部份中文甲磺酸去铁胺处方资料（仅供参考） 除铁能 - Deferoxamine (Desferal) 中文名：除铁能注射剂，甲磺酸去铁胺注射剂 药理类别：重金属拮抗剂 学名：Deferoxamine 类别： INT , 剂量： VIAL ATC7药理类别：V03AC0​​1 deferoxamine 孕妇用药分级： C 级 在对照的动物研究试验中显示该药学物对胚胎有不良反应（致畸胎性或杀胚胎性或其他），但未进行人体怀孕妇女研究；或者尚无对照的人体怀孕妇女或动物研究试验。只有在可能的利益大于潜在的危险，才可使用此药物。 药理作用 本品为铁的螫合剂，它对铁离子(Fe+3)和铝离子(Al+3)都有很强的亲和力，可与之结合成水溶性螫合物，由肾脏快速安排出。 适应症 铁质沉着症、急性铁中毒、铝质沉着症。 用法用量 1. 急性中毒─1g肌注，接着每4小时0.5g共2剂，然后视需要每4～12小时一次 2. 静脉滴注─剂量和肌注相同，速度为1小时15mg/kg。 3. 慢性铁负荷量过多：肌注─1天0.5～1g；皮下─1天1g～2g。注射8～24小时以上，可使一种微量输注帮浦(Miniinfusion pump)。 药动力学 吸收 Desferioxamine(DFO)在静脉或皮下注射后，可迅速被吸收；但在黏膜完整未受损的胃肠道中，其吸收程度则极差。当进行腹膜透析时，DFO可经由透析液投予而吸收。 分布 健康志愿者肌肉注射10mg/kg DFO，30分钟后，可测得最高血中浓度为15.5umole/l(8.7ug/ml)。注射1小时后。ferrioxamine(FO)的最高血中浓度为3.7umole/l(2.3ug/ml)。体外实验显示，不到10%的DFO会与血清蛋白结合。 Desferioxamine可通过胎盘，但是否也会渗入乳汁则未知。 代谢 在铁蓄积症患者的尿中，可分离检测出4种DFO的代谢物。DFO的代谢过程中，会发生下列生物转化反应：经由转胺作用与氧化作用可生成一种酸代谢物，经由beta氧化作用，也可生成一种酸代谢。而经由去羧基作用与经由N-羟化作用则均生成中性代谢物。 清除 在健康志愿体，DFO及FO的排除均为双相的。在快速的第一相中，DFO之半衰期为1 小时，而FO之半衰期为2.4小时：在缓慢的第二相中，两者之半衰期均为6 小时。注射入体内之剂量，在6 小时内，22%以DFO及1%以FO之型式出现于尿中。 特殊临床状况之动力学 血色素沉着症之患者，肌肉注射10mg/kg DFO，1小时后，可测得DFO最高血中浓度为7.0umole/l(3.9ug/ml)，及FO最高血中浓度为15.7umole/l(9.6 ug/ml)。这类患者之DFO及FO排除半衰期分别为5.6小时与4.6小时。注射人体内之剂量，在6小时后，17%以DFO及12%以FO之型式于尿中排出。 肾衰期患者，于透析间隔期间，在1小时内，静脉输注40mg/kg DFO，其输注终了时之血中浓度为152 umole/l(85.2ug/ml)。若在透析之同时，输注投予DFO，则其血中浓度会降至13%与低于27%之间。以上这两种情况，FO之血中浓度均约为7.0umol/l(4.3ug/ml)；而aluminoxamine之血中浓度则约为2-3nmole/ml(1.2-1.8ug/ml)。停止静脉输注后，DFO的血中浓度以20分钟的半衰期快速下降，而有少部份之剂量以14小时之较长半衰期进行排除。Aluminoxamine之血中浓度持续上升至停止输注后48小时，并达到约7umole/l(4ug/ml)之浓度；接着经过透析之后，aluminoxamine的血中浓度可降至2.2umole/l(1.3ug/ml)。 副作用 皮疹、注射部位疼痛，低血压、心跳加速，呼吸窘迫症，视力、听觉受损等。 交互作用 1.与prochlorperazine(phenothiazine之衍生物)同时投予，会导致暂时性的意识损害、椎体异常、及昏迷。 2.合并使用Desferal与高剂量的维他命C(每日超过500mg)治疗严重慢性铁蓄积症患者，偶尔会发生心脏​​机能损害，此现象在停止使用维他命C之后即可恢复。 3.与Desferal结合之镓-67会自尿中快速排除，镓-67之显影效果会因此扭曲，建议在进行造影树之48小时前应停用Desferal。 禁忌 便秘、对本类药物及其赋型剂过敏者。 注意事项 1. 本品注射后排于尿中，会使尿液呈红色，如若呈红褐色，表示血清中铁质浓度仍高，还须继续治疗。 2. 长期或高剂量使用本品​​会造成慢性体内铁质过量，所以要定期做眼底镜检查及听力测验。 药品保存方式 药品应置于摄氏15 ~ 25度干燥处所；如发生变质或过期，不可再使用。 Desferal(deferoxamine mesylate)injection SPL UNCLASSIFIED SECTION Desferal® deferoxamine mesylate for injection USP Vials Rx only Prescribing Information  DESCRIPTION Desferal, deferoxamine mesylate USP, is an iron-chelating agent, available in vials for intramuscular, subcutaneous, and intravenous administration. Desferal is supplied as vials containing 500 mg and 2 g of deferoxamine mesylate USP in sterile, lyophilized form. Deferoxamine mesylate is N-[5-[3-[(5-aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-(N-hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid monomethanesul-fonate (salt), and its structural formula is Deferoxamine mesylate USP is a white to off-white powder. It is freely soluble in water and slightly soluble in methanol. Its molecular weight is 656.79. CLINICAL PHARMACOLOGY Desferal chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions. It readily chelates iron from ferritin and hemosiderin but not readily from transferrin; it does not combine with the iron from cytochromes and hemoglobin. Desferal does not cause any demonstrable increase in the excretion of electrolytes or trace metals. Theoretically, 100 parts by weight of Desferal is capable of binding approximately 8.5 parts by weight of ferric iron. Desferal is metabolized principally by plasma enzymes, but the pathways have not yet been defined. The chelate is readily soluble in water and passes easily through the kidney, giving the urine a characteristic reddish color. Some is also excreted in the feces via the bile. INDICATIONS AND USAGE Desferal is indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias. Acute