Jynarque FDA Approval History

Last updated by Judith Stewart, BPharm on March 2, 2021.

FDA Approved: Yes (First approved April 23, 2018)
Brand name: Jynarque
Generic name: tolvaptan
Dosage form: Tablets
Company: Otsuka Pharmaceutical Co., Ltd
Treatment for: Adults at Risk of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease

Jynarque (tolvaptan) is a selective vasopressin V₂-receptor antagonist indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

Recommended Dosage

• The initial dosage for Jynarque is 60 mg orally per day as 45 mg taken on waking and 15 mg taken 8 hours later.
• The dose is titrated to 60 mg plus 30 mg, then to 90 mg plus 30 mg per day if tolerated with at least weekly intervals between titrations.
• Patients may down-titrate based on tolerability.
• If a dose of Jynarque is not taken at the scheduled time, the next dose should be taken at its scheduled time.
• Patients should drink enough water to avoid thirst or dehydration.

WARNING: RISK OF SERIOUS LIVER INJURY

• 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

• CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to Jynarque. Avoid concomitant use of Jynarque with strong CYP3A inducers
• OATP1B1/3 and OAT3 Transporter Substrates: Caution should be used in patients who take Jynarque and OATP1B1/B3 and OAT3 substrates (e.g., statins, bosentan, glyburide, nateglinide, repaglinide, methotrexate, furosemide), as the plasma concentrations of these substrates may be increased.
• BCRP Transporter Substrates: Tolvaptan is an inhibitor of BCRP. Patients who take Jynarque, should avoid concomitant use with BCRP substrates (e.g., rosuvastatin)
• 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.

Additional Information

Tolvaptan was first approved by the FDA in 2009 as Samsca (Otsuka Pharmaceutical Co., Ltd.) for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.

Development timeline for Jynarque

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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