Bosentan is a prescription oral medication sold under the brand name Tracleer, belonging to a class of drugs known as endothelin receptor antagonists. It is used in specific medical situations to manage symptoms and improve quality of life. The use of bosentan requires careful medical supervision due to its specific effects and potential risks. It is dispensed as a tablet or a tablet for suspension.
Medical Uses of Bosentan
Bosentan is primarily prescribed for the treatment of pulmonary arterial hypertension (PAH). PAH is a condition characterized by high blood pressure in the arteries that carry blood from the heart to the lungs. This increased pressure forces the right side of the heart to work harder, which can lead to significant health problems over time.
The condition is categorized into different functional classes by the World Health Organization (WHO), and bosentan is used for patients with WHO Functional Class II-IV symptoms. By addressing the high blood pressure in the pulmonary arteries, bosentan can improve a person’s ability to exercise. Studies have demonstrated its effectiveness in slowing down the clinical worsening of the condition, which can delay the progression of symptoms and physical limitations.
The medication is used in adults and children three years of age and older. Its application extends to various causes of PAH, including cases that are idiopathic (of unknown cause), heritable, or associated with connective tissue diseases or certain types of congenital heart disease.
Mechanism of Action
Bosentan functions by targeting a natural substance called endothelin-1 (ET-1). In people with pulmonary arterial hypertension, the levels of ET-1 in the blood plasma and lung tissue are often elevated. Endothelin-1 is a potent vasoconstrictor, meaning it causes blood vessels to narrow. This narrowing increases resistance to blood flow, contributing to the high blood pressure seen in PAH.
Bosentan works as a dual endothelin receptor antagonist, which means it blocks two types of receptors: endothelin-A (ETA) and endothelin-B (ETB). These receptors are located on the surface of endothelial cells, which line the blood vessels, and on vascular smooth muscle cells. Bosentan has a slightly higher affinity for the ETA receptor subtype.
By competitively blocking these receptors, bosentan prevents ET-1 from binding and exerting its effects. This action interrupts the signal for blood vessels to tighten.
As a result, the vascular smooth muscles relax, leading to vasodilation, or the widening of the blood vessels. This widening primarily occurs in the pulmonary arteries, which lowers the blood pressure within the lungs and reduces the heart’s workload.
Side Effects and Risks
The use of bosentan is associated with a range of potential side effects, from common to serious. Among the more frequently reported side effects are:
- Headaches
- Flushing of the skin
- Nasal congestion
- Joint pain
- Diarrhea
- Palpitations
A significant risk associated with bosentan is the potential for serious liver injury. The medication can cause elevations in liver enzymes, which are indicators of liver stress or damage. In some cases, this can progress to more severe liver problems, including liver failure. Symptoms of liver issues include nausea, vomiting, fever, abdominal pain, yellowing of the skin or eyes (jaundice), and unusual fatigue.
Another major risk is that bosentan can cause severe birth defects, and it is strictly contraindicated for use during pregnancy.
Other serious risks include fluid retention, which can lead to peripheral edema (swelling in the hands, feet, or ankles) and may require medical intervention. In males, bosentan has been shown to decrease sperm count, which could affect fertility. A dose-related decrease in hemoglobin and hematocrit has also been observed.
Important Safety Information and Monitoring
Due to the risks of liver damage and birth defects, bosentan is available only through a restricted program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS) Program. This program enforces strict safety protocols to ensure the benefits of the medication outweigh its risks.
A central requirement of the REMS program is regular monitoring through blood tests. Before starting treatment, all patients must undergo a blood test to check their liver function. These liver function tests must be repeated every month for the duration of treatment to detect any signs of liver injury early. If liver enzyme levels rise significantly, the dosage may be reduced or the treatment discontinued.
For females of childbearing potential, monthly pregnancy tests are mandatory before starting, during treatment, and for one month after the final dose. Reliable contraception is required, and because hormonal methods may not be effective, the use of two forms of birth control is often necessary. The medication should not be used by anyone who is pregnant or has moderate to severe liver impairment.
Patients should inform their doctor of all other medications they are taking, as bosentan can interact with various drugs. Its concentration can be increased when taken with cyclosporine A and its effectiveness can be reduced by medications like rifampicin. It can also decrease the effectiveness of hormonal contraceptives and other drugs like simvastatin and warfarin.