中文药名: 甲泼尼龙琥珀酸钠无菌粉

生产厂家: Pfizer

通用名称：注射用甲泼尼龙琥珀酸钠
商品名称：米乐松
英文名称：Methylprednisolone Sodium Succinate for Injection
成份: 本品主要成份为甲泼尼龙琥珀酸钠，化学名称：11β，17α，21-三羟基 -6α- 甲基孕甾-1，4-二烯-3，20-二酮-21-琥珀酸钠。
性状: 本品为白色或类白色的疏松块状物。 

药理毒理

药理作用
本品为人工合成的、抗炎作用强的注射用类固醇。除了具有糖皮质激素的药理作用外，与泼尼松龙相比，有更强的抗炎作用和较弱的水、钠潴留作用。
毒理研究
某些动物试验表明，妊娠期间服用大剂量皮质类固醇可能引起胎儿畸形。
药代动力学

据国外文献资料报道：
在体内，胆碱酯酶迅速将甲泼尼龙琥珀酸钠水解为游离的甲泼尼龙。
在体内，甲泼尼龙与白蛋白及皮质激素转运蛋白形成弱的、可解离的结合，结合型甲泼尼龙约为40~90%。
以20分钟静脉滴注甲泼尼龙30mg/kg，或以30分钟至60分钟静脉滴注甲泼尼龙1g，约15分钟后血浆峰浓度近20μg/ml。静脉推注甲泼尼龙40mg，约25分钟后血浆峰浓度达到42~47μg/100ml。肌肉推注甲泼尼龙40mg，约120分钟后血浆峰浓度达到34μg/100ml。肌肉注射后的血浆峰浓度低于静脉注射，但肌肉注射后血浆药物水平持续时间较长，因此两种给药方法可给予等量的甲泼尼龙。考虑到糖皮质激素的作用机制，两种给药方法间这些细小的差异在临床上无重要意义。通常在给药 4~6 小时后可以观察到临床反应；而在治疗哮喘时，给药1或2小时后即可观察到第一个有效的结果。甲泼尼龙琥珀酸钠的血浆半衰期为2.3~4小时，并且与给药方法无关。
甲泼尼龙属中效糖皮质激素，其生物半衰期为12~36小时。糖皮质激素的细胞内活性使得它们的血浆半衰期与药理半衰期有显著差异。即使在血浆中已检测不到糖皮质激素，其药理活性仍持续存在。糖皮质激素抗炎活性的持续时间与下丘脑-垂体-肾上腺（HPA）轴被抑制的时间相同。
甲泼尼龙与可的松同样经肝脏代谢。主要代谢产物为20β-羟基甲泼尼龙和20β-羟基-6α-甲基泼尼松。这些代谢产物以葡萄糖醛酸盐、硫酸盐和非结合型化合物的形式随尿液排出。
静脉注射14C标记的甲泼尼龙，96小时后在尿液中可回收75%总放射活性，5天后在粪便中可回收9%，20%的放射活性存在于胆汁内。
适应症

