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2017年12月21日，美国食品和药品监管局今天批准血管紧张素angiotensin II(商标名 Giapreza，La Jolla制药) 注射为成年中有败血症或其他分配性休克静脉输注增加血压。
Diluted solution may be stored at room temperature or under refrigeration. Discard prepared solution after 24 hours at room temperature or under refrigeration. Administration The recommended starting dosage of GIAPREZA is 20 nanograms (ng)/kg/min via continuous intravenous infusion. Administration through a central venous line is recommended. Monitor blood pressure response and titrate GIAPREZA every 5 minutes by increments of up to 15 ng/kg/min as needed to achieve or maintain target blood pressure. Do not exceed 80 ng/kg/min during the first 3 hours of treatment. Maintenance doses should not exceed 40 ng/kg/min. Doses as low as 1.25 ng/kg/min may be used. Once the underlying shock has sufficiently improved, down-titrate every 5 to 15 minutes by increments of up to 15 ng/kg/min based on blood pressure. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Stability data: GIAPREZA vials should be stored in the refrigerator (36-46°F, 2-8°C). Discard prepared diluted solution after 24 hours at room temperature or under refrigeration. Diluted solution may be stored at room temperature or under refrigeration. Discard prepared solution after 24 hours at room temperature or under refrigeration. Discard vial and any unused portion of the drug product after use. WARNINGS See warnings and precautions below. DESCRIPTION Description: Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure. GIAPREZA is a sterile, aqueous solution of synthetic human angiotensin II for intravenous administration by infusion. Each 1 mL of GIAPREZA contains 2.5 mg angiotensin II equivalent to an average of 2.9 mg angiotensin II acetate, 25 mg mannitol, and Water for Injection adjusted with sodium hydroxide and/or hydrochloric acid to pH of 5.5. The chemical name of the synthetic angiotensin II acetate is L-Aspartyl-L-arginyl-L-valyl-Ltyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine, acetate salt. The counter ion acetate is present in a non-stoichiometric ratio. It is a white to off-white powder, soluble in water. CLINICAL PHARMACOLOGY: Mechanism of Action: Angiotensin II raises blood pressure by vasoconstriction and increased aldosterone release. Direct action of angiotensin II on the vessel wall is mediated by binding to the G-protein-coupled angiotensin II receptor type 1 on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction. INDICATIONS AND USAGE: GIAPREZA increases blood pressure in adults with septic or other distributive shock. USE IN SPECIFIC POPULATIONS 8.1. Pregnancy Risk Summary The published data on angiotensin II use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have not been conducted with GIAPREZA. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Septic or other distributive shock is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic or other distributive shock is likely to increase the risk of maternal and fetal morbidity and mortality. 8.2. Lactation Risk Summary It is not known whether GIAPREZA is present in human milk. No data are available on the effects of angiotensin II on the breastfed child or the effects on milk production. 8.4. Pediatric Use The safety and efficacy of GIAPREZA in pediatric patients have not been established. 8.5. Geriatric Use In ATHOS-3, 48% of the total patient population was aged 65 years and older. There was no significant difference in safety or efficacy between patients less than 65 and those 65 years or older when treated with GIAPREZA. CONTRAINDICATIONS Contraindications: None PRECAUTIONS WARNINGS AND PRECAUTIONS: 5.1 Risk for Thrombosis The safety of GIAPREZA was evaluated in 321 adults with septic or other distributive shock in a randomized, double-blind, placebo-controlled study, ATHOS-3. There was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received GIAPREZA compared to placebo-treated patients in the ATHOS-3 study (13% vs. 5%). The major imbalance was in deep venous thromboses. Use concurrent venous thromboembolism (VTE) prophylaxis. ADVERSE REACTIONS: •The most common adverse reactions reported in greater than 10% in GIAPREZA treated patients were thromboembolic events. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact La Jolla Pharmaceutical Company at 1-800-651-3861 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. DOSAGE AND ADMINISTRATION: 2.1. Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. GIAPREZA must be administered as an intravenous infusion. GIAPREZA must be diluted in 0.9% sodium chloride prior to use. Dilute the contents of one vial of GIAPREZA in 0.9% saline to achieve a final concentration of 5,000 ng/mL or 10,000 ng/mL. Discard vial and any unused portion of the drug product after use. Table 1: Preparation of Diluted Solution
Diluted solution may be stored at room temperature or under refrigeration. Discard prepared solution after 24 hours at room temperature or under refrigeration. |