Vasopressin (Vasostrict, Pitressin; also known as AVP, ADH)
Arginine Vasopressin (AVP); also known as Argipressin, [Arg8]-vasopressin, Antidiuretic Hormone (ADH), 8-Arginine Vasopressin (8-AVP)
Vasopressin (arginine vasopressin, AVP) is an endogenous cyclic nonapeptide hormone and FDA-approved vasopressor that acts via V1a (Ki ~4.70 nM), V1b (Ki ~5.84 nM), V2 (sub-nanomolar EC50), and oxytocin receptors (Ki ~1.65-7.92 nM) to regulate blood pressure, water balance, and stress responses; it is FDA-approved for vasodilatory shock and used clinically in diabetes insipidus, cardiac arrest, and variceal bleeding (VASST trial: PMID 18305265; FDA NDA 204485; IUPHAR ligandId=2168).
Last updated: 2026-03-13
Safety Summary
Vasopressin's acute safety profile is well characterized from large RCTs. In the VASST trial (n=778), serious adverse event rates were similar between vasopressin and norepinephrine (~10.3% vs 10.5%, PMID 18305265). The primary safety concern is dose-dependent ischemic complications: digital ischemia occurred in approximately 2-3% of patients in RCTs, with meta-analyses showing a pooled RR of 2.65 (95% CI 1.26-5.56) for digital ischemia with vasopressin compared to catecholamines alone (Yao et al., Front Pharmacol 2020). Mesenteric ischemia is a rare but serious risk, with a worldwide pharmacovigilance analysis (PMC9168038) confirming this signal. Hyponatremia results from the V2-mediated antidiuretic effect and requires monitoring of serum sodium and fluid balance. Decreased cardiac output occurs through increased afterload. Tachyarrhythmias are less frequent than with catecholamines (network meta-analysis PMC5606402 shows vasopressin has lower arrhythmia risk than dopamine). Transient diabetes insipidus after discontinuation of prolonged infusion has been reported and is reversible. Drug interactions: additive pressor effects with catecholamines (monitor hemodynamics), indomethacin doubles offset time, ganglionic blocking agents increase pressor response, SIADH-causing drugs (chlorpropamide, cyclophosphamide, SSRIs, thiazides) potentiate effects and increase hyponatremia risk. No significant CYP-mediated interactions (proteolytic clearance). No significant immunogenicity concerns (endogenous peptide); historical reports of anti-vasopressin antibodies are rare and not a contemporary clinical concern (PMID 443972). No abuse potential. No evidence of tolerance or dependence. No carcinogenic or cumulative organ toxicity signals in long-term pharmacovigilance. Pregnancy: increased clearance due to placental vasopressinase; uterine contraction risk. Pediatric: safety/efficacy not established in FDA labeling. meta-analysis, Drugs.com interaction checker.
Known Side Effects
common
common
common
common
common
uncommon (~2-3% in RCTs)
rare
rare
rare
uncommon
uncommon
rare
uncommon
Who Should NOT Use This
Per FDA label (NDA 212593/204485). Allergic reaction risk.
V1a-mediated vasoconstriction increases risk of ischemic complications (digital, mesenteric, coronary). Use extreme caution and monitor perfusion, extremities, ECG, lactate.
Impaired renal clearance may increase exposure and V2-mediated water retention. Monitor renal function closely.
Category C. May cause uterine contractions. Placental vasopressinase increases clearance in 2nd/3rd trimester, potentially requiring dose adjustment. No adequate controlled human studies. Use only if clearly needed with obstetric oversight.
Vasopressin is metabolized by the liver. Labels note increased bilirubin/transaminases but do not provide specific dosing adjustments. Monitor liver function tests.
Indomethacin prolongs vasopressin effects (approximately doubles offset time).
These drugs increase pressor and antidiuretic response to vasopressin, increasing risk of hyponatremia and excessive vasoconstriction.
Talk to Your Doctor
Before considering Vasopressin (Vasostrict, Pitressin; also known as AVP, ADH), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-10]
Evidence Assessment
Vasopressin is FDA-approved (NDA 204485, Vasostrict, approved 2014; NDA 212593) for increasing blood pressure in adults with vasodilatory shock. Multiple large RCTs support its use, including the VASST trial (n=778, NEJM 2008, PMID 18305265), the VANISH trial (n=409, JAMA 2016, PMID 27483065), Cochrane systematic review (26 RCTs, 21,704 patients), and numerous meta-analyses. It appears in the Surviving Sepsis Campaign guidelines as a recommended adjunct vasopressor. Multiple generic formulations are commercially available.
1Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (VASST)PMID 18305265
Russell JA, Walley KR, Singer J, et al. - New England Journal of Medicine (2008) - Multicenter randomized double-blind controlled trial - 778 (396 vasopressin, 382 norepinephrine)
No significant difference in 28-day mortality (35.4% vs 39.3%, P=0.26). 90-day mortality 43.9% vs 49.6%, P=0.11. Predefined subgroup with less severe shock showed lower mortality with vasopressin (26.5% vs 35.7%, P=0.05). Serious adverse events similar (~10.3% vs 10.5%). Digital ischemia ~2-3%.
Limitations: No significant mortality benefit in overall population. Subgroup finding was predefined but not the primary endpoint. Single fixed-dose vasopressin regimen.
2Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical TrialPMID 27483065
Gordon AC, Mason AJ, Thirunavukkarasu N, et al. - JAMA (2016) - Multicenter randomized double-blind factorial trial (2x2 with hydrocortisone) - 409
No significant difference in kidney failure-free days. Vasopressin group had lower use of renal replacement therapy (25.4% vs 35.3%, P=0.03). Factorial design also tested hydrocortisone. Similar safety profile.
Limitations: Primary endpoint not met. 2x2 factorial design with corticosteroids creates complex interactions. UK-based population.
3Clinical Efficiency of Vasopressin or Its Analogs in Comparison With Catecholamines Alone on Patients With Septic Shock: A Systematic Review and Meta-Analysis
Yao RQ, et al. - Frontiers in Pharmacology (2020) - Systematic review and meta-analysis - 23 RCTs, 4,225 patients
Pooled 28/30-day mortality RR 0.94 (95% CI 0.87-1.01) -- no statistically significant mortality reduction. Increased digital ischemia risk (pooled RR 2.65, 95% CI 1.26-5.56). Signal for reduced renal replacement therapy in some analyses.
Limitations: Heterogeneity in dosing, timing, and trial quality across included studies. Different vasopressin analogs pooled.
4Adrenaline and vasopressin for cardiac arrest (Cochrane Review)
Finn J, Jacobs I, Williams TA, et al. - Cochrane Database of Systematic Reviews (2019) - Cochrane systematic review and meta-analysis - 26 RCTs, 21,704 participants pooled
Vasopressin may increase survival to hospital admission vs standard-dose adrenaline (pooled RR 1.27, 95% CI 1.04-1.54). No consistent improvement in neurological outcomes or long-term survival. Combination vasopressin+epinephrine showed no clear advantage for long-term outcomes.
Limitations: Heterogeneity across trials. Many older studies with varying quality. No consistent long-term neurological benefit.
5Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials
Polito A, Parisini E, Ricci Z, et al. - Critical Care (2012) - Systematic review and meta-analysis - 9 RCTs pooled
Vasopressin/terlipressin showed catecholamine-sparing effects and modest mortality signal in pooled analysis. Reduced norepinephrine requirements consistently.
Limitations: Heterogeneous trial designs and dosing protocols.
6Network meta-analysis of vasopressors in septic shock
Various - Critical Care / related journal (2017) - Network meta-analysis - Multiple RCTs pooled
Vasopressin and norepinephrine showed mortality and arrhythmia advantages versus dopamine. Dopamine associated with higher mortality and arrhythmia rates. Vasopressin has lower arrhythmia signal than catecholamine vasopressors.
Limitations: Network meta-analysis indirect comparisons have inherent limitations.
7Intranasal vasopressin for social deficits in autism spectrum disorder (pilot RCT)
Parker KJ et al. - Various (2022) - Randomized placebo-controlled pilot trial - Small (pilot)
Some improvements on specific social or attention tasks in children with ASD reported in pilot studies. Mixed results across studies. Primary endpoint results mixed.
Limitations: Small sample sizes. Mixed primary outcomes. Investigational/early-phase. Not powered for definitive efficacy conclusions.
8Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3)
Khanna A, et al. - New England Journal of Medicine (2017) - Phase 3 randomized controlled trial - 344
Angiotensin II produced higher MAP response at 3 hours vs placebo (69.9% vs 23.4%, P<0.001) in catecholamine-refractory shock. Provides comparison context for vasopressin positioning as prior-line agent.
Limitations: Not a direct vasopressin comparator. Placebo-controlled, not head-to-head.
9Pragmatic Trial of Vasopressin in Septic ShockNCT06217562
Not specified (ongoing) - ClinicalTrials.gov (2024) - Pragmatic randomized trial (ongoing) - Target not specified in raw data
Ongoing trial evaluating vasopressin in septic shock. Results not yet available.
Limitations: Ongoing; no results posted as of March 2026.
10Early-Initiation Vasopressin ProtocolNCT06265259
Not specified (ongoing) - ClinicalTrials.gov (2024) - Randomized trial (ongoing) - Not specified in raw data
Evaluating early initiation of vasopressin. Results not yet available.
Limitations: Ongoing; no results posted.