部份中文丹曲林钠 处方资料（仅供参考）
英文药名: Dantrium(Dantrolene Sodium Capsules)

中文药名: 丹曲林钠胶囊
药品名称
【药品名称】
通用名：丹曲林钠胶囊
英文名：Dantrolene Sodium Capsules, Dantrium,Danlene,Dantamacrin.
【成分】丹曲林钠。
化学名称：1-[[[5-（4-硝基苯）-2-呋喃基]-2，4-咪唑啉二酮钠盐水合物。
分子式：C14H9N4NaO5.7/2H2O
分子量：399.29
【性状】本胶囊内容物为橙黄色结晶性粉末。
药理毒理
丹曲林钠是一种直接作用于骨骼肌的肌松剂。其主要作用部位是骨骼肌的肌浆网，通过抑制肌浆网释放钙离子而减弱肌肉收缩。
药代动力学
口服后吸收慢，不完全。经肝脏代谢后其代谢产物由肾脏排出体外，成人口服100mg后其半衰期(t1/2)平均为8.7小时，骨骼肌松弛的时间及程度与应用剂量相关。
适应症
用于各种原因引起的上运动神经元损伤所遗留的痉挛性肌张力增高状态，如脑卒中、脑外伤、脊髓损伤、脑性瘫痪、多发性脑血管硬化等。
用法用量
成人
*常规剂量
*口服给药痉挛：初始剂量一次25mg，一日1次；以后每周逐渐增加，最大剂量一次50mg，一日3次。
[国外用法用量参考]
成人
*常规剂量
*口服给药
1.痉挛：初始剂量一次25mg，一日1次，连用7日；之后一次25mg，一日3次，连用7日；之后一次50mg，一日3次，连用7日；之后一次100mg，一日3次。最大剂量一次100mg，一日4次。若45日内症状未改善应停药。
2.预防恶性高热：一日4-8mg/kg，分3-4次服用，手术前1-2日给予。末次给药应在术前3-4小时，并尽量减少服药饮水量。
3.预防恶性高热复发：一次1-2mg/kg，一日4次，连用1-3日。
*静脉注射恶性高热：最小初始剂量为1mg/kg。若症状未改善或复发，应重复上述剂量，累积剂量可达10mg/kg，症状改善时的累积剂量常为2.5mg/kg。
*静脉滴注预防恶性高热：麻醉前75分钟给予本药2.5mg/kg，滴注时间约1小时，手术过程中可能还需追加本药。
儿童
*常规剂量
*口服给药
1.痉挛：初始剂量一次0.5mg/kg，一日1次，连用7日；之后一次0.5mg/kg，一日3次，连用7日；之后一次1mg/kg，一日3次，连用7日；之后一次2mg/kg，一日3次。若45日内症状未改善应停药。
2.预防恶性高热复发：同成人。
*静脉注射恶性高热：同成人。
*静脉滴注预防恶性高热：同成人。
任何疑问，请遵医嘱！
给药说明
1.正使用雌激素的女性禁用本药。
2.本药与5%葡萄糖溶液和0.9%氯化钠溶液呈配伍禁忌。
不良反应
1.可见肌无力、嗜睡、眩晕、疲劳、腹泻。
2.罕见心动过速、血压波动、心包炎、胸腔积液、血尿、排尿障碍等，严重时应停药。
3.长期使用可能引起肝、肾功能损害。
[国外不良反应参考]
1.心血管系统可见心动过速、血压波动、静脉炎、心力衰竭和心包炎。
2.中枢神经系统可见头晕、眩晕、嗜睡、失眠、精神混乱、神经质、动作失调、醉感，通常为一过性，严重时应停药；还可见抑郁，罕见幻听、幻视。
3.呼吸系统可见呼吸抑制、窒息感，罕见肺水肿。
4.肌肉骨骼系统可见肌痛、背痛、肌无力。
5.泌尿生殖系统可见尿频、结晶尿、血尿、排尿困难、尿潴留、夜尿。
6.肝脏可见氨基转移酶升高、轻度高胆红素血症、黄疸、致命性肝损害。
7.胃肠道可见胃肠道梗阻、流涎、味觉改变、吞咽困难、食欲缺乏、恶心、呕吐、胃刺激、胃肠道出血、腹痛性痉挛、腹泻、便秘，严重时应暂时停药。
8.血液可见再生障碍性贫血、白细胞减少、血小板减少、淋巴瘤。
9.皮肤可见皮疹、荨麻疹、湿疹、痤疮、头发生长异常、出汗、光敏反应。
10.眼可见角膜浑浊、多泪、视力障碍和复视。
11.其它可见胸腔积液、寒战和发热，静脉注射可引起过敏、风疹和红斑。
注意事项
1.禁忌症
(1)对本药过敏者。
(2)严重肝、肾功能不全患者。
(3)功能性痉挛患者。
(4)关节病变及外伤后肌痉挛患者。
(5)35岁以上妇女。
(6)孕妇。
(7)哺乳期妇女。
(8)5岁以下儿童。
(9)活动性肝病(急性肝炎、活动性肝硬化)患者(国外资料)。
2.慎用
(1)有心血管史者。
(2)有呼吸系统疾病史者。
(3)有肝病史或肝功能不全者。
(4)肌萎缩侧索硬化患者(国外资料)。
3.药物对妊娠的影响孕妇禁用；美国药品和食品管理局(FDA)对本药的妊娠安全性分级为C级。
4.药物对哺乳的影响哺乳期妇女禁用。
5.用药前后及用药时应当检查或监测用药期间应定期检查肝、肾功能。
规格
25mg, 50mg, 100mg
Dantrium® (dantrolene sodium)capsules
Dantrium (dantrolene sodium) has a potential for hepatotoxicity, and should not be used in conditions other than those recommended. Symptomatic hepatitis (fatal and non-fatal) has been reported at various dose levels of the drug. The incidence reported in patients taking up to 400 mg/day is much lower than in those taking doses of 800 mg or more per day. Even sporadic short courses of these higher dose levels within a treatment regimen markedly increased the risk of serious hepatic injury.
