Once you’ve confirmed an ADPKD diagnosis Taking a holistic assessment can identify appropriate patients for JYNARQUE® (tolvaptan)

Yes No eGFR appears normal • Truncating • Overweight and obesity, BMI ≥25 kg/m • Hypertension before age 35 • Urologic events before age 35 (gross hematuria, cyst infection, or flank pain related to cysts) • Proteinuria and microalbuminuria • Family history of ESKD at or before age 58 Kidney length 1,5† Total kidney volume (TKV)* Gold Standard Method 4 PKD1 mutation Be on the lookout for any ONE of these independently validated risk factors associated with rapid progression 1,7-9 : >16.5 cm at <45 years means patient is at risk of rapid progression When MRI/CT-calculated TKV is not available, ultrasound can be used to measure kidney length If yes If yes If yes Use htTKV and age to plot along the Mayo Classification chart—a patient in Class 1C, 1D, or 1E is at high risk of rapid progression 2 5,6 5,6 MRI/CT reliably measures kidney size to calculate TKV Kidney size is a strong predictor of risk of rapid progression before eGFR begins to decline 2,3 Other factors There is a significant delay between when evidence of kidney function decline is visible and when kidney damage has occurred 2 Evidence of rapidly progressing ADPKD While eGFR appears normal, it may not be telling the whole story eGFR decline of ≥5 mL/min/1.73 m within 1 year OR eGFR decline of ≥2.5 mL/min/1.73 m per year over a period of 5 years 2 2 Does your patient have rapidly declining eGFR? 1 That means they could be an appropriate patient for treatment. Learn about Bob and see his treatment journey That means they could be an appropriate patient for treatment. Learn about Tim and see his treatment journey That means they could be an appropriate patient for treatment. Learn about Julia and see her treatment journey
eGFR decline of ≥5 mL/min/1.73 m 2 within 1 year OR eGFR decline of ≥2.5 mL/min/1.73 m 2 per year over a period of 5 years Does your patient have rapidly declining eGFR? 1 No While eGFR appears normal, it may not be telling the whole story That means they could be an appropriate patient for treatment. Learn about Bob and see his treatment journey • Truncating PKD1 mutation • Overweight and obesity, BMI ≥25 kg/m 2 • Hypertension before age 35 • Urologic events before age 35 (gross hematuria, cyst infection, or flank pain related to cysts) • Proteinuria and microalbuminuria • Family history of ESKD at or before age 58 Be on the lookout for any ONE of these independently validated risk factors associated with rapid progression 1,7-9 : MRI/CT reliably measures kidney size to calculate TKV 5,6 Use htTKV and age to plot along the Mayo Classification chart— a patient in Class 1C, 1D, or 1E is at high risk of rapid progression 5,6 Total kidney volume (TKV)* Kidney size is a strong predictor of risk of rapid progression before eGFR begins to decline 2,3 There is a significant delay between when evidence of kidney function decline is visible and when kidney damage has occurred 2 Gold Standard Method 4 Other factors When MRI/ CT-calculated TKV is not available, ultrasound can be used to measure kidney length >16.5 cm at <45 years means patient is at risk of rapid progression Kidney length 1,5† That means they could be an appropriate patient for treatment. Learn about Tim and see his treatment journey If yes If yes That means they could be an appropriate patient for treatment. Learn about Julia and see her treatment journey Other factors eGFR appears normal Yes Evidence of rapidly progressing ADPKD If yes

Physician should use their clinical judgment when assessing each patient for treatment with JYNARQUE.

Patient images and patient cases are fictional.

BMI=body mass index; CKD=chronic kidney disease; CT=computed tomography; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; htTKV=height-adjusted total kidney volume; MRI=magnetic resonance imaging.

*Identifying a TKV greater than expected for your patient’s age can provide an early and reliable marker for rapid disease progression in ADPKD.10,11

†A kidney length of >16.5 cm was shown to predict development of CKD Stage 3 within 8 years in patients with ADPKD who were <45 years of age and who had CKD Stage 1 or 2.3

Select Important Safety Information:

Contraindications:

  • History, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease
  • Taking strong CYP3A inhibitors
  • With uncorrected abnormal blood sodium concentrations
  • Unable to sense or respond to thirst
  • Hypovolemia
  • Hypersensitivity (e.g., anaphylaxis, rash) to JYNARQUE or any component of the product
  • Uncorrected urinary outflow obstruction
  • Anuria

Additional resources for you and your patients

Access Resources

  1. Gansevoort RT, Arici M, Benzing T, et al. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant. 2016;31(3):337-348.
  2. Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7(10):556-566.
  3. Bhutani H, Smith V, Rahbari-Oskoui F, et al; for the CRISP Investigators. A comparison of ultrasound and magnetic resonance imaging shows that kidney length predicts chronic kidney disease in autosomal dominant polycystic kidney disease. Kidney Int. 2015;88(1):146-151.
  4. Zhang W, Blumenfeld JD, Prince MR. MRI in autosomal dominant polycystic kidney disease. J Magn Reson Imaging. 2019;50(1):41-51.
  5. Magistroni R, Corsi C, Martí T, Torra R. A review of the imaging techniques for measuring kidney and cyst volume in establishing autosomal dominant polycystic kidney disease progression. Am J Nephrol. 2018;48:67-78.
  6. Irazabal MV, Rangel LJ, Bergstralh EJ, et al. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015;26(1):160-172.
  7. Rastogi A, Ameen KM, Al-Baghdadi M, et al. Autosomal dominant polycystic kidney disease: updated perspectives. Ther Clin Risk Manag. 2019;15:1041-1052.
  8. Nowak K, You Z, Gitomer B, et al. Overweight and obesity are predictors of progression in early autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2018;29(2):571-578.
  9. Cornec-Le Gall E, Audrézet MP, Rousseau A, et al. The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2016;27(3):942-951.
  10. Chapman AB, Bost JE, Torres VE, et al. Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2012;7(3):479-486.
  11. Yu ASL, Shen C, Landsittel DP, et al. Baseline total kidney volume and the rate of kidney growth are associated with chronic disease progression in autosomal dominant polycystic kidney disease. Kidney Int. 2018;93(3):691-699.
INDICATION and IMPORTANT SAFETY INFORMATION