除非用于某些内分泌失调的疾病的替代治疗，糖皮质激素仅仅是一种对症治疗的药物。
1、抗炎治疗：
-风湿性疾病：作为短期使用的辅助药物（帮助患者渡过急性期或危重期），用于：创伤后骨关节炎；骨关节炎引发的滑膜炎；类风湿性关节炎，包括幼年型类风湿性关节炎（个别患者可能需要低剂量维持治疗）；急性或亚急性滑囊炎；上踝炎；急性非特异性踺鞘炎；急性痛风性关节炎；银屑病关节炎；强直性脊柱炎。
-胶原疾病（免疫复合物疾病）：用于下列疾病危重期或维持治疗：系统性红斑狼疮（和狼疮性肾炎）；急性风湿性心肌炎；全身性皮肌炎（多发性肌炎）；结节性多动脉炎；古德帕斯彻综合征（Good　pasture′s Syndrome）。
-皮肤疾病：天疱疮；严重的多形红斑（Stevens-Johnson 综合征）；剥脱性皮炎；大疱疱疹性皮炎；严重的脂溢性皮炎；严重的银屑病；蕈样真菌病；荨麻疹。
-过敏状态：用于控制如下以常规疗法难以处理的严重的或造成机能损伤的过敏性疾病；支气管哮喘；接触性皮炎；异位性皮炎；血清病；季节性或全年性过敏性鼻炎；
药物过敏反应；荨麻疹样输血反应；急性非感染性喉头水肿（肾上腺素为首选药物）。
-眼部疾病：严重的眼部急慢性过敏和炎症，例如：眼部带状疱疹；虹膜炎、虹膜睫状体炎；脉络膜视网膜炎；扩散型后房色素层炎和脉络膜炎；视神经炎；交感性眼炎。
-胃肠道疾病：帮助患者渡过以下疾病的危重期；溃疡性结肠炎（全身治疗）；局限性回肠炎（全身治疗）。
-呼吸道疾病：肺部肉瘤病；铍中毒；与适当的抗结核化疗法合用于暴发性或扩散型肺结核；其它方法不能控制的吕弗勒氏综合症（Loffler’s Syndrome）；吸入性肺炎。
-水肿状态：用于无尿毒症的自发性或狼疮性肾病综合征的利尿及缓解蛋白尿。
2、免疫抑制治疗：
-器官移植。
3、治疗血液疾病及肿瘤：
-血液疾病：获得性（自身免疫性）溶血性贫血；成人自发性血小板减少性紫癜（仅允许静脉注射，禁忌肌内注射）；成人继发性血小板减少；成红细胞减少（红细胞性贫血）；先天性（红细胞）再生不良性贫血。
-肿瘤：用于下列疾病的姑息治疗；成人白血病和淋巴瘤；儿童急性白血病。
4、治疗休克：
-肾上腺皮质机能不全诱发的休克，或因肾上腺皮质机能不全而使休克对常规治疗无反应（氢化可的松为常用药；若不希望有盐皮质激素活性，可使用甲基强的松龙）。
对常规治疗无反应的失血性、创伤性及手术性休克。尽管没有完善的（双盲对照）临床研究，但动物实验的资料显示甲泼尼龙可能对常规疗法（例如：补液）无效的休克有效。同时请参见“注意事项”中的“感染性休克”部分。
5、其它：
-神经系统：由原发性或转移性肿瘤、和（或）手术及放疗引起的脑水肿；多发性硬化症急性危重期；急性脊髓损伤。治疗应在创伤后8小时内开始。
-与适当的抗结核化疗法合用，用于伴有蛛网膜下腔阻塞或趋于阻塞的结核性脑膜炎。
-累及神经或心肌的旋毛虫病。
-预防癌症化疗引起的恶心、呕吐。
6、内分泌失调：原发性或继发性肾上腺皮质机能不全；急性肾上腺皮质机能不全；（以上疾病氢化可的松或可的松为首选药物，如有需要，合成的糖皮质激素可与盐皮质激素合用。）
已知患有或可能患有肾上腺皮质机能不全的患者，在手术前和发生严重创伤或疾病时给药。先天性肾上腺增生；非化脓性甲状腺炎；癌症引起的高钙血症。
用法用量

