TOLVAPTAN

What it is

Tolvaptan Lupin is indicated to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease. Tolvaptan Lupin tablets are for oral use and contain 15 mg, 30 mg, 45 mg, 60 mg or 90 mg of tolvaptan as the active ingredient.

Approved indications

— Slowing the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease.

Dosing overview

Tolvaptan Lupin is administered twice daily in split dose regimens, with total daily doses of 60 mg, 90 mg or 120 mg. The initial dose is 60 mg tolvaptan per day as a split-dose regimen of 45 mg + 15 mg (45 mg taken upon waking and prior the morning meal and 15 mg taken 8 hours later). The initial dose is to be titrated upward to a split-dose regimen of 90 mg tolvaptan (60 mg + 30 mg) per day and then to a target split-dose regimen of 120 mg tolvaptan (90 mg + 30 mg) per day, if tolerated, with at least weekly intervals between titrations. The morning dose is to be taken at least 30 minutes before the morning meal. The second daily dose can be taken with or without food.

Key safety warnings

Tolvaptan has been associated with idiosyncratic elevations of blood alanine and aspartate aminotransferases (ALT and AST), rarely associated with concomitant elevations in bilirubin — total (BT). In post-marketing experience with tolvaptan in ADPKD, acute liver failure requiring liver transplantation has been reported. Blood testing for hepatic transaminases is required prior to initiation of Tolvaptan Lupin, then continually monthly for 18 months, then every 3 months thereafter during treatment with Tolvaptan Lupin. Prescriber education and certification on the risk of liver injury and the importance of regular liver function monitoring is mandatory. Tolvaptan may cause adverse reactions related to water loss such as thirst, polyuria, nocturia, and pollakiuria. Therefore, patients must have access to water (or other aqueous fluids) and be able to drink sufficient amounts of these fluids. Volume status must be monitored in patients taking tolvaptan because treatment with tolvaptan may result in severe dehydration which constitutes a risk factor for renal dysfunction.

Contraindications

Tolvaptan Lupin is contraindicated in patients with hypersensitivity to the active substance, benzazepine derivatives or to any of the excipients; elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment that meet the requirements for permanent discontinuation of tolvaptan; volume depletion; anuria; hypernatraemia; patients who cannot perceive or respond to thirst; pregnancy; and breastfeeding.

PBS listing

Tolvaptan Lupin is registered on the ARTG with strengths of 15 mg, 30 mg, 45 mg, 60 mg and 90 mg in multiple composite pack and blister pack configurations, with registrations effective from 30 October 2024. No PBS pricing or restriction information is available from the provided sources.

Regulatory history

Tolvaptan Lupin received ARTG registration on 30 October 2024 across multiple strength formulations. The PBAC considered this indication in November 2021, noting potential reasons for low utilisation including the boxed warning, mandatory prescriber education, effectiveness of lifestyle modifications, treatment-associated side effects, and a laborious initial authority process.