Treprostinil

{{Infobox drug

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| Watchedfields = changed

| verifiedrevid = 477864833

| image = Treprostinil.svg

| width = 250

| alt =

| image2 = Treprostinil2.png

| alt2 =

| pronounce =

| tradename = Remodulin, Orenitram, Tyvaso, others

| Drugs.com = {{drugs.com|monograph|treprostinil-sodium}}

| MedlinePlus =

| DailyMedID = Treprostinil

| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = Subcutaneous, intravenous, inhalation, by mouth

| class =

| ATC_prefix = B01

| ATC_suffix = AC21

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| legal_NZ =

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| legal_UK =

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| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Remodulin- treprostinil injection, solution; Sterile diluent for remodulin- water injection, solution | website=DailyMed | date=9 October 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6c80bb38-e8db-4138-9f0d-dbbf9c673185 | access-date=21 May 2024}}{{cite web | title=Orenitram- treprostinil tablet, extended release; Orenitram- treprostinil kit | website=DailyMed | date=7 November 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ed2003a-c801-411e-831e-d06079bb0d7c | access-date=21 May 2024}}{{cite web | title=Tyvaso- treprostinil inhalant | website=DailyMed | date=8 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609 | access-date=21 May 2024}}{{cite web | title=Tyvaso DPI- treprostinil inhalant; Tyvaso DPI- treprostinil kit | website=DailyMed | date=26 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f | access-date=21 May 2024}}

| legal_EU = Rx-only

| legal_EU_comment =

| legal_UN =

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| legal_status = Rx-only

| bioavailability = ~100%

| protein_bound =

| metabolism = Substantially metabolized by the liver

| metabolites =

| onset =

| elimination_half-life = 4 hours

| duration_of_action =

| excretion = Urine (79% of administered dose is excreted as 4% unchanged drug and 64% as identified metabolites); feces (13%)

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 81846-19-7

| CAS_supplemental =

| PubChem = 6918140

| IUPHAR_ligand = 5820

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00374

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5293353

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = RUM6K67ESG

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D06213

| KEGG2_Ref = {{keggcite|changed|kegg}}

| KEGG2 = D08628

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 50861

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201254

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| synonyms =

| IUPAC_name = (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid

| C=23 | H=34 | O=5

| SMILES =

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = PAJMKGZZBBTTOY-ZFORQUDYSA-N

| density =

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}}

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension.{{cite journal | vauthors = Torres F, Rubin LJ | title = Treprostinil for the treatment of pulmonary arterial hypertension | journal = Expert Review of Cardiovascular Therapy | volume = 11 | issue = 1 | pages = 13–25 | date = January 2013 | pmid = 23259441 | doi = 10.1586/erc.12.160 | s2cid = 29661141 }}

Treprostinil was approved for use in the United States in May 2002.{{cite web | title=Drug Approval Package: Remodulin (Treprostinil Sodium) NDA #021272 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-272_Remodulin.cfm | access-date=9 April 2020}}

Medical uses

Treprostinil is indicated for the treatment of pulmonary arterial hypertension in people with NYHA Class II-IV symptoms to diminish symptoms associated with exercise.

Adverse effects

Since treprostinil is a vasodilator, its antihypertensive effect may be compounded by other medications that affect the blood pressure, including calcium channel blockers, diuretics, and other vasodilating agents.
Because of treprostinil's inhibiting effect on platelet aggregation, there is an increased risk of bleeding, especially among patients who are also taking anticoagulants.
It is not known whether treprostinil is excreted in breast milk. Caution is advised when administering this medication to nursing women.
Caution is advised when administering treprostinil to patients who have impaired kidney or liver function.

Common side effects depending on route of administration:

85% of patients report pain or other reaction at the infusion site.{{cite journal | vauthors = Kumar P, Thudium E, Laliberte K, Zaccardelli D, Nelsen A | title = A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration | journal = Clinical Pharmacokinetics | volume = 55 | issue = 12 | pages = 1495–1505 | date = December 2016 | pmid = 27286723 | pmc = 5107196 | doi = 10.1007/s40262-016-0409-0 }}

Administration

=For infusion=

Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion.

=Inhaled form=

The inhaled form of treprostinil was approved by the FDA in July 2009, and is sold under the brand name Tyvaso.

=Oral form=

The oral form of treprostinil was approved by the FDA in December 2013, and is sold under the brand name Orenitram.

History

During the 1960s a UK research team, headed by Professor John Vane began to explore the role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons, Vane discovered that aspirin and other oral anti-inflammatory drugs worked by inhibiting the synthesis of prostaglandins. This finding opened the door to a broader understanding of the role of prostaglandins in the body.

Vane and a team from the Wellcome Foundation had identified a lipid mediator they called “PG-X,” which inhibited platelet aggregation. PG-X, which later would become known as prostacyclin, was 30 times more potent than any other known anti-aggregatory agent.{{citation needed|date=December 2015}}

By 1976, Vane and fellow researcher Salvador Moncada published the first paper on prostacyclin, in the scientific journal Nature.{{cite journal | vauthors = Moncada S, Gryglewski R, Bunting S, Vane JR | title = An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation | journal = Nature | volume = 263 | issue = 5579 | pages = 663–665 | date = October 1976 | pmid = 802670 | doi = 10.1038/263663a0 | s2cid = 4279030 | bibcode = 1976Natur.263..663M }}

Treprostinil (Remodulin) was approved for use in the United States in May 2002, and again in July 2018.{{cite web | title=Drug Approval Package: Remodulin | website=U.S. Food and Drug Administration (FDA) | date=7 February 2019 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208276Orig1s000TOC.cfm | access-date=9 April 2020}} Tyvaso, the inhaled form of treprostinil, was approved for use in the United States in July 2009.{{cite web | title=Drug Approval Package: Tyvaso (Treprostinil) Inhalation Solution NDA #022387 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022387s000TOC.cfm | access-date=9 April 2020}} Orenitram was approved in December 2013.{{cite web | title=Drug Approval Package: Orenitram (Treprostinil) Extended Release Tablets NDA #203496 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203496Orig1s000TOC.cfm | access-date=9 April 2020}}

Treprostinil (Trepulmix) was approved for use in the European Union in April 2020.{{cite web | title=Trepulmix EPAR | website=European Medicines Agency (EMA) | date=29 January 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/trepulmix | access-date=9 April 2020}}

Research

Treprostinil therapy may be effective in treating Degos disease.{{cite journal | vauthors = Shapiro LS, Toledo-Garcia AE, Farrell JF | title = Effective treatment of malignant atrophic papulosis (Köhlmeier-Degos disease) with treprostinil--early experience | journal = Orphanet Journal of Rare Diseases | volume = 8 | pages = 52 | date = April 2013 | pmid = 23557362 | pmc = 3636001 | doi = 10.1186/1750-1172-8-52 | doi-access = free }}