本品必须遵医嘱用药。
*作为对生命构成威胁的情况的辅助药物时：推荐剂量为15~30mg/kg体重， 应至少30分钟作静脉注射。根据临床需要，此剂量可在医院内于48小时内每隔 4~6 小时重复一次（参见“注意事项”）。
*冲击疗法：用于疾病严重恶化和（或）对常规治疗（如：非甾体类药，金盐及青霉胺）无反应的疾病。
建议方案：
-类风湿性关节炎：一日1g，静脉注射，用1、2、3或4日；或一月1g，静脉注射，用6个月。因大剂量皮质类固醇能引起心律失常，因此仅限在医院内使用本治疗方法，以便及时作心电图及除颤。每次应至少用30分钟给药，如果治疗后一周内病情无好转， 或因病情需要，本治疗方案可重复。
*预防肿瘤化疗引起的恶心及呕吐；
建议方案：
-关于化疗引起的轻至中度致吐：在化疗前1小时、以至少5分钟静脉注射250mg 甲泼尼龙。在给予首剂甲泼尼龙时，可同时给予氯化酚噻嗪以增强效果。
-关于化疗引起的重度致吐：化疗前1小时、化疗开始时及化疗结束后，以至少5分钟静脉注射甲泼尼龙，同时给予适量的灭吐灵或丁酰苯类药物，随后在化疗开始时及结束时分别静脉注射250mg甲泼尼龙。
*急性脊髓损伤：
治疗应在损伤后8小时内开始。初始剂量为30mg/kg体重甲泼尼龙，在持续的医疗监护下，以15分钟静脉注射。
仅此适应症能以此速度进行大剂量注射，并且要在心电监护并能提供除颤器的情况下进行。
短时间内静脉注射大剂量甲泼尼龙（以少于10分钟的时间给予大于500mg的甲泼尼龙）可能引起心律失常、循环性虚脱及心脏停搏。
大剂量注射后暂停45分钟，随后以每小时5.4mg/kg体重的速度持续静脉滴注23小时。应选择与大剂量注射不同的注射部位安置输液泵。
*其它适应症的初始剂量从10mg到500mg不等，以临床疾病而变化。大剂量甲基强的松龙可用于短期内控制某些急性重症疾病，如：支气管哮喘、血清病、荨麻疹样输血反应及多发性硬化症急性恶化期。小于等于250mg的初始剂量应至少用5分钟静脉注射；大于250mg的初始剂量应至少用30分钟静脉注射。根据患者的反应及临床需要，间隔一段时间后可静脉注射或肌内注射下一剂量。皮质类固醇只可辅助，不可替代常规疗法。婴儿和儿童可减量，但依据应是疾病的严重程度及患者的反应，而不是年龄和体型。每24小时的总量不应少于0.5mg/kg。
用药数天后，必须逐步递减用药剂量或逐步停药。如果慢性疾病自发缓解，应停止治疗。长期治疗的患者应定期作常规实验室检查，如：尿常规，饭后2小时血糖，血压和体重，胸部X线检查。有溃疡史或明显消化不良的患者应作上消化道X线检查，中断长期治疗的患者也需要作医疗监护。
甲泼尼龙溶液可静脉注射或肌内注射给药，或静脉滴注给药，紧急情况的治疗应使用静脉注射。溶液的制备：临用前用灭菌注射用水或5%葡萄糖注射液或0.9%氯化钠注射液溶解。起始治疗方法可能是用至少5分钟（剂量小于或等于250mg）或至少30分钟（剂量大于250mg）静脉注射甲泼尼龙；下一剂量可能减少并用同样方法给药。如果需要，该药可稀释后给药，方法为将已溶解的药品与5%葡萄糖注射液或0.9%氯化钠注射液混合，混合后立即使用。
任何疑问，请遵医嘱！
不良反应

据国外研究资料报道：
可能会观察到全身性不良反应。 尽管在短期时很少出现，但仍应仔细随访，这是类固醇治疗的随访工作的一部分，并不针对某一药物。糖皮质激素（如甲泼尼龙）可能的不良反应为：
*体液与电解质紊乱：相当于可的松和氢化可的松，合成的衍生物（如甲泼尼龙）较少发生盐皮质激素作用。限钠、补钾的饮食可能是必要的。所有皮质类固醇都会增加钙离子的丧失。
钠潴留；体液潴留；某些敏感患者的充血性心力衰竭；钾离子丧失；低钾性碱中毒；高血压。
*肌肉骨骼系统：
肌无力；类固醇性肌病；骨质疏松；压迫性脊椎骨折；无菌性坏死；病理性骨折；
*胃肠道：
可能发生穿孔或出血的消化道溃疡；消化道出血；胰腺炎；食管炎；肠穿孔；
*皮肤病：妨碍伤口愈合；皮肤变薄脆弱；瘀点和瘀斑；反复局部皮下注射可能引起局部皮肤萎缩。
*神经病：颅内压升高；假性脑肿瘤；癫痫发作；眩晕；
服用皮质类固醇可能出现下列精神紊乱的症状：欣快感、失眠、情绪变化、个性改变及重度抑郁直至明显的精神病表现。
*内分泌：月经失调；出现柯兴氏体态；抑制儿童生长；抑制垂体-肾上腺皮质轴；糖耐量降低；引发潜在的糖尿病；增加糖尿病患者对胰岛素和口服降糖药的需求。
*眼部：
长期使用糖皮质激素可能引起后房囊下白内障、青光眼（可能累及视神经），并增加眼部继发性真菌或病毒感染的机会。为防止角膜穿孔，糖皮质激素应慎用于眼部单纯疱疹患者；眼内压增高；眼球突出。
*代谢方面：
因蛋白质分解造成的负氮平衡。
*免疫系统：掩盖感染；潜在感染发作；机会性感染；过敏反应；可能抑制皮试反应。
*以下不良反应与胃肠道外给予皮质类固醇激素有关：
过敏反应，伴有或不伴有循环性虚脱；心脏停搏；支气管痉挛；低血压或高血压；心律不齐。
据报道，短时间内静脉注射大剂量甲泼尼龙（10分钟内所给的量超过0.5g）会引起心律不齐和（或）循环性虚脱和（或）心脏停搏。也有报道大剂量甲基强的松龙会引起心动过缓，但与给药速度或滴注时间可能无关。另有报道大剂量糖皮质激素会引起心动过速。
禁忌

