Endocrine Abstracts

Tolvaptan, a vasopressin V2-receptor antagonist, is licensed for managing hyponatraemia in the syndrome of inappropriate antidiuretic hormone (SIADH). We report a rare case of drug-induced liver injury (DILI) following low-dose Tolvaptan. A 51-year-old female with SIADH had symptomatic hyponatraemia despite fluid restriction and sodium supplementation. Tolvaptan was initiated at 3.75 mg twice weekly, uptitrated to once daily, in preparation for elective surgery. Baseline liver function tests (LFTs) were normal. After six weeks, serum sodium normalised (122 mmol/l to 134 mmol/l), however ALT rose from 14U/l to 405U/l (normal range 0-32). Synthetic liver function and clinical examination remained normal. The patient had no history of liver disease, alcohol excess, or use of hepatotoxic drugs or CYP3A4 inhibitors. A non-invasive liver screen was negative. Tolvaptan was stopped and her LFTs normalised within 6 weeks. A yellow card report was completed and a drug allergy recorded. DILI is a recognised complication of high-dose Tolvaptan, particularly at high doses (60-120 mg/day) used in autosomal dominant polycystic kidney disease (ADPKD), where it can lead to liver failure (1). This has led to strict counselling and LFT monitoring guidelines in ADPKD, however whilst the BNF recommends LFT monitoring, guidelines do not exist for the use of low-dose Tolvaptan in SIADH. The pathogenesis of Tolvaptan-induced DILI remains unclear, although host-dependent susceptibility appears important regardless of dose (2). Those developing DILI should stop the drug, and recurrence risk is high if restarted (1). Here we show that clinically significant DILI can occur with low-dose Tolvaptan with no reliable predictors of susceptibility. All patients receiving regular Tolvaptan should undergo LFT monitoring irrespective of dose. We recommend monthly LFTs for 18 months, then 3-monthly thereafter. Patients should be counselled on potential risks, and any signs of liver injury should prompt immediate discontinuation.

References:

1. DOI: 10.1007/s40264-015-0327-3.

2. DOI: 10.1093/ndt/gfab312.