Iloprost

Iloprost, sold under the brand name Ventavis among others, is a medication used to treat pulmonary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon, frostbite, and other conditions in which the blood vessels are constricted and blood cannot flow to the tissues.^[4] Iloprost is a prostacyclin mimetic.^[1]

Iloprost

Clinical data
Trade names	Ventavis, Ilomedine, Aurlumyn
AHFS/Drugs.com	Monograph
MedlinePlus	a612032
License data	US DailyMed: Iloprost
Routes of administration	Inhalation, intravenous
ATC code	B01AC11 (WHO)
Legal status
Legal status	US: ℞-only[1][2] EU: Rx-only[3] In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Not determined[1]
Protein binding	60%[1]
Metabolism	Via β-oxidation to inactive tetranor-iloprost[1]
Elimination half-life	20–30 minutes[1]
Excretion	Kidney (68%) and fecal (12%)[1]
Identifiers
IUPAC name 5-{(E)-(1S,5S,6R,7R)-7-hydroxy-6[(E)-(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-ynyl]-bicyclo[3.3.0]octan-3-ylidene}pentanoic acid
CAS Number	78919-13-8 Y 73873-87-7
PubChem CID	5311181
DrugBank	DB01088 Y
ChemSpider	4470703 N
UNII	JED5K35YGL
KEGG	D02721 Y
ChEMBL	ChEMBL236025 Y
CompTox Dashboard (EPA)	DTXSID2041046
ECHA InfoCard	100.163.887
Chemical and physical data
Formula	C22H32O4
Molar mass	360.494 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC#CCC(C)[C@@H](/C=C/[C@H]1[C@@H](C[C@H]2[C@@H]1C/C(=C/CCCC(=O)O)/C2)O)O
InChI InChI=1S/C22H32O4/c1-3-4-7-15(2)20(23)11-10-18-19-13-16(8-5-6-9-22(25)26)12-17(19)14-21(18)24/h8,10-11,15,17-21,23-24H,5-7,9,12-14H2,1-2H3,(H,25,26)/b11-10+,16-8+/t15?,17-,18+,19-,20+,21+/m0/s1 N Key:HIFJCPQKFCZDDL-ACWOEMLNSA-N N
NY (what is this?)  (verify)

For pulmonary arterial hypertension, iloprost is given via inhalation. Iloprost works by opening (dilating) the blood vessels to allow the blood to flow through them. It was developed by the pharmaceutical company Schering AG and is marketed by Bayer Schering Pharma AG in the European Union and by Actelion Pharmaceuticals in the US.

Medical uses

In the US, iloprost is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration.^[1]

In the EU, iloprost is indicated for the treatment of people with primary pulmonary hypertension, classified as New York Heart Association functional class III, to improve exercise capacity and symptoms.^[3]

In February 2024, the US Food and Drug Administration approved iloprost (Aurlumyn) to treat severe frostbite to reduce the risk of finger or toe amputation.^[2][5]

Clinical pharmacology

Iloprost is a synthetic analogue of prostacyclin PGI₂. Iloprost dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer. While Iloprost is an analog of PGI₂ that activates PGI₂'s receptor, the prostacyclin receptor, to stimulate vasodilation, it has little selectivity in that it binds to and activates all four receptors for prostaglandin E2 viz., prostaglandin EP1 receptor, prostaglandin EP2 receptor, prostaglandin EP3 receptor, and prostaglandin EP4 receptor.^[6] Activation of the EP2 and EP4 receptors cause vasodilation but activation of the EP3 receptor causes vasoconstriction.

Contraindications

Contraindications include: unstable angina; within 6 months of myocardial infarction; decompensated cardiac failure (unless under close medical supervision); severe arrhythmias; congenital or acquired heart-valve defects; within 3 months of cerebrovascular events; pulmonary veno-occlusive disease; conditions which increase risk of bleeding.

Common side effects

In clinical studies, common adverse reactions due to inhaled iloprost included: vasodilation (flushing, 27%), cough (39%), headache (30%), flu syndrome (14%), nausea (13%), neck spasms (12%), hypotension (11%), insomnia (8%), and fainting (syncope) (8%); other serious adverse events reported with the use of Ventavis included congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, swelling of the limbs (especially around the ankles and feet), and kidney failure.

Serious adverse events reported with the use of inhaled iloprost include congestive heart failure, chest pain, supraventricular tachycardia, shortness of breath, peripheral edema, and kidney failure.

References

1. "Ventavis- iloprost solution". DailyMed. 26 July 2022. Archived from the original on 19 February 2024. Retrieved 19 February 2024.
2. "Aurlumyn- iloprost injection, solution". DailyMed. 11 March 2024. Retrieved 6 May 2024.
3. "Ventavis EPAR". European Medicines Agency (EMA). 26 August 2013. Archived from the original on 12 November 2020. Retrieved 19 February 2024.
4. "Iloprost Information" (PDF). Archived from the original (PDF) on 6 April 2016. Retrieved 5 February 2009.
5. "FDA Approves First Medication to Treat Severe Frostbite" (Press release). U.S. Food and Drug Administration (FDA). 14 February 2024. Archived from the original on 16 February 2024. Retrieved 16 February 2024. This article incorporates text from this source, which is in the public domain.
6. Moreno JJ (February 2017). "Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis". European Journal of Pharmacology. 796: 7–19. doi:10.1016/j.ejphar.2016.12.004. PMID 27940058. S2CID 1513449.

Further reading

• Olschewski H, Simonneau G, Galiè N, Higenbottam T, Naeije R, Rubin LJ, et al. (August 2002). "Inhaled iloprost for severe pulmonary hypertension". The New England Journal of Medicine. 347 (5): 322–329. doi:10.1056/NEJMoa020204. PMID 12151469.
• Meizer R, Meraner D, Meizer E, Radda C, Landsiedl F, Aigner N (January 2009). "Outcome of painful bone marrow edema of the femoral head following treatment with parenteral iloprost". Indian Journal of Orthopaedics. 43 (1): 36–39. doi:10.4103/0019-5413.45321 (inactive 1 November 2024). PMC 2739485. PMID 19753177.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)