全身性霉菌感染及已知对药物成分过敏者禁用。特殊危险人群：
对属于下列特殊危险人群的患者应采取严密的医疗监护并应尽可能缩短疗程（同时参见“注意事项”和“不良反应”）；儿童；糖尿病患者；高血压患者；有精神病史者；有明显症状的某些感染性疾病，如结核病；或有明显症状的某些病毒性疾病，如波及眼部的疱疹及带状疱疹。
注意事项

-特殊危险人群：
对属于下列特殊危险人群的患者应采取严密的医疗监护并应尽可能缩短疗程：
-儿童：长期每天服用分次给予糖皮质激素会抑制儿童的生长，这种治疗方法只可用于非常危重的情况。
-糖尿病患者：引发潜在的糖尿病或增加糖尿病患者对胰岛素和口服降糖药的需求。
-高血压患者：使动脉性高血压病情恶化。
-有精神病史者：已有的情绪不稳和精神病倾向可能会因服用皮质类固醇而加重。
-因糖皮质激素治疗的并发症与用药的剂量和时间有关，对每个病例均需就剂量、疗程及每日给药还是隔日给药来权衡利弊。
-采用皮质类固醇治疗异常紧急状况的患者，在紧急状况发生前、发生时和发生后需加大速效皮质类固醇的剂量。
-皮质类固醇可能会掩盖感染的若干症状，治疗期间亦可能发生新的感染。皮质类固醇可能会减弱抵抗力而无法使感染局限。
-一项为明确甲泼尼龙对感染性休克的有效性所作的研究发现，参加研究时已有血清肌酐水平升高或激素治疗开始后有继发感染的病人死亡率较高。
-甲泼尼龙用于结核活动期患者时，应仅限于暴发性或扩散型结核病，皮质激素可与适当的抗结核病药物联用以控制病情，如皮质类固醇用于结核病潜伏期或结核菌素试验阳性的患者时，必须小心观察以防病情复发。此类患者长期服用皮质类固醇期间应接受化学预防治疗。
-由于极少数经胃肠道外接受类固醇治疗的患者发生过过敏反应（如支气管痉挛），因此在给药前应采取适当的预防措施，特别对有药物过敏史的患者。
-逐量递减用药量可减少因用药而产生的肾上腺皮质机能不全现象。这种相对机能不全现象可在停药后持续数月，因而在此期间一旦出现紧急情况应恢复服药；由于盐皮质激素的分泌也可能被抑制，应同时补充盐份和（或）给与盐皮质激素。
-甲状腺功能减退和肝硬化会增强皮质类固醇的作用。
-皮质类固醇应慎用于眼部单纯疱疹患者，以免引起角膜穿孔。
-糖皮质激素应慎用于非特异性溃疡性结肠炎的患者。
-应注意观察长期接受类固醇激素治疗的婴儿及儿童的生长发育情况。
-某些制剂中含苯甲醇。据报道苯甲醇与致命的早产儿“喘息综合症”（以持续喘息为特征的呼吸紊乱）有关。
-在解释整套生物学检查和数据时（如：皮试，甲状腺素水平），应将类固醇治疗因素考虑在内。
-通常情况下应尽量缩短疗程（同时参见“用法用量”）。长期治疗后停药也应在医疗监护下进行（逐量递减，评估肾上腺皮质功能）。肾上腺皮质机能不全最重要的症状为无力、体位性低血压及抑郁。
-避免在三角肌注射，因为此部位皮下萎缩发病率高。
-尽管视力障碍属极少见的不良反应，但仍建议患者小心驾驶汽车和操作机器。
-配伍禁忌：
静脉注射甲泼尼龙溶液时的相容性与稳定性，及它与静脉输注液中其他药物的相容性与稳定性取决于混合液的pH、浓度、放置时间、温度及甲泼尼龙自身的溶解性。
为了避免相容性和稳定性问题，建议无论用静脉注射、还是静脉滴注均应尽可能将甲泼尼龙溶液与其他药物分开给药。
-甲泼尼龙琥珀酸钠不应作为颅脑损伤的常规治疗。
孕妇及哺乳期妇女用药