Iron Intoxication Desferal is an adjunct to, and not a substitute for, standard measures used in treating acute iron intoxication, which may include the following: induction of emesis with syrup of ipecac; gastric lavage; suction and maintenance of a clear airway; control of shock with intravenous fluids, blood, oxygen, and vasopressors; and correction of acidosis. Chronic Iron Overload Desferal can promote iron excretion in patients with secondary iron overload from multiple transfusions (as may occur in the treatment of some chronic anemias, including thalassemia). Long-term therapy with Desferal slows accumulation of hepatic iron and retards or eliminates progression of hepatic fibrosis. Iron mobilization with Desferal is relatively poor in patients under the age of 3 years with relatively little iron overload. The drug should ordinarily not be given to such patients unless significant iron mobilization (e.g., 1 mg or more of iron per day) can be demonstrated. Desferal is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder. CONTRAINDICATIONS Known hypersensitivity to the active substance. Desferal is contraindicated in patients with severe renal disease or anuria, since the drug and the iron chelate are excreted primarily by the kidney. (See WARNINGS). WARNINGS Ocular and auditory disturbances have been reported when Desferal was administered over prolonged periods of time, at high doses, or in patients with low ferritin levels. The ocular disturbances observed have been blurring of vision; cataracts after prolonged administration in chronic iron overload; decreased visual acuity including visual loss, visual defects, scotoma; impaired peripheral, color, and night vision; optic neuritis, cataracts, corneal opacities, and retinal pigmentary abnormalities. The auditory abnormalities reported have been tinnitus and hearing loss including high frequency sensorineural hearing loss. In most cases, both ocular and auditory disturbances were reversible upon immediate cessation of treatment (see PRECAUTIONS/Information for Patients and ADVERSE REACTIONS/Special Senses). Visual acuity tests, slit-lamp examinations, funduscopy and audiometry are recommended periodically in patients treated for prolonged periods of time. Toxicity is more likely to be reversed if symptoms or test abnormalities are detected early. Increases in serum creatinine (possibly dose-related), acute renal failure and renal tubular disorders, associated with the administration of deferoxamine, have been reported in postmarketing experience (see ADVERSE REACTIONS). Monitor patients for changes in renal function. High doses of Desferal and concomitant low ferritin levels have also been associated with growth retardation. After reduction of Desferal dose, growth velocity may partially resume to pretreatment rates (see PRECAUTIONS/Pediatric Use). Adult respiratory distress syndrome, also reported in children, has been described following treatment with excessively high intravenous doses of Desferal in patients with acute iron intoxication or thalassemia. PRECAUTIONS General Flushing of the skin, urticaria, hypotension, and shock have occurred in a few patients when Desferal was administered by rapid intravenous injection. THEREFORE, DESFERAL SHOULD BE GIVEN INTRAMUSCULARLY OR BY SLOW SUBCUTANEOUS OR INTRAVENOUS INFUSION. Iron overload increases susceptibility of patients to Yersinia enterocolitica and Yersinia pseudotuberculosis infections. In some rare cases, treatment with Desferal has enhanced this susceptibility, resulting in