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 详细处方信息以本药内容附件PDF文件（201072222570216.pdf）的“原文Priscribing Information”为准
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部分中文HYDROXYUREA处方资料（仅供参考）

药品名称
药品名称：羟基脲
英文名：Hydroxycarbamide
中文别名：氨基甲酰基羟胺、氨甲酰基胺、羟基脲素、羟脲
英文别名：Hudura、Hydrea、Hydroxicarbamidum、Hydroxyurea、Idroxicarbamidum
别名：氨基甲酰基羟胺、氨甲酰基胺、羟基脲素、羟脲、Hudura、Hydrea、Hydroxicarbamidum、Hydroxyurea、Idroxicarbamidum
性状：本品为白色结晶性粉末；无臭，味微涩。本品在水中易溶，在乙醇中微溶，在乙醚中不溶。
熔点: 本品的熔点为138～145℃，熔融时同时分解。

药物动力学
本品口服吸收较快，2小时后血清浓度已达高峰，6小时后消失，Ｔ1/2为3～4小时，可透过血脑屏障。主要在肝内代谢，由尿中排泄，4小时内能排出60％，12小时内80％。

适应症
主要用于治疗慢性粒细胞白血病(慢粒)、慢粒的加速期和急变期、真性红细胞增多症，另对头颈部原发性鳞癌、复发性转移性卵巢癌等亦有一定疗效; 与放射治疗同时应用或作为放射增敏剂，可增加治疗头颈部肿瘤的疗效。

用法用量
1．成人常用量
①慢粒，可根据患者用药前病情及白细胞数高低而决定剂量，一般开始剂量为每日按体重20—30mg/kg，1次或分2次口服，当白细胞下降至10×109/L以下时减量至约为每日20mg/kg，口服维持或改间歇服用。
②头颈癌、卵巢癌等，剂量为每次按体重60—80mg/kg或按体表面积2000—3000mg/平方米，每3日口服1次，单独服用或与放疗合用；亦可每日按体重20—30mg/kg，每日1次口服给药。
2. 小儿常用量尚未确定。
(1)对饮食牛奶、乳糖或对酒石黄(tartrazine)不能忍受者，对服用以乳糖或酒石黄作为赋形剂的本品胶囊亦可能不能忍受。
(2)患者避免接受死(或活)病毒疫苗的免疫接种，由于服用本品会使患者的免疫机制受抑制，对接种疫苗后产生抗体的反应亦减弱，且要经3个月后才能恢复，因而要停用本品3个月到1年后才可以考虑接种疫苗。本品与活病毒同时合用时，会增强病毒的增殖能力与毒性，因而白血病患者在获完全缓解后离最后一次化疗日3个月以上才能考虑活病毒疫苗接种。与患者密切接触的家属成员等亦应延缓口服脊髓灰质炎疫苗。
(3)服用本品时应适量增加液体的摄入量，以增加尿量及尿酸的排出。
(4)治疗前后及治疗期要严密定期随访血常规、血小板计数、血尿素氮、尿酸、肌酐浓度。
(5)本品的使用剂量必须根据患者对治疗的反应、耐受性等而调节。
(6)若服用本品已达6周仍未见效，应考虑停服本品而改换其他药物治疗。
(7)在服用本品过程中，若出现显著的粒细胞或血小板减低，例如白细胞下降至2.5×109／L或血小板下降至100×109/L以下，应暂停服用本品，并予相应的处理。
(8)与放疗合用时，应在放疗前7日开始给药，并严密观察血象，若出现严重的放疗不良反险亦应考虑减少或暂停服用本品。
任何疑问,请遵医嘱!

不良反应
(1)造血系统：较常见的有白细胞减少、贫血或红细胞形态的异常。白细胞减低通常在治疗开始约10日后发生，少数可合并感染，红细胞可出现巨幼红改变，形态类似恶性贫血，但其发生与维生素Bl2或叶酸缺乏无关。患者的血清铁清除率迟缓、红细胞对铁利用率减少。较少的有血小板减少。
(2)消化系统：较常见的有胃纳减退、恶心、呕吐，较少见的有便秘，长期服用本品可发生口腔粘膜炎、口腔溃疡等。
(3)其它：皮疹、红斑、瘙痒等皮肤反应及脱发较为少见，可偶然发生由于大量白细胞迅速崩溃而引起的血尿酸增高或尿酸性肾病，偶然可见到头痛、倦睡、头晕、幻觉、惊厥等神经毒性表现。骨髓抑制,白细胞及血小板减少.药热,胃肠道反应.有报道可引起睾丸缩小及致畸胎作用。其他还有色素沉着、超敏反应、局部损伤及对射线过敏等等。

