Pharmacokinetics Of Pomalidomide In A Patient Receiving Hemodialysis Using A High-Cutoff Filter.
Published 2017 · Medicine
To the Editor: Pomalidomide is an oral immunomodulatory drug with antitumoral efficacy against relapsed or refractory multiple myeloma. It binds moderately (16%-42%) to plasma proteins. It is mainly eliminated by cytochrome-mediated hydroxylation in the liver. Its high plasma free fraction and low molecular weight (273 g/mol) make it susceptible to glomerular filtration. Despite that,,4% of the dose is excreted unchanged in urine, suggesting that substantial tubular reabsorption may occur. Pomalidomide elimination does not seem to be substantially affected by moderately decreased kidney function, but data from patients with advanced kidney failure are limited and clinical trials regarding its disposition in this subpopulation are ongoing. In theory, pomalidomide could be significantly removed by hemodialysis because this technique replaces glomerular filtration without affecting further reabsorption. The FDA recently published updated pomalidomide dosage recommendations for patients requiring dialysis, advising a 25% dose reduction (ie, 3 mg/d). Per the manufacturer, there is an increase in pomalidomide’sAUC (of 38%) and the rate of severe adverse events (by 64%) in dialysis patients. Multiple myeloma is frequently associated with alterations in kidney function, and high-cutoff (HCO) dialysis is increasingly used in this condition to ensure blood purification and remove nephrotoxic light chains. However, data regarding pomalidomide disposition during HCO dialysis are lacking. HCO dialysis implies longer, more frequent sessions, using higher filter permeability for substances in the molecular weight range of 15 to 45 kDa, and requiring albumin substitution; it may therefore lead to higher drug elimination compared to traditional intermittent hemodialysis. We report the pharmacokinetics of pomalidomide during HCO dialysis in a patient with multiple myeloma and kidney failure.