JINARC® (tolvaptan) Prescribing Information Please refer to the full Summary of Product Characteristics (SmPC) before prescribing. Presentation: Tablets: 15mg, 30mg, 45mg, 60mg or 90mg of tolvaptan. Indication: JINARC is indicated to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with CKD stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease. Dosage: Adults ≥ 18 years and older: Treatment must be initiated and monitored under the supervision of physicians with expertise in managing ADPKD with full understanding of the risks of JINARC including hepatic toxicity/monitoring requirements. Administer twice daily as a split dose regimen of 45mg/15mg, 60mg/30mg or 90mg/30mg (total daily dose of 60mg, 90mg or 120mg). Morning dose: At least 30 minutes before breakfast. Second dose: 8 hours after morning dose, with or without food. Initial dosage 60mg per day (split-dose 45mg/15mg), titrated upward to 90mg per day (split-dose 60mg/30mg), then to 120 mg per day (split-dose 90mg/30mg). At least weekly intervals between titrations. Maintain patients on the highest tolerable dose. Age: No effect on JINARC plasma concentrations but safety and effectiveness not established in patients over 50. Mild/moderate hepatic impairment: No adjustment needed. Severe hepatic impairment: Monitor regularly. Renal impairment: Dose adjustment not needed but JINARC has not been studied in patients with CrCl<10mL/min or on dialysis. Safety and efficacy in CKD stage 5 not adequately explored and therefore discontinue JINARC if renal insufficiency progresses to CKD stage 5. JINARC must not be taken with grapefruit juice. Paediatric use: Not recommended, safety and efficacy not established. Contraindications: Hypersensitivity to any component of JINARC. Before initiation, elevated liver enzymes and/or signs or symptoms of liver injury meeting criteria for permanent JINARC discontinuation. Volume depletion. Hypernatraemia. Patients who cannot perceive or respond to thirst. Pregnancy. Breastfeeding. Warnings and Precautions: Patients to have adequate access to, and be able to drink, sufficient amounts of water. Urinary output must be secured. Idiosyncratic hepatotoxicity: JINARC has been associated with elevations of ALT and AST with infrequent concomitant bilirubin elevations. Fluid and electrolyte status must be monitored in all patients. Electrolyte monitoring at least every 3 months during long-term treatment. Correct sodium abnormalities prior to JINARC initiation. Fertility, pregnancy and lactation: Women of childbearing potential must use adequate contraception. Pregnancy and breastfeeding: JINARC is contraindicated. Prescribers must comply with the following regarding liver function: To mitigate the risk of significant liver injury liver function tests (LFTs) must be performed prior to initiation, monthly for 18 months and 3-monthly thereafter. JINARC is contraindicated
if baseline LFTs fulfil criteria for permanent discontinuation. Other baseline LFT abnormalities: Hepatologist advice recommended before initiation. Permanently discontinue JINARC treatment if: ALT or AST >8x upper limit of normal (ULN), ALT or AST > 5xULN for more than 2 weeks, ALT or AST > 3xULN and BT> 2xULN or International Normalized Ratio [INR] >1.5 or ALT or AST > 3xULN with persistent symptoms of hepatic injury. If symptoms or signs of liver injury or ALT or AST increases seen during treatment discontinue JINARC and repeat LFTs as soon as possible and until symptoms/signs resolve. If ALT or AST remain below 3xULN therapy may be cautiously continued. See SmPC for full information. Drug Interactions: Caution with CYP3A inhibitors, inducers, substrates and digoxin. Dose reduction required for patients taking moderate or strong CYP3A inhibitors. Undesirable Effects: The following were observed in ADPKD clinical trials: Very common (≥1/10): Thirst, polydipsia, polyuria, pollakiuria, nocturia, headache, dizziness, diarrhoea, dry mouth, fatigue. Common (≥1/100 to <1/10): Abnormal hepatic function, dehydration, increased ALT, increased AST, hypernatraemia, decreased appetite, decreased weight, hyperuricaemia, hyperglycaemia, insomnia, palpitations, dyspnoea, abdominal distension, constipation, dyspepsia, GORD, rash, pruritus, muscle spasms, asthenia. Uncommon (≥1/1000 to <1/100): Increased bilirubin. In post-marketing experience, anaphylaxis (including anaphylactic shock and rash generalised) reported very rarely following tolvaptan administration. See SmPC for other undesirable effects. Overdose: No specific antidote for overdose. Profuse and prolonged aquaresis is anticipated. Manage supportively including appropriate replacement of water and/or electrolytes. Dialysis may not be effective in removing tolvaptan. Legal Category: POM. Marketing Authorisation Numbers: 15mg x 7 days (EU/1/15/1000/001) £302.05, 30mg x 7 days (EU/1/15/1000/003) £302.05, 45mg/15mg x 28 days (EU/1/15/1000/007) £1,208.20, 60mg/30mg x 28 days (EU/1/15/1000/010) £1,208.20, 90mg/30mg x 28 days (EU/1/15/1000/013) £1,208.20. Marketing Authorisation Holder: Otsuka Pharmaceutical Europe Ltd. Gallions, Wexham Springs, Framewood Road, SL3 6PJ, UK. Further information from: Otsuka Pharmaceutical (UK) Ltd. Tel 0808 168 6726 or email
[email protected]. Date of Preparation: May 2015. OPUK/0315/JIN/1109.
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Otsuka UK at
[email protected] or call 07795 426048.