禁忌
(1)由于本品有诱变、致畸胎、致癌的潜在可能，故应避免在妊娠初期的3个月内或哺乳期内服用。
(2)老年患者对本品较敏感，且肾功能可能较差，故服用本品时应适当减少剂量。
(3)下列情况禁用：水痘、带状疱疹及各种严重感染。下列情况应慎用：严重贫血未纠正前、骨髓抑制、肾功能不全、痛风、尿酸盐结石史等。有报道可引起睾丸缩小及致畸胎作用。

药物相互作用
(1)由于本品有可能提高服用者血尿酸的浓度，因此与别嘌醇、秋水仙碱、丙磺舒等合用治疗痛风时，必须调节上述抗痛风药物剂量，以控制痛风病变及血尿酸的浓度。本品与别嘌醇合用时能预防并逆转本品所致的高尿酸血症。
(2)与能引起白细胞或血小板减低的药物或放射疗法联合应用时，应严密观察患者的血象，并根据血白细胞及血小板数适当调节羟基脲的用量。(3)本品与烷化剂和放射线无交叉耐药性。

规格  
羟基脲500mg
(1).抗癌:一日40-60mg/kg,一周2次,一疗程6周.可大剂量间歇给药,每8小时1次,剂量60mg/kg,或6小时1次,剂量100mg/kg,24小时一疗程,间歇4-7天.
(2).顽固和脓疱性银屑病:日0.5-1.5g,4-8周一疗程.

HYDREA®
(hydroxyurea) Capsules, USP

DRUG DESCRIPTION
HYDREA® (hydroxyurea capsules, USP) is an antineoplastic agent available for oral use as capsules providing 500 mg hydroxyurea. Inactive ingredients: citric acid, colorants (D&C Yellow No. 10, FD&C Blue No. 1, FD&C Red 40, and D&C Red 28), gelatin, lactose, magnesium stearate, sodium phosphate, and titanium dioxide.

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INDICATIONS
Significant tumor response to HYDREA (hydroxyurea capsules, USP) has been demonstrated in melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary.

Hydroxyurea used concomitantly with irradiation therapy is intended for use in the local control of primary squamous cell (epidermoid) carcinomas of the head and neck, excluding the lip.

Procedures for proper handling and disposal of cytotoxic drugs should be considered. Several guidelines on this subject have been published.1-4

To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing HYDREA capsules. HYDREA capsules should not be opened. Personnel should avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. More information is available in the references listed below.

Because of the rarity of melanoma, resistant chronic myelocytic leukemia, carcinoma of the ovary, and carcinomas of the head and neck in pediatric patients, dosage regimens have not been established.

All dosage should be based on the patient's actual or ideal weight, whichever is less. Concurrent use of HYDREA with other myelosuppressive agents may require adjustment of dosages.

Solid Tumors
Intermittent Therapy
80 mg/kg administered orally as a single dose every third day

Continuous Therapy
20 to 30 mg/kg administered orally as a single dose daily

Concomitant Therapy with Irradiation
Carcinoma of the head and neck—80 mg/kg administered orally as a single dose every third day

Administration of hydroxyurea should begin at least seven days before initiation of irradiation and continued during radiotherapy as well as indefinitely afterwards provided that the patient may be kept under adequate observation and evidences no unusual or severe reactions.

Resistant Chronic Myelocytic Leukemia
Until the intermittent therapy regimen has been evaluated, CONTINUOUS therapy (2030 mg/kg administered orally as a single dose daily) is recommended.

An adequate trial period for determining the antineoplastic effectiveness of hydroxyurea is six weeks of therapy. When there is regression in tumor size or arrest in tumor growth, therapy should be continued indefinitely. Therapy should be interrupted if the white blood cell count drops below 2500/mm³, or the platelet count below 100,000/mm³. In these cases, the counts should be reevaluated after three days, and therapy resumed when the counts return to acceptable levels. Since the hematopoietic rebound is prompt, it is usually necessary to omit only a few doses. If prompt rebound has not occurred during combined HYDREA and irradiation therapy, irradiation may also be interrupted.