JYNARQUE is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

WARNING: RISK OF SERIOUS LIVER INJURY

WARNING: RISK OF SERIOUS LIVER INJURY

  • JYNARQUE® (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported
  • Measure transaminases (ALT, AST) and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
  • Because of the risks of serious liver injury, JYNARQUE is available only through a Risk Evaluation and Mitigation Strategy program called the JYNARQUE REMS Program

CONTRAINDICATIONS:

  • History, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease
  • Taking strong CYP3A inhibitors
  • With uncorrected abnormal blood sodium concentrations
  • Unable to sense or respond to thirst
  • Hypovolemia
  • Hypersensitivity (e.g., anaphylaxis, rash) to JYNARQUE or any component of the product
  • Uncorrected urinary outflow obstruction
  • Anuria

Serious Liver Injury: JYNARQUE can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported in the post-marketing ADPKD experience. Discontinuation in response to laboratory abnormalities or signs or symptoms of liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) can reduce the risk of severe hepatotoxicity. To reduce the risk of significant or irreversible liver injury, assess ALT, AST and bilirubin prior to initiating JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.

Hypernatremia, Dehydration and Hypovolemia: JYNARQUE therapy increases free water clearance which can lead to dehydration, hypovolemia and hypernatremia. Instruct patients to drink water when thirsty, and throughout the day and night if awake. Monitor for weight loss, tachycardia and hypotension because they may signal dehydration. Ensure abnormalities in sodium concentrations are corrected before initiating therapy. If serum sodium increases above normal or the patient becomes hypovolemic or dehydrated and fluid intake cannot be increased, suspend JYNARQUE until serum sodium, hydration status and volume status parameters are within the normal range.

Inhibitors of CYP3A: Concomitant use of JYNARQUE with drugs that are moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, and conivaptan) increases tolvaptan exposure. Use with strong CYP3A inhibitors is contraindicated; dose reduction of JYNARQUE is recommended for patients taking moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking JYNARQUE.

Adverse Reactions: Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia.

Other Drug Interactions:

  • Strong CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to JYNARQUE. Avoid concomitant use of JYNARQUE with strong CYP3A inducers
  • V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V2-agonist

Pregnancy and Lactation: Based on animal data, JYNARQUE may cause fetal harm. In general, JYNARQUE should be discontinued during pregnancy. Advise women not to breastfeed during treatment with JYNARQUE.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

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INDICATION and IMPORTANT SAFETY INFORMATION
INDICATION and IMPORTANT SAFETY INFORMATION

JYNARQUE is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

WARNING: RISK OF SERIOUS LIVER INJURY

WARNING: RISK OF SERIOUS LIVER INJURY

  • JYNARQUE® (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported
  • Measure transaminases (ALT, AST) and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
  • Because of the risks of serious liver injury, JYNARQUE is available only through a Risk Evaluation and Mitigation Strategy program called the JYNARQUE REMS Program

CONTRAINDICATIONS:

  • History, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease
  • Taking strong CYP3A inhibitors
  • With uncorrected abnormal blood sodium concentrations
  • Unable to sense or respond to thirst
  • Hypovolemia
  • Hypersensitivity (e.g., anaphylaxis, rash) to JYNARQUE or any component of the product
  • Uncorrected urinary outflow obstruction
  • Anuria

Serious Liver Injury: JYNARQUE can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported in the post-marketing ADPKD experience. Discontinuation in response to laboratory abnormalities or signs or symptoms of liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) can reduce the risk of severe hepatotoxicity. To reduce the risk of significant or irreversible liver injury, assess ALT, AST and bilirubin prior to initiating JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.

Hypernatremia, Dehydration and Hypovolemia: JYNARQUE therapy increases free water clearance which can lead to dehydration, hypovolemia and hypernatremia. Instruct patients to drink water when thirsty, and throughout the day and night if awake. Monitor for weight loss, tachycardia and hypotension because they may signal dehydration. Ensure abnormalities in sodium concentrations are corrected before initiating therapy. If serum sodium increases above normal or the patient becomes hypovolemic or dehydrated and fluid intake cannot be increased, suspend JYNARQUE until serum sodium, hydration status and volume status parameters are within the normal range.

Inhibitors of CYP3A: Concomitant use of JYNARQUE with drugs that are moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, and conivaptan) increases tolvaptan exposure. Use with strong CYP3A inhibitors is contraindicated; dose reduction of JYNARQUE is recommended for patients taking moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking JYNARQUE.

Adverse Reactions: Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia.

Other Drug Interactions:

  • Strong CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to JYNARQUE. Avoid concomitant use of JYNARQUE with strong CYP3A inducers
  • V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V2-agonist

Pregnancy and Lactation: Based on animal data, JYNARQUE may cause fetal harm. In general, JYNARQUE should be discontinued during pregnancy. Advise women not to breastfeed during treatment with JYNARQUE.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.