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Immunity · Nasal spray

VIP

Compounded Rx

Checked · 18 sources · 8 corrections on this page · No vendors · No affiliates · No one buys a word of it

0 controlled immune trials

Preclinical for this use · Phase 3 for COVID-19 respiratory failure · one clinic's series of 20

Compounded Rx · On FDA’s 503A list — a licensed pharmacy can compound it for you.

Bottom line

Real biology, real limitations in the clinical data.

Also called
  • Vasoactive Intestinal Peptide
  • Aviptadil (synthetic VIP, RLF-100)
  • 28-aa secretin-family neuropeptide
Category
Peptide — Neuropeptide (Secretin/Glucagon Family)
Molecular Weight
3,326 Da
Sequence
28 aa — secretin/glucagon superfamily
Half-life
~2 minutes (IV) — extremely short
Route (studied)
IV, intranasal, inhaled (people)
Route (sold)
Nasal spray (compounded Rx); powder vials (research)
FDA Status
Not approved (Aviptadil Phase 3 negative); VIP is on FDA’s 503A Category 1 list (updated May 14, 2026)
Discovery
Said & Mutt, 1970
Receptors
VPAC1 / VPAC2 (G-protein-coupled)
Pivotal Trials
COVID ARDS (COVID-AIV), PAH inhaled, CIRS (Shoemaker)
WADA Status
Not specifically named; approved as aviptadil (Invicorp, with phentolamine) in Sweden and France, so S0 does not apply
Cost & Access
Compounded (intranasal) / Research-only

Also for immunity

The other four questions

What does it do? It relaxes blood vessels (Petkov et al., 2003), and in cell and animal studies it damps inflammation, helps run the brain's daily clock and raises surfactant production (Delgado & Ganea, 2013; Harmar et al., 2012; TESICO trial, 2023).
Who uses it? People treated for CIRS (a diagnosis tied to water-damaged buildings) with a compounded nasal spray; the clinic that published on it reported using it in more than 600 patients (Shoemaker et al., 2013).
Does the evidence hold up? Its effects in cells and animals are well documented (Delgado & Ganea, 2013), but in its one completed Phase 3 trial, IV aviptadil did no better than placebo in 461 adults in hospital with COVID-19 respiratory failure (TESICO trial, 2023). The nasal-spray use rests on one clinic's open-label series of 20 patients (Shoemaker et al., 2013); no controlled trial of it has been published.
Bottom line? Real biology, real limitations in the clinical data.

Dosing from the Literature

Published for immune use: 50 µg by nasal spray, 4 times a day, given to 20 adults with CIRS in one clinic's uncontrolled series (Shoemaker et al., 2013). Not published: a controlled trial of that use.

Route / ContextDoseFrequencyNotes
Intranasal (Shoemaker CIRS)50 µg a dose4× dailyTrial: open-label, 20 adults with CIRS whose illness persisted after the clinic's earlier protocol steps, for at least 18 months; after 6 months they adjusted the number of daily doses to their symptoms (Shoemaker et al., 2013).
IV infusion (aviptadil, COVID-19 respiratory failure)600, then 1,200, then 1,800 pmol/kgOne 12-hour infusion a day for 3 daysTrial: TESICO, Phase 3; 231 adults in hospital with COVID-19 respiratory failure got aviptadil and 230 placebo; stopped for futility (TESICO trial, 2023). The earlier COVID-AIV trial used the same 50, 100 and 150 pmol/kg per hour (ClinicalTrials.gov NCT04311697).
Inhaled (pulmonary hypertension studies)200 µg a day, as 4 inhalationsDaily, 12–24 weeksTrial: open-label, 8 patients with severe primary pulmonary hypertension (Petkov et al., 2003). A single 100 µg dose was given to 20 patients with pulmonary hypertension during right-heart catheterisation (Leuchte et al., 2008).
Intracavernous injection (Invicorp, with phentolamine)25 µg aviptadil + 2 mg phentolamineAt most once a day and 3 times a weekLabel (Invicorp, Norway, 2026): adult men with erectile dysfunction.
Where VIP Sits in the Shoemaker Protocol

In the Shoemaker protocol, VIP is the last step. The 20 patients in its published trial had already been through the earlier steps without recovering, among them removal from the water-damaged building, cholestyramine, clearing MARCoNS (multiple antibiotic-resistant coagulase-negative staphylococci) from deep in the nose, and treatments aimed at abnormal hormone, ADH/osmolality and inflammatory-marker results. The group reported that, in its earlier use, VIP worked less well in patients who still carried MARCoNS, had depressed visual contrast sensitivity or had a mold index (ERMI) above 2 in their settled dust, and it excluded such patients from the trial (Shoemaker et al., 2013).

