What is bosentan used for. How does bosentan work. What are the potential side effects of bosentan. Who should not take bosentan. How is bosentan administered. What precautions should be taken when using bosentan.

Understanding Bosentan: A Comprehensive Overview

Bosentan is a medication that plays a crucial role in treating certain cardiovascular conditions. It belongs to a class of drugs known as endothelin receptor antagonists. This medication works by blocking the action of endothelin, a substance in the body that causes blood vessels to narrow. By doing so, bosentan helps to widen blood vessels and improve blood flow, making it easier for the heart to pump blood effectively.

Primary Uses of Bosentan

Bosentan is primarily prescribed for the following conditions:

• Pulmonary arterial hypertension (PAH)
• Chronic thromboembolic pulmonary hypertension (CTEPH)
• Digital ulcers in patients with systemic sclerosis

Is bosentan effective in treating pulmonary arterial hypertension? Clinical studies have shown that bosentan can significantly improve exercise capacity and slow the progression of PAH in many patients. It has been found to reduce symptoms such as shortness of breath and fatigue, thereby enhancing the quality of life for those suffering from this condition.

The Mechanism of Action: How Bosentan Works

To understand how bosentan functions in the body, it’s essential to delve into its mechanism of action. Bosentan specifically targets endothelin receptors, which are found on the smooth muscle cells of blood vessels. By blocking these receptors, bosentan prevents the constriction of blood vessels and promotes vasodilation.

Key Points in Bosentan’s Mechanism:

1. Blocks both endothelin-A and endothelin-B receptors
2. Reduces pulmonary vascular resistance
3. Improves cardiac output
4. Decreases blood pressure in the pulmonary arteries

How quickly does bosentan start working? While some patients may experience improvements in symptoms within a few weeks, the full benefits of bosentan may take several months to become apparent. Consistent use as prescribed by a healthcare provider is crucial for optimal results.

Potential Side Effects and Safety Considerations

As with any medication, bosentan can cause side effects. It’s important for patients and healthcare providers to be aware of these potential adverse reactions to ensure safe and effective use of the drug.

Common Side Effects

The most frequently reported side effects of bosentan include:

• Headache
• Flushing
• Nasal congestion
• Dizziness
• Joint pain
• Fatigue

Are these side effects typically severe? In most cases, these side effects are mild to moderate and tend to diminish over time as the body adjusts to the medication. However, if any side effects persist or worsen, it’s important to consult with a healthcare provider.

Serious Side Effects and Warnings

While less common, bosentan can potentially cause more serious side effects that require immediate medical attention:

• Liver damage
• Anemia
• Fluid retention
• Decreased sperm count in men
• Birth defects if taken during pregnancy

Can bosentan cause liver damage? Yes, bosentan has been associated with rare cases of serious liver damage. As a result, patients taking this medication must undergo regular liver function tests. The frequency of these tests is typically monthly, but may be adjusted based on individual patient factors and response to treatment.

Contraindications and Precautions

Certain individuals should not take bosentan or should use it with caution under close medical supervision. Understanding these contraindications and precautions is crucial for patient safety.

Who Should Not Take Bosentan?

Bosentan is contraindicated in the following situations:

• Pregnancy
• Women of childbearing potential not using reliable contraception
• Concurrent use of cyclosporine A
• Moderate to severe liver impairment
• Known hypersensitivity to bosentan or any component of the formulation

Why is bosentan contraindicated during pregnancy? Bosentan has been shown to cause significant birth defects in animal studies. The risk to human fetuses is considered high, and therefore, the use of bosentan during pregnancy is strictly prohibited. Women of childbearing potential must use two reliable forms of contraception while taking bosentan and for at least one month after discontinuing the medication.

Special Precautions

Certain patient groups require special consideration when using bosentan:

1. Patients with liver disease
2. Individuals with anemia
3. Those with fluid retention or edema
4. Patients with pulmonary veno-occlusive disease

How should patients with liver disease be monitored while taking bosentan? Patients with liver disease require close monitoring of liver function. This typically involves more frequent liver function tests, possibly as often as every two weeks. The dose of bosentan may need to be adjusted or the medication discontinued if liver function worsens.

Administration and Dosage Guidelines

Proper administration of bosentan is crucial for its effectiveness and safety. Healthcare providers determine the appropriate dosage based on several factors, including the patient’s age, weight, and specific medical condition.

