Angiotensin II acetate is a synthetic form of endogenous angiotensin II, a peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and increased blood pressure.1, 3, 4, 5, 7, 9
Angiotensin II acetate is used for its vasoconstrictive effects to increase blood pressure in patients with septic or other forms of distributive shock.1, 3, 4, 5, 7
Vasopressors are used as standard therapy in the management of septic shock when fluid resuscitation alone fails to restore blood pressure.2, 4, 7 Current treatment guidelines recommend norepinephrine as the first-line vasopressor of choice in adults with septic shock.2 Angiotensin II may provide an additional treatment option for patients who do not respond adequately to traditional vasopressors.4, 5, 7, 8, 9
In a randomized, double-blind, placebo-controlled study (Angiotensin II for the Treatment of High-Output Shock [ATHOS-3]), angiotensin II substantially increased mean arterial pressure (MAP) in patients with distributive shock (91% of cases caused by sepsis) who remained hypotensive (MAP of 55-70 mm Hg) despite fluid and vasopressor therapy.1, 4 A total of 321 adults who were receiving more than 0.2 mcg/kg per minute of norepinephrine or an equivalent dosage of another vasopressor for at least 6 hours but no longer than 48 hours were enrolled in the study and received an IV infusion of angiotensin II (initial dosage of 20 ng/kg per minute) or placebo.1, 4 During the first 3 hours of treatment, dosage of angiotensin II was titrated to achieve a target MAP of at least 75 mm Hg, while dosages of other vasopressors were maintained; in the subsequent 3 to 48 hours, dosage of angiotensin II was titrated to maintain MAP of 65-70 mm Hg, while dosages of other vasopressors were reduced or discontinued.1, 4, 6 The primary end point was MAP response (defined as a MAP of at least 75 mm Hg or an increase in MAP from baseline of at least 10 mm Hg, without an increase in baseline vasopressor therapy) at 3 hours.1, 4 The primary end point was achieved in 70% of patients receiving angiotensin II compared with 23% of patients receiving placebo.1, 4 The median time to reach target MAP with angiotensin II was approximately 5 minutes.1 The rapid treatment effect permitted reductions in both the dosage of angiotensin II and dosages of concomitant vasopressors.1, 4 At 30 minutes, the median dosage of angiotensin II was 10 ng/kg per minute.1 Patients who received angiotensin II had lower catecholamine requirements compared with those who received placebo.4 In addition, there was a trend toward a 28-day mortality benefit with angiotensin II compared with placebo (mortality rate of 46 versus 54%, respectively); however, the difference was not statistically significant.1, 6
Additional studies are needed to further elucidate the role of angiotensin II in the management of shock, particularly in regard to the patient populations that are most likely to benefit, the optimal timing of administration, long-term benefits and harm, and comparative efficacy with other vasopressors.4, 5, 8, 9
Angiotensin II acetate is administered by continuous IV infusion.1 It is recommended that the drug be infused through a central venous line.1
Prior to administration, the commercially available injection concentrate must be diluted in 0.9% sodium chloride injection to a final concentration of 5000 or 10,000 ng/mL depending on the patient's fluid status.1 In patients who are not fluid restricted, a concentration of 5000 ng/mL may be prepared by adding 1 mL (2.5 mg) of the injection concentrate to an infusion bag containing 500 mL of 0.9% sodium chloride injection.1 In patients who are fluid restricted, a concentration of 10,000 ng/mL may be prepared by adding 1 mL (2.5 mg) of the injection concentrate to an infusion bag containing 250 mL of 0.9% sodium chloride injection.1 Diluted solutions may be stored at room temperature or under refrigeration for up to 24 hours.1
Solutions of angiotensin II should be inspected visually for particulate matter and discoloration prior to administration.1
Dosage of angiotensin II acetate is expressed in terms of angiotensin II.1
The recommended initial dosage of angiotensin II in adults with septic or other distributive shock is 20 ng/kg per minute by continuous IV infusion.1 Dosage should be titrated based on blood pressure response.1 The infusion rate may be increased by increments of up to 15 ng/kg per minute as frequently as every 5 minutes as needed to achieve or maintain the target blood pressure.1 During the first 3 hours of treatment, dosage should not exceed 80 ng/kg per minute.1 Once the underlying shock has sufficiently improved, the infusion rate should be titrated downward by decrements of up to 15 ng/kg per minute every 5 to 15 minutes as tolerated to maintain target blood pressure.1 During maintenance therapy, dosage should not exceed 40 ng/kg per minute.1 Dosages as low as 1.25 ng/kg per minute may be used.1
In the ATHOS-3 study, mean arterial pressure (MAP) increased rapidly following administration of angiotensin II, allowing for rapid down-titration of the initial dosage of 20 ng/kg per minute in 67% of the patients within 30 minutes; the median dosage at 30 minutes was 10 ng/kg per minute.1, 4
The manufacturer makes no special population dosage recommendations at this time.1
The manufacturer states that there are no known contraindications to the use of angiotensin II acetate.1
