A 43-year-old man was referred to our hospital in June 2014 because of severe heart failure. He was diagnosed with familial dilated cardiomyopathy and was administered oral tolvaptan and amiodarone for atrial and ventricular tachycardia. Since up-titration of carvedilol had failed and he was dependent on dobutamine, a left ventricular assist device (LVAD) was implanted. Tolvaptan and furosemide were both discontinued after LVAD implantation and he was discharged from the hospital. Thirteen months later, he was hospitalized for lethargy and hyponatremia of 108 mEq/L, with an antidiuretic hormone level of 2.5 pg/mL, which suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH). We discontinued amiodarone and administered fludrocortisones. However, hyponatremia persisted for a few more days, eventually resulting in delirium and damage to the LVAD driveline. He received an urgent pump exchange and hyponatremia was gradually improved. We considered the possibility that amiodarone-induced SIADH was masked by tolvaptan therapy before LVAD implantation.
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http://dx.doi.org/10.1536/ihj.16-656 | DOI Listing |
Kidney Int Rep
June 2020
Clinical Pharmacology, Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, USA.
Introduction: Tolvaptan, a treatment for autosomal dominant polycystic kidney disease (ADPKD), inhibits vasopressin V2 receptor signaling, which causes aquaretic adverse events (AAEs). The short-term efficacy and tolerability of a once-daily, modified-release (MR) formulation was assessed relative to the twice-daily, immediate-release (IR) formulation.
Methods: This Phase 2 multicenter, randomized (1:1:1:1), placebo-controlled, double-blind, placebo-masked, parallel-group study (NCT01451827) compared tolvaptan MR 50 mg once daily or tolvaptan MR 80 mg once daily with tolvaptan IR 60/30 mg daily split dose and placebo over 8 weeks in 177 subjects.
Kidney Int Rep
June 2020
Quantitative Pharmacology, Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, USA.
Introduction: Tolvaptan, for treatment of autosomal dominant polycystic kidney disease (ADPKD), is provided as immediate-release (IR) tablets administered twice daily in split-dose regimens to suppress urine osmolality to <300 mOsm/kg. A modified-release (MR) formulation was developed for once-daily (QD) dosing to increase compliance and mitigate urinary symptom burden. This phase 2, dose-ranging study (NCT01210560) compared pharmacokinetics, pharmacodynamics, and tolerability of several MR regimens with IR in patients with ADPKD.
View Article and Find Full Text PDFInt Heart J
December 2017
Second Department of Internal Medicine, University of Toyama.
A 43-year-old man was referred to our hospital in June 2014 because of severe heart failure. He was diagnosed with familial dilated cardiomyopathy and was administered oral tolvaptan and amiodarone for atrial and ventricular tachycardia. Since up-titration of carvedilol had failed and he was dependent on dobutamine, a left ventricular assist device (LVAD) was implanted.
View Article and Find Full Text PDFDrug Test Anal
October 2016
Oslo University Hospital, Norwegian Doping Control Laboratory, Oslo, Norway.
Tolvaptan is prohibited by the World Anti-doping Agency (WADA) under class S5 - Diuretics and masking agents. Less than 1% of the administrated dose is excreted by humans in urine. Knowledge concerning the metabolism in humans, and especially the excretion of metabolites in human urine, is limited.
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