Action and Spectrum

Actions and Spectrum:

Actions:

bosentan is a dual endothelin receptor antagonist (ERA). It works by blocking the lungs’ endothelin A (ETA) and endothelin B (ETB) receptors. Endothelin-1 is a vasoconstrictor and mitogenic peptide produced by the body. By blocking the endothelin receptors, bosentan reduces the effects of endothelin-1 and dilates the blood vessels in the lungs. Hence it improves blood flow and reduces pulmonary arterial pressure.

Spectrum:

bosentan has a broad effect on the pulmonary vasculature, leading to a reduction in pulmonary vascular resistance and an improvement in symptoms and exercise capacity in patients with PAH. It is generally considered to be a safe and effective treatment option for PAH, although it can cause side effects in some patients, such as liver damage, anemia, and fluid retention.

Drug Interaction

Adverse Reaction

Frequency Defined

10%:

Hgb decreased (57%)

Respiratory tract infection (22%)

Nasopharyngitis (11%)

Flushing (10%)

Headache (16%)

Edema (11%)

Hypotension (10%)

1-10%:

Hypotension (4%)

Palpitations (4%)

Anemia (4%)

Chest pain (5%)

Syncope (5%)

Sinusitis (4%)

Arthralgia (4%)

Abnormal AST/ALT (4%)

Black Box Warning

Black Box Warning:

A black box warning, also known as a boxed warning, is the most severe type of warning required by the US Food and Drug Administration (FDA) for prescription drugs. Black box warnings are used to alert healthcare professionals and patients about potentially serious risks associated with drug use.

In the case of bosentan, the black box warning is related to the potential risk of liver toxicity associated with drug use. bosentan has been associated with elevations in liver enzymes, liver injury, and liver failure, some of which have been fatal. Patients taking bosentan are advised to undergo regular monitoring of liver function, and the drug should be discontinued if liver function test results are significantly elevated.

Contraindication / Caution

Contraindication/Caution:

Contraindications:

• Pregnancy: bosentan is contraindicated in pregnant women as it has been shown to cause harm to the fetus. Women taking bosentan should use effective contraception and should not become pregnant while taking the drug.
• Severe liver impairment: bosentan should not be used in patients with severe liver impairment due to the risk of liver toxicity associated with the drug.
• Concomitant use with cyclosporine: bosentan should not be used with cyclosporine as the combination may lead to increased exposure to bosentan and increased risk of adverse effects.
  Cautions:
• Liver function: bosentan has been associated with elevations in liver enzymes and liver injury. Patients taking bosentan should undergo regular monitoring of liver function, and the drug should be discontinued if liver function test results are significantly elevated.
• Interactions with other drugs: bosentan may interact with other drugs, including warfarin, birth control pills, and certain antibiotics. Patients taking bosentan should inform their healthcare provider about all the medications they are taking.
• Hemodynamics: bosentan may cause changes in hemodynamics, including hypotension and decreased cardiac output. Patients taking bosentan should be monitored for changes in hemodynamics and should inform their healthcare provider if they experience any symptoms of hypotension.

Pregnancy / Lactation

Pregnancy consideration:

Limited data is available regarding the use in pregnant women.

Breastfeeding warnings:

The developmental and health benefits of both infant and mother should be considered.

Pregnancy category:

Category A: well-controlled and satisfactory studies do not show risk to the fetus in the first/later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: No data is available for the drug under this category.

Pharmacology

Pharmacology:

bosentan is a dual endothelin receptor antagonist (ERA) that works by blocking the effects of endothelin 1, a potent vasoconstrictor and mitogenic peptide, on the endothelin A (ETA) and endothelin B (ETB) receptors. By blocking the endothelin receptors, bosentan dilates the blood vessels in the lungs, improving blood flow and reducing pulmonary arterial pressure.

Pharmacodynamics:

In the case of bosentan, the pharmacodynamic action involves blocking the endothelin receptors, specifically the endothelin A (ETA) and endothelin B (ETB) receptors, in the lungs. By blocking the endothelin receptors, bosentan reduces the effects of endothelin-1 and dilates the blood vessels in the lungs, leading to improved blood flow and reduced pulmonary arterial pressure.

Pharmacokinetics:

The pharmacokinetics of bosentan can be described as follows:

Absorption

Bioavailability is 50%

Peak plasma time is 3-5hours

The duration of action is 24 hours

Distribution

Protein-bound is more than 98%

The volume of distribution is 18 L

Metabolism

The drug is metabolized by hepatic CYP2C9 & CYP3A4

Steady state reaches within 3-5 days

Elimination

Half-life is achieved in 5-8 hours

The rate of total clearance is 4 L/hr

Excretion:

The drug is majorly excreted in feces and minimally in urine

Adminstartion

Administration:

bosentan is usually administered orally in the form of tablets. The recommended dose and duration of treatment will depend on the individual patient’s condition and response to the medication.
Typically, bosentan is taken twice a day with food, and your doctor may adjust the dose over time to achieve the best results.

Patient Information Leaflet

Patient information leaflet

Generic Name: bosentan

Pronounced: boe-SEN-tan

Why do we use bosentan?

bosentan is a medication used to treat pulmonary arterial hypertension (PAH). Which is a high blood pressure that affects the blood vessels in your lungs, which toughens heart to pump blood through your lungs.