Liver dysfunction as evidenced by blood chemical abnormalities alone (liver enzyme elevations) has been observed in patients exposed to Dantrium for varying periods of time. Overt hepatitis has occurred at varying intervals after initiation of therapy, but has been most frequently observed between the third and twelfth month of therapy. The risk of hepatic injury appears to be greater in females, in patients over 35 years of age, and in patients taking other medication(s) in addition to Dantrium (dantrolene sodium). Dantrium should be used only in conjunction with appropriate monitoring of hepatic function including frequent determination of SGOT or SGPT. If no observable benefit is derived from the administration of Dantrium after a total of 45 days, therapy should be discontinued. The lowest possible effective dose for the individual patient should be prescribed.
DESCRIPTION
The chemical formula of Dantrium (dantrolene sodium) is hydrated 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt. It is an orange powder, slightly soluble in water, but due to its slightly acidic nature the solubility increases somewhat in alkaline solution. The anhydrous salt has a molecular weight of 336. The hydrated salt contains approximately 15% water (3-1/2 moles) and has a molecular weight of 399. The structural formula for the hydrated salt is:
Dantrium is supplied in capsules of 25 mg, 50 mg, and 100 mg.
CLINICAL PHARMACOLOGY
In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the skeletal muscle at a site beyond the myoneural junction, directly on the muscle itself. In skeletal muscle, Dantrium dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum.
This effect appears to be more pronounced in fast muscle fibers as compared to slow ones, but generally affects both. A central nervous system effect occurs, with drowsiness, dizziness, and generalized weakness occasionally present. Although Dantrium does not appear to directly affect the CNS, the extent of its indirect effect is unknown. The absorption of Dantrium after oral administration in humans is incomplete and slow but consistent, and dose-related blood levels are obtained. The duration and intensity of skeletal muscle relaxation is related to the dosage and blood levels. The mean biologic half-life of Dantrium in adults is 8.7 hours after a 100-mg dose.
Specific metabolic pathways in the degradation and elimination of Dantrium in human subjects have been established. Metabolic patterns are similar in adults and pediatric patients. In addition to the parent compound, dantrolene, which is found in measurable amounts in blood and urine, the major metabolites noted in body fluids are the 5-hydroxy analog and the acetamido analog. Since Dantrium is probably metabolized by hepatic microsomal enzymes, enhancement of its metabolism by other drugs is possible.
However, neither phenobarbital nor diazepam appears to affect Dantrium metabolism.
Clinical experience in the management of fulminant human malignant hyperthermia, as well as experiments conducted in malignant hyperthermia susceptible swine, have revealed that the administration of intravenous dantrolene, combined with indicated supportive measures, is effective in reversing the hypermetabolic process of malignant hyperthermia.
Known differences between human and swine malignant hyperthermia are minor. The prophylactic administration of oral or intravenous dantrolene to malignant hyperthermia susceptible swine will attenuate or prevent the development of signs of malignant hyperthermia in a manner dependent upon the dosage of dantrolene administered and the intensity of the malignant hyperthermia triggering stimulus. Limited clinical experience with the administration of oral dantrolene to patients judged malignant hyperthermia susceptible, when combined with clinical experience in the use of intravenous dantrolene for the treatment of malignant hyperthermia and data derived from the above cited animal model experiments, suggests that oral dantrolene will also attenuate or prevent the development of signs of human malignant hyperthermia, provided that currently accepted practices in the management of such patients are adhered to (see INDICATIONS AND USAGE); intravenous dantrolene should also be available for use should the signs of malignant hyperthermia appear.