Dosing Disclaimer

There is no FDA-approved VIP product. The one approved product found, Invicorp (authorised in Norway), combines aviptadil with phentolamine as an injection for erectile dysfunction (Invicorp label, 2026). The other doses above are those given in published studies, to the people named.

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What It Is

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide in the secretin/glucagon/PACAP superfamily. It was first isolated and named in 1970 by Sami Said and Viktor Mutt from porcine small intestinal extract for its vasodilatory activity (Said & Mutt, Science 1970; PMID 5450698). Over the following decades it became clear that VIP is endogenously produced throughout the body — in enteric neurons, pancreatic islets, brain (particularly the suprachiasmatic nucleus), lung, heart, and immune cells — and is one of the most broadly pleiotropic (having many effects at once) neuropeptides in mammalian biology.

The synthetic form of VIP is known as aviptadil (research code RLF-100), developed originally by Mondobiotech and subsequently by Relief Therapeutics and NRx Pharmaceuticals. Aviptadil has been investigated in pulmonary arterial hypertension (inhaled formulation), COVID-19-related acute respiratory distress syndrome (IV formulation, the COVID-AIV / STOP-COVID trials), and sarcoidosis. None of these programs has produced an FDA-approved product; Phase 3 results in both the PAH and COVID ARDS indications were negative or equivocal.

In the non-FDA / peptide-community context, VIP is used almost exclusively through the intranasal route as the final step of the Shoemaker protocol for Chronic Inflammatory Response Syndrome (CIRS) — a controversial diagnostic framework developed by Dr. Ritchie Shoemaker for illness associated with biotoxin exposure from water-damaged buildings. In the Shoemaker framework, CIRS patients characteristically have low serum VIP, and intranasal VIP replacement after sequential correction of upstream abnormalities (cholestyramine/Welchol binding, MARCoNS eradication, osmolality correction) is proposed to normalize immune-inflammatory markers (TGF-β1, MMP-9, C4a). Published evidence is primarily from Shoemaker's own practice-based case series; independent RCT validation does not exist.

VIP's extremely short plasma half-life (~2 minutes IV) creates formulation and delivery challenges. Intranasal delivery via compounded spray bypasses first-pass considerations and is the community's dominant route. Aviptadil for systemic indications has typically been delivered by IV infusion or aerosol inhalation.