General Dosing Information

Bosentan is typically administered as follows:

• Starting dose: 62.5 mg twice daily for 4 weeks
• Maintenance dose: 125 mg twice daily
• Tablets can be taken with or without food
• Dosage may be adjusted based on patient response and tolerability

Should bosentan be taken with food? Bosentan can be taken with or without food. However, taking it with food may help reduce the risk of gastrointestinal side effects in some patients. Consistency in administration (either always with food or always without) can help maintain stable blood levels of the medication.

Special Dosing Considerations

Certain patient groups may require dosage adjustments:

1. Children and adolescents: Dosing is based on body weight
2. Patients with liver impairment: Lower doses may be necessary
3. Patients on certain medications: Dose adjustments may be required due to drug interactions

How is bosentan dosed in pediatric patients? In children, bosentan dosing is typically based on body weight. The usual starting dose is 2 mg/kg twice daily, which may be increased to a maintenance dose of 4 mg/kg twice daily after 4 weeks, depending on the child’s response and tolerability.

Drug Interactions and Considerations

Bosentan can interact with various medications, potentially altering its effectiveness or increasing the risk of side effects. It’s crucial for patients to inform their healthcare providers about all medications, supplements, and herbal products they are taking.

Key Drug Interactions

Some notable drug interactions with bosentan include:

• Cyclosporine A: Concurrent use is contraindicated
• Hormonal contraceptives: May reduce effectiveness of birth control
• Sildenafil and other phosphodiesterase inhibitors: May require dose adjustments
• Warfarin: May reduce anticoagulant effect
• Statins: May decrease effectiveness of cholesterol-lowering medications

Why does bosentan interact with hormonal contraceptives? Bosentan can induce certain liver enzymes that metabolize hormonal contraceptives, potentially reducing their effectiveness. This interaction is particularly important because of the need for reliable contraception in women taking bosentan. Alternative or additional forms of contraception are typically recommended.

Managing Drug Interactions

To manage potential drug interactions, healthcare providers may:

1. Adjust dosages of interacting medications
2. Recommend alternative medications
3. Increase monitoring for potential side effects
4. Advise on the timing of medication administration

How can patients help prevent drug interactions with bosentan? Patients can play a crucial role in preventing drug interactions by maintaining an up-to-date list of all their medications, including over-the-counter drugs and supplements. This list should be shared with all healthcare providers, including pharmacists, to ensure comprehensive medication management.

Monitoring and Follow-up Care

Regular monitoring is essential for patients taking bosentan to ensure its safe and effective use. This involves a combination of clinical assessments, laboratory tests, and patient education.

Key Aspects of Monitoring

The monitoring protocol for patients on bosentan typically includes:

• Monthly liver function tests
• Regular hemoglobin level checks
• Pregnancy tests for women of childbearing potential
• Assessment of fluid retention and edema
• Evaluation of PAH symptoms and exercise capacity

How often should liver function be monitored in patients taking bosentan? Liver function tests are typically performed monthly throughout the duration of bosentan therapy. However, more frequent testing may be necessary for patients with pre-existing liver conditions or those showing signs of liver dysfunction.

Patient Education and Self-Monitoring

Patients play a crucial role in their own care when taking bosentan. They should be educated on:

1. Recognizing signs of liver problems (e.g., jaundice, dark urine)
2. Importance of adherence to the medication regimen
3. Need for reliable contraception (for women of childbearing potential)
4. Potential drug interactions and the importance of informing all healthcare providers about bosentan use
5. Reporting any new or worsening symptoms promptly

What signs should patients watch for that might indicate a problem with bosentan? Patients should be alert for signs such as unexplained nausea, vomiting, abdominal pain, fatigue, loss of appetite, dark urine, or yellowing of the skin or eyes. These symptoms could indicate liver problems and should be reported to a healthcare provider immediately.

Long-term Outlook and Management

For many patients with pulmonary arterial hypertension or other conditions treated with bosentan, long-term management is necessary. Understanding the long-term effects, benefits, and considerations of bosentan therapy is crucial for both patients and healthcare providers.

Long-term Benefits

Long-term use of bosentan has been associated with several potential benefits:

• Improved exercise capacity
• Reduced progression of PAH
• Enhanced quality of life
• Potential reduction in hospitalizations related to PAH
• Improved survival rates in some patient populations

Does long-term use of bosentan improve survival in PAH patients? While individual responses can vary, several studies have suggested that long-term bosentan therapy may improve survival rates in patients with PAH. However, the extent of this benefit can depend on various factors, including the severity of the disease at the start of treatment and adherence to the overall treatment plan.

