|Biological half-life||5 hours|
|Chemical and physical data|
|Molar mass||551.614 g/mol|
|3D model (JSmol)|
|(what is this?)|
Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer.
Bosentan is used to treat people with moderate pulmonary arterial hypertension and to reduce the number of digital ulcers — open wounds on especially on fingertips and less commonly the knuckles — in people with systemic scleroderma.
Bosentan causes harm to fetuses and pregnant women must not take it, and women must not become pregnant while taking it (Pregnancy Category X). It may render hormonal contraceptives ineffective so other forms of birth control must be used.
In the US it is only available from doctors who follow an FDA-mandated risk evaluation and mitigation strategy (REMS) with respect to risks to fetuses and its risks of causing liver damage. The doctor must document a negative pregnancy test for women before prescribing the drug, counsel about contraception, and give regular pregnancy tests. Because there is a high risk that bosentan causes liver damage, the REMS plan also requires pre-testing for elevated transaminases and regular testing while the drug is being taken.
In addition to the risk of causing birth defects and of causing liver damage, bosentan has a high risk of causing edema, pulmonary veno-occlusive disease, decreasing sperm counts, and decreases in hemoglobin and hematocrit.
Very common adverse effects (occurring in more than 10% of people) include headache, elevated transaminases, and edema. Common adverse effects (between 1% and 10% of people) include anemia, reduced hemoglobin, hypersensitivity reactions, skin inflammation, itchiness, rashes, red skin, flushing, fainting, heart palpitations, low blood pressure, nasal congestion, gastro-esophageal reflux disease, and diarrhea.
Mechanism of action
Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. By blocking this interaction, bosentan decreases pulmonary vascular resistance. Bosentan has a slightly higher affinity for ET-A than ET-B.
Bosentan was studied in heart failure in a trial called REACH-1 that was terminated early in 1997 due to toxicity at the dose that was being studied; as of 2001 the results of that trial had not been published.
By 2013 worldwide sales of bosentan were $1.57 billion. The patents on bosentan started expiring in 2015.
- "Tracleer (bosentan) 62.5 mg and 125mg film-coated tablets". UK Electronic Medicines Compendium. May 2017. Retrieved 6 August 2017.
- "US Bosentan label" (PDF). FDA. October 2016. Retrieved 6 August 2017. For label updates see FDA index page for NDA 021290
- Abraham, S; Steen, V (2015). "Optimal management of digital ulcers in systemic sclerosis.". Therapeutics and clinical risk management. 11: 939–47. PMC . PMID 26109864. doi:10.2147/TCRM.S82561.
- "Approved Risk Evaluation and Mitigation Strategies (REMS)". FDA. Retrieved 6 August 2017.
- Funke C, Farr M, Werner B, Dittmann S, Uberla K, Piper C, Niehaus K, Horstkotte D (Apr 2010). "Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells.". Journal of General Virology. 91 (8): 1959–70. PMID 20392896. doi:10.1099/vir.0.020065-0.
- van Veldhuisen, DJ; Poole-Wilson, PA (August 2001). "The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure.". International journal of cardiology. 80 (1): 19–27. PMID 11532543.
- Helfand, Carly (2015). "The top 10 patent losses of 2015: Tracleer". FiercePharma.