Medication Therapy of High-Dose Methotrexate: An Evidence-Based Practice Guideline Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

Abstract

Objectives: A lot of medication risks related to high-dose methotrexate\n(HDMTX) therapy still remain to be identified and standardized. This\nstudy aims to establish an evidence-based practice guideline for\nindividualized medication of HDMTX. Methods: The practice guideline was\nlaunched by the Division of Therapeutic Drug Monitoring, Chinese\nPharmacological Society. The guideline was developed following the WHO\nhandbook for guideline development and the methodology of evidence-based\nmedicine (EBM). The guideline was initially registered in the\nInternational Practice Guidelines Registry Platform (IPGRP-2017CN021).\nSystematic reviews were conducted to synthesis available evidence. A\nmulticenter cross-sectional study was conducted by questionnaires to\nevaluate patients’ perception and willingness on individualized\nmedication of HDMTX. The Grading of Recommendations Assessment,\nDevelopment, and Evaluation (GRADE) approach was used to rate the\nquality of evidence and to grade the strength of recommendations.\nResults: Multidisciplinary working groups were included in this\nguideline, including clinicians, pharmacists, methodologists,\npharmacologists and pharmacoeconomic specialists. A total of 124\npatients were involved to integrate patient values and preferences.\nFinally, the guideline presents 28 recommendations, regarding evaluation\nprior to medication (renal function, liver function, pleural effusion,\ncomedications, genetic testing), pre-treatment and routine dosing\nregimen, therapeutic drug monitoring (necessity, method, timing, target\nconcentration), leucovorin rescue (initial timing, dosage regimen and\noptimization), management of toxicities. Of them, 12 are strong\nrecommendations. Conclusions: We developed an evidence-based practice\nguideline with respect to HDMTX medication using a rigorous and\nmultidisciplinary approach. This guideline provides comprehensive and\npractical recommendations involving the whole process of HDMTX\nmedication to health care providers.