Angiotensin II (Giapreza®): A Comprehensive Pharmacological and Clinical Monograph for the Management of Distributive Shock

Executive Summary

Angiotensin II, marketed under the brand name Giapreza®, is a synthetic formulation of the endogenous human peptide hormone that functions as a potent vasoconstrictor. This biotech therapeutic is indicated for adults with septic or other forms of distributive shock who remain hypotensive despite adequate fluid resuscitation and standard-of-care vasopressor therapy. Its approval marks a significant development in critical care medicine, introducing the first therapeutic agent that directly targets the renin-angiotensin-aldosterone system (RAAS) to restore vascular tone in shock states.

The primary mechanism of action involves agonism of the Angiotensin II Type 1 (AT1) receptor, leading to rapid and potent vasoconstriction and a subsequent increase in mean arterial pressure (MAP). Clinical evidence, principally from the pivotal ATHOS-3 trial, has robustly demonstrated its efficacy in achieving hemodynamic targets within minutes of administration, often allowing for a reduction in the dosage of concomitant catecholamine vasopressors. This catecholamine-sparing effect is a key therapeutic benefit, potentially mitigating the adverse effects associated with high-dose catecholamine use.

The principal safety concern associated with Angiotensin II therapy is a statistically significant increase in the risk of both arterial and venous thromboembolic events. This risk necessitates the concurrent administration of venous thromboembolism (VTE) prophylaxis. The drug's pharmacokinetic profile is characterized by an extremely short half-life of less than one minute, which allows for precise and rapid dose titration but mandates continuous intravenous infusion via a central line in an intensive care setting.