一些动物试验表明，妊娠期间服用大剂量皮质类固醇可能引起胎儿畸形。
因未作过足够的人类生殖研究，因而当皮质类固醇用于孕妇、哺乳妇女或准备生育的妇女时，应仔细权衡其益处与它对母亲和胚胎或胎儿的潜在威胁之间的关系。只有当确实需要时，皮质类固醇才可用于孕妇。如果在怀孕期间必须停用已长期服用的皮质类固醇（与其它长期疗法相同），停药过程必须逐步进行（同时参见“用法用量”）。然而某些疾病的治疗（如肾上腺皮质机能不全的替代治疗）可能需要继续，甚至增加剂量。因皮质类固醇很容易透过胎盘，对怀孕期间用过大剂量皮质类固醇的母亲生育的婴儿，应仔细观察和评价是否有肾上腺皮质机能减退的迹象。
甲基强的松龙对分娩的影响还未知。
皮质类固醇随乳汁分泌。
儿童用药

长期每天分次服用给予糖皮质激素会抑制儿童的生长, 这种治疗方法只可用于非常严重的情况。婴儿和儿童可减量，但依据应是疾病的严重程度及患者的反应，而不是年龄和体型。每24小时的总量不应少于0.5mg/kg。
老年用药

遵医嘱慎用。
药物相互作用

有益的药物相互作用：
-预防肿瘤化疗引起的恶心和呕吐；轻至中度致吐的化疗方案；
-氯化酚噻嗪可与首剂甲泼尼龙（化疗前1小时）合用以增强效果。
中度致吐的化疗方案：
灭吐灵或丁酰苯类药物可与首剂甲泼尼龙（化疗前1小时）合用以增强效果。
-甲泼尼龙与其他抗结核化疗联合，可用于治疗暴发性或扩散型肺结核及伴有蛛网膜下腔阻塞或趋于阻塞的结核性脑膜炎。
-甲泼尼龙经常与烷化剂、抗代谢类药物及长春花碱类药物联合用于肿瘤疾病，如白血病及淋巴瘤。
有害的药物相互作用： ,/br>-糖皮质激素与致溃疡药物（如水杨酸盐和甾体抗炎药）合用，会增加发生消化道并发症的危险。糖皮质激素与噻嗪类利尿药合用，会增加糖耐量异常危险。糖皮质激素会增加糖尿病患者对胰岛素和口服降糖药的需求。
-服用皮质类固醇的患者不可接种牛痘，也不可接受其它免疫措施，特别是大剂量服用的患者，因为有出现神经系统并发症和（或）缺乏抗体反应的危险。
-皮质类固醇与乙酰水杨酸联合用于凝血酶原过少的患者时应谨慎。
-有报道同时服用甲泼尼龙和环胞菌素会引起惊厥。因为上述两种药物会相互抑制对方的代谢，所以服用任一药物时引起的惊厥和其它不良反应在同时服用两种药物时更易发生。
药物过量

未发现甲泼尼龙急性过量引起的综合征。长期过量会引起典型的柯兴氏症状。甲泼尼龙可经透析排出。

SOLU-MEDROL (methylprednisolone sodium succinate) injection, powder, for solution
[Pharmacia and Upjohn Company]

For Intravenous or Intramuscular Administration

DESCRIPTION

SOLU-MEDROL Sterile Powder contains methylprednisolone sodium succinate as the active ingredient. Methylprednisolone sodium succinate, USP, occurs as a white, or nearly white, odorless hygroscopic, amorphous solid. It is very soluble in water and in alcohol; it is insoluble in chloroform and is very slightly soluble in acetone.

