^PrJINARC^® Important safety information

Indications and clinical use:

^PrJINARC^® (tolvaptan) is indicated to slow the progression of kidney enlargement and kidney function decline in adult patients with autosomal dominant polycystic kidney disease (ADPKD). In ADPKD, kidney enlargement reflects renal cyst burden.

• In order to select patients who might best benefit from the effects of JINARC, clinical trials evaluated ADPKD patients having a total kidney volume (TKV) ≥750 mL, and/or renal function corresponding to a CKD-EPI eGFR ≥25 mL/min/1.73m², at the time of initiation of treatment.
• JINARC treatment should be initiated and monitored under the supervision of a nephrologist or specialist with expertise in the management of patients with ADPKD and a full understanding of the benefits and risks of tolvaptan therapy including hepatic toxicity and monitoring requirements.
• Careful consideration and discussion of the appropriateness of JINARC treatment should be undertaken between the prescriber and patient before initiation of therapy, taking into account the potential benefits and risks of treatment. Upon mutual agreement to undertake treatment with JINARC, a signed, duly-documented, manufacturer and product-specific Patient-Prescriber Agreement Form (PPAF) is required outlining the relevant patient selection criteria to be considered, expected benefits and risks of treatment, and the need for mandatory hepatic function monitoring.
• JINARC Controlled Hepatic Safety Monitoring and Distribution Programme: JINARC is available for treatment of patients with ADPKD only through a manufacturer and product-specific controlled hepatic safety monitoring and distribution (HSMD) programme conducted and maintained by, or for, the market authorisation holder of JINARC. A duly signed manufacturer and product-specific PPAF is required for enrollment in the HSMD programme. For more information on the programme, please call 1-844-254-6272
• Safety and effectiveness have not been established in geriatrics (>65).

Contraindications:

JINARC is contraindicated in:

• Patients who have been asked to permanently discontinue tolvaptan
• Patients with known or suspected hypersensitivity to tolvaptan, benzazepine or benzazepine derivatives (e.g., mirtazapine) or any of the excipients
• Patients with hypovolemia
• Patients with hypernatremia
• Patients with anuria
• Patients who do not have access to fluids or who cannot respond to the physiologic sensation of thirst
• Patients with a history, signs or symptoms of significant liver impairment or injury, excluding uncomplicated polycystic liver disease
• Patients using strong CYP3A inhibitors, e.g., ketoconazole, itraconazole, clarithromycin, telithromycin, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone
• Pregnancy
• Nursing women
• Patients with one of the following rare hereditary diseases: Galactose intolerance, Lapp lactase deficiency or Glucose-galactose malabsorption

Most serious warnings and precautions:

Idiosyncratic hepatic toxicity: JINARC use has led to idiosyncratic elevations of blood alanine and aspartate aminotransferases (ALT & AST), rarely associated with concomitant elevations of total bilirubin. To help mitigate the risk of liver injury, blood testing for hepatic transaminases and total bilirubin is required prior to initiation of JINARC, then blood testing for hepatic transaminases is required:

• monthly for 18 months
• every 3 months for the next 12 months
• every 3–6 months thereafter during treatment with JINARC

Therefore, JINARC is available for treatment of patients with ADPKD only through a controlled hepatic safety monitoring and distribution programme conducted and maintained by, or for, the market authorization holder of JINARC.

Other relevant warnings and precautions:

• Risk of dehydration
• Interactions with moderate CYP3A inhibitors, CYP3A inducers or P-glycoprotein inhibitors
• Hepatotoxicity: Acute liver failure
• Anaphylaxis
• Hypernatremia: Concomitant use with hypertonic saline solutions or drugs that may increase serum sodium should be avoided
• Hyperkalemia
• Hyperuricemia
• Hypotension: Co-administration with antihypertensive medications may cause increase in hypotension-related adverse events, including dizziness or syncope
• Serum sodium abnormalities must be corrected prior to JINARC initiation
• Use of contraception in women of childbearing potential
• Vasopressin analogues: Co-administration not recommended
• Caution when driving vehicles or operating machinery

For more information:

Consult the Product Monograph at jinarcmonograph.ca  for adverse reactions, interactions, dosing, monitoring tests and conditions of clinical use. The Product Monograph is also available by calling 1-877-341-9245.