部分中文Stimate处方资料(仅供参考) 人血浆蛋白因子 ——-选自 “国际重组蛋白药物的市场和研发趋势分析 (1)重组人凝血因子VIII,适应症是血友病A。最早上市的为Recombinate (Baxter和Genetics,野生型),现有5个同类产品,最畅销的是Kogenate(Bayer,野生型)及Advate(Baxter,野生型),2005年销售分别为8亿[21]和6亿美元[22]。 STIMATE-desmopressin acetate spray, metered Mol. Wt. 1183.34 Empirical formula: C46H64N14O12S2 •C2H4O2•3H2O 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate. Stimate® Nasal Spray is provided as an aqueous solution for intranasal use. Each mL contains: CLINICAL PHARMACOLOGY Desmopressin acetate has been shown to be more potent than arginine vasopressin in increasing plasma levels of Factor VIII activity in patients with hemophilia and von Willebrand's disease Type I. Dose-response studies were performed in healthy persons using doses of 150 to 450 µg, administered as one to three sprays. The response to Stimate® Nasal Spray is dose-related, with maximal plasma levels of 150 to 250 percent of initial concentrations achieved for both Factor VIII and von Willebrand factor.1 The increase is rapid and evident within 30 minutes, reaching a maximum at about 1.5 hours.1 The percentage increase of Factor VIII and von Willebrand factor levels in patients with mild hemophilia A and von Willebrand's disease was not notably different from that observed in normal healthy individuals when treated with 300 µg of Stimate® Nasal Spray.1-4 In patients with von Willebrand's disease, levels of Factor VIII coagulant activity and von Willebrand factor antigen remained greater than 30 U/dL for 8 hours after a 300 µg dose of Stimate® Nasal Spray.5 After 300 µg of Stimate® Nasal Spray, the percentage increase of Factor VIII and von Willebrand factor levels in patients with mild hemophilia A and von Willebrand's disease was less than observed after 0.3 µg/kg of intravenous desmopressin acetate.2-4 Plasminogen activator activity increases rapidly after intravenous desmopressin acetate infusion, but there has been no clinically significant fibrinolysis in patients treated with desmopressin acetate. The effect of repeated intravenous desmopressin acetate administration when doses were given every 12 to 24 hours has generally shown a diminution of the Factor VIII activity increase noted after a single dose. It is possible to reproduce the initial response in some patients after an interval of one week, but other patients may require as long as 6 weeks.2,4,6 The half-life of Stimate® Nasal Spray was between 3.3 and 3.5 hours, over the range of intranasal doses, 150 to 450 µg.1 Plasma concentrations of Stimate® Nasal Spray were maximal approximately 40 to 45 minutes after dosing.1 The bioavailability of Stimate® Nasal Spray when administered by the intranasal route as a 1.5 mg/mL solution is between 3.3 and 4.1 percent.1 The change in structure of arginine vasopressin to desmopressin acetate has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle. INDICATIONS AND USAGE Desmopressin acetate is also available as a solution for injection (DDAVP® Injection) when the intranasal route may be compromised. These situations include nasal congestion and blockage, nasal discharge, atrophy of nasal mucosa, and severe atrophic rhinitis. Intranasal delivery may also be inappropriate where there is an impaired level of consciousness. Hemophilia A Desmopressin acetate will also stop bleeding in patients with hemophilia A with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding.2,3 In the outpatient setting during two clinical trials where patients recorded bleeding episodes, Stimate® Nasal Spray provided effective hemostasis 100% of the time in 2 of the 5 patients. For those patients not responding in 100% of bleeding occasions, 45% (14 of 31) of bleeding episodes were effectively controlled with Stimate® Nasal Spray. Desmopressin acetate is not indicated for the treatment of hemophilia A with Factor VIII coagulant activity levels equal to or less than 5%, or for the treatment of hemophilia B, or in patients who have Factor VIII antibodies. von Willebrand's Disease (Type I) Desmopressin acetate will also stop bleeding in mild to moderate von Willebrand's disease patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas, mucosal bleeding or menorrhagia.2,3 In the outpatient setting during two clinical trials where patients recorded bleeding episodes, Stimate® Nasal Spray provided effective hemostasis 100% of the time in 75% of the patients (n=16). For those patients not responding in 100% of bleeding occasions, 78% (64 of 82) of bleeding episodes were effectively controlled with Stimate® Nasal Spray. Patients may respond in a variable fashion depending on the type of molecular defect they have. Bleeding time and Factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen should be checked after initial administration of Stimate® Nasal Spray to ensure that adequate levels have been achieved. Stimate® Nasal Spray is not indicated for the treatment of severe classic von Willebrand's disease (Type I) and when there is evidence of an abnormal molecular form of Factor VIII antigen. See WARNINGS. CONTRAINDICATIONS WARNINGS Patients who do not have need of antidiuretic hormone for its antidiuretic effect, in particular those who are young or elderly, should be cautioned to ingest only enough fluid to satisfy thirst, in order to decrease the potential occurrence of water intoxication and hyponatremia. Fluid intake should be adjusted downward, particularly in very