Ongoing Management Considerations

Long-term management of patients on bosentan involves several key considerations:

1. Regular assessment of treatment efficacy
2. Continuous monitoring for side effects
3. Adjustment of therapy as needed based on disease progression
4. Management of comorbid conditions
5. Consideration of combination therapy with other PAH medications

How often should the efficacy of bosentan be reassessed in long-term users? The efficacy of bosentan should be reassessed regularly, typically every 3-6 months or more frequently if there are changes in symptoms or clinical status. This assessment may include measures of exercise capacity, such as the 6-minute walk test, as well as echocardiography and other relevant diagnostic tests.

Future Perspectives and Research

Ongoing research continues to explore the potential of bosentan and related medications in treating various cardiovascular conditions. Areas of current interest include:

• Combination therapy approaches
• Use in other forms of pulmonary hypertension
• Long-term safety and efficacy data
• Potential applications in other vascular disorders
• Development of new endothelin receptor antagonists

What new developments are on the horizon for endothelin receptor antagonists like bosentan? Research is ongoing to develop new endothelin receptor antagonists with potentially improved efficacy or safety profiles. Additionally, studies are exploring the use of these medications in combination with other PAH therapies to enhance overall treatment outcomes.

In conclusion, bosentan represents a significant advancement in the treatment of pulmonary arterial hypertension and related conditions. Its unique mechanism of action, targeting endothelin receptors, offers hope for many patients struggling with these challenging cardiovascular disorders. However, the use of bosentan requires careful consideration of its benefits and risks, close monitoring, and ongoing management. As research continues, our understanding of how to best utilize this medication in various clinical scenarios will likely continue to evolve, potentially opening up new avenues for treatment and improving outcomes for patients with PAH and other vascular disorders.

Bosentan Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Warnings:

Bosentan may rarely cause serious (possibly fatal) liver damage. Rarely, liver problems have happened in people after stopping treatment with bosentan. Your doctor will perform liver function tests before you start treatment and once a month during treatment. Tell your doctor right away if you notice nausea/vomiting that doesn’t stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, or dark urine.

Bosentan must not be used during pregnancy because it may cause serious harm (such as birth defects) in an unborn baby. Women of childbearing age must have a negative pregnancy test before starting this medication and monthly during treatment. To prevent pregnancy, use at least two reliable forms of birth control as directed by your doctor while taking bosentan and for at least one month after stopping bosentan. If you become pregnant or think you may be pregnant, tell your doctor right away. (See also Precautions section.)

To receive this medication in the United States, you must understand, agree to, and carefully follow the requirements of the Bosentan REMS Program. If you live in Canada or any other country, consult your doctor and pharmacist for your country’s regulations.

Warnings:

Bosentan may rarely cause serious (possibly fatal) liver damage. Rarely, liver problems have happened in people after stopping treatment with bosentan. Your doctor will perform liver function tests before you start treatment and once a month during treatment. Tell your doctor right away if you notice nausea/vomiting that doesn’t stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, or dark urine.

Bosentan must not be used during pregnancy because it may cause serious harm (such as birth defects) in an unborn baby. Women of childbearing age must have a negative pregnancy test before starting this medication and monthly during treatment. To prevent pregnancy, use at least two reliable forms of birth control as directed by your doctor while taking bosentan and for at least one month after stopping bosentan. If you become pregnant or think you may be pregnant, tell your doctor right away. (See also Precautions section.)

To receive this medication in the United States, you must understand, agree to, and carefully follow the requirements of the Bosentan REMS Program. If you live in Canada or any other country, consult your doctor and pharmacist for your country’s regulations.

… Show More

Uses

How to use Bosentan Tablet For Suspension

Read the Medication Guide provided by your pharmacist before you start using bosentan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually twice daily (in the morning and evening). If half tablets are needed for your dose, break the tablets along the score line. Do not break the tablets into quarters. Put the tablet(s) in a small amount of water to dissolve. Once dissolved, drink all the mixture right away. Unused half tablets may be stored back in the opened blister for up to 7 days.

The dosage is based on your medical condition, weight, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Your dose may need to be gradually decreased.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

Tell your doctor if your condition does not get better or if it gets worse.

Side Effects

See also Warning section.

Dizziness, flushing, stuffy nose, or joint pain may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fast/pounding heartbeat, unusual tiredness, swelling ankles/feet, unusual/sudden weight gain, fainting, shortness of breath, coughing up blood.