However, the need for postponement of irradiation has been rare; radiotherapy has usually been continued using the recommended dosage and technique. Severe anemia, if it occurs, should be corrected without interrupting hydroxyurea therapy. Because hematopoiesis may be compromised by extensive irradiation or by other antineoplastic agents, it is recommended that hydroxyurea be administered cautiously to patients who have recently received extensive radiation therapy or chemotherapy with other cytotoxic drugs.

Pain or discomfort from inflammation of the mucous membranes at the irradiated site (mucositis) is usually controlled by measures such as topical anesthetics and orally administered analgesics. If the reaction is severe, hydroxyurea therapy may be temporarily interrupted; if it is extremely severe, irradiation dosage may, in addition, be temporarily postponed. However, it has rarely been necessary to terminate these therapies.

Severe gastric distress, such as nausea, vomiting, and anorexia, resulting from combined therapy may usually be controlled by temporary interruption of hydroxyurea administration.

Renal Insufficiency
As renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of HYDREA in patients with renal impairment. (See PRECAUTIONS and CLINICAL PHARMACOLOGY.) Close monitoring of hematologic parameters is advised in these patients.

Hepatic Insufficiency
There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.

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HOW SUPPLIED
HYDREA® (hydroxyurea capsules, USP)
500 mg capsules in bottles of 100 (NDC 0003-0830-50).

Capsule identification number: 830. The cap is opaque green and the body is opaque pink. They are imprinted on both sections in black ink with “HYDREA” and “830.”

Storage
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Keep tightly closed.

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SIDE EFFECTS
Reported adverse reactions are bone marrow depression (leukopenia, anemia, and thrombocytopenia), gastrointestinal symptoms (stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation), and dermatological reactions such as maculopapular rash, skin ulceration, dermatomyositis-like skin changes, peripheral and facial erythema. Hyperpigmentation, atrophy of skin and nails, scaling, and violet papules have been observed in some patients after several years of long-term daily maintenance therapy with HYDREA. Skin cancer has been reported. Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy (see WARNINGS). Dysuria and alopecia have been reported. Large doses may produce moderate drowsiness. Neurological disturbances have occurred and were limited to headache, dizziness, disorientation, hallucinations, and convulsions. HYDREA may cause temporary impairment of renal tubular function accompanied by elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels. Abnormal bromsulphalein (BSP) retention has been reported. Fever, chills, malaise, edema, asthenia, and elevation of hepatic enzymes have also been reported.

Adverse reactions observed with combined hydroxyurea and irradiation therapy are similar to those reported with the use of hydroxyurea or radiation treatment alone. These effects primarily include bone marrow depression (anemia and leukopenia), gastric irritation, and mucositis. Almost all patients receiving an adequate course of combined hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression ( < 100,000 cells/mm³) has occurred in the presence of marked leukopenia. HYDREA may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.

The association of hydroxyurea with the development of acute pulmonary reactions consisting of diffuse pulmonary infiltrates, fever, and dyspnea has been reported. Pulmonary fibrosis also has been reported.

In HIV-infected patients who received hydroxyurea in combination with antiretroviral agents, in particular, didanosine plus stavudine, fatal and nonfatal pancreatitis and hepatotoxicity, and severe peripheral neuropathy have been reported. Patients treated with hydroxyurea in combination with didanosine, stavudine, and indinavir in Study ACTG 5025 showed a median decline in CD4 cells of approximately 100/mm³. (See WARNINGS and PRECAUTIONS.)

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DRUG INTERACTIONS
Prospective studies on the potential for hydroxyurea to interact with other drugs have not been performed.

Concurrent use of hydroxyurea and other myelosuppressive agents or radiation therapy may increase the likelihood of bone marrow depression or other adverse events. (See WARNINGS and ADVERSE REACTIONS.)

Since hydroxyurea may raise the serum uric acid level, dosage adjustment of uricosuric medication may be necessary.

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WARNINGS
Treatment with hydroxyurea should not be initiated if bone marrow function is markedly depressed (see CONTRAINDICATIONS). Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia. However, the recovery from myelosuppression is rapid when therapy is interrupted. It should be borne in mind that bone marrow depression is more likely in patients who have previously received radiotherapy or cytotoxic cancer chemotherapeutic agents; hydroxyurea should be used cautiously in such patients.

Patients who have received irradiation therapy in the past may have an exacerbation of postirradiation erythema.

