Regulatory status

Status at a glance

503A compounding status

Not nominated

We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.

Status recorded · FDA source document

FDA approval
An FDA-approved product contains this peptide
503B outsourcing
Not determined
Anti-doping (WADA)
Not on the WADA Prohibited List
DEA schedule
Not a controlled substance

About peptide status

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Status as of

Key takeaway

Angiotensin II is a natural peptide hormone and the main active signal of the renin-angiotensin system, which the body uses to raise blood pressure by tightening blood vessels. A synthetic version is FDA-approved as Giapreza, an intravenous drug given in intensive care to raise dangerously low blood pressure in adults with septic or other distributive shock. In its pivotal ATHOS-3 trial it raised blood pressure in about 70% of patients compared with 23% on placebo, though it also carries a risk of blood clots.

At a glance

FDA status
FDA-approved peptide, sold as Giapreza, given as an intravenous infusion in intensive care
How it works
Synthetic copy of a natural hormone that raises blood pressure by constricting blood vessels
Main uses
Raising blood pressure in adults with septic or other distributive shock, usually alongside other vasopressors
Key trial
Raised blood pressure in about 70% of patients in its pivotal trial, compared with 23% on placebo
Evidence strength
FDA approved

Summary

Angiotensin II is a natural hormone that raises blood pressure. A synthetic form, Giapreza, is FDA-approved for shock. See how it works and what trials show.

What is angiotensin II?

Angiotensin II is a peptide hormone made of eight amino acids that the body uses to control blood pressure, and a synthetic form of it is used as a drug. It is the main active molecule of the renin-angiotensin system, the hormone cascade that regulates blood pressure and fluid balance.

As a medicine, it is a laboratory-made copy of the human hormone, developed by La Jolla Pharmaceutical, now part of Innoviva, and sold as Giapreza. It is given only as a continuous intravenous infusion in a hospital, not as an injection a person takes at home.

The history of angiotensin II

Angiotensin II was discovered twice at once, and that is how it got its name. The table below traces it from discovery to approval.

Study findings for Angiotensin II
Period Event
Late 1930s and early 1940sTwo research groups independently isolated the same blood-pressure-raising substance from the kidney's renin pathway. A team led by Irvine Page in the United States called it angiotonin, while a group led by Eduardo Braun-Menéndez in Argentina called it hypertensin. For years the literature carried both names.
1958The two camps compromised and blended their terms into a single word, angiotensin, which is still used today
2017Approved by the FDA as an intravenous drug for shock, more than seven decades after its discovery

For most of the following decades, the molecule was studied as a hormone and as a target to block, since many common blood-pressure medicines (ACE inhibitors and ARBs) work by reducing its activity. Using the hormone itself as a treatment came much later, when it was developed as an intravenous drug for shock.

How does angiotensin II work?

Angiotensin II raises blood pressure by binding to receptors on the muscle lining the blood vessels and making them tighten. It acts mainly through the AT1 receptor on vascular smooth muscle, and activating it constricts the vessels, which raises blood pressure quickly. This is the final active step of the renin-angiotensin system: the kidney releases renin, which starts a chain that produces angiotensin I, and an enzyme called ACE converts that into angiotensin II, the potent form.

Beyond directly tightening vessels, angiotensin II signals the adrenal glands to release aldosterone, a hormone that makes the body hold on to sodium and water, and it promotes the release of vasopressin, another blood-pressure hormone. In shock, this matters because it gives clinicians a way to raise blood pressure through a pathway separate from the standard catecholamine drugs such as norepinephrine, which helps when those drugs alone are not enough.

In the pivotal ATHOS-3 trial of patients with vasodilatory shock who were already on high-dose vasopressors, adding angiotensin II raised blood pressure to the target in 69.9% of patients, compared with 23.4% on placebo. It is given as a continuous infusion and adjusted to blood pressure, and because the peptide is cleared from the blood within about a minute, its effect can be dialed up or down quickly.

Is it FDA-approved?

Editor’s note

Status: FDA-approved peptide, sold as Giapreza, given as an intravenous infusion in intensive care

Category: FDA-approved · Primary body area: Heart & blood

Yes. The FDA approved angiotensin II as Giapreza in December 2017 to increase blood pressure in adults with septic or other distributive shock. It was a notable approval because it introduced a new type of vasopressor, giving intensive care teams a hormone-based option to add when standard drugs are not controlling dangerously low blood pressure.

What is angiotensin II prescribed for?

Angiotensin II is prescribed in the intensive care unit to raise blood pressure in adults whose blood pressure is dangerously low from septic or other distributive shock, a state in which the blood vessels lose their tone and dilate. It is typically added on top of standard vasopressors such as norepinephrine and vasopressin for patients who are not responding adequately to those alone, rather than used first. It is a short-term, closely monitored hospital treatment, not an outpatient medication.

What are the side effects?

The most important safety concern is a risk of blood clots. In its trial, angiotensin II was associated with thrombotic events, including deep vein thrombosis, and the label recommends giving clot-prevention treatment (venous thromboembolism prophylaxis) while a patient is receiving it. According to the prescribing information, other reported effects included:

  • Low platelet counts
  • A fast heart rate
  • Fungal infection
  • Delirium
  • Acidosis
  • High blood sugar
  • Reduced blood flow to the hands and feet

Because it is used only in intensive care, patients receiving it are already under close monitoring.

Sources: FDA prescribing information for Giapreza (angiotensin II); the pivotal ATHOS-3 randomized controlled trial in the New England Journal of Medicine (Khanna et al., 2017, DOI: 10.1056/NEJMoa1704154), indexed on PubMed; and published histories of the renin-angiotensin system. This document is educational and does not constitute medical advice.

Registered human trials

0 registered human trials on ClinicalTrials.gov that we reviewed

Sources

  1. [1]

    renin-angiotensin system

    Primary ncbi.nlm.nih.gov

  2. [2]

    Giapreza

    Primary giapreza.com

  3. [3]

    angiotonin

    Primary PubMed

  4. [4]

    AT1 receptor (PDF)

    Primary U.S. Food and Drug Administration

  5. [5]

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