In men, this medication can decrease sperm production, which may affect the ability to father a child. Talk to your doctor for more details.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

See also Warning section.

Before taking bosentan, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, anemia.

This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Alcohol may also increase the risk of serious liver problems.

This medication may contain aspartame. If you have phenylketonuria (PKU) or any other condition that requires you to limit/avoid aspartame (or phenylalanine) in your diet, ask your doctor or pharmacist about using this medication safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication must not be used during pregnancy. It may harm an unborn baby. It is important to prevent pregnancy while using this medication. Discuss the use of at least two reliable forms of birth control (such as condoms, birth control pills) with your doctor. If you become pregnant or think you may be pregnant, tell your doctor right away.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

A product that may interact with this drug is: sparsentan.

Other medications can affect the removal of bosentan from your body, which may affect how bosentan works. Examples include cyclosporine, HIV protease inhibitors (such as atazanavir), among others.

This drug can speed up the removal of other drugs from your body, which may affect how they work. Examples of affected drugs include daridorexant, elacestrant, glyburide, certain products used to treat chronic hepatitis C (asunaprevir, ombitasvir/paritaprevir/ritonavir), among others.

This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Talk to your doctor or pharmacist about using an additional reliable birth control method while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.

Does Bosentan Tablet For Suspension interact with other drugs you are taking?

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Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe headache, severe dizziness, nausea, vomiting.

Do not share this medication with others.

Lab and/or medical tests (such as liver function, pregnancy tests, hemoglobin/hematocrit) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Keep the tablets stored in the blister package until right before use. Tablets or half tablets from the open blisters may be stored back in the opened blister for up to 7 days. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Bosentan – StatPearls – NCBI Bookshelf

Omar M. Masarweh; Abhishek Bhardwaj.

Author Information and Affiliations

Last Update: May 29, 2023.

Continuing Education Activity

Pulmonary artery hypertension has proven to cause significant mortality and morbidity worldwide. The first-line treatment option for pulmonary artery hypertension has been an endothelin 1 antagonist, such as bosentan. Bosentan is a medication used in the management and treatment of pulmonary artery hypertension. This activity will highlight the mechanism of action, adverse event profile, toxicity, off-label use, dosing, pharmacodynamics, and monitoring pertinent for members of the interprofessional team to treat patients with pulmonary artery hypertension.

Objectives:

• Identify the mechanism of action of bosentan.

• Describe the potential drug-drug interactions of bosentan.

• Outline appropriate monitoring for patients using bosentan.

• Explain interprofessional team strategies for improving care coordination and communication to advance the treatment of pulmonary artery hypertension and improve outcomes when using bosentan.

Access free multiple choice questions on this topic.

Indications

Bosentan is FDA approved for the treatment of patients with pulmonary arterial hypertension (PAH) with significant physical limitations to increase their exercise ability and decrease the rate of clinical worsening.[1][2][3] There are several non-FDA-approved uses of bosentan to treat idiopathic or congenital PAH in the pediatric population aged three years and older.[4] New studies have shown that it may be useful in treating chronic thromboembolic pulmonary hypertension (CTEPH). Clinical trials in the use of endothelial receptor antagonists, such as bosentan, for the treatment of Eisenmenger syndrome have shown some promise, with further research necessary to investigate its safety profile and efficacy. [5] Furthermore, non-FDA-approved uses of bosentan include adjunct therapy for thromboangiitis obliterans, also known as Buerger disease.[6]

Mechanism of Action

Endothelins consists of a group of 21 amino acid peptides with three different isoforms, ET-1, ET-2, and ET-3, with ET-1 being the most abundant and found in sites such as the airway epithelium, parenchymal cells of the lung, pulmonary tumors, pulmonary vasculature, kidneys, small intestine, and cardiac myocytes.[7] Once produced and secreted, endothelins bind to endothelin G protein-coupled receptors, of which two primary forms exist, endothelin A and endothelin B (ETA and ETB, respectively). Although these receptors are present throughout the lung tissue, ETA receptors have their highest concentrations in the pulmonary vasculature and airway smooth muscle. In contrast, ETB receptors are most abundantly present in the endothelium.[8]

The binding of endothelin to the ETA receptors causes vasoconstriction, while binding to the ETB receptors causes bronchoconstriction. Due to the location and function of endothelins, implications point to them in many respiratory diseases such as asthma, pulmonary hypertension, COPD, connective tissue diseases, bronchiolitis obliterans, and lung transplant rejection. The intended role of bosentan is to antagonize these receptors in lung tissue, causing the smooth muscle along the pulmonary vasculature to relax, decreasing pulmonary pressures and resistance. In clinical studies, bosentan proved to prevent ET-1 mediated cellular proliferation.[8]

