INDICATION and IMPORTANT SAFETY INFORMATION
Tolvaptan tablets are 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
Tolvaptan tablets 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 tolvaptan tablets are available only through a Risk Evaluation and Mitigation Strategy program called
Because of the risks of serious liver injury tolvaptan tablets are available only through a Risk Evaluation and Mitigation Strategy program called the Tolvaptan for ADPKD Shared System REMS. Prescribers, Pharmacies and patients must enroll in the 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 tolvaptan tablets or any component of the product
Uncorrected urinary outflow obstruction
Anuria
Serious Liver Injury: Tolvaptan tablets 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 tolvaptan tablets, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.
Hypernatremia, Dehydration and Hypovolemia: Tolvaptan tablets 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 tolvaptan tablets until serum sodium, hydration status and volume status parameters are within the normal range.
Inhibitors of CYP3A: Concomitant use of tolvaptan tablets 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 tolvaptan tablets are recommended for patients taking moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking tolvaptan tablets.
Adverse Reactions: The most common reasons for discontinuation of Tolvaptan tablets in a randomized trial were polyuria, pollakiuria and nocturia. The most common treatment emergent adverse reactions in the same trial (>3% and >1.50/0 of placebo) were: thirst, dry mouth, fatigue, dizziness, dyspepsia, decrease appetite, abdominal distention, dry skin, hyperuricemia, and palpitations.
Other Drug Interactions:
Strong CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to tolvaptan tablets. Avoid concomitant use of tolvaptan tablets with strong CYP3A inducers
V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of tolvaptan tablets with a V2-agonist
Pregnancy and Lactation: Based on animal data, tolvaptan tablets may cause fetal harm. In general, tolvaptan tablets should be discontinued during pregnancy. Advise women not to breastfeed during treatment with tolvaptan tablets.
To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).
PP-TOL-0004
©2025 Lupin Pharmaceuticals, Inc.
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