美国FDA于2001年11月21日批准了第一个用于治疗重度脓毒症的生物工程制剂Xigris。
这种新制剂是通过基因工程技术生产出的一种人体蛋白——活化蛋白C，它可以干扰人体对严重感染的一些有害反应，包括血栓形成，后者可导致器官衰竭甚至死亡。
FDA首席执行代表 Schwetz说，Xigris是一种可挽救严重脓毒症病人生命的新药，Xigris的获准上市将使这种威胁生命的疾病的治疗取得重大的进展。脓毒症一般由严重感染引起，时常危及生命。美国每年有约75万人患脓毒症，尽管应用抗生素治疗，但仍有约30%的病人死亡。
在一项随机安慰剂对照多中心临床试验中，纳入了1700例脓毒症患者，在28天的研究期内，总死亡率降低了6%(从31%降至25%)。虽然Xigris没有降低病情较轻患者的死亡率，但在死亡高危患者中死亡率降低了13%(从44%降至31%)。
由于活化蛋白C可干扰血液凝固，Xigris的最严重副作用是出血，包括出血性卒中。在连续4天输入药物期间，有2.4%的患者发生严重出血事件，而对照组为1%。有高危出血倾向的患者被排出试验，另外与脓毒症无关的病危的患者也未纳入研究。
有活动性内出血的患者、近期因卒中、头部或脊柱手术或严重脑外伤而有出血倾向的患者禁用Xigris。
FDA的公告告诫临床医师，由于脓毒症可危及生命，而Xigris的使用又存在潜在的危险，因此必须针对每一患者仔细权衡使用Xigris的利和弊。
Xigris (Drotrecogin Alfa Activated)
Xigris (drotrecogin alfa [activated]) is indicated in the treatment for sepsis, a disease that implies various bacteria getting in the blood vessels and affecting the blood. They end up creating toxins, resulting in an infected blood. If untreated, the disease affects a particular organ, according to the bacteria. It results in an acute disease that usually leads to death. Therefore, most sepsis cases are fatal. The medication has been tested on the patients with a regular sepsis, not the severe advanced form. Judging by the tests results, the mortality risk has been decreased. However, it hasn’t been tested yet for the severe form of sepsis.
Administration and dosage
Xigris (drotrecogin alfa [activated]) must be administered only by experienced specialist doctors. The treatment should start as soon as the disease is noticed. The optimal period to begin is of 48 hours after the first symptoms. If the patient starts within 24 hours, things are even better. A quick round of blood tests must be taken before the treatment.
The initial dose is of 24μg/kg, but it has to be adapted according to the patient’s age, weight, renal or hepatic dysfunctions and gender. However, those who suffer from severe sepsis don’t need adjustments.
The dosage should be administered over a 96 hours perfusion.
Contraindications
Xigris (drotrecogin alfa [activated]) is not indicated in the patients younger than 18. Those who suffer from internal hemorrhages, severe renal or hepatic disorders or any allergies to the ingredients are also not allowed to get this treatment. Instead, the specialist doctor will try to find an alternative.
Xigris (drotrecogin alfa [activated]) also requires prudence. If the patient goes through a different treatment at the same time, the doctor must be notified about it in order to exclude unwanted reactions. The effect of this medication in pregnant and nursing women is still unknown. The patients who get it are open to unknown risks, therefore it should be avoided, unless it is really necessary and the mother’s life depends on it.
The risks over driving or dealing with harmful machinery are also unknown.
Side effects
Since it deals with the blood and it actually tries to clean it as part of the healing process, Xigris (drotrecogin alfa [activated]) increases the bleeding risks. A harmless little wound may easily become hemorrhagic. Most patients who have been through the tests have presented at least one such case.
The hemorrhages may affect the nervous, gastrointestinal, urinary or tegumentary systems. These adverse reactions affect less than 1% of the patients though.
There aren’t any known adverse reactions to overdoses.
