This observational study investigated the influence of febrile neutropenia on the emergency of ARC for the first time. ARC was strongly associated with VCM pharmacokinetics, and two-thirds of the ARC patients had subtherapeutic VCM concentrations. In patients with ARC, individualized dosing regimens are required to achieve the target trough concentration.

A daily dosage of 7.5 mg or less was recommended to prevent hypernatremia in short- as well as long-term tolvaptan treatment, and mainly elderly patients were at risk for hypernatremia.

The Japanese VCM dosing nomogram was effective in minimizing the number of instances of supratherapeutic VCM serum concentrations; however, it lacked accuracy in achieving target trough concentrations. The accuracy of the nomogram could be enhanced by categorizing patients according to age. Nevertheless, this study provides novel evidence of the usefulness of this nomogram in avoiding subtherapeutic concentrations of VCM in patients with risk factors for augmented renal clearance.