One consequence of antagonizing the ETB receptors results in a relative increase in the amount of circulating ET-1.[8][7]

Administration

Bosentan is administered orally as a film-coated tablet or as an oral suspension. When used in the treatment of pulmonary artery hypertension, bosentan is given twice daily at either 125 mg or 250 mg doses for adults. In the pediatric population, patients less than 12 years old, bosentan dosage ranges from 31.25 mg to 125 mg twice daily. [8]

Adverse Effects

In clinical trials with bosentan for the treatment of pulmonary artery hypertension, the most common adverse effects included headache (22%), flushing (9%), syncope (7%), and hepatic dysfunction (8%). In these clinical trials, less common adverse effects included cough, dyspnea, respiratory tract infections, chest pain, hypotension, sinusitis, dizziness, and in some cases worsening of PAH.[8] According to the FDA labeling of bosentan, embryo-fetal toxicity occurred in animal studies. Therefore pregnancy testing should be conducted on any female of reproductive age or any female that thinks she could be pregnant. Other less common adverse effects include fluid retention, which may lead to hospitalization of patients with preexisting heart failure.[8] Additionally, less common adverse effects observed included a transient decrease in sperm count and decreases in hemoglobin and hematocrit.[8]

Contraindications

Contraindications to bosentan include females who are or may become pregnant due to the risk of embryo-fetal toxicity. Due to the high risk, any female who is eligible for bosentan must be on two or more forms of reliable contraception during treatment, as well as for one month following completion of therapy.[8] Additional contraindications include using bosentan while taking cyclosporin A. Clinical studies have shown concomitant use of bosentan and cyclosporin A has resulted in drastic increases in the plasma level of bosentan, increasing the risk for adverse effects and toxicity. Further contraindication includes the use of bosentan in patients taking glyburide due to the increased risk of hepatotoxicity, resulting in increased levels of liver enzymes.[8] Finally, anyone allergic to bosentan or any of its parts should not take bosentan due to the risk of hypersensitivity reactions resulting in DRESS syndrome, anaphylaxis, rash, and angioedema.[8]

Monitoring

When given at therapeutic doses, bosentan levels reach steady-state after 3 to 5 days of therapy. The hepatic cytochrome P450 enzyme system metabolizes bosentan into two active metabolites. Only one of the metabolites (Ro 48-5033) can exert effects similar to bosentan, however, with only less than 20% of the effect.[7] Due to the hepatic clearance of the drug and interaction with the cytochrome P450 system, bosentan is contraindicated with any CYP2C9 and 3A4 substrates, inducers, or inhibitors, as well as glyburide and cyclosporine. Other drug-drug interactions that may require careful monitoring due to bosentan’s ability to increase drug metabolism by the cytochrome P450 system include protease inhibitors, certain azole antifungals, erythromycin, and amiodarone.[8] One crucial drug-drug interaction occurs with warfarin. In one clinical trial, co-administration of bosentan and warfarin resulted in a significant decrease in warfarin’s anticoagulation effects; therefore, careful INR monitoring may be necessary.

Due to bosentan’s embryo-fetal toxicity, female patients must be on more than one form of contraception before starting therapy and for one month following termination of treatment. [8]

Toxicity

Bosentan is well tolerated, and when patients receive appropriate monitoring presents a very low risk for toxicity. However, when given with cyclosporin A, bosentan’s plasma levels increased 30-fold and resulted in severe headaches, nausea, and vomiting.[8] However, no serious adverse effects or toxicity were present in these patients. In one postmarket period, one episode of overdose by a male patient who took 10000 mg of bosentan resulted in nausea, vomiting, hypotension, blurred vision, and sweating. The patient was able to make a full recovery following adequate blood pressure support.[8]

Enhancing Healthcare Team Outcomes

Before bosentan emerged as a treatment for pulmonary arterial hypertension, the only other available treatments were intravenous medications, such as epoprostenol. Bosentan has since become first-line therapy for patients with pulmonary artery hypertension and has been shown in clinical trials to be effective as monotherapy or more widely used as part of combination therapy. Due to its relatively low possibility of toxicity, ease of administration, effectiveness, and disease-modifying abilities, bosentan remains one of the go-to medications when treating patients with pulmonary artery hypertension. Continued research is needed to understand which combination therapy proves to have the best outcomes while maintaining little to no toxicity.[8]

When using bosentan for pulmonary arterial hypertension, it is best to employ an interprofessional team approach with clinicians (including mid-level practitioners), specialists, specialty-trained nursing staff, and pharmacists, all collaborating across disciplines to guide cases to optimal outcomes with minimal adverse effects or drug interactions. [Level 5]

Review Questions

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References

1.

