部份中文甲吡唑处方资料（仅供参考） 英文名：Fomepizole 商品名：Antizol 中文名：甲吡唑注射剂 药理作用 甲吡唑用于乙二醇中毒的解救主要是通过抑制乙醇脱氢酶来实现的。乙二醇是抗冻剂和冷却剂中的主要成分，在体内乙醇脱氢酶的作用下会产生有毒的乙二醇代谢物(可能是乙二醛)。乙二醇急性中毒的临床表现有：中枢神经系统抑制、严重的代谢性酸中毒、肾功能衰竭和昏迷等。甲吡唑能够抑制乙醇脱氢酶的活性，从而有效地抑制了乙二醇代谢物的产生，最终达到治疗目的。 药动学特性 甲吡唑可供静注，蛋白结合率低，表观分布容积为0.8l.kg-1，半衰期为5h。其主要经肝脏代谢，可能与细胞色素P-450系统有关，消除过程与剂量大小有关，为非线性消除，无法用米氏方程来描述。本品主要经肾脏排泄，尿中的原型药物很少，主要是代谢产物4-carboxypyrazole，肾清除率为0.016ml.min-1.kg-1。 乙二醇中毒的早期患者，每12h静注400～1200mg，血药浓度可达到17～31μg.ml-1。中毒晚期进行透析的患者，给予负荷剂量20mg.kg-1，并持续静注(透析的同时)甲吡唑1.5mg.kg-1.h-1其血药浓度将高于14μg.ml-1。有研究表明治疗时的血药浓度应为8～15μg.ml-1或更高。 临床应用 乙二醇中毒；对于肾功能尚可的患者单独应用甲吡唑即有效，与乙醇治疗乙二醇中毒相比较，甲吡唑应用起来更方便、更安全。临床应用表明，及早应用甲吡唑(摄入乙二醇3～16h内)，1日2次(静注或口服)即可消除酸中毒而不需进行血液透析。对于伴随肾功能衰竭的患者应用甲吡唑的同时还应进行透析。 乙醇过敏；通过抑制乙醇脱氢酶来减少乙醛的积累达到治疗目的。如果提前1h预防性的口服甲吡唑10mg.kg-1则能阻止过敏症状的出现。 甲醇中毒　动物实验表明甲吡唑对甲醇中毒有效。 用法用量 本品供静脉注射，用生理盐水稀释。中毒早期肾功能良好者，首次静注800或1200mg，然后每12h静注减少用量如600mg，300mg或400mg，100mg或200mg，50mg或100mg，直到血中检测不到乙二醇或其浓度低于0.1g.L-1。肾功能衰竭的患者不必调整剂量。中毒晚期，出现无尿性肾功能衰竭的患者，应进行血液透析。血液透析对甲吡唑有明显的清除作用，故需要提高剂量。一般首次负荷剂量为10～20mg.kg-1，透析期间的组持剂量为1～1.5mg.kg-1vh-1。 不良反应及禁忌 最常见的不良反应是转氨酶的升高，其它的有眩晕、头疼、高甘油三酯血症、嗜酸性粒细胞增多、皮疹、恶心(口服时)等。对甲吡唑过敏者禁用。 注意事项 据研究表明，甲吡唑可以抑制乙醇脱氢酶，而反过来乙醇有可抑制甲吡唑代谢，因而甲吡唑和乙醇可以相互抑制对方的消除，从而加强各自的作用。故临床上应注意乙醇和甲吡唑之间的这种相互作用。 注射用甲吡唑(fomepizole)简介 1998年初美国FDA批准了注射用甲吡唑(商品名为Antizol，由Orphan Medical公司生产)上市。甲吡唑(4-methylpyrazole，4-甲基吡唑)是一种乙醇脱氢酶抑制剂，可以口服或静注，主要用于乙二醇中毒的解救。结构式如下。 完整说明书附件： 1）：http://www.info.pmda.go.jp/go/pack/3929411A1020_1_03/ 2）：https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c045b5a8-b220-4f0a-a831-155b29c19454&type=display Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate] [Prescribed dose] [100ml] [30 min] Stability data: Dosing: loading dose: 15 mg/kg, followed by 10 mg/kg q12h x 4 doses, then 15 mg/kg q12h thereafter until ethylene glycol levels <20 mg/dl. Dialysis should be considered in addition to fomepizole in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol level >50 mg/dl. Fomepizole is dialyzable and should be given q4h during hemodialysis. Mechanism of Action Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol, the main component of most antifreezes and coolants, is metabolized to glycoaldehyde, which undergoes subsequent sequential oxidations to yield glycolate, glyoxylate, and oxalate. Glycolate and oxalate are the metabolic by-products primarily responsible for the metabolic acidosis and renal damage seen in ethylene glycol toxicosis. The lethal dose of ethylene glycol in humans is approximately 1.4 mL/kg. Methanol, the main component of windshield wiper fluid, is slowly metabolized via alcohol dehydrogenase to formaldehyde with subsequent oxidation via formaldehyde dehydrogenase to yield formic acid. Formic acid is primarily responsible for the metabolic acidosis and visual disturbances (e.g., decreased visual acuity and potential blindness) associated with methanol poisoning. A lethal dose of methanol in humans is approximately 1-2 mL/kg. Fomepizole has been shown in vitro to block alcohol dehydrogenase enzyme activity in dog, monkey, and human liver. The concentration of fomepizole at which alcohol dehydrogenase is inhibited by 50% in vitro is approximately 0.1 µmol/L. In a study of dogs given a lethal dose of ethylene glycol, three animals each were administered fomepizole, ethanol, or left untreated (control group). The three animals in the untreated group became progressively obtunded, moribund, and died. At necropsy, all three dogs had severe renal tubular damage. Fomepizole or ethanol, given 3 hours after ethylene glycol ingestion, attenuated the metabolic acidosis and prevented the renal tubular damage associated with ethylene glycol intoxication. Several studies have demonstrated that Antizol plasma concentrations of approximately 10 µmol/L (0.82 mg/L) in monkeys are sufficient to inhibit methanol metabolism to formate, which is also mediated by alcohol dehydrogenase. Based on these results, concentrations of Antizol in humans in the range of 100 to 300 µmol/L (8.6-24.6 mg/L) have been targeted to assure adequate plasma concentrations for the effective inhibition of alcohol dehydrogenase. In healthy volunteers, oral doses of Antizol (10-20 mg/kg) significantly reduced the rate of elimination of moderate doses of ethanol, which is also metabolized through the action of alcohol dehydrogenase. DOSAGE AND ADMINISTRATION Treatment Guidelines If ethylene glycol or methanol poisoning is left untreated, the natural progression of the poisoning leads to accumulation of toxic metabolites, including glycolic and oxalic acids (ethylene glycol intoxication) and formic acid (methanol intoxication). These metabolites can induce metabolic acidosis, nausea/vomiting, seizures, stupor, coma, calcium oxaluria, acute tubular necrosis, blindness, and death. The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites. Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment. Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as Antizol, and correction of metabolic abnormalities. In patients with high ethylene glycol or methanol concentrations ( 50 mg/dL), significant metabolic acidosis, or renal failure, hemodialysis should be considered to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols. Treatment with Antizol Begin Antizol treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL. Hemodialysis Hemodialysis should be considered in addition to Antizol in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL. Patients should be dialyzed to correct metabolic abnormalities and to lower the ethylene glycol concentrations below 50 mg/dL. Discontinuation of Antizol Treatment Treatment with Antizol may be discontinued when ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH. Dosing of Antizol A loading dose of 15 mg/kg should be administered, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes (see Administration). Dosage with Renal Dialysis Antizol® (fomepizole) Injection is dialyzable and the frequency of dosing should be increased to every 4 hours during hemodialysis. Antizol Dosing in Patients Requiring Hemodialysis DOSE AT THE BEGINNING OF HEMODIALYSIS If <6 hours since last Antizol dose If 6 hours since last Antizol dose Do not administer dose Administer next scheduled dose DOSING DURING HEMODIALYSIS Dose every 4 hours DOSING AT THE TIME HEMODIALYSIS IS COMPLETED Time between last dose and the end of hemodialysis   <1 hour Do not administer dose at the end of hemodialysis 1–3 hours Administer 1/2 of next scheduled dose >3 hours Administer next scheduled dose MAINTENANCE DOSING OFF HEMODIALYSIS Give next scheduled dose 12 hours from last dose administered Administration Antizol solidifies at temperatures less than 25° C (77° F). If the Antizol solution has become solid in the vial, the solution should be liquefied by running the vial under warm water or by holding in the hand. Solidification does not affect the efficacy, safety, or stability of Antizol. Using sterile technique, the appropriate dose of Antizol should be drawn from the vial with a syringe and injected into at least 100 mL of sterile 0.9% sodium chloride injection or dextrose 5% injection. Mix well. The entire contents of the resulting solution should be infused over 30 minutes. Antizol, like all parenteral products, should be inspected visually for particulate matter prior to administration. Stability Antizol diluted in 0.9% sodium chloride injection or dextrose 5% injection remains stable and sterile for at least 24 hours when stored refrigerated or at room temperature. Antizol does not contain preservatives. Therefore, maintain sterile conditions, and after dilution do not use beyond 24 hours. Solutions showing haziness, particulate matter, precipitate, discoloration, or leakage should not be used. HOW SUPPLIED Antizol is supplied as a sterile, preservative-free solution for intravenous use as: Supplied in packages of four vials. Each vial contains 1.5 mL (1 g/mL) of fomepizole. NDC 68727-200-02 Store at controlled room temperature, 20° to 25° C (68° to 77° F) --------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: ANTIZOL 1GM/ML 1.5ML/VIAL 原产地英文药品名: FOMEPIZOLE 原产地英文化合物名称: 4-methylpyrazole 中文参考商品译名: ANTIZOL 1克/毫升 1.5毫升/瓶 中文参考药品译名: 甲吡唑 中文参考化合物名称: 4-甲基吡唑 生产厂家英文名: PALADIN LABS --------------------------------------------------------------- 产地国家: 日本 原产地英文商品名: Fomepizole(ホメピゾール点滴静注「タケダ」) 1GM/ML 1.5ML/VIAL 原产地英文药品名: FOMEPIZOLE 原产地英文化合物名称: 4-methylpyrazole 中文参考商品译名: Fomepizole(ホメピゾール点滴静注「タケダ」)1克/毫升 1.5毫升/瓶 中文参考药品译名: 甲吡唑 中文参考化合物名称: 4-甲基吡唑 生产厂家英文名: Takeda --------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: FOMEPIZOLE(ANTIZOL GENERIC) 1GM/ML 1.5ML/VIAL 原产地英文药品名: FOMEPIZOLE 原产地英文化合物名称: 4-methylpyrazole 中文参考商品译名: 甲吡唑(ANTIZOL仿制药) 1克/毫升 1.5毫升/瓶 中文参考药品译名: 甲吡唑 中文参考化合物名称: 4-甲基吡唑