Tolvaptan-induced Liver Injury: Who is at Risk? A Case Report and Literature Review

Abstract

Hyponatremia is a common clinical condition encountered in the hospital setting. Syndrome of inappropriate antidiuretic hormone (SIADH) is an important and one of the most common causes of hyponatremia. SIADH accounts for approximately one-third of all cases of hyponatremia. Tolvaptan is a vasopressin receptor antagonist used to treat SIADH. Hepatoxicity is a rare yet dangerous side effect from Tolvaptan use. We present a case of cholestatic liver injury in an elderly female who presented with hyponatremia. She received two doses of tolvaptan 15mg and developed worsening in her total bilirubin (T Bili) and alkaline phosphatase (Alk Phos) levels. Tolvaptan is known to cause elevated transaminase levels and the mechanism of action is thought to be idiosyncratic. Fortunately, the patient responded with an improvement in T Bili and Alk Phos levels after stopping tolvaptan. This case highlights the cautious use of tolvaptan in elderly patients with SIADH as even small doses can potentiate hepatotoxicity.

The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles

“…Currently, there is no cure for ADPKD and tolvaptan is the only FDA approved treatment for ADPKD 6 . Despite enthusiasm, tolvaptan has been reported to cause several side effects including polyuria, thirst, nocturia, and drug‐induced liver damage 7‐10 . According to a study of 961 ADPKD patients undergoing tolvaptan treatment, the adverse event rates for thirst and nocturia were found to be approximately 55% and 29% 9 .…”

“…Polyuria affected 38% of patients and was the primary reason for dose reduction and drug discontinuation due to its significant impact on patients' quality of life 11,12 . Moreover, tolvaptan is known to cause liver toxicity and elevated liver enzyme levels, which may further deteriorate liver health, as liver cysts and fibrosis are common extrarenal manifestations of ADPKD 8,13 . As a result, frequent monitoring of liver function is required for patients on tolvaptan treatment 14,15 .…”

“…6 Despite enthusiasm, tolvaptan has been reported to cause several side effects including polyuria, thirst, nocturia, and drug-induced liver damage. [7][8][9][10] According to a study of 961 ADPKD patients undergoing tolvaptan treatment, the adverse event rates for thirst and nocturia were found to be approximately 55% and 29%. 9 Polyuria affected 38% of patients and was the primary reason for dose reduction and drug discontinuation due to its significant impact on patients' quality of life.…”

“…11,12 Moreover, tolvaptan is known to cause liver toxicity and elevated liver enzyme levels, which may further deteriorate liver health, as liver cysts and fibrosis are common extrarenal manifestations of ADPKD. 8,13 As a result, frequent monitoring of liver function is required for patients on tolvaptan treatment. 14,15 Like tolvaptan, many drugs for CKD lead to non-specific uptake and undesired adverse effects, 16,17 and hence, the development of a targeted drug delivery platform that can directly unload drugs to diseased kidneys has the potential to reduce systemic side effects without compromising therapeutic efficacy.…”

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“…The authors received no funding for this review. [41]: -1.5% discontinued due to liver dysfunction -4.5% showed a clinical significant increase in aminotransferases -0.9% showed an increase in bilirubin levels -0% of acute liver failure All cases showed resolution in LFTs after tolvaptan discontinuation Post-marketing studies [42,43]:…”