The chemical name for methylprednisolone sodium succinate is pregna-1,4-diene-3,20-dione,21-(3-carboxy-1-oxopropoxy)-11,17-dihydroxy-6-methyl-monosodium salt, (6α, 11β), and the molecular weight is 496.53. The structural formula is represented below:

Methylprednisolone sodium succinate is so extremely soluble in water that it may be administered in a small volume of diluent and is especially well suited for intravenous use in situations in which high blood levels of methylprednisolone are required rapidly.

SOLU-MEDROL is available in several strengths and packages for intravenous or intramuscular administration.

40 mg Act-O-Vial® System (Single-Dose Vial)

Each mL (when mixed) contains methylprednisolone sodium succinate equivalent to 40 mg methylprednisolone; also 1.6 mg monobasic sodium phosphate anhydrous; 17.46 mg dibasic sodium phosphate dried; and 25 mg lactose hydrous.

125 mg Act-O-Vial System (Single-Dose Vial)

Each 2 mL (when mixed) contains methylprednisolone sodium succinate equivalent to 125 mg methylprednisolone; also 1.6 mg monobasic sodium phosphate anhydrous; and 17.4 mg dibasic sodium phosphate dried.

500 mg Vial

Each 8 mL (when mixed as directed) contains methylprednisolone sodium succinate equivalent to 500 mg methylprednisolone; also 6.4 mg monobasic sodium phosphate anhydrous; 69.6 mg dibasic sodium phosphate dried.

500 mg Act-O-Vial System (Single-Dose Vial)

Each 4 mL (when mixed) contains methylprednisolone sodium succinate equivalent to 500 mg methylprednisolone; also 6.4 mg monobasic sodium phosphate anhydrous; and 69.6 mg dibasic sodium phosphate dried.

1 gram Vial

Each 16 mL (when mixed as directed) contains methylprednisolone sodium succinate equivalent to 1 gram methylprednisolone; also 12.8 mg monobasic sodium phosphate anhydrous; 139.2 mg dibasic sodium phosphate dried.

1 gram Act-O-Vial System (Single-Dose Vial)

Each 8 mL (when mixed) contains methylprednisolone sodium succinate equivalent to 1 gram methylprednisolone; also 12.8 mg monobasic sodium phosphate anhydrous; and 139.2 mg dibasic sodium phosphate dried.

When necessary, the pH of each formula was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range of 7 to 8 and the tonicities are, for the 40 mg per mL solution, 0.50 osmolar; for the 125 mg per 2 mL, 500 mg per 8 mL and 1 gram per 16 mL solutions, 0.40 osmolar; for the 1 gram per 8 mL solution, 0.44 osmolar. (Isotonic saline = 0.28 osmolar).

IMPORTANT — Use only the accompanying diluent when reconstituting SOLU-MEDROL.
Use within 48 hours after mixing

ACTIONS

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Methylprednisolone is a potent anti-inflammatory steroid with greater anti-inflammatory potency than prednisolone and even less tendency than prednisolone to induce sodium and water retention.

Methylprednisolone sodium succinate has the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity. The relative potency of SOLU-MEDROL Sterile Powder and hydrocortisone sodium succinate, as indicated by depression of eosinophil count, following intravenous administration, is at least four to one. This is in good agreement with the relative oral potency of methylprednisolone and hydrocortisone.

INDICATIONS

When oral therapy is not feasible, and the strength, dosage form and route of administration of the drug reasonably lend the preparation to the treatment of the condition, SOLU-MEDROL Sterile Powder is indicated for intravenous or intramuscular use in the following conditions:

Endocrine Disorders

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance)
Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used)
Preoperatively and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful
Shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is suspected
Congenital adrenal hyperplasia
Hypercalcemia associated with cancer
Nonsuppurative thyroiditis

Rheumatic Disorders

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:
Post-traumatic osteoarthritis
Synovitis of osteoarthritis
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
Acute and subacute bursitis
Epicondylitis
Acute nonspecific tenosynovitis
Acute gouty arthritis
Psoriatic arthritis
Ankylosing spondylitis

Collagen Diseases

During an exacerbation or as maintenance therapy in selected cases of:
Systemic lupus erythematosus
Systemic dermatomyositis (polymyositis)
Acute rheumatic carditis