generalized infections by providing these bacteria with a siderophore otherwise missing. In such cases, Desferal treatment should be discontinued until the infection is resolved. In patients receiving Desferal, rare cases of mucormycosis, some with a fatal outcome, have been reported. If any of the suspected signs or symptoms occur, Desferal should be discontinued, mycological tests carried out and appropriate treatment instituted immediately. In patients with severe chronic iron overload, impairment of cardiac function has been reported following concomitant treatment with Desferal and high doses of vitamin C (more than 500 mg daily in adults). The cardiac dysfunction was reversible when vitamin C was discontinued. The following precautions should be taken when vitamin C and Desferal are to be used concomitantly: Vitamin C supplements should not be given to patients with cardiac failure. Start supplemental vitamin C only after an initial month of regular treatment with Desferal. Give vitamin C only if the patient is receiving Desferal regularly, ideally soon after setting up the infusion pump. Do not exceed a daily vitamin C dose of 200 mg in adults, given in divided doses. Clinical monitoring of cardiac function is advisable during such combined therapy. In patients with aluminum-related encephalopathy and receiving dialysis, Desferal may cause neurological dysfunction (seizures), possibly due to an acute increase in circulating aluminum (see ADVERSE REACTIONS). Desferal may precipitate the onset of dialysis dementia. Treatment with Desferal in the presence of aluminum overload may result in decreased serum calcium and aggravation of hyperparathyroidism. Drug Interactions Vitamin C: Patients with iron overload usually become vitamin C deficient, probably because iron oxidizes the vitamin. As an adjuvant to iron chelation therapy, vitamin C in doses up to 200 mg for adults may be given in divided doses, starting after an initial month of regular treatment with Desferal (see PRECAUTIONS). Vitamin C increases availability of iron for chelation. In general, 50 mg daily suffices for children under 10 years old and 100 mg daily for older children. Larger doses of vitamin C fail to produce any additional increase in excretion of iron complex. Prochlorperazine: Concurrent treatment with Desferal and prochlorperazine, a phenothiazine derivative, may lead to temporary impairment of consciousness. Gallium-67: Imaging results may be distorted because of the rapid urinary excretion of Desferal-bound gallium-67. Discontinuation of Desferal 48 hours prior to scintigraphy is advisable. Information for Patients Patients experiencing dizziness or other nervous system disturbances, or impairment of vision or hearing, should refrain from driving or operating potentially hazardous machines (see ADVERSE REACTIONS). Patients should be informed that occasionally their urine may show a reddish discoloration. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies in animals have not been performed with Desferal. Cytotoxicity may occur, since Desferal has been shown to inhibit DNA synthesis in vitro. Pregnancy Category C Delayed ossification in mice and skeletal anomalies in rabbits were observed after Desferal was administered in daily doses up to 4.5 times the maximum daily human dose. No adverse effects were observed in similar studies in rats. There are no adequate and well-controlled studies in pregnant women. Desferal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Desferal is administered to a nursing woman. Pediatric Use Pediatric