Bannwarth B, Schaeverbeke T, Labat L, Marce S, Demotes-Mainard F, Dehais J
Centre de Pharmacologie, CHU Pellegrin, Bordeaux.
Rev Rhum Ed Fr. 1994 May;61(5):337-42.
Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. However, toxicity is the main reason for methotrexate withdrawal. Most adverse effects are mild abnormalities, such as digestive symptoms, stomatitis, elevations in transaminase levels, and moderate decreases in peripheral blood cell counts. Potentially life-threatening effects include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus-related lymphomas have been reported. Neurological disorders, cutaneous reactions and renal lesions have been ascribed to low-dose methotrexate. Prior renal dysfunction and concomitant administration of a number of drugs, including cotrimoxazole, have been shown to increase methotrexate toxicity. However, susceptibility to the toxic effects of methotrexate varies widely across individuals. The effectiveness of folate supplementation in preventing methotrexate toxicity remains controversial.
甲氨蝶呤是类风湿关节炎患者长期持续用药率最高的药物。然而,毒性是停用甲氨蝶呤的主要原因。大多数不良反应为轻度异常,如消化道症状、口腔炎、转氨酶水平升高以及外周血细胞计数中度下降。潜在的危及生命的效应包括过敏性肺炎和全血细胞减少。肝硬化的发生率低于银屑病患者。已有机会性感染和与爱泼斯坦-巴尔病毒相关的淋巴瘤的报道。神经功能障碍、皮肤反应和肾脏损害与低剂量甲氨蝶呤有关。既往肾功能不全以及同时使用多种药物(包括复方新诺明)已被证明会增加甲氨蝶呤的毒性。然而,个体对甲氨蝶呤毒性的易感性差异很大。补充叶酸预防甲氨蝶呤毒性的有效性仍存在争议。