Dermatologic Diseases

Pemphigus
Severe erythema multiforme (Stevens-Johnson syndrome)
Exfoliative dermatitis
Bullous dermatitis herpetiformis
Severe seborrheic dermatitis
Severe psoriasis
Mycosis fungoides

Allergic States

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in:
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Seasonal or perennial allergic rhinitis
Drug hypersensitivity reactions
Urticarial transfusion reactions
Acute noninfectious laryngeal edema (epinephrine is the drug of first choice)

Ophthalmic Diseases

Severe acute and chronic allergic and inflammatory processes involving the eye, such as:
Herpes zoster ophthalmicus
Iritis, iridocyclitis
Chorioretinitis
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthalmia
Anterior segment inflammation
Allergic conjunctivitis
Allergic corneal marginal ulcers
Keratitis

Gastrointestinal Diseases

To tide the patient over a critical period of the disease in:
Ulcerative colitis (systemic therapy)
Regional enteritis (systemic therapy)

Respiratory Diseases

Symptomatic sarcoidosis
Berylliosis
Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy
Loeffler's syndrome not manageable by other means
Aspiration pneumonitis

Hematologic Disorders

Acquired (autoimmune) hemolytic anemia
Idiopathic thrombocytopenic purpura in adults (IV only; IM administration is contraindicated)
Secondary thrombocytopenia in adults
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia

Neoplastic Diseases

For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood

Edematous States

To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus

Nervous System

Acute exacerbations of multiple sclerosis

Miscellaneous
Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement

CONTRAINDICATIONS

SOLU-MEDROL Sterile Powder is contraindicated in systemic fungal infections and patients with known hypersensitivity to the product and its constituents.

WARNINGS

In patients on corticosteroid therapy subjected to any unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infections with any pathogen including viral, bacterial, fungal, protozoan or helminthic infections, in any location of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function.1

These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.2

A study has failed to establish the efficacy of SOLU-MEDROL in the treatment of sepsis syndrome and septic shock. The study also suggests that treatment of these conditions with SOLU-MEDROL may increase the risk of mortality in certain patients (i.e., patients with elevated serum creatinine levels or patients who develop secondary infections after SOLU-MEDROL).

Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Usage in pregnancy

Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers, or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids.

The use of SOLU-MEDROL Sterile Powder in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with appropriate antituberculous regimen.

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Because rare instances of anaphylactic (eg, bronchospasm) reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.

There are reports of cardiac arrhythmias and/or circulatory collapse and/or cardiac arrest following the rapid administration of large IV doses of SOLU-MEDROL (greater than 0.5 gram administered over a period of less than 10 minutes). Bradycardia has been reported during or after the administration of large doses of methylprednisolone sodium succinate, and may be unrelated to the speed or duration of infusion.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration  affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

PRECAUTIONS

General precautions

Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.

Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.

The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction should be gradual.

Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency;  hypertension; osteoporosis; and myasthenia gravis.

Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy.

Discontinuation of corticosteroids may result in clinical remission.

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that corticosteroids affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect (see DOSAGE AND ADMINISTRATION).

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (eg, myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (eg, pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevations of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

DRUG INTERACTIONS

The pharmacokinetic interactions listed below are potentially clinically important. Mutual inhibition of metabolism occurs with concurrent use of cyclosporin and methylprednisolone; therefore, it is possible that adverse events associated with the individual use of either drug may be more apt to occur. Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of methylprednisolone and may require increases in methylprednisolone dose to achieve the desired response. Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of methylprednisolone and thus decrease its clearance. Therefore, the dose of methylprednisolone should be titrated to avoid steroid toxicity. Methylprednisolone may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when methylprednisolone is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypoprothrombinemia. The effect of methylprednisolone on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulant when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.

Information for the Patient

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

ADVERSE REACTIONS

Fluid and Electrolyte Disturbances

Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension

Musculoskeletal

Muscle weakness
Steroid myopathy
Loss of muscle mass
Severe arthralgia
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Osteoporosis
Tendon rupture, particularly of the Achilles tendon

Gastrointestinal

Peptic ulcer with possible perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT), and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation.

