Important Safety Information

Indications and clinical use:

LUPIN-TOLVAPTAN is indicated to slow the progression of kidney enlargement and kidney function decline in 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 LUPIN-TOLVAPTAN, 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/1.73 m2, at the time of initiation of treatment.
  • LUPIN-TOLVAPTAN 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 LUPIN-TOLVAPTAN 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 LUPIN-TOLVAPTAN, a signed, duly documented, manufacturer and product-specific patient-prescriber agreement (PPAF) is required outlining relevant patient selection criteria to be considered, expected benefits and risks of treatment, and the need for mandatory hepatic function monitoring.
  • Controlled Distribution Program: LUPIN-TOLVAPTAN is available for treatment of patients with ADPKD only through a manufacturer and product-specific controlled distribution program (CDP) conducted and maintained by, or for, the market authorisation holder of LUPIN-TOLVAPTAN. A duly signed manufacturer and product-specific PPAF is required for enrollment in the CDP. For more information on the programme, please call [insert phone number].
  • Geriatrics (>65 years of age): The safety and effectiveness of LUPIN-TOLVAPTAN in geriatric patients has not been established.
  • Pediatrics (<18 years of age): LUPIN-TOLVAPTAN has not been studied in pediatric patients with ADPKD. Its use is not recommended in this patient population.

Contraindications:

LUPIN-TOLVAPTAN 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: LUPIN-TOLVAPTAN use has led to idiosyncratic elevations of blood alanine and aspartate aminotransferases (ALT and 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 LUPIN-TOLVAPTAN, 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 LUPIN-TOLVAPTAN

Therefore, LUPIN-TOLVAPTAN is available for treatment of patients with ADPKD only through a controlled distribution program conducted and maintained by, or for, the market authorization holder of LUPIN-TOLVAPTAN.

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 LUPIN-TOLVAPTAN initiation
  • Use of contraception in women of childbearing potential
  • Vasopressin analogues: Co-administration not recommended
  • Caution when driving vehicles or operation machinery

For more information:

Consult the Product Monograph here for adverse reactions, dosing, monitoring tests and conditions of clinical use. The Product Monograph is also available by calling 1-844-587-4623 or emailing drugsafety@lupin.com.

ADPKD=autosomal dominant polycystic kidney disease; ALT=alanine aminotransferases; AST=aspartate aminotransferases; CDP=Controlled Distribution Program; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; CYP3A=cytochrome P450 3A; eGFR=estimated glomerular Filtration rate; PPAF=Patient-Prescribe Agreement Form; TKV=total kidney volume.

Reference: 1. LUPIN-TOLVAPTAN DRAFT Product Monograph. Lupin Pharma Canada Ltd. January 28, 2025.