patients receiving Desferal should be monitored for body weight and growth every 3 months. Safety and effectiveness in pediatric patients under the age of 3 years have not been established (see INDICATIONS AND USAGE, WARNINGS, PRECAUTIONS/Drug Interactions/Vitamin C, and ADVERSE REACTIONS). Geriatric Use Clinical Studies of Desferal did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from the younger subjects. Postmarketing reports suggest a possible trend for an increased risk of eye disorders in the geriatric population, specifically the occurrence of color blindness, maculopathy, and scotoma. However, it is unclear if these eye disorders were dose related. Although the number of reports was very small, certain elderly patients may be predisposed to eye disorders when taking Desferal. Postmarketing reports also suggest that there may be an increased risk of deafness and hearing loss in the geriatric population. (see ADVERSE REACTIONS). In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Hepatic Impairment No studies have been performed in patients with hepatic impairment. ADVERSE REACTIONS The following adverse reactions have been observed, but there are not enough data to support an estimate of their frequency. At the Injection Site: Localized irritation, pain, burning, swelling, induration, infiltration, pruritus, erythema, wheal formation, eschar, crust, vesicles, local edema. Injection site reactions may be associated with systemic allergic reactions (see Body as a Whole, below). Hypersensitivity Reactions and Systemic Allergic Reactions: Generalized rash, urticaria, anaphylactic reaction with or without shock, angioedema. Body as a Whole: Local injection site reactions may be accompanied by systemic reactions like arthralgia, fever, headache, myalgia, nausea, vomiting, abdominal pain, or asthma. Infections with Yersinia and Mucormycosis have been reported in association with Desferal use (see PRECAUTIONS). Cardiovascular: Tachycardia, hypotension, shock. Digestive: Abdominal discomfort, diarrhea, nausea, vomiting. Hematologic: Blood dyscrasia (thrombocytopenia, leucopenia). Hepatic: Increased transaminases, hepatic dysfunction. Musculoskeletal: Muscle spasms. Growth retardation and bone changes (e.g., metaphyseal dysplasia) are common in chelated patients given doses above 60 mg/kg, especially those who begin iron chelation in the first three years of life. If doses are kept to 40 mg/kg or below, the risk may be reduced (see WARNINGS, PRECAUTIONS/Pediatric Use). Nervous System: Neurological disturbances including dizziness, peripheral sensory, motor, or mixed neuropathy, paresthesias, seizures; exacerbation or precipitation of aluminum-related dialysis encephalopathy (see PRECAUTIONS/Information for Patients). Special Senses: High-frequency sensorineural hearing loss and/or tinnitus are uncommon if dosage guidelines are not exceeded and if dose is reduced when ferritin levels decline. Visual disturbances are rare if dosage guidelines are not exceeded. These may include decreased acuity, blurred vision, loss of vision, dyschromatopsia, night blindness, visual field defects, scotoma, retinopathy (pigmentary degeneration), optic neuritis, and cataracts (see WARNINGS). Respiratory: Acute respiratory distress syndrome (with dyspnea, cyanosis, and/or interstitial infiltrates) (see WARNINGS). Skin: Very rare generalized rash. Urogenital: Dysuria, acute renal failure, increased serum creatinine and renal tubular disorders (see CONTRAINDICATIONS and WARNINGS). Postmarketing Reports There are postmarketing reports of