young and elderly patients, in order to decrease the potential occurrence of water intoxication and hyponatremia.1 Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma. Stimate® Nasal Spray should not be used to treat patients with Type IIB von Willebrand's disease since platelet aggregation may be induced. PRECAUTIONS General Stimate® Nasal Spray should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, because these patients are prone to hyponatremia. There have been rare reports of thrombotic events (thrombosis7, acute cerebrovascular thrombosis, acute myocardial infarction) following desmopressin acetate injection in patients predisposed to thrombus formation. No causality has been determined; however, the drug should be used with caution in these patients. Severe allergic reactions have been reported rarely.2,8-10 Fatal anaphylaxis has been reported in one patient who received intravenous DDAVP® (desmopressin acetate). It is not known whether antibodies to desmopressin acetate are produced after repeated administration. Since Stimate® Nasal Spray is used intranasally, changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption in which case Stimate® Nasal Spray should be discontinued until the nasal problems resolve. For such situations, DDAVP® Injection should be considered. Information for Patients: Patients should also be advised that if bleeding is not controlled, the physician should be contacted.2,3 Hemophilia A von Willebrand's Disease Drug Interactions DDAVP® Injection has been used with epsilon aminocaproic acid without adverse effects. Carcinogenicity, Mutagenicity, Impairment of Fertility: Pregnancy Category B: Nursing Mothers: Pediatric Use: Geriatric Use: Therefore, in elderly patients fluid intake should be adjusted downward in an effort to decrease the potential occurrence of water intoxication and hyponatremia. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures, which could lead to coma. Patients who do not have need of antidiuretic hormone for its antidiuretic effect should be cautioned to ingest only enough fluid to satisfy thirst, in an effort to decrease the potential occurrence of water intoxication and hyponatremia. As for all patients, dosing for geriatric patients should be appropriate to their overall situation. ADVERSE REACTIONS In addition to those listed above, the following have also been reported in clinical trials with Stimate® Nasal Spray: Somnolence, dizziness, itchy or light-sensitive eyes, insomnia, chills, warm feeling, pain, chest pain, palpitations, tachycardia, dyspepsia, edema, vomiting, agitation and balanitis.1-4 DDAVP® Injection (desmopressin acetate) has infrequently produced changes in blood pressure causing either a slight elevation or a transient fall and a compensatory increase in heart rate. Severe allergic reactions including anaphylaxis have been reported rarely with DDAVP® Injection. See WARNINGS for the possibility of water intoxication, hyponatremia and coma.11 OVERDOSAGE There is no known specific antidote for desmopressin acetate or Stimate® Nasal Spray. An oral LD50 has not been established. An intravenous dose of 2 mg/kg in mice demonstrated no effect. DOSAGE AND ADMINISTRATION Hemophilia A and von Willebrand's Disease (Type I) The necessity for repeat administration of Stimate® Nasal Spray or use of any blood products for hemostasis should be determined by laboratory response as well as the clinical condition of the patient. The tendency toward tachyphylaxis (lessening of response) with repeated administration given more frequently than every 48 hours should be considered in treating each patient. The nasal spray pump can only deliver doses of 0.1 mL (150 µg) or multiples of 0.1 mL. If doses other than these are required, DDAVP® Injection may be used. The spray pump must be primed prior to the first use. To prime pump, press down 4 times. The bottle should be discarded after 25 doses since the amount delivered thereafter per spray may be substantially less than 150 µg of drug. HOW SUPPLIED KEEP REFRIGERATED AT 2-8°C (36-46°F). When traveling, product will maintain stability for up to 3 weeks when stored at room temperature, 22°C (72°F). PATIENT INSTRUCTION GUIDE A better way to deliver Delivering desmopressin acetate more efficiently Your doctor has prescribed Stimate® Nasal Spray for the treatment of mild hemophilia A or mild to moderate von Willebrand's disease (Type 1). Follow the dosage schedule that is specified. The convenient nasal spray pump provides an efficient, reliable way to administer your medication. It is important, however, to adhere completely to the following instructions so that you will always receive a consistent dose of your medication. CAUTION: The nasal spray pump accurately delivers 25 doses of 150 micrograms per spray. Any solution remaining after 25 sprays should be discarded since the amount delivered thereafter per spray may be substantially less than 150 micrograms of drug. Do not transfer any remaining solution to another bottle. Please read the following instructions carefully before using the spray pump. Using your Stimate® Nasal Spray Pump -------------------------------------------------------- |
Stimate(人血浆蛋白因子1.5毫克)简介:
部分中文Stimate处方资料(仅供参考)
人血浆蛋白因子
——-选自 “国际重组蛋白药物的市场和研发趋势分析
(1)重组人凝血因子VIII,适应症是血友病A。最早上市的为Recombinate (Baxter和Genetic ... 责任编辑:admin
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