An increased incidence of arterial and venous thromboembolic events, particularly deep venous thrombosis (DVT), was reported in patients receiving angiotensin II compared with those receiving placebo in the ATHOS-3 study (13 versus 5%, respectively).1, 6 DVT occurred in 7 (4.3%) patients who received angiotensin II compared with none of the patients who received placebo.1 Preclinical studies and studies in healthy individuals also have demonstrated prothrombotic effects of the drug.6
Concurrent use of venous thromboembolism (VTE) prophylaxis is recommended during angiotensin II therapy.1
There are insufficient data in pregnant women to determine whether angiotensin II is associated with a risk of adverse developmental effects.1 Animal reproduction studies have not been conducted with the drug.1
Septic or other distributive shock is a medical emergency that can be fatal if untreated; a delay in treatment in pregnant women with hypotension associated with shock is likely to increase the risk of maternal and fetal morbidity and mortality.1
It is not known whether angiotensin II is distributed into human milk of if the drug has any effects on the nursing infant or on milk production.1
Safety and efficacy of angiotensin II have not been established in pediatric patients.1
In the ATHOS-3 study, 48% of the total patient population was 65 years of age or older.1 No substantial differences in safety or efficacy of angiotensin II have been observed between geriatric patients (65 years of age or older) and younger adults.1
The pharmacokinetics of angiotensin II are not expected to be altered by hepatic impairment.1
The pharmacokinetics of angiotensin II are not expected to be altered by renal impairment.1
Adverse reactions reported in 4% or more of patients receiving angiotensin II in clinical studies include thromboembolic events (e.g., DVT), thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia, and peripheral ischemia.1
No drug interaction studies have been performed to date with angiotensin II acetate.6 Concomitant use of angiotensin-converting enzyme (ACE) inhibitors may increase the response to angiotensin II and concomitant use of angiotensin II receptor antagonists (ARBs) may decrease the response to angiotensin II.1
Angiotensin II acetate is a synthetic preparation of endogenous human angiotensin II, a peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that plays an essential role in blood pressure regulation.1, 3, 4, 5, 7, 9 The drug is a potent vasoconstrictor that is used to increase blood pressure in patients with septic or other forms of distributive shock.1, 5, 9
In patients with septic shock, a variety of physiologic responses are activated to restore effective circulating volume, vascular resistance, and arterial pressure, including activation of RAAS and production of angiotensin II.5, 9 There is some evidence suggesting that patients with septic shock may have a relative deficiency of angiotensin II that may be reversed with exogenous administration of angiotensin II.5, 9 Angiotensin II increases blood pressure through direct vasoconstriction of the peripheral vasculature in addition to other mechanisms (e.g., aldosterone secretion, vasopressin release, activation of the sympathetic nervous system).1, 3, 4, 5, 8, 9 The physiologic effects of angiotensin II are mediated by specific G protein-coupled receptors located in the kidneys, vascular smooth muscle, lung, heart, brain, adrenal gland, pituitary gland, and liver.1, 5, 8, 9 The angiotensin II receptor type 1 (AT1 receptor) is responsible for the vasoconstrictive effects of angiotensin II; activation of the receptor stimulates calcium/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction.1, 5, 8 Angiotensin II also has been shown to have cardiac remodeling properties and preferential vasoconstrictive effects on renal efferent arterioles.5, 8, 9
Following IV infusion, angiotensin II is rapidly metabolized by aminopeptidase A to angiotensin 2-8 (angiotensin III) and by angiotensin-converting enzyme 2 to angiotensin 1-7 in plasma, erythrocytes, and many other major organs (e.g., intestine, kidney, liver, lungs).1 Angiotensin III retains approximately 40% of the activity of angiotensin II, while angiotensin 1-7 exhibits opposing actions to angiotensin II and causes vasodilation, natriuresis, and reduced blood pressure.1, 5, 9 The plasma half-life of angiotensin II is less than 1 minute.1 Elimination of the drug is not dependent on renal or hepatic routes.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions November 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. La Jolla. Giapreza® (angiotensin II) injection for intravenous infusion prescribing information. San Diego, CA; 2017 Dec.
2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377.
3. Busse LW, Wang XS, Chalikonda DM, et al. Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety. Crit Care Med. 2017 Aug;45(8):1285-1294.
4. Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377:419-430.
5. Bussard RL, Busse LW. Angiotensin II : a new therapeutic option for vasodilatory shock. Therapeutics and Clinical Risk Management . 2018:14 1287-1298.
6. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209360Orig1s000: Summary review. From FDA website. [Web]
7. . Angiotensin II (Giapreza) for septic shock. Med Lett Drugs Ther . 2018; 60:199-200. [PubMed 30653477]
8. Rodriguez R and Fernandez EM. Role of angiotensin II in treatment of refractory distributive shock. Am J Health Syst Pharm. 2019; 76: 101-107.
9. Antonucci E, Gleeson PJ, Annoni F et al. Angiotensin II in Refractory Septic Shock. Shock . 2017; 47:560-566. [PubMed 27879559]
10. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209360Orig1s000: SClinical Pharmacology and Biopharmaceutics Review. From FDA website. [Web]