Ambrisentan

Ambrisentan
Names
Trade namesLetairis, Volibris, Pulmonext, others
IUPAC name
  • (2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid
Clinical data
Drug classEndothelin receptor antagonist[1]
Main usesPulmonary hypertension[2]
Side effectsSwelling, palpitations, headache, constipation[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: X (High risk)
  • US: N (Not classified yet)
    Routes of
    use    		Oral
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa612023
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • UK: POM (Prescription only)
    • US: ℞-only
    • EU: Rx-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    BioavailabilityUndetermined
    Protein binding99%
    Elimination half-life15 hours (terminal)
    Chemical and physical data
    FormulaC22H22N2O4
    Molar mass378.428 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(O)[C@@H](Oc1nc(cc(n1)C)C)C(OC)(c2ccccc2)c3ccccc3
    InChI
    • InChI=1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1 checkY
    • Key:OUJTZYPIHDYQMC-LJQANCHMSA-N checkY

    Ambrisentan, sold under the brand name Letairis among others, is a medication used for pulmonary hypertension.[2] It improved the ability to exercise and slows worsening.[2] It is not useful in those with pulmonary fibrosis.[2] It is taken by mouth.[2]

    Common side effects include swelling, palpitations, headache, and constipation.[2] Other side effects may include anemia, flushing, ringing in the ears, and liver problems.[3] Use in pregnancy may harm the baby.[3] It works by blocking the endothelin receptor, specifically the type A endothelin receptor (ETA).[1]

    Ambrisentan was approved for medical use in the United States in 2007 and Europe in 2008.[2][4] In the United Kingdom it costs the NHS about £1,600 per month.[3] In the United States this amount costs about 5,100 USD as of 2021.[5]

    Medical uses

    Ambrisentan is used for the treatment of pulmonary arterial hypertension (WHO Group 1) in people with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.[6]

    Dosage

    It is taken at a dose of 5 to 10 mg once per day.[4]

    Side effects

    Pregnancy

    Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. In addition to this, endothelin receptors are also known to play a role in neural crest cell migration, growth, and differentiation. As such, endothelin receptor antagonists such as Ambrisentan are known to be teratogenic.

    Ambrisentan has a high risk of liver damage, and of birth defects if a woman becomes pregnant while taking it. In the U.S., doctors who prescribe it, and patients who take it, must enroll in a special program, the LETAIRIS Education and Access Program (LEAP), to learn about those risks. Ambrisentan is available only through specialty pharmacies.

    Research

    Last Updated 9/2/2015

    8/15/2015 Reprod. Toxicol.Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. As such, endothelin receptor antagonists such as Ambrisentan are teratogenic.[7]
    8/27/2015 NEJMAmbrisentan when used in combination therapy with tadalafil was found to be more efficacious in treating treatment naive patients with WHO class II or III Pulmonary Arterial Hypertension than monotherapy using either drug.[8]

    References

    1. 1 2 Vatter H, Seifert V (2006). "Ambrisentan, a non-peptide endothelin receptor antagonist". Cardiovasc Drug Rev. 24 (1): 63–76. doi:10.1111/j.1527-3466.2006.00063.x. PMID 16939634.
    2. 1 2 3 4 5 6 7 8 "Ambrisentan Monograph for Professionals". Drugs.com. Archived from the original on 4 July 2021. Retrieved 21 July 2021.
    3. 1 2 3 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 195. ISBN 978-0-85711-369-6.
    4. 1 2 "Volibris". Archived from the original on 23 July 2021. Retrieved 21 July 2021.
    5. ↑ "Ambrisentan Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 10 April 2021. Retrieved 21 July 2021.
    6. ↑ "Letairis- ambrisentan tablet, film coated". DailyMed. 4 September 2019. Archived from the original on 10 August 2020. Retrieved 18 April 2020.
    7. ↑ de Raaf MA, Beekhuijzen M, Guignabert C, Vonk Noordegraaf A, Bogaard HJ (2015). "Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension". Reproductive Toxicology. 56: 45–51. doi:10.1016/j.reprotox.2015.06.048. PMID 26111581.
    8. ↑ Galiè, Nazzareno; Barberà, Joan A.; Frost, Adaani E.; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M.; McLaughlin, Vallerie V.; Peacock, Andrew J.; Simonneau, Gérald; Vachiery, Jean-Luc; Grünig, Ekkehard; Oudiz, Ronald J.; Vonk-Noordegraaf, Anton; White, R. James; Blair, Christiana; Gillies, Hunter; Miller, Karen L.; Harris, Julia H.N.; Langley, Jonathan; Rubin, Lewis J. (2015). "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension". New England Journal of Medicine. 373 (9): 834–44. doi:10.1056/NEJMoa1413687. hdl:2445/97236. PMID 26308684.
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