药品信息: 美国食品与药物管理局（FDA）批准罕用药物RiaSTAP用于治疗罕见遗传性缺陷即先天性纤维蛋白原缺乏症患者的出血症状。如果不进行治疗，此类患者存在致命性出血的潜在风险。
纤维蛋白原可促进血块形成和防止出血，因此在血液凝固过程中起重要作用。先天性纤维蛋白原缺乏症患者自身无法产生足够数量的纤维蛋白原。纤维蛋白原在肝脏中产生，血浆中的正常浓度为250～400 mg/dL。
FDA生物制品评估和研究中心主任Jesse Goodman 博士称：“该产品为数量很少的先天性纤维蛋白原缺乏症患者提供了急需的治疗方案。如果此类患者出血发生于脑部或其他器官后未得到治疗，可能会引起失血、器官损伤甚至死亡。”
在美国仅有150～300例纤维蛋白原缺乏症患者。此类患者通常是在出生时因发生脐带部位出血而确诊。存在此缺陷的儿童需要限制活动以降低因微小创伤发生出血的风险。
RiaSTAP是一种静脉应用的纤维蛋白原浓缩液，提取自健康人的血浆。该产品适用于无纤维蛋白原或纤维蛋白原水平低的无纤维蛋白原血症患者，或纤维蛋白原水平低于50 mg/dL的低纤维蛋白原血症患者。
该产品并不适用于异常纤维蛋白原血症患者，此类患者的纤维蛋白原水平正常，但是纤维蛋白原功能存在缺陷，因此存在出血或凝血并发症风险。
RiaSTAP的批准是基于一项纳入15例无纤维蛋白原血症患者的研究结果。该研究结果显示，患者在接受RiaSTAP 70 mg/kg剂量治疗后，纤维蛋白原达到了防止出血的预期目标水平。此外，15例患者中有14例血浆检测结果显示最大血块硬度（可能预测临床益处的替代指标）增加。RiaSTAP的最常见不良反应为发热和头痛。
RiaSTAP的临床益处将在一项上市后研究中进一步验证。该研究将纳入无纤维蛋白原血症和低纤维蛋白原血症两类患者。
罕用药（Orphan drugs）是指应用于治疗罕见疾病的药物或生物制品。研发此类产品的制造商有资格从政府部门获得特定利益以作为交换。RiaSTAP[纤维蛋白原浓缩液（人源性）]的开发符合FDA加速批准规则。
该药由德国马尔堡的CSL Behring公司制造。
RiaSTAP
Generic Name: fibrinogen
Dosage Form: injection, powder, lyophilized, for solution
Indications and Usage for RiaSTAP
RiaSTAP®, Fibrinogen Concentrate (Human) is indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.
RiaSTAP is not indicated for dysfibrinogenemia.
RiaSTAP Dosage and Administration
For intravenous use only. Reconstitute prior to use.
Should be administered under the supervision of a physician.
Treatment of Congenital Fibrinogen Deficiency
RiaSTAP dosing, duration of dosing and frequency of administration should be individualized based on the extent of bleeding, laboratory values, and the clinical condition of the patient.
RiaSTAP dose when baseline fibrinogen level is known
Dose should be individually calculated for each patient based on the target plasma fibrinogen level based on the type of bleeding, actual measured plasma fibrinogen level and body weight, using the following formula (see Pharmacokinetics [12.3]):
RiaSTAP dose when baseline fibrinogen level is not known
If the patient's fibrinogen level is not known, the recommended dose is 70 mg per kg of body weight administered intravenously.
Monitoring of patient's fibrinogen level is recommended during treatment with RiaSTAP. A target fibrinogen level of 100 mg/dL should be maintained until hemostasis is obtained.
Preparation and Reconstitution
The procedures below are provided as general guidelines for preparation and reconstitution of RiaSTAP.
Do not use RiaSTAP beyond the expiration date. RiaSTAP contains no preservative. Use aseptic technique when preparing and reconstituting RiaSTAP.
Reconstitute RiaSTAP at room temperature as follows:
1.Remove the cap from the product vial to expose the central portion of the rubber stopper.
2.Clean the surface of the rubber stopper with an antiseptic solution and allow it to dry.
3.Using an appropriate transfer device or syringe, transfer 50 mL of Sterile Water for Injection into the product vial.