deferoxamine-associated renal dysfunction, including renal failure. Monitor patients for changes in renal function (e.g., increased serum creatinine). OVERDOSAGE Acute Toxicity Intravenous LD50s (mg/kg): mice, 287; rats, 329. Signs and Symptoms Inadvertent administration of an overdose or inadvertent intravenous bolus administration/rapid intravenous infusion may be associated with hypotension, tachycardia and gastrointestinal disturbances; acute but transient loss of vision, aphasia, agitation, headache, nausea, pallor, CNS depression including coma, bradycardia and acute renal failure have been reported. Acute respiratory distress syndrome has been reported following treatment with excessively high intravenous doses of Desferal in patients with acute iron intoxication and in patients with thalassemia. Treatment There is no specific antidote. Desferal should be discontinued and appropriate symptomatic measures undertaken. Desferal is readily dialyzable. DOSAGE AND ADMINISTRATION Acute Iron Intoxication Intramuscular Administration This route is preferred and should be used for ALL PATIENTS NOT IN SHOCK. A dose of 1000 mg should be administered initially. This may be followed by 500 mg every 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered every 4-12 hours. The total amount administered should not exceed 6000 mg in 24 hours. For reconstitution instructions for intramuscular administration see Table 1. Intravenous Administration THIS ROUTE SHOULD BE USED ONLY FOR PATIENTS IN A STATE OF CARDIOVASCULAR COLLAPSE AND THEN ONLY BY SLOW INFUSION. THE RATE OF INFUSION SHOULD NOT EXCEED 15 MG/KG/HR FOR THE FIRST 1000 MG ADMINISTERED. SUBSEQUENT IV DOSING, IF NEEDED, MUST BE AT A SLOWER RATE, NOT TO EXCEED 125 MG/HR. For reconstitution instructions for intravenous administration see Table 2. The reconstituted solution is added to physiologic saline, (e.g., 0.9% sodium chloride, 0.45% sodium chloride), glucose in water, or Ringer’s lactate solution. An initial dose of 1000 mg should be administered at a rate NOT TO EXCEED 15 mg/kg/hr. This may be followed by 500 mg over 4 hours for two doses. Depending upon the clinical response, subsequent doses of 500 mg may be administered over 4-12 hours. The total amount administered should not exceed 6000 mg in 24 hours. As soon as the clinical condition of the patient permits, intravenous administration should be discontinued and the drug should be administered intramuscularly. Chronic Iron Overload Subcutaneous Administration A daily dose of 1000-2000 mg (20-40 mg/kg/day) should be administered over 8-24 hours, utilizing a small portable pump capable of providing continuous mini-infusion. The duration of infusion must be individualized. In some patients, as much iron will be excreted after a short infusion of 8-12 hours as with the same dose given over 24 hours. For reconstitution instructions for subcutaneous administration see Table 3. Intravenous Administration The standard recommended method of Desferal administration is via slow subcutaneous infusion over 8 – 12 hours. In patients with intravenous access, the daily dose of Desferal can be administered intravenously. The standard dose is 20 – 40 mg/kg/day for children and 40 – 50 mg/kg/day over 8 – 12 hours in adults for 5 – 7 days per week. In children, average doses should not exceed 40 mg/kg/day until growth has ceased. In adults, average doses should not exceed 60 mg/kg/day. The intravenous infusion rate should not exceed 15 mg/kg/hour. For reconstitution instructions for intravenous administration see Table 2. In patients who