Mechanism of Action

  • VPAC1 receptor activation — VPAC1 is expressed on immune cells (T lymphocytes, macrophages, monocytes, dendritic cells) and in the brain, intestine, lung and liver (Delgado & Ganea, 2013). In immune cells it signals through adenylate cyclase, cAMP and protein kinase A, the main pathway for VIP's anti-inflammatory effects in cell and mouse studies (Delgado & Ganea, 2013).
  • VPAC2 receptor activation — VPAC2 is expressed most in the thalamus and the suprachiasmatic nucleus (the brain's master clock), in smooth muscle of the cardiovascular, gut and reproductive systems, on pancreatic β-cells, and on T cells once they are activated (Harmar et al., 2012). Mice lacking VPAC2 lose normal circadian rhythms, and VIP's protection against excitotoxic brain lesions in newborn mice probably acts through it (Harmar et al., 2012).
  • PAC1 cross-reactivity — PAC1 is selective for PACAP, which is more than 100 times as potent as VIP at most forms of the receptor (Harmar et al., 2012); a form found on macrophages binds the two equally (Delgado & Ganea, 2013).
  • Immune modulation (Th1 → Th2/Treg shift) — In LPS-stimulated macrophages and microglia, VIP lowered TNF-α, IL-6 and IL-12 and raised IL-10; in cell and mouse studies it favors Th2 over Th1 cells and induces regulatory T cells, while its effect on Th17 cells is mixed (Delgado & Ganea, 2013). This is the central immune claim — VIP is an endogenous "brake" on pro-inflammatory signaling in the immune repertoire (Delgado & Ganea, Amino Acids 2013; PMID 22139413).
  • Neuroprotection — In newborn mice, VIP protected against excitotoxin-induced white-matter lesions, probably through VPAC2 (Harmar et al., 2012).
  • Pulmonary effects — VIP is a potent pulmonary and systemic vasodilator: inhaled, it lowered mean pulmonary artery pressure in 8 patients with primary pulmonary hypertension, a disease in which the same study found VIP deficient in serum and lung tissue (Petkov et al., JCI 2003; PMID 12727925).
  • Circadian rhythm regulation — VIP is made by neurons of the suprachiasmatic nucleus (SCN), the brain's master clock, and acts there through VPAC2; mice lacking VIP or VPAC2 have severely disrupted circadian rhythms of electrical activity, clock-gene expression, physiology and behavior (Harmar et al., 2012).
  • Gastrointestinal regulation — VIP relaxes smooth muscle, and its action on VPAC1 in the intestinal lining is thought to drive the chloride and water secretion behind the watery-diarrhea (Verner-Morrison) syndrome caused by VIP-secreting tumors (VIPomas) (Harmar et al., 2012).
  • Surfactant production — In laboratory studies aviptadil increases surfactant production, one of the lung-protective effects on which the COVID-19 respiratory-failure trials were based (TESICO trial, 2023).
  • Extremely short plasma half-life — 1.7 minutes after an IV injection of Invicorp in healthy men (Invicorp label, 2026).

What the Research Shows

  • Discovery (Said & Mutt, 1970; PMID 5450698) — Foundational paper isolating VIP from porcine intestine and describing its vasodilatory and secretory activity.
  • Pulmonary arterial hypertension — open-label (Petkov et al., JCI 2003; PMID 12727925) — Inhaled VIP reduced pulmonary artery pressure and improved hemodynamics in primary PAH patients. Basis for subsequent development program.
  • Pulmonary hypertension, single dose (Leuchte et al., 2008, Eur Respir J) — One inhaled 100 µg dose in 20 patients with pulmonary hypertension (9 with PAH) during right-heart catheterisation, without a control group: a small, short-lived pulmonary vasodilation, with no side effects and no change in systemic blood pressure.
  • PAH program — discontinued — The inhaled VIP PAH program did not produce an approved product; competing approved PAH therapies (endothelin receptor antagonists, PDE5 inhibitors, prostacyclin analogs) captured the indication.
  • COVID-19 ARDS — RLF-100 / aviptadil — Youssef et al., medRxiv 2020 brief report described IV aviptadil in COVID ARDS with signal for oxygenation improvement. Subsequent randomized COVID-AIV and ACTIV-3b / TESICO Phase 3 trials produced negative or equivocal results; FDA did not grant EUA.
  • CIRS / mold illness — Shoemaker (Health 2013) — Shoemaker RC et al., Health 2013;5(3):396-401 described intranasal VIP correction of CIRS symptoms after completion of upstream Shoemaker protocol. Practice-based case series; not independent RCT.
  • Sarcoidosis pilot — Inhaled VIP explored in small sarcoidosis cohorts with exploratory endpoints; not advanced to Phase 3.
  • Delgado et al. 2013 (Amino Acids; PMID 22139413) — Comprehensive review of VIP's immune functions and preclinical therapeutic potential in autoimmune models (RA, IBD, MS).
  • VIP in COVID inflammation — Preclinical and observational work establishing low VIP in COVID-related pulmonary inflammation, underlying the aviptadil ARDS hypothesis that was not validated in Phase 3.
  • Autoimmune preclinical models — Animal models of RA, IBD, experimental autoimmune encephalomyelitis demonstrate VIP reduces disease severity. Clinical translation has been limited.
  • VIPoma / Verner-Morrison syndrome — VIP-secreting pancreatic tumors produce characteristic WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria). Provides "excess VIP" biology counterpoint to therapeutic-dose VIP framework.
  • Biological plausibility vs clinical translation gap — VIP is one of the clearest examples in neuropeptide therapeutics of a compound with extensive basic-science rationale across many diseases (asthma, PAH, ARDS, autoimmune, Alzheimer's, CIRS, etc.) but a weak-to-negative clinical-translation record when tested in well-designed RCTs. The plausibility-to-evidence gap is itself instructive about how preclinical mechanism and clinical efficacy diverge.
  • Asthma and airway reactivity — VIP in asthma was one of the earliest proposed clinical uses (Said 1991). Small clinical experience did not translate into a viable therapeutic given the short half-life and the success of competing asthma pharmacology.
  • Alzheimer's / neurodegeneration — Preclinical neuroprotection work in APP/PS1 and other AD models shows VIP-analog variants (stearyl-norleucine-VIP / SNV, ADNP derivatives) protect against cognitive decline. No approved AD indication.
  • Autoimmune disease models — Collagen-induced arthritis, experimental autoimmune encephalomyelitis, and trinitrobenzene sulfonic acid colitis models all show VIP reduces disease severity. Translation to human autoimmune therapeutics never delivered.
  • COVID-era renewed interest — VIP's pulmonary biology (surfactant, bronchodilation, anti-inflammatory) seemed uniquely suited to COVID ARDS. The RLF-100 / aviptadil Phase 3 COVID program deployed at scale during 2020–2023 and produced negative or equivocal primary endpoints across multiple trials, ending the near-term pharmaceutical pathway.
Research Limitations

