 | |
| Names | |
|---|---|
| Trade names | Tracleer, Stayveer |
| |
| Clinical data | |
| Drug class | Endothelin receptor antagonist[1] |
| Main uses | Pulmonary artery hypertension (PAH),systemic sclerosis[1][2] |
| Side effects | Respiratory tract infection,low red blood cells, fever[1] |
| Pregnancy category | |
| Routes of use | By mouth |
| External links | |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605001 |
| Legal | |
| License data | |
| Legal status | |
| Pharmacokinetics | |
| Bioavailability | 50% |
| Protein binding | >98% |
| Metabolism | Liver |
| Eliminationhalf-life | 5 hours |
| Chemical and physical data | |
| Formula | C27H29N5O6S |
| Molar mass | 551.62 g·mol−1 |
| 3D model (JSmol) | |
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Bosentan, sold under the brand nameTracleer among others, is a medication used to treatpulmonary artery hypertension (PAH) andsystemic sclerosis.[1][2] It is taken by mouth.[2] It may be used in those over the age of 2.[1]
Common side effects includerespiratory tract infection,low red blood cells, and fever.[1] Other side effects may include swelling, liver probelms, andpulmonary veno-occlusive disease.[1] Use in pregnancy may harm the baby.[1] It is aendothelin receptor antagonist.[1]
Bosentan was approved for medical use in the United States in 2001 and Europe in 2022.[1][3] It is avaliable as ageneric medication.[2] In the United Kingdom 4 weeks of treatment costs about £110 as of 2021.[2] This amount in the United States is about 1,100 USD.[5]
Bosentan is used to treat people with moderatepulmonary arterial hypertension and to reduce the number of digital ulcers — open wounds on especially on fingertips and less commonly the knuckles — in people withsystemic scleroderma.[1][4][6]
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 renderhormonal contraceptives ineffective so other forms of birth control must be used.[1][4]
In the US it is only available from doctors who follow an FDA-mandatedrisk 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.[7] Because there is a high risk that bosentan causesliver damage, the REMS plan also requires pre-testing forelevated transaminases and regular testing while the drug is being taken.[7] Bosentan is also contraindicated in patients takingglyburide due to an increased risk of increased liver enzymes and liver damage when these two agents are taken together.[1]
Bosentan is available as film-coated tablets (62.5 mg or 125 mg) or as dispersable tablets for oral suspension (32 mg).[1] It is started at 62.5 mg twice per day for 4 weeks and than increased to 125 mg twice per day.[2]
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 inhemoglobin andhematocrit.[1][4]
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.[1][4]
Bosentan is a competitive antagonist ofendothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A receptors causesconstriction of the pulmonary blood vessels.[8] Conversely, binding of endothelin-1 to ET-B receptors has been associated with both vasodilation and vasoconstriction of vascular smooth muscle, depending on the ET-B subtype (ET-B1 or ET-B2) and tissue.[9] Bosentan blocks both ET-A and ET-B receptors, but is thought to exert a greater effect on ET-A receptors, causing a total decrease in pulmonary vascular resistance.[1]
Absolute bioavailability of bosentan is about 50% in healthy subjects.[10] Peak plasma concentration of bosentan with the dispersable tablets for oral suspension is 14% less on average compared to peak concentration of the oral tablets.[1]
Bosentan is a substrate ofCYP3A4 andCYP2C9.CYP2C19 may also play a role in its metabolism.[1] It is also a substrate of the hepatic uptake transporter organic anion-transporting polypeptides (OATPs) OATP1B1, OATP1B3, and OATP2B1.[11][12]
Elimination of bosentan is mostly hepatic, with minimal contribution from renal and fecal excretion.[13]
Use of bosentan with cyclosporine is contraindicated because cyclosporine A has been shown to markedly increase serum concentration of bosentan.[1]
Bosentan was studied inheart 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.[14]
It was approved for pulmonary artery hypertension in the US in November 2001,[1][15] and in the European Union in May 2002.[4][3]
By 2013, worldwide sales of bosentan were $1.57 billion. The patents on bosentan started expiring in 2015.[16]
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