Chen X, Zhai Z, Huang K, Xie W, Wan J, Wang C. Bosentan therapy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: A systemic review and meta-analysis. Clin Respir J. 2018 Jun;12(6):2065-2074. [PubMed: 29393580]

2.

Daizadeh I. Pulmonary Arterial Hypertension: A Case Study in FDA Expedited Program Designations. Ther Innov Regul Sci. 2019 Mar;53(2):264-269. [PubMed: 29874936]

3.

Oldfield V, Lyseng-Williamson KA. Bosentan: a review of its use in pulmonary arterial hypertension and systemic sclerosis. Am J Cardiovasc Drugs. 2006;6(3):189-208. [PubMed: 16780392]

4.

Pedersen J, Hedegaard ER, Simonsen U, Krüger M, Infanger M, Grimm D. Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn. Basic Clin Pharmacol Toxicol. 2018 Oct;123(4):392-406. [PubMed: 29855164]

5.

Elshafay A, Truong DH, AboElnas MM, Idrees H, Metwali HG, Vuong NL, Saad OA, Hirayama K, Huy NT. The Effect of Endothelin Receptor Antagonists in Patients with Eisenmenger Syndrome: A Systematic Review. Am J Cardiovasc Drugs. 2018 Apr;18(2):93-102. [PubMed: 28660556]

6.

Narváez J, García-Gómez C, Álvarez L, Santo P, Aparicio M, Pascual M, López de Recalde M, Borrell H, Nolla JM. Efficacy of bosentan in patients with refractory thromboangiitis obliterans (Buerger disease): A case series and review of the literature. Medicine (Baltimore). 2016 Nov;95(48):e5511. [PMC free article: PMC5134796] [PubMed: 27902617]

7.

Boss C, Bolli MH, Gatfield J. From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective. Bioorg Med Chem Lett. 2016 Aug 01;26(15):3381-94. [PubMed: 27321813]

8.

Mathier MA, Ishizawar D. Bosentan. Expert Opin Pharmacother. 2010 Apr;11(6):1023-34. [PubMed: 20307226]

Disclosure: Omar Masarweh declares no relevant financial relationships with ineligible companies.

Disclosure: Abhishek Bhardwaj declares no relevant financial relationships with ineligible companies.

Bosentan instructions, price in pharmacies of Ukraine

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Creation date: 04/27/2021
Update date: 07/12/2023

Bosentan – zasіb for treatment of legenous arterial hypertension. It decreases like a legenevium, so it is a systemic judgmental operation, which leads to an increase in the heart rate without an increase in the frequency of the heart rates.

Indications

Treatment of legenous arterial hypertension for increased tolerance to physical intensification and clinical symptoms in patients of class III for functional WHO classification. Efficiency has been demonstrated in the following conditions:

Contraindications

• Increased susceptibility to bosentan or to any additional drug indications.
• Hepatic insufficiency of mild to severe form (class B or C according to the Child-Pugh scale).
• Changes in the activity of hepatic transferases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), greater than lower in 3 times higher than the upper mean of normal.
• One-hour infusion of cyclosporine A.
• Vagity.
• Women of reproductive age who do not win over the best methods of contraception.

Side effects

Most common side reactions:

• head count;
• snag
• liver dysfunction test;
• anemia/decreased hemoglobin (9.9%).

Contraindications during pregnancy and breastfeeding

Bosentan is contraindicated for women of reproductive age, during pregnancy and breastfeeding.

Children

Relief of spontaneous reactions in case of caring for motor transport or other mechanisms more inconsistency, which can be pushed into the building by car transport or by other mechanisms.

Overdose

The most widespread unacceptable reaction – headache from the lung to the death stage.
Severe overdose can lead to pronounced arterial hypotension, which affects the active support of the cardiovascular system.

Take care of the safety

Save at a temperature not higher than 25 °C in an area inaccessible to children.