VIP's effects on immune cells, blood vessels and the brain's clock are well documented in cell and animal studies (Delgado & Ganea, 2013; Harmar et al., 2012). In people, its one completed Phase 3 trial found no benefit: IV aviptadil did no better than placebo in 461 adults in hospital with COVID-19 respiratory failure (TESICO trial, 2023). The inhaled pulmonary-hypertension studies were small and open-label (Petkov et al., 2003; Leuchte et al., 2008), and intranasal VIP for CIRS rests on one clinic's open-label series of 20 patients (Shoemaker et al., 2013); no controlled trial of that use has been published.

Human Data

  • PAH inhaled VIP — two open-label studies — Petkov 2003 (8 patients with primary pulmonary hypertension, 12–24 weeks), Leuchte 2008 (one dose in 20 patients with pulmonary hypertension). Positive early signals; did not translate into approved product.
  • COVID ARDS aviptadil IV — COVID-AIV / STOP-COVID / ACTIV-3b — Multiple trials examining aviptadil in severe COVID respiratory failure. Negative or equivocal primary endpoints; FDA declined emergency use authorization.
  • Shoemaker CIRS practice case series — Shoemaker RC, Health 2013 describing intranasal VIP correction of CIRS biomarkers (TGF-β1, MMP-9, C4a) and symptoms in 20 patients after completion of upstream protocol steps; VIP and MSH levels rose but stayed below the clinic's control values.
  • VIPoma case literature — Extensive clinical literature on VIP-secreting neuroendocrine tumors and the WDHA syndrome.
  • Sarcoidosis pilots — Small exploratory inhaled VIP cohorts.
  • No FDA-approved VIP or aviptadil product — Neither the PAH nor COVID development programs produced an approved product.

Reconstitution & Storage

VIP is sold as a nasal spray compounded by 503A pharmacies on prescription (it is on FDA’s 503A Category 1 list and on no 503B list), and as freeze-dried powder sold as a research chemical.

FormPreparationConcentrationStorage
Compounded nasal sprayMade up by a 503A pharmacyConcentration not published; the one trial gave 50 µg a dose (Shoemaker et al., 2013)Set by the pharmacy's label, with a beyond-use date
IV aviptadil (research trials)Prepared on site by the hospital pharmacy (TESICO trial, 2023)Dosed by body weight (see Dosing)Not given in the trial report
Invicorp (aviptadil with phentolamine)Ready-made solution in 0.35 mL glass ampoules25 µg aviptadil + 2 mg phentolamine per ampouleRefrigerated at 2–8°C, not frozen (Invicorp label, 2026)
  • Short plasma half-life — 1.7 minutes after an IV injection of Invicorp in healthy men (Invicorp label, 2026). The COVID-19 trials gave aviptadil as 12-hour infusions in hospital (TESICO trial, 2023).