4.Gently swirl the product vial to ensure the product is fully dissolved. Do not shake the vial.
After reconstitution, the RiaSTAP solution should be colorless and clear to slightly opalescent. Inspect visually for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains particulates. Do not freeze RiaSTAP solution. Discard partially used vials.
RiaSTAP is stable for 24 hours after reconstitution when stored at 20-25oC and should be administered within this time period.
Administration
Do not mix RiaSTAP with other medicinal products or intravenous solutions, and should be administered through a separate injection site.
Use aseptic technique when administering RiaSTAP.
Administer RiaSTAP at room temperature by slow intravenous injection at a rate not exceeding 5 mL per minute.
Dosage Forms and Strengths
RiaSTAP is available as a single-use vial containing 900 mg to 1300 mg lyophilized fibrinogen concentrate powder for reconstitution with 50 mL of Sterile Water for Injection.
The actual fibrinogen potency for each lot is printed on the vial label and carton.
Contraindications
RiaSTAP is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis to RiaSTAP or its components.
Warnings and Precautions
Allergic Reactions
Allergic reactions may occur. If symptoms of allergic or early signs of hypersensitivity reactions (including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur, immediately discontinue administration (see Patient Counseling Information [17.1]). The treatment required depends on the nature and severity of the reaction.
Thrombosis
Thrombosis may occur spontaneously in patients with congenital fibrinogen deficiency with or without the use of fibrinogen replacement therapy.1 Thromboembolic events have been reported in patients treated with RiaSTAP. Weigh the benefits of RiaSTAP administration versus the risk of thrombosis. Patients receiving RiaSTAP should be monitored for signs and symptoms of thrombosis. (see Patient Counseling Information [17.2])
Transmissible Infectious Agents
RiaSTAP is made from human plasma. Products made from human plasma may contain infectious agents (e.g., viruses and theoretically the Creutzfeldt-Jakob disease agent [CJD]) that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing. (see Description [11]). Despite these measures, such products may still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products (see Patient Counseling Information [17.3]). All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to CSL Behring at 1-866-915-6958.
Adverse Reactions
The most serious adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic-anaphylactic reactions and thromboembolic episodes, including myocardial infarction, pulmonary embolism, deep vein thrombosis, and arterial thrombosis.
The most common adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic reactions and generalized reactions such as chills, fever, nausea, and vomiting.
Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical studies and may not reflect the rates observed in practice.
The most common adverse reactions observed in more than one subject in clinical studies (frequency >1%) were fever and headache.
Postmarketing Experience
Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.
Adverse reactions reported in patients receiving RiaSTAP for treatment of fibrinogen deficiency include allergic-anaphylactic reactions (including rash, dyspnea, etc.), general reactions such as chills, fever, nausea, vomiting and thromboembolic complications such as myocardial infarction, pulmonary embolism, and deep vein thrombosis.
The following adverse reactions, identified by system organ class, have shown a possible causal relationship with RiaSTAP.
•Allergic-anaphylactic reactions: anaphylaxis, dyspnea, rash
•Cardiovascular: thromboembolism, pulmonary embolism (see Warnings and Precautions, Thrombosis [5.2])
•General/Body as a Whole: chills, fever, nausea, vomiting
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with RiaSTAP. It is not known whether RiaSTAP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. RiaSTAP should be used during pregnancy only if clearly needed.
Labor and Delivery
RiaSTAP has not been studied for use during labor and delivery.
Nursing Mothers
RiaSTAP has not been studied in nursing mothers with congenital fibrinogen deficiency.
Pediatric Use
RiaSTAP studies have included subjects below the age of 16 years. In the pharmacokinetic study (see Pharmacokinetics [12.3]), 2 children (8 and 11 years), 3 adolescents (12, 14 and 16 years), were studied. Subjects less than 16 years of age (n = 4) had shorter half-life (69.9 ± 8.5h) and faster clearance (0.7 ± 0.1 mg/L) compared to adults (half-life: 82.3 ± 20.0h, clearance: 0.53 ± 0.1 mg/L). The number of subjects less than 16 years of age in this study limits statistical interpretation.
Geriatric Use
The safety and efficacy of RiaSTAP in the geriatric population has not been studied. There were an insufficient number of subjects in this age group to determine whether they respond differently from younger subjects.
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