Bosentan instructions

BOZENTAN ACCORD 125 MG TABLETS
(UA/19077/01/02)

Release form:

tablets, covered with plaid membrane, 125 mg each, 14 tablets, covered with plaited membrane, in a blister, 4 blisters in a pack

Stock:

1 tablet to take: bosentan (seemingly monohydrate) – 125,000 mg

Manufacturer:

India/Malta

BOSENTAN ACCORD 125 MG FILM-COATED TABLETS
(UA/19783/01/02)

Release form:

tablets, covered with plaid membrane, 14 tablets, covered with plaid membrane, in a blister, 4 blisters in a pack

Stock:

1 tablet, coated with a plaited shell, mixed with: bosentan (looks like monohydrate) 125 mg

Manufacturer:

Netherlands/Poland

BOZENTAN ACCORD 62. 5 MG TABLETS
(UA/19077/01/01)

Release form:

tablets, covered with plaid membrane, 62.5 mg each, 14 tablets, covered with plaid membrane, in a blister, 4 blisters in a pack

Stock:

1 tablet to take: bosentan (seemingly monohydrate) – 62.500 mg

Manufacturer:

India/Malta

BOSENTAN ACCORD 62. 5 MG FILM-COATED TABLETS
(UA/19783/01/01)

Release form:

tablets, covered with plaid membrane, 14 tablets, covered with plaid membrane, in a blister, 4 blisters in a pack

Stock:

1 tablet, coated with a plaited shell, mixed with: bosentan (looks like monohydrate) 62.5 mg

Manufacturer:

Netherlands/Poland

BOZENTAN ZENTIVA
(UA/16744/01/01)

Release form:

tablets, coated with a plaited shell, 62. 5 mg, 14 tablets in a blister, 1, 4 or 8 blister in a cardboard pack

Stock:

1 tablet, coated with a plaited shell, vengeance for bosentan (looks like monohydrate) 62.5 mg

Manufacturer:

Cyprus

BOZENTAN ZENTIVA
(UA/16744/01/02)

Release form:

tablets, coated with a plaited shell, 125 mg, 14 tablets in a blister, 1, 4 or 8 blister in a cardboard pack

Stock:

1 tablet, coated with velvet shell, to bosentan (looks like monohydrate) 125 mg

Manufacturer:

Cyprus

BOZENTAN SANDOZ® (BOSENTAN SANDOZ®)
(UA/16618/01/01)

Release form:

tablets, coated with plaid membrane, 62. 5 mg each, blister, to be filled 14 tablets, covered with plaited membrane, cardboard box, to be covered 4 blisters

Stock:

1 tablet to take: bosentan (in the form of bosentan monohydrate) 62.5 mg

Manufacturer:

Turechchina

BOZENTAN SANDOZ® (BOSENTAN SANDOZ®)
(UA/16618/01/02)

Release form:

tablets, coated with plaid shell, 125 mg each, blister, 14 tablets, packed with plaid shell, cardboard box, 4 blisters

Stock:

1 tablet to take: bosentan (in the form of bosentan monohydrate) 125 mg

Manufacturer:

Turechchina

BOZENTAN SANDOS® 125
(UA/17011/01/02)

Release form:

tablets, coated with plaid membrane, 125 mg each, blister, to be filled 14 tablets, covered with plaited membrane, 4 blisters in a cardboard box

Stock:

1 lozenge: bosentan monohydrate 129. 082 mg (equivalent to 125 mg bosentan)

Manufacturer:

Turechchina

BOZENTAN SANDOS® 62.5
(UA/17011/01/01)

Release form:

tablets, covered with plaid membrane, 62. 5 mg each, blister, to be filled 14 tablets, covered with plaited membrane, 4 blisters in a cardboard box

Stock:

1 lozenge: bosentan monohydrate 64.541 mg (equivalent to 62.5 mg bosentan)

Manufacturer:

Turechchina

BOZENTAN 125mg N60 tabs b.p.o. ASPECTUS PHARMA – Pharm-ID – Unified nomenclature guide for drug packages

Bosentan is metabolized with the participation of CYP2C9 and CYP3A4 isoenzymes. With simultaneous use with inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole), the concentration of bosentan in the blood plasma increases. The effect of inhibition of the CYP2C9 isoenzyme on the concentration of bosentan in plasma has not been studied; such combinations require caution. Simultaneous use with fluconazole, which mainly inhibits the CYP2C9 isoenzymeand slightly – the CYP3A4 isoenzyme, may be accompanied by an increase in the concentration of bosentan in the blood plasma; this combination is not recommended. For the same reason, concomitant use of bosentan with strong inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, itraconazole or ritonavir) and an inhibitor of the CYP2C9 isoenzyme (such as voriconazole) is not recommended.