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Side Effects & Risks

Important

In its one completed Phase 3 trial, IV aviptadil did no better than placebo for adults in hospital with COVID-19 respiratory failure (TESICO trial, 2023). Intranasal use for CIRS has been reported only by the clinic that proposed it, in uncontrolled series (Shoemaker et al., 2013). Consult a licensed healthcare provider.

  • Nasal spray (intranasal) — In the one published series, 20 adults used the spray for 18 months with no dropouts for side effects; one had a temporary rise in lipase, without abdominal pain, that resolved while still using VIP (Shoemaker et al., 2013).
  • Diarrhea / loose stools — During IV aviptadil infusions, 40% of 231 adults in hospital with COVID-19 had diarrhea, against 11% on placebo (TESICO trial, 2023); VIP acting on the intestinal lining is thought to drive chloride and water secretion (Harmar et al., 2012). In that trial diarrhea, flushing, fast heart rate and low blood pressure were more common on the second and third days, when the dose was higher, and 10% of the aviptadil group had an infusion stopped for an adverse event, against 6% on placebo (TESICO trial, 2023).
  • Hypotension — VIP is a potent systemic and pulmonary vasodilator (Petkov et al., 2003). Low blood pressure was recorded during the infusions in 58% of the IV aviptadil group, against 41% on placebo (TESICO trial, 2023); inhaled VIP did not change systemic blood pressure in two small pulmonary-hypertension studies (Petkov et al., 2003; Leuchte et al., 2008).
  • Flushing — Facial flushing in 15% of the IV aviptadil group, against 6% on placebo (TESICO trial, 2023). The label of Invicorp, which combines aviptadil with phentolamine, calls mild, passing flushing of the face or upper body common (Invicorp label, 2026).
  • Headache — Listed as uncommon (under 1 in 100), with dizziness, on the Invicorp label (Invicorp label, 2026).
  • Tachycardia / palpitations — A fast heart rate in 10% of the IV aviptadil group, against 5% on placebo (TESICO trial, 2023); the Invicorp label lists palpitations and tachycardia as uncommon and says to stop treatment if tachycardia occurs (Invicorp label, 2026).
  • Invicorp injection — For this injection into the penis, the label lists bruising as common, and prolonged erection, priapism and penile nodules or fibrosis after repeated injections as rare (Invicorp label, 2026).
  • Drug interactions — The Invicorp label reports no interactions seen with blood-pressure or other cardiovascular medicines, lists caution with anticoagulants, and says not to combine it with other erectile-dysfunction drugs such as sildenafil (Invicorp label, 2026). Because IV aviptadil lowers blood pressure (TESICO trial, 2023), an added effect with other blood-pressure-lowering drugs is a theoretical concern.
  • Pregnancy / lactation — No trial has studied VIP in pregnancy or breastfeeding; the Invicorp label notes that no animal reproduction studies have been done (Invicorp label, 2026).
  • Active malignancy — Most common human tumors carry VPAC1 receptors (Harmar et al., 2012), and overexpression of VIP receptors has been associated with cancerous growth (Gozes & Furman, 2004). The concern is theoretical, based on that receptor biology.
  • Cardiovascular disease — The Invicorp label lists caution in severe cardiovascular or cerebrovascular disease (Invicorp label, 2026).
  • WADA status — Not specifically named on the WADA Prohibited List.

Bloodwork & Monitoring

No trial or guideline sets monitoring for VIP nasal spray or research powder. In the one published CIRS series, the clinic measured VIP, MSH, C4a, TGF-β1, VEGF, MMP-9, estradiol, testosterone, 25-OH vitamin D, lipase, blood counts (CBC) and a metabolic panel (CMP) in 20 adults before any treatment, after the earlier protocol steps and after 12 and 18 months of VIP, plus T-regulatory cells and pulmonary artery pressure on exercise echocardiography. By 18 months C4a, TGF-β1 and MMP-9 no longer differed from the clinic's controls, CBC and CMP had not changed, and VIP and MSH had risen but stayed below control values (Shoemaker et al., 2013). Serum VIP averaged 42.4 pg/mL in 45 healthy controls in one study (Petkov et al., 2003) and 28.9 pg/mL in the Shoemaker clinic's controls (Shoemaker et al., 2013).

