediastinal disorders Dyspnoea 11 Very common Common Uncommon Not known 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 Dry skin, Rash, Pruritus, Urticaria Musculoskeletal and connective tissue disorders Arthralgia, Muscle spasms, Myalgia 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, Weight increased Bilirubin increased Blood creatine phosphokinase increased 1 observed in post-marketing with tolvaptan in ADPKD.
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. 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 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. 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).
6)
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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e. estimated glomerular filtration rate [eGFR] < 20) may be increased; these patients should be carefully monitored for hepatic toxicity. 1). 73 m2). No data are available for patients with CKD stage 5. 4). Hepatic impairment In patients with severe hepatic impairment the benefits and risks of treatment with Jinarc must be evaluated carefully.
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. 5 Tablets must be swallowed without chewing and with a glass of water.
Liver transplantation was necessary. 8 % (4/484) patients on placebo in a double-blind, placebo-controlled trial in patients with ADPKD. 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 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.
Testing must continue at increased time frequency until symptoms/signs/laboratory abnormalities stabilise or resolve, at which point Jinarc may be re-initiated. 6 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.
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.
8). 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.
g. in case of vomiting or diarrhoea. 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. 3). 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 7 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 […]