Dermatologic

Impaired wound healing
Thin fragile skin
Petechiae and ecchymoses
Facial erythema
Increased sweating
May suppress reactions to skin tests

Neurological

Increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually after treatment
Convulsions
Vertigo
Headache

Endocrine

Development of Cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness
Menstrual irregularities
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents in diabetics

Ophthalmic

Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos

Metabolic

Negative nitrogen balance due to protein catabolism
The following additional adverse reactions are related to parenteral corticosteroid therapy:
Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
Anaphylactic reaction with or without circulatory collapse, cardiac arrest, bronchospasm
Urticaria
Nausea and vomiting
Cardiac arrhythmias; hypotension or hypertension

DOSAGE AND ADMINISTRATION

When high dose therapy is desired, the recommended dose of SOLU-MEDROL Sterile Powder is 30 mg/kg administered intravenously over at least 30 minutes. This dose may be repeated every 4 to 6 hours for 48 hours.

In general, high dose corticosteroid therapy should be continued only until the patient's condition has stabilized; usually not beyond 48 to 72 hours.

Although adverse effects associated with high dose short-term corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be indicated.

In other indications initial dosage will vary from 10 to 40 mg of methylprednisolone depending on the clinical problem being treated. The larger doses may be required for short-term management of severe, acute conditions. The initial dose usually should be given intravenously over a period of several minutes. Subsequent doses may be given intravenously or intramuscularly at intervals dictated by the patient's response and clinical condition. Corticoid therapy is an adjunct to, and not replacement for conventional therapy.

Dosage may be reduced for infants and children but should be governed more by the severity of the condition and response of the patient than by age or size. It should not be less than 0.5 mg per kg every 24 hours.

Dosage must be decreased or discontinued gradually when the drug has been administered for more than a few days. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. Routine laboratory studies, such as urinalysis, two-hour postprandial blood sugar, determination of blood pressure and body weight, and a chest X-ray should be made at regular intervals during prolonged therapy. Upper GI X-rays are desirable in patients with an ulcer history or significant dyspepsia.

SOLU-MEDROL may be administered by intravenous or intramuscular injection or by intravenous infusion, the preferred method for initial emergency use being intravenous injection. To administer by intravenous (or intramuscular) injection, prepare solution as directed. The desired dose may be administered intravenously over a period of several minutes. If desired, the medication may be administered in diluted solutions by adding Water for Injection or other suitable diluent (see below) to the Act-O-Vial and withdrawing the indicated dose.

To prepare solutions for intravenous infusion, first prepare the solution for injection as directed. This solution may then be added to indicated amounts of 5% dextrose in water, isotonic saline solution or 5% dextrose in isotonic saline solution.

Multiple Sclerosis

In treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (4 mg of methylprednisolone is equivalent to 5 mg of prednisolone).

DIRECTIONS FOR USING THE ACT-O-VIAL SYSTEM

1. Press down on plastic activator to force diluent into the lower compartment.
2. Gently agitate to effect solution.
3. Remove plastic tab covering center of stopper.
4. Sterilize top of stopper with a suitable germicide.
5. Insert needle squarely through center of stopper until tip is just visible. Invert vial and withdraw dose.

STORAGE CONDITIONS

Protect from light.

Store unreconstituted product at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Store solution at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Use solution within 48 hours after mixing.

HOW SUPPLIED

SOLU-MEDROL Sterile Powder is available in the following packages:

40 mg Act-O-Vial System (Single-Dose Vial)	1 gram Act-O-Vial System (Single-Dose Vial)
25 x1 mL NDC 0009-0039-28	8 mL NDC 0009-0018-20
125 mg Act-O-Vial System (Single-Dose Vial)	500 mg (Multi-Dose Vial)
25 x 2 mL NDC 0009-0047-22	8 mL NDC 0009-0758-01
500 mg Act-O-Vial System (Single-Dose Vial)	1 gram (Multi-Dose Vial)
4 mL NDC 0009-0003-02	16 mL NDC 0009-0698-01

REFERENCES

1Fekety R. Infections associated with corticosteroids and immunosuppressive therapy. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. Philadelphia: WBSaunders Company 1992:1050–1.

2Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticoids. Rev Infect Dis 1989:11(6):954–63.

Rx only

LAB-0420-1.0
October 2009

PRINCIPAL DISPLAY PANEL - 40 mg Vial Label

1 mL Act-O-Vial®
NDC 0009-0039-30

Solu-Medrol®

methylprednisolone sodium
succinate for injection, USP

40 mg*

Preservative-Free