Angiotensin II

also known as: Giapreza, Ang II, AT-II, LJPC-501, synthetic human angiotensin II

Giapreza — the first new vasopressor class approved in decades. FDA-approved December 2017 (La Jolla Pharmaceutical) for catecholamine-resistant septic / distributive shock based on the ATHOS-3 trial (NEJM 2017, n=321). Engages a third vasoconstrictor pathway (RAAS / AT1) independent of catecholamines and vasopressin — useful when both of those axes are desensitised.

A synthetic octapeptide identical to the endogenous human angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) — the effector hormone of the renin-angiotensin-aldosterone system — developed and marketed by La Jolla Pharmaceutical Company under the brand name Giapreza®. FDA-approved December 21, 2017 on priority review, based on the ATHOS-3 Phase 3 trial (Angiotensin II for the Treatment of High-Output Shock; Khanna et al, NEJM 2017; n=321) in catecholamine-refractory distributive shock. Primary endpoint was MAP response at 3 hours: 69.9% of Giapreza patients versus 23.4% of placebo reached target MAP ≥75 mmHg or a ≥10 mmHg rise without increased catecholamines. The trial was not powered for mortality. Innoviva acquired La Jolla Pharmaceutical Company in 2022. EMA marketing authorisation application submitted 2018; product has had a varied European regulatory path. Notable label concerns: thromboembolism signal (13% Giapreza vs 5% placebo in ATHOS-3) — concurrent VTE prophylaxis is required.

Mechanism of action

Agonist at the AT1 receptor (Gq-coupled) on vascular smooth muscle, producing direct vasoconstriction independent of catecholamine receptors and vasopressin receptors. This third vasoconstrictor pathway is often preserved in septic shock when adrenergic and vasopressin responsiveness are impaired by receptor desensitisation, uncoupling, and depletion of the underlying ligands. Additional AT1-mediated effects include aldosterone release (Gq, adrenal glomerulosa), sympathetic facilitation (central and peripheral), and renal tubular sodium reabsorption. The AT2 receptor produces opposing vasodilatory effects but is quantitatively minor at therapeutic doses. Clinical dosing is titrated to MAP with maximum recommended doses of 80 ng/kg/min in the first 3 hours and 40 ng/kg/min for maintenance, as a catecholamine-sparing addition rather than replacement.

Primary uses

Catecholamine-resistant septic shock (FDA-approved)
Other distributive / vasodilatory shock unresponsive to conventional vasopressors (FDA-approved)

Typical dosing

20 ng/kg/min starting; up to 80 ng/kg/min max for first 3 hours, then up to 40 ng/kg/min ng/kg/min (continuous IV infusion) continuous infusion (intravenous (central line preferred))

Use with VTE prophylaxis due to thromboembolism signal (13% vs 5% in ATHOS-3). ACE inhibitor co-administration may potentiate effect; ARB co-administration may attenuate it. Not cleared renally or hepatically — no dose adjustment in organ dysfunction.

Regulatory status

FDA-approved December 21, 2017 (Giapreza®, La Jolla Pharmaceutical Company; now part of Innoviva). US indication: increasing blood pressure in adults with septic or other distributive shock. Priority review. EMA marketing authorisation granted 2019. Acquired product now managed by Innoviva Specialty Therapeutics (the La Jolla acquisition closed 2022).

References

[fda-pi] Giapreza® (angiotensin II) Prescribing Information. La Jolla Pharmaceutical Company / Innoviva Specialty Therapeutics. Initial US approval December 21, 2017.
[clinical-trial] Khanna A, English SW, Wang XS, et al. "Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3)." N Engl J Med, 2017;377(5):419-430.
[review] Chawla LS, Busse L, Brasha-Mitchell E, et al. "Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study." Crit Care, 2014;18(5):534.

Related peptides

Vasopressin

Vasostrict — the endogenous antidiuretic hormone as an ICU vasopressor. FDA-approved April 2014 for adults with vasodilatory shock (post-cardiotomy, sepsis) who remain hypotensive despite fluids and catecholamines. Works through V1a receptors on vascular smooth muscle — a receptor axis pharmacologically distinct from catecholamine receptors, preserving its vasopressor effect when adrenergic receptors are desensitised.

Terlipressin

Terlivaz — the first and only FDA-approved drug for hepatorenal syndrome (HRS). FDA-approved September 2022 (Mallinckrodt) for adults with HRS with rapid reduction in kidney function, after a multi-decade regulatory history including four prior Complete Response Letters and the successful CONFIRM Phase 3 trial (NEJM 2021).

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.