1 ML angiotensin II 0.5 MG/ML Injection [Giapreza]

INDICATIONS AND USAGE Angiotensin II Injection increases blood pressure in adults with septic or other distributive shock. Angiotensin II Injection is a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. (1)

DOSAGE AND ADMINISTRATION Dilute Angiotensin II Injection in 0.9% sodium chloride prior to use. See Full Prescribing Information for instructions on preparation and administration of injection. Diluted solution may be stored at room temperature or under refrigeration and should be discarded after 24 hours. Angiotensin II Injection must be administered as an intravenous infusion. ( 2.1 ) • Start Angiotensin II Injection intravenously at 20 nanograms (ng)/kg/min. Titrate as frequently as every 5 minutes by increments of up to 15 ng/kg/min as needed. During the first 3 hours, the maximum dose should not exceed 80 ng/kg/min. Maintenance dose should not exceed 40 ng/kg/min. ( 2.2 ) 2.1. Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Angiotensin II Injection must be administered as an intravenous infusion. Angiotensin II Injection must be diluted in 0.9% sodium chloride prior to use. Dilute the contents of one vial of Angiotensin II Injection 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 F l u i d Restricted? V i al Strength Withdraw Amount (m L ) I n f usion Bag Size (mL) Final Concentration (ng/mL) No 2.5 mg/mL 1 500 5,000 Yes 2.5 mg/mL 1 250 10,000 Diluted solution may be stored at room temperature or under refrigeration. Discard prepared solution after 24 hours at room temperature or under refrigeration. 2.2. Administration The recommended starting dosage of Angiotensin II Injection is 20 nanograms (ng)/kg/min via continuous intravenous infusion. Administration through a central venous line is recommended. Monitor blood pressure response and titrate Angiotensin II Injection 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.

WARNINGS AND PRECAUTIONS • There is a potential for venous and arterial thrombotic and thromboembolic events in patients who receive Angiotensin II. Use concurrent venous thromboembolism (VTE) prophylaxis. ( 5.1 , 6.1 ) 5.1 Risk for Thrombosis The safety of Angiotensin II 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 Angiotensin II 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.

CONTRAINDICATIONS None. None (4.1)

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 Ca 2+ /calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction.