Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis

Kitazawa,Fumiaki; Fuchida,Shin‑Ichi; Ise,Fumitaka; Kado,Yoko; Ueda,Kumi; Kokufu,Takatoshi; Okano,Akira; Hatsuse,Mayumi; Murakami,Satoshi; Nakayama,Yuko; Takara,Kohji; Shimazaki,Chihiro

doi:10.3892/ol.2017.6133

Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis

Authors:
- Fumiaki Kitazawa
- Shin‑Ichi Fuchida
- Fumitaka Ise
- Yoko Kado
- Kumi Ueda
- Takatoshi Kokufu
- Akira Okano
- Mayumi Hatsuse
- Satoshi Murakami
- Yuko Nakayama
- Kohji Takara
- Chihiro Shimazaki
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Affiliations: Department of Pharmacy, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Kyoto 603‑8151, Japan, Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Kyoto 603‑8151, Japan, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyōgo 670‑8524, Japan
Published online on: May 8, 2017 https://doi.org/10.3892/ol.2017.6133
Pages: 475-479

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Abstract

The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light‑chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low‑dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7‑fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy‑induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin‑6. In conclusion, clinically important interactions between warfarin and lenalidomide and low‑dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values significantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.

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