In the COVID-19 trial, blood pressure was checked at least every 2 hours during each IV infusion and for 2 hours after (TESICO trial, 2023). The Invicorp label lists regular check-ups, for example every 3 months, for men who inject it themselves (Invicorp label, 2026).

Quick Compare — VIP vs KPV vs Thymosin α1 vs BPC-157

VIP is one of several community-used peptides targeting immune and inflammation biology. Clear comparison:

FeatureVIP (Aviptadil)KPVThymosin α1BPC-157
Sequence28 aa (secretin/glucagon family)Tripeptide Lys-Pro-Val (α-MSH C-terminus)28 aa (thymic origin)15 aa (gastric origin)
Primary receptorVPAC1 / VPAC2Melanocortin MC1R/MC5R-adjacentTLR9VEGFR2, FAK-paxillin
Half-life~2 min (IV) — very shortHoursHours~4–6 hrs
Approved drugNo FDA approval (aviptadil Phase 3 failed); authorised in Norway as Invicorp, with phentolamine, for erectile dysfunction (Invicorp label, 2026)NoYes (Zadaxin, >30 countries)No (removed from Category 2 Apr 22, 2026; rulemaking pending)
Community primary useCIRS (Shoemaker intranasal)Chronic GI inflammation, autoimmuneImmune restoration, hepatitisTissue repair, GI healing
Evidence strengthPhase 3 failed; case series (Shoemaker)Preclinical + small clinicalMultiple Phase 2/3 + approval~150 preclinical papers; limited clinical
RouteIntranasal / IV / inhaledOral / SubQSubQSubQ / oral
  • VIP vs KPV — Both are community anti-inflammatory peptides. KPV operates via melanocortin biology (shorter acute half-life effect but orally bioavailable); VIP operates via VPAC receptors with broader pleiotropic effects but requires intranasal or IV delivery due to extreme half-life constraint.
  • VIP vs Thymosin α1 — Thymosin α1 has approved pharmaceutical status for hepatitis; VIP has no FDA-approved indication despite Phase 3 investment; the one authorisation found is Norway's, for erectile dysfunction in combination with phentolamine (Invicorp label, 2026). Different biology (adaptive immune polarization vs VPAC-cAMP signaling).
  • VIP vs BPC-157 — Overlapping GI-healing claims. BPC-157 has a much more developed preclinical tissue-repair database; VIP's GI use is more inflammatory/immune-modulatory than structural-repair-focused.
  • Shoemaker CIRS protocol — VIP is the protocol's last step; none of the other three peptides in this table is among its published steps (Shoemaker et al., 2013).

→ See KPV profile  •  → See Thymosin α1 profile  •  → See BPC-157 profile

Commonly Stacked With

Cholestyramine (Shoemaker protocol)

In the Shoemaker protocol, the bile-acid binder cholestyramine is the second step, after removal from the water-damaged building, and is continued while the later steps, VIP last, are added (Shoemaker et al., 2013).

MARCoNS clearance (Shoemaker protocol)

In the Shoemaker protocol, clearing MARCoNS (multiple antibiotic-resistant coagulase-negative staphylococci) from deep in the nose is the third step, and patients still carrying them were excluded from the VIP trial (Shoemaker et al., 2013).

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Legal Status

Current Status — April 2026

VIP / aviptadil is not FDA-approved for any indication. The Phase 3 program for aviptadil in COVID-19-related respiratory failure (COVID-AIV / ACTIV-3b / TESICO) produced negative or equivocal primary endpoints, and the FDA did not grant emergency use authorization. The inhaled VIP program for pulmonary arterial hypertension was not advanced to approval.

VIP is available as a compounded preparation from 503A compounding pharmacies in the United States, including as the nasal spray used in the Shoemaker CIRS protocol (Shoemaker et al., 2013). Vasoactive intestinal peptide is on FDA’s 503A Category 1 list (updated May 14, 2026), so state-licensed pharmacies may compound it for individual prescriptions under FDA’s interim policy. It is not on the 503B bulks list or in any 503B category, so outsourcing facilities can’t compound it from bulk.

VIP is not currently on the FDA Category 2 Bulk Drug Substances list, and it was not among the 12 peptides FDA removed from that list in April 2026 (FDA 503A categories list, April 22, 2026). Compounded VIP availability remains subject to evolving regulatory oversight and individual pharmacy compliance.