are poorly compliant, Desferal may be administered prior to or following same day blood transfusion (for example 1 gram over 4 hours on the day of transfusion); however, the contribution of this mode of administration to iron balance is limited. Desferal should not be administered concurrently with the blood transfusion as this can lead to errors in interpreting side effects such as rash, anaphylaxis and hypotension. Intramuscular Administration A daily dose of 500-1000 mg may be administered intramuscularly. The total daily dose should not exceed 1000 mg. For reconstitution instructions for intramuscular administration see Table 1. Reconstitution and Preparation Table 1: Preparation for Intramuscular Administration       RECONSTITUTE DESFERAL WITH STERILE WATER FOR INJECTION Vial Size Amount of Sterile Water for Injection Required for Reconstitution Total Drug Content after Reconstitution Final Concentration per mL after Reconstitution 500 mg 2 mL 500 mg/2.35 mL 213 mg/mL 2 grams 8 mL 2 grams/9.4 mL 213 mg/mL Table 2: Preparation for Intravenous Administrations RECONSTITUTE DESFERAL WITH STERILE WATER FOR INJECTION Vial Size Amount of Sterile Water for Injection Required for Reconstitution Total Drug Content after Reconstitution Final Concentration per mL after Reconstitution 500 mg 5 mL 500 mg/5.3 mL 95 mg/mL 2 grams 20 mL 2 grams/21.1 mL 95 mg/mL Table 3: Preparation for Subcutaneous Administration       RECONSTITUTE DESFERAL WITH STERILE WATER FOR INJECTION Vial Size Amount of Sterile Water for Injection Required for Reconstitution Total Drug Content after Reconstitution Final Concentration per mL after Reconstitution 500 mg 5 mL 500 mg/5.3 mL 95 mg/mL 2 grams 20 mL 2 grams/21.1 mL 95 mg/mL The reconstituted Desferal solution is an isotonic, clear and colorless to slightly- yellowish solution. The drug should be completely dissolved before the solution is withdrawn. Desferal reconstituted with Sterile Water for Injection IS FOR SINGLE USE ONLY. Discard unused portion. The product should be used immediately after reconstitution (commencement of treatment within 3 hours) for microbiological safety. When reconstitution is carried out under validated aseptic conditions (in a sterile laminar flow hood using aseptic technique), the product may be stored at room temperature for a maximum period of 24 hours before use. Do not refrigerate reconstituted solution. Reconstituting Desferal in solvents or under conditions other than indicated may result in precipitation. Turbid solutions should not be used. HOW SUPPLIED Vials - each containing 500 mg of sterile, lyophilized deferoxamine mesylate Cartons of 4 vials……………………………………………NDC 0078-0467-91 Vials - each containing 2 g of sterile, lyophilized deferoxamine mesylate Cartons of 4 vials…………………………………NDC 0078-0347-51 Do not store above 25°C (77°F). http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=A7174843-5965-49FC-B842-F7EFF7B48BBC 排鐵劑 Deferoxamine Deferoxamine (DFO，Desferal®，除铁能)： 在1960年从一种链霉菌 (Streptomyces pilosus ) 纯化出来，是第一个被使用在人体的注 射型排铁剂。属于hexadentate类的药物，与铁离子以1：1的方式结合。 1963年开始临床使用以来，至今仍是治疗铁质过度负担的首选药物，安全且有效。使用于因铁质沉积所致的心脏衰竭、肝硬化、内分泌系统破坏等并发症都能有效加以预防与治疗，尤其能减缓心脏衰竭的发生，被认为是延长病患寿命的主要因素。 一般建议剂量在小孩是20~40毫克/公斤/天 (若小于五岁，使用剂量不得超过40毫克/公斤/天)，成人使用剂量为30~60毫克/公斤/天。长期使用的安全性,少数病患会出现局部或全身性过敏反应，长期高剂量治疗时可能会出现听觉、视觉功能障碍，感染以及影响骨骼生长。 因此在使用此药物时，需每1~3个月追踪血清储铁蛋白(Serum ferritin)以评估排铁状况，每年接受听力、视力以及生长评估检查。然而此药物半衰期短 (约20~30分钟) 加上无法口服吸收，所以必须长时间皮下或静脉注射来达到排铁的效果。 一般建议每次注射时间为8~10小时，每周5~7天。因为DFO使用上的不方便性使得约有1/3到1/2的病人无法配合使用，进而影响其排铁效果。因此为了使用上的方便性，口服排铁剂的的研究开​​发也就蕴育而生。再加上评估体内含铁量的方法逐步进展，使得近几年来口服排铁剂的临床试验如雨后春笋般的快速发展。