With ADPKD, there is a lot to consider

Patients with stable eGFR could be at risk of rapid progression1,2

Stable eGFR vs. Rapidly Declining eGFR, Graph Stable eGFR vs. Rapidly Declining eGFR, Graph

ADPKD=autosomal dominant polycystic kidney disease; eGFR=estimated glomerular filtration rate.

Measuring eGFR alone doesn't always reveal how ADPKD is progressing1

Kidney growth and damage often occur before kidney function declines1,3,5

Kidney Function vs. Kidney Size Over Time, Graph Kidney Function vs. Kidney Size Over Time, Graph

2-step risk identification can help determine if JYNARQUE is appropriate for your patients whose eGFR appears stable

Step 1:
Identify Risk Factors

Even when eGFR appears normal, irreversible kidney damage may
still be occurring1,2

Patients presenting with any of these independently validated risk factors could be experiencing rapid ADPKD progression6

Truncating PKD1

mutation7

Overweight and obesity
(BMI ≥25 kg/m2)8

Hypertension before

age 357

Urologic events before

age 35 (gross hematuria,
cyst infection, or flank pain related to cysts)7

Proteinuria and
microalbuminuria6

Family history of ESKD

at or before age 584

ADPKD=autosomal dominant polycystic kidney disease;
BMI=body mass index; eGFR=estimated glomerular filtration rate;
ESKD=end-stage kidney disease.

Step 2:
Measure Kidneys

If at least ONE risk factor is identified,
a kidney measurement should be ordered

Why it’s important to obtain a kidney measurement

Kidney size is a strong predictor of ADPKD progression before eGFR begins
to decline9

A CRISP cohort analysis, published in Kidney International, showed that a one-time TKV measurement can help assess the rate of future kidney function decline10

When requesting kidney measurements, ask the radiologist for:

  • Maximal bilateral kidney dimensions (L x W x D)
  • and/or
  • A calculated TKV

When you receive measurements:

L=length; W=width; D=depth.

ADPKD=autosomal dominant polycystic kidney disease;
eGFR=estimated glomerular filtration rate;
TKV=total kidney volume.

Treating patients with ADPKD when kidney function appears stable

Treating Patients When Kidney Function Appears Stable, Video

Rapidly declining eGFR means the risk of ADPKD progression is fully realized3,4

Kidney Function vs. Kidney Size Over Time, Graph Kidney Function vs. Kidney Size Over Time, Graph

Rapid disease progression is defined as reliable eGFR decline ≥3.0 mL/min/1.73 m2 per year over a period of ≥4 years with no other confounding cause than ADPKD and indexed for age: 18-39 years: any eGFR; 40-44 years: eGFR <90 mL/min/1.73 m2; 45-49 years: eGFR <75 mL/min/1.73 m2; 50-55 years: eGFR <60 mL/min/1.73 m2.4

If your patients are showing evidence of rapidly progressing ADPKD, consider whether JYNARQUE may be an appropriate treatment choice.

Treating patients with rapidly declining eGFR

Treating Patients with rapidly declining eGFR, Video

  1. Grantham JJ, Chapman AB, Torres VE. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol. 2006;1(1):148-157.
  2. Grantham JJ, Torres VE, Chapman AB, et al. Volume progression in polycystic kidney disease. N Engl J Med. 2006;354(20):2122-2130.
  3. Gansevoort RT, Arici M, Benzing T, et al. Recommendations for the use of tolvapatan 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.
  4. Muller RU, Messchendorp A, Birn H, et al. An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International. Nephrol Dial Transplant. 2022;37:825-839.
  5. Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7(10):556-566.
  6. Rastogi A, Ameen KM, Al-Baghdadi M, et al. Autosomal dominant polycystic kidney disease: updated perspectives. Ther Clin Risk Manag. 2019;15:1041-1052.
  7. 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.
  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. 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.
  10. Yu ASL, Shen C, Landsittel DP, et al; for the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP). Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease. Kidney Int. 2019;95(5):1253-1261.
  11. 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.

Hear about identifying appropriate
patients for JYNARQUE

VIEW VIDEO

Supporting information

Pivotal Trial Data

Full Safety Data

Patient Profiles

Patient Counseling Tips

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.