In HIV-infected patients during therapy with hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. Hepatotoxicity and hepatic failure resulting in death have been reported during post-marketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided.

Peripheral neuropathy, which was severe in some cases, has been reported in HIV-infected patients receiving hydroxyurea in combination with antiretroviral agents, including didanosine, with or without stavudine.

Severe anemia must be corrected before initiating therapy with hydroxyurea.

Erythrocytic abnormalities: megaloblastic erythropoiesis, which is self-limiting, is often seen early in the course of hydroxyurea therapy. The morphologic change resembles pernicious anemia, but is not related to vitamin B12 or folic acid deficiency. Hydroxyurea may also delay plasma iron clearance and reduce the rate of iron utilization by erythrocytes, but it does not appear to alter the red blood cell survival time.

Elderly patients may be more sensitive to the effects of hydroxyurea, and may require a lower dose regimen (see PRECAUTIONS: Geriatric Use).

In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemia has been reported. It is unknown whether this leukemogenic effect is secondary to hydroxyurea or associated with the patient's underlying disease.

Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy. Due to potentially severe clinical outcomes for the cutaneous vasculitic ulcers reported in patients with myeloproliferative disease, hydroxyurea should be discontinued if cutaneous vasculitic ulcerations develop and alternative cytoreductive agents should be initiated as indicated.

Carcinogenesis and Mutagenesis
Hydroxyurea is genotoxic in a wide range of test systems and is thus presumed to be a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemia has been reported. It is unknown whether this leukemogenic effect is secondary to hydroxyurea or is associated with the patient's underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxyurea.

Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times the maximum recommended human oral daily dose on a mg/m² basis) thrice weekly for 6 months to female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.

Pregnancy
Drugs which affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents. The physician should carefully consider this possibility before administering this drug to male or female patients who may contemplate conception.

HYDREA can cause fetal harm when administered to a pregnant woman. Hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1fold of the human dose given on a mg/m² basis. Hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m² basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m² basis) in rabbits. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Hydroxyurea crosses the placenta. Single doses of ≥ 375 mg/kg (about 1.7 times the maximum recommended human daily dose on a mg/m² basis) to rats caused growth retardation and impaired learning ability. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

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PRECAUTIONS
General
Therapy with hydroxyurea requires close supervision. The complete status of the blood, including bone marrow examination, if indicated, as well as kidney function and liver function should be determined prior to, and repeatedly during, treatment. The determination of the hemoglobin level, total leukocyte counts, and platelet counts should be performed at least once a week throughout the course of hydroxyurea therapy. If the white blood cell count decreases to less than 2500/mm³, or the platelet count to less than 100,000/mm³, therapy should be interrupted until the values rise significantly toward normal levels. Severe anemia, if it occurs, should be managed without interrupting hydroxyurea therapy.

Hydroxyurea should be used with caution in patients with marked renal dysfunction. (See CLINICAL PHARMACOLOGY: Special Populations and DOSAGE AND ADMINISTRATION.)

Hydroxyurea is not indicated for the treatment of HIV infection; however, if HIV-infected patients are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended. Patients who develop signs and symptoms of pancreatitis should permanently discontinue therapy with hydroxyurea. (See WARNINGS and ADVERSE REACTIONS.)

An increased risk of hepatotoxicity, which may be fatal, may occur in patients treated with hydroxyurea, and in particular, in combination with didanosine and stavudine. This combination should be avoided.

Carcinogenesis, Mutagenesis, Impairment of Fertility
See WARNINGS for Carcinogenesis and Mutagenesis information.

Impairment of Fertility: Hydroxyurea administered to male rats at 60 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m² basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.

Pregnancy
Pregnancy Category D. (See WARNINGS.)

Nursing Mothers
Hydroxyurea is excreted in human milk.

Because of the potential for serious adverse reactions with hydroxyurea, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established.

Geriatric Use
Elderly patients may be more sensitive to the effects of hydroxyurea, and may require a lower dose regimen.

This drug is known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION: Renal Insufficiency).

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OVERDOSE
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have also been observed.

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CONTRAINDICATIONS
Hydroxyurea is contraindicated in patients with marked bone marrow depression, i.e., leukopenia ( < 2500 WBC) or thrombocytopenia ( < 100,000), or severe anemia.

HYDREA is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.

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 详细处方信息以本药内容附件PDF文件（201072222570216.pdf）的“原文Priscribing Information”为准
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2010年7月23日更新