INDICATIONS AND USAGE
CONTRAINDICATIONS
Active hepatic disease, such as hepatitis and cirrhosis, is a contraindication for use of Dantrium. Dantrium is contraindicated where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain or maintain increased function.
WARNINGS
It is important to recognize that fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with Dantrium therapy.
At the start of Dantrium therapy, it is desirable to do liver function studies (SGOT, SGPT, alkaline phosphatase, total bilirubin) for a baseline or to establish whether there is pre-existing liver disease. If baseline liver abnormalities exist and are confirmed, there is a clear possibility that the potential for Dantrium hepatotoxicity could be enhanced, although such a possibility has not yet been established.
Liver function studies (e.g., SGOT or SGPT) should be performed at appropriate intervals during Dantrium therapy.
If such studies reveal abnormal values, therapy should generally be discontinued. Only where benefits of the drug have been of major importance to the patient, should reinitiation or continuation of therapy be considered. Some patients have revealed a return to normal laboratory values in the face of continued therapy while others have not.
If symptoms compatible with hepatitis, accompanied by abnormalities in liver function tests or jaundice appear, Dantrium should be discontinued.
If caused by Dantrium and detected early, the abnormalities in liver function characteristically have reverted to normal when the drug was discontinued.
Dantrium therapy has been reinstituted in a few patients who have developed clinical and/or laboratory evidence of hepatocellular injury. If such reinstitution of therapy is done, it should be attempted only in patients who clearly need Dantrium and only after previous symptoms and laboratory abnormalities have cleared. The patient should be hospitalized and the drug should be restarted in very small and gradually increasing doses. Laboratory monitoring should be frequent and the drug should be withdrawn immediately if there is any indication of recurrent liver involvement. Some patients have reacted with unmistakable signs of liver abnormality upon administration of a challenge dose, while others have not.
Dantrium should be used with particular caution in females and in patients over 35 years of age in view of apparent greater likelihood of drug-induced, potentially fatal, hepatocellular disease in these groups.
PRECAUTIONS
Dantrium should be used with caution in patients with impaired pulmonary function, particularly those with obstructive pulmonary disease, and in patients with severely impaired cardiac function due to myocardial disease. It should be used with caution in patients with a history of previous liver disease or dysfunction (see WARNINGS).
ADVERSE REACTIONS
The most frequently occurring side effects of Dantrium have been drowsiness, dizziness, weakness, general malaise, fatigue, and diarrhea. These are generally transient, occurring early in treatment, and can often be obviated by beginning with a low dose and increasing dosage gradually until an optimal regimen is established. Diarrhea may be severe and may necessitate temporary withdrawal of Dantrium therapy. If diarrhea recurs upon readministration of Dantrium, therapy should probably be withdrawn permanently.
Other less frequent side effects, uled according to system, are:
Gastrointestinal: Constipation, rarely progressing to signs of intestinal obstruction, GI bleeding, anorexia, swallowing difficulty, gastric irritation, abdominal cramps, nausea and/or vomiting.
Hepatobiliary: Hepatitis (see WARNINGS).
Neurologic: Speech disturbance, seizure, headache, light-headedness, visual disturbance, diplopia, alteration of taste, insomnia, drooling.
Cardiovascular: Tachycardia, erratic blood pressure, phlebitis, heart failure.
Hematologic: Aplastic anemia, anemia, leukopenia, lymphocytic lymphoma, thrombocytopenia.
Psychiatric: Mental depression, mental confusion, increased nervousness.
Urogenital: Increased urinary frequency, crystalluria, hematuria, difficult erection, urinary incontinence and/or nocturia, difficult urination and/or urinary retention.
Integumentary: Abnormal hair growth, acne-like rash, pruritus, urticaria, eczematoid eruption, sweating.
Musculoskeletal: Myalgia, backache.
Respiratory: Feeling of suffocation, respiratory depression.
Special Senses: Excessive tearing.
Hypersensitivity: Pleural effusion with pericarditis, anaphylaxis.
Other: Chills and fever.
The published literature has included some reports of Dantrium use in patients with Neuroleptic Malignant Syndrome (NMS). Dantrium capsules are not indicated for the treatment of NMS and patients may expire despite treatment with Dantrium capsules.
DRUG ABUSE AND DEPENDENCE
Drug abuse and dependency potential has not been eva luated in human or animal studies.
OVERDOSE
Symptoms which may occur in case of overdose include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g. lethargy, coma), vomiting, diarrhea, and crystalluria. For acute overdose, general supportive measures should be employed along with immediate gastric lavage.
Intravenous fluids should be administered in fairly large quantities to avert the possibility of crystalluria. An adequate airway should be maintained and artificial resuscitation equipment should be at hand. Electrocardiographic monitoring should be instituted, and the patient carefully observed. To date, no experience has been reported with dialysis and its value in Dantrium overdose is not known.