VIP is not named on the WADA Prohibited List. Aviptadil is approved in Sweden and France (Invicorp, with phentolamine), so S0, which covers substances with no current government approval, does not apply (WADA Prohibited List 2026).

Cost & Access

VIP is not FDA-approved but is available through 503A compounding pharmacies in the United States, including as the nasal spray used in Shoemaker's CIRS protocol (Shoemaker et al., 2013). A clinician's prescription is required, and compounded-VIP availability depends on continued bulk-substance supply under 503A rules.

Outside the compounding-pharmacy route, research-grade VIP is available from research-chemical vendors for laboratory research purposes only.

RLF-100, the IV and inhaled form of aviptadil, has no approved indication and is not commercially available outside research / compassionate-use contexts; the one approved aviptadil product found is Invicorp, an injection for erectile dysfunction that combines it with phentolamine, authorised in Norway since 2015 (Invicorp label, 2026). The collapse of the COVID-19 aviptadil Phase 3 program effectively ended the near-term pharmaceutical-development pathway for the compound.

Estimated pricing as of April 2026. Actual costs vary by provider, location, and prescription status. Kalios does not sell compounds.

References

  1. Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970;169(3951):1217-1218. PMID: 5450698.
  2. Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013;45(1):25-39. PMID: 22139413.
  3. Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003;111(9):1339-1346. PMID: 12727925.
  4. Leuchte HH, Baezner C, Baumgartner RA, Bevec D, Bacher G, Neurohr C, Behr J. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. PMID: 18978135.
  5. Youssef JG, Said SI, Reichman JR, Alshaibi M. A Brief Report on RLF-100 (Aviptadil) in the Treatment of Critical COVID-19 Patients with Respiratory Failure. medRxiv. 2020. (Preprint basis for aviptadil COVID development program.)
  6. Shoemaker RC, House DE, Ryan JC. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health. 2013;5(3):396-401. DOI: 10.4236/health.2013.53053.
  7. Said SI. Vasoactive Intestinal Polypeptide (VIP) in Asthma. Ann N Y Acad Sci. 1991;629:305-318. PMID: 1683200.
  8. Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. 2004;56(2):249-290. PMID: 15169929.
  9. Dickson L, Finlayson K. VPAC and PAC receptors: From ligands to function. Pharmacol Ther. 2009;121(3):294-316. PMID: 19109992.
  10. Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR, Vaudry D, Vaudry H, Waschek JA, Said SI. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166(1):4-17. PMID: 22289055.
  11. Verner JV, Morrison AB. Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med. 1958;25(3):374-380. PMID: 13571250.
  12. Zhao H, Zhu H, Huang J, Zhu Y, Hong M, Zhu H, Zhang J, Li S, Yang L, Lian Y, Huang S. The synergy of vasoactive intestinal peptide and melatonin during anti-inflammation in collagen-induced arthritis rats. Mol Med Rep. 2018;17(5):6723-6732.
  13. Gozes I, Furman S. Clinical endocrinology and metabolism. Potential clinical applications of vasoactive intestinal peptide: a selected update. Best Pract Res Clin Endocrinol Metab. 2004;18(4):623-640. PMID: 15533779.
  14. ClinicalTrials.gov. Aviptadil (RLF-100) in the Treatment of Acute Respiratory Distress Syndrome Due to COVID-19 (COVID-AIV). Multiple NCT registrations. 2020–2024.
  15. NIH / ACTIV-3b / TESICO trial publications on aviptadil in hospitalized COVID-19 with respiratory failure (Lancet Respir Med, 2023).
  16. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
  17. Evolan Pharma AB. Invicorp 25 mikrogram/2 mg injeksjonsvæske, oppløsning (aviptadil 25 µg, phentolamine mesilate 2 mg): preparatomtale (summary of product characteristics, in Norwegian). Direktoratet for medisinske produkter (Norwegian Medical Products Agency), marketing authorisation 13-9854; first authorised July 21, 2015, renewed February 21, 2020; text updated July 9, 2026. produktinformasjon.legemiddelsok.no/preparatomtaler/13-9854.pdf. Read October 4, 2026.
  18. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.

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Tested together in people

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Checked 13 Oct 2026