The subject of the present invention is to provide a combination medicine that can prevent or inhibit the acquisition of tolerance to a pyrimidine metabolism antagonist, a preventive or inhibitory medicine for tolerance of a pyrimidine metabolism antagonist, and a treatment method for diseases using the combination medicine. According to the present invention, a combination medicine is provided, which comprises a pyrimidine metabolism antagonist and 5-hydroxy-1H-imidazole-4-carboxamide, and the single administration amount of compound A is 50 mg/m 2 ～500 mg/m 2 , The daily dosage is 100 mg/m 2 ～1000 mg/m 2 .本發明的課題在於提供一種可預防或抑制獲得嘧啶代謝拮抗劑耐受性的組合醫藥、嘧啶代謝拮抗劑的耐受的預防或抑制藥、以及使用所述組合醫藥的疾病的處置方法。根據本發明，提供一種組合醫藥，其包含嘧啶代謝拮抗劑與5-羥基-1H-咪唑-4-甲醯胺，且化合物A的一次施用量為50 mg/m2～500 mg/m2，一天施用量為100 mg/m2～1000 mg/m2。
