Bosentan blocks endothelin, a substance made by the body that causes blood vessels in the arteries of the lungs to constrict. Endothelin causes abnormal growth of the muscular layer in the vessel wall, which narrows the lumen, or inside of the blood vessel. Narrowing of the blood vessels increases the pressure, making it harder for the right heart to push blood through the lungs to get oxygen.

Bosentan blocks the action of endothelin so blood vessels relax, lung pressures go down, and the right heart can more easily push blood through the lungs. Low lung pressure also reduces stress on the right heart. When the right heart function improves, it generally improves a person’s ability to be more active, as shown in research studies.

Approved doses: 62.5 mg and 125 mg tablets.

You can take this tablet orally with or without food. Your health care provider will determine which strength is right for you.

Bosentan has limited distribution, which means you can’t fill your prescription at a local pharmacy. Your doctor must prescribe bosentan through a specialty pharmacy.

Women, regardless of reproductive potential, must enroll in the Bosentan Risk Evaluation and Mitigation Strategies program because the drug can cause serious birth defects. People with reproductive potential must take monthly pregnancy tests and comply with contraception requirements. Male patients don’t have to enroll in the REMS program.

Your insurance company might require prior approval before you can start therapy.

Bosentan is generally well tolerated. The most frequent side effects are:

Respiratory tract infections.

Swelling of legs or abdomen (fluid retention)
Fluid retention is a known side effect of endothelin receptor antagonists, such as bosentan. In clinical trials, the swelling was generally mild and occurred more frequently in older adults. Notify your doctor if you experience swelling or any other side effects. You might have to take a diuretic or reduce salt and fluid in your diet to help remove more fluid through your kidneys.

Decreased red blood cell count
Red blood cell counts should be checked at one and three months after starting bosentan therapy. Your doctor should continue to monitor your red blood cell counts every three months while you take bosentan. Some people have decreased red blood cell counts, but it rarely requires blood transfusion.

 

Less common side effects

Elevated liver enzymes
Due to potential liver damage, you must take liver function tests before starting therapy and every month while taking bosentan. Elevated liver enzymes could indicate liver disease. Your health care provider will guide you on how to manage your liver enzymes or reduce your dose or stop the medicine.

Liver function is considered elevated when enzymes are more than three times higher than the upper limit of normal. About 10% of people who take this medication are thought to have elevated liver function.

Generally, bosentan should be stopped if you have signs and symptoms of abnormal liver function or injury abnormal or more than twice the normal level of bilirubin, in addition to elevated liver enzymes.

Decreased sperm count
Some men have had decreased sperm counts while taking bosentan.

The body breaks down bosentan in a way that can cause significant interactions with other drugs. Discuss any medications you take (including over the counter and herbal preparations) you’re your doctor to avoid potential or known drug interactions, such as:

• Reduced efficacy of birth control pills.
• Bosentan shouldn’t be used with cyclosporine A or glyburide.
• Ritonavir or ritonavir-containing combination drugs require a special approach and dose changes if used with bosentan. A doctor should adjust the dosage.
• For patients taking rifampin and bosentan, drug levels could change.
• Based on animal studies, patients should use caution if they take tacrolimus while taking bosentan. This hasn’t been studied in humans.
• Increased levels of bosentan in the blood if used with ketoconazole.
• While drug levels in the blood change with combined use of sildenafil and bosentan, the differences don’t appear to be clinically important.
• Allergies are possible, but not likely. Talk to your health care provider if you feel you are having an allergic reaction to the treatment.

Monitoring for potential side effects

For people who take cholesterol-lowering medications, doctors should carefully monitor cholesterol levels to determine whether the cholesterol medication dose needs to be changed.

Certain patient populations must take precautions while taking bosentan, while others should avoid it. Learn about who can and who shouldn’t take this medication:

Pregnant and breastfeeding patients
Pregnant women shouldn’t take bosentan. Bosentan has harmed fetuses in research studies of rats and rabbits. Patients shouldn’t become pregnant while taking bosentan. To prevent pregnancy, patients should use two forms of contraception when taking bosentan, including surgical treatment to prevent pregnancy, such as a tubal ligation, and a copper T380A or LNg 20 intrauterine device.

Because of potential harm to the fetus, women must take pregnancy tests before starting therapy and every month while taking bosentan. Patients who become pregnant while taking bosentan should notify their doctors and stop treatment immediately. It’s not known whether bosentan passes into breast milk, so nursing mothers shouldn’t take bosentan.

People with liver/kidney disease
Bosentan isn’t recommended for people with PH who have significant liver disease. For patients with significant kidney disease, the dose doesn’t need to be changed. Liver function should be carefully monitored through blood tests.