ST LOUIS (MD Consult) - On September 16, 2009, the US Food and Drug Administration (FDA) announced that it is requiring manufacturers of promethazine to include a boxed warning on the drug's label regarding the safety of injectable formulations. Promethazine hydrochloride (injectable) is approved for a variety of indications, including allergic reactions, sedation, motion sickness, nausea, and vomiting associated with anesthesia and surgery, and as an adjunct to analgesics for control of postoperative pain.
The FDA was prompted to take this action after it reviewed the published literature and post marketing adverse event reports submitted to its Adverse Event Reporting System from 1969 to 2009. During this review, cases of gangrene requiring amputation associated with intravenous (IV) administration of promethazine were noted. The most common amputations involved the fingers and hands. Numerous other cases of injection reactions, such as injection-site pain, redness, phlebitis, cyanosis, swelling, blistering, necrosis, and nerve damage, were also found.
The preferred route of promethazine administration is deep intramuscular injection. Subcutaneous injection is contraindicated. The new Boxed Warning section will remind practitioners of the risks of severe tissue injury, including gangrene, that may occur with IV administration. Severe tissue injury can occur from perivascular extravasation, unintentional intraarterial injection, and intraneuronal or perineuronal infiltration of promethazine. After injection of the drug, practitioners should be alert for signs and symptoms of potential tissue injury, including burning or pain at the site of injection, phlebitis, swelling, and blistering.
The FDA is requiring a revision to the Dosage and Administration section of promethazines's label in addition to the aforementioned changes to the Boxed Warning section. This revision is meant to increase the visibility and accessibility of specific recommendations for the maximum concentration (25 mg/mL) and rate of administration (25 mg/min) of promethazine when IV administration is required. Practitioners are also being reminded to ensure the patency of a properly functioning IV line before the drug is delivered in this manner. Infusions should be stopped immediately if a patient complains of pain during promethazine administration.
圣路易斯(MD Consult)——2009年9月16日，美国食品药品管理局(FDA)宣布，当局正要求异丙嗪的生产厂家在其药品说明书中添加一个有关其注射制剂安全性的黑框警告。盐酸异丙嗪(注射制剂)已获准用于治疗多种适应证，其中包括过敏反应、镇静、晕动病、恶心、以及麻醉和手术所致的呕吐等，亦可作为控制术后疼痛的辅助止痛药。
在对发表的文献及1969年至2009年间上交至其不良事件报告系统的上市后不良事件报告进行审查后，FDA采取此措施。审查过程中观察到异丙嗪静脉用药导致坏疽需截肢的病例。截肢最常累及手指和手掌。审查中还发现许多出现注射反应的病例，诸如注射部位痛、发红、静脉炎、紫绀、肿胀、起泡、坏死和神经损伤。
异丙嗪推荐给药途径为深层肌肉注射，禁止皮下注射。新的黑框警告部分将提醒医生该药的严重组织损伤风险，其中包括坏疽，此情况可由静脉给药所致。严重组织损伤可见于下列情况：异丙嗪血管周围外渗、无意的动脉内注射以及神经元内或神经元周围渗透。注射此药后，医生必须警惕其潜在的组织损伤症状和体征，其中包括注射部位灼热或疼痛、静脉炎、肿胀以及起泡等。
除了前文对黑框警告部分所做的改动外，FDA还要求对异丙嗪说明书的剂量和给药部分进行修订。修订的目的为，在需要经静脉以最大剂量(25 mg/ml)和最大速率(25 mg/min)给予异丙嗪时，加强医生对特殊建议的认识和了解。同时，当局亦提醒医生们在经上述途径给药之前确保所选择的静脉功能正常。在异丙嗪给药过程中，患者一旦主诉疼痛，则应立即停止输注。
