Successful determination of nilotinib dosage by therapeutic drug monitoring in a patient with chronic myeloid leukemia developing hepatic dysfunction: A case report

Nakahara, Ryosuke; Sumimoto, Takahiro; Ogata, Masao; Sato, Yuhki

doi:10.1002/ccr3.2191

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…We developed a rapid, sensitive, and efficient UPLC-MS/MS method to simul ously determine osimertinib, aumolertinib, and furmonertinib concentrations in hu Therapeutic drug monitoring (TDM) is an important technique for formulating dosing regimens for drugs with strong toxic effects, and great individual differences measured by drug concentrations in biological samples can identify inter-patient differences and improve the therapeutic effects of drugs while reducing AEs [22][23][24]. Several studies have also shown that TDM can improve the therapeutic efficacy of TKIs, supporting rational clinical use [25][26][27][28]. The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is a standard analytical tool for TDM and is widely used in clinical practice for precise treatment with targeted oral drugs.…”

Section: Introductionmentioning

confidence: 99%

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

Li¹,

Ma³

et al. 2022

Molecules

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The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib, aumolertinib, and furmonertinib represent a new treatment option for patients with EGFR p.Thr790 Met (T790 M)-mutated non-small cell lung cancer (NSCLC). Currently, there are no studies reporting the simultaneous quantification of these three drugs. A simple ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of osimertinib, aumolertinib, and furmonertinib concentrations in human plasma, and it was applied for therapeutic drug monitoring (TDM). Plasma samples were processed using the protein precipitation method (acetonitrile). A positive ion monitoring mode was used for detecting analytes. D3-Sorafenib was utilized as the internal standard (IS), and the mobile phases were acetonitrile (containing 0.1% formic acid) and water with gradient elution on an XSelect HSS XP column (2.1 mm × 100.0 mm, 2.5 µm, Waters, Milford, MA, USA) at a flow rate of 0.5 mL·min−1. The method’s selectivity, precision (coefficient of variation of intra-day and inter-day ≤ 6.1%), accuracy (95.8–105.2%), matrix effect (92.3–106.0%), extraction recovery, and stability results were acceptable according to the guidelines. The linear ranges were 5–500 ng·mL−1, 2–500 ng·mL−1, and 0.5–200 ng·mL−1 for osimertinib, aumolertinib, and furmonertinib, respectively. The results show that the method was sensitive, reliable, and simple and that it could be successfully applied to simultaneously determine the osimertinib, aumolertinib, and furmonertinib blood concentrations in patients. These findings support using the method for TDM, potentially reducing the incidence of dosing blindness and adverse effects due to empirical dosing and inter-patient differences.

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Section: Introductionmentioning

confidence: 99%

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

Li¹,

Ma³

et al. 2022

Molecules

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“…Better management consists of therapeutic drug monitoring (TDM). Nakahara et al 3 from Japan reported a successful dose of Nilotinib adjustment after hepatic dysfunction grade 3.…”

Section: Discussionmentioning

confidence: 99%

“…2 Since its approval in 2007, Nilotinib has emerged as a second-generation TKI (2G TKI) with antileukemic activity remarkably effective and reasonably safe medication for the treatment of CML. 2,3 We report the case of a patient with CML who developed unfortunately life-threatening liver toxicity secondary to Nilotinib. Actually, European LeukemiaNet (ELN) recommends adapting treatment choices according to patient history and comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Life threatening hepatotoxicity induced by Nilotinib

Khelifa¹

2022

J Oncol Pharm Pract

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Introduction Tyrosine kinase inhibitor had changed the prognosis of chronic myeloid leukemia (CML) and the overall survival had reached 95%. Unfortunately, adverse events (AEs) remain an obstacle to following successful treatment in CML impairing the quality of life and sometimes endangering the lives of patients. To this end, we show this clinical case to discuss strategies to deal with rare AEs in a way to preserve the patient's life and to maintain not only a good response to treatment but also confidence and compliance of the patient. Case report We report the case of a 57-year-old woman diagnosed with CML at the chronic phase who developed rare life-threatening hepatotoxicity (major cytolysis and prothrombin time fall) secondary to Nilotinib used as second-line treatment. This complication settled despite an optimal molecular response. Management and outcome We discuss below the follow-up and management in our center and according to the literature with more sophisticated pharmacological methods. Discussion Although we used to monitor disease molecular response to treatment, we need solutions and manuscripts for monitoring drug dose parameters to avoid unusual dangerous effects risking the patient life. We conclude that monitoring the disease as well as the treatment pharmacokinetics is mandatory to better carry on CML patients.

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“…We have previously reported a case report of successful determination of nilotinib dosage by TDM in a patient with CML developing hepatic dysfunction. 21 The safety and efficacy of imatinib for CML have been reviewed. 22 Maintaining an optimal trough plasma imatinib concentration is important for ensuring maximum efficacy in patients with CML.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, TDM of TKIs is an important tool for CML treatment. We have previously reported a case report of successful determination of nilotinib dosage by TDM in a patient with CML developing hepatic dysfunction 21 . The safety and efficacy of imatinib for CML have been reviewed 22 .…”

Section: Discussionmentioning

confidence: 99%

Successful determination of imatinib re‐administration dosage by therapeutic drug monitoring in a case of chronic myeloid leukemia initiating dialysis for acute renal dysfunction

Nakahara

Sumimoto

Tanaka

et al. 2021

Clinical Case Reports

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Successful determination of nilotinib dosage by therapeutic drug monitoring in a patient with chronic myeloid leukemia developing hepatic dysfunction: A case report

Cited by 9 publications

References 10 publications

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

Life threatening hepatotoxicity induced by Nilotinib

Successful determination of imatinib re‐administration dosage by therapeutic drug monitoring in a case of chronic myeloid leukemia initiating dialysis for acute renal dysfunction

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