Bosentan is an inducer of CYP2C9 and CYP3A4 isoenzymes, and CYP2C19 is also suspected in vitro. Therefore, with the simultaneous use of bosentan and drugs, the metabolism of which is mediated by these isoenzymes, their concentration in blood plasma decreases. Consideration should be given to the possibility of reducing the effectiveness of drugs, the metabolism of which is carried out with the participation of the same isoenzymes. It may be necessary to adjust the dose of concomitantly used medicinal products after starting bosentan, changing its dose or discontinuing it.

Co-administration of bosentan and cyclosporine (a calcineurin inhibitor) is contraindicated. With this combination, the minimum initial concentration of bosentan in the blood plasma increases by 30 times compared with the use of bosentan in monotherapy. C _ss bosentan in plasma increases by 3-4 times compared with the concentration of bosentan in monotherapy. A possible mechanism for this interaction is the inhibition of the transport protein responsible for the entry of bosentan into hepatocytes by cyclosporine. The concentration of cyclosporine in the blood plasma is reduced by almost 50%.

Co-administration of tacrolimus and sirolimus with bosentan has not been studied in clinical studies, but it is expected that plasma concentrations of bosentan may increase in a manner similar to cyclosporine. Plasma concentrations of tacrolimus and sirolimus may decrease when co-administered with bosentan. Therefore, bosentan should not be co-administered with tacrolimus or sirolimus. If it is necessary to use this combination, it is necessary to monitor the patient’s condition and the concentrations of tacrolimus and sirolimus in the blood plasma.

With the simultaneous use of bosentan at a dose of 125 mg 2 times / day for 5 days, the concentration of glibenclamide (CYP3A4 isoenzyme substrate) in blood plasma decreases by 40%, which may be accompanied by a significant decrease in the hypoglycemic effect of glibenclamide. The plasma concentration of bosentan is also reduced by 29%. In addition, in patients receiving concomitant treatment, the risk of increased activity of hepatic transaminases increases. Both active substances, glibenclamide and bosentan, have an inhibitory effect on the bile salt transport pump, which may explain the increase in liver transaminase activity. In connection with the above, bosentan should not be used simultaneously with glibenclamide. There are no data on possible drug interactions with other sulfonylurea derivatives.

With simultaneous use of bosentan for 7 days at a dose of 125 mg 2 times / day and oral contraceptive for a single dose – a combined preparation containing 1 mg of norethisterone and 35 μg of ethinyl estradiol, there was a decrease in AUC for its components by 14% and 31%, respectively . In some patients, the reduction in exposure to norethisterone and ethinylestradiol reached 56% and 66%, respectively. Thus, hormonal contraception cannot be considered sufficiently effective, regardless of the route of administration of the drug – orally, by injection, transdermally, or in the form of implants.

With simultaneous use in healthy volunteers with bosentan at a dose of 500 mg 2 times / day for 6 days, the concentration of S-warfarin (CYP2C9 isoenzyme substrate) and R-warfarin (CYP3A4 isoenzyme substrate) in blood plasma decreases by 29% and 38% respectively. The experience of the simultaneous use of bosentan and warfarin in patients with PAH was not accompanied by clinically significant changes in the MHO and the dose of warfarin (at the end of the study compared with baseline values). In addition, the frequency of dose adjustments of warfarin during the study due to changes in INR or due to side effects did not differ between patients receiving bosentan or placebo. Dose adjustment of warfarin or other oral anticoagulants is not required at the beginning of bosentan therapy, however, mandatory monitoring of INR is recommended, especially at the beginning of bosentan use and during the stages of dose increase.

With simultaneous use of bosentan at a dose of 125 mg 2 times / day for 5 days, the concentration of simvastatin (a substrate of the CYP3A4 isoenzyme) and its active form of beta-hydroxy acid in blood plasma decreases by 34% and 46%, respectively. The simultaneous use of simvastatin does not affect the concentration of bosentan in plasma. With the combined use of simvastatin and bosentan, it is recommended to control the concentration of cholesterol in the blood plasma, followed by dose adjustment of simvastatin.

Simultaneous use for 6 days of bosentan at a dose of 62. 5 mg 2 times / day and ketoconazole, a potent inhibitor of the CYP3A4 isoenzyme, is accompanied by an increase in the concentration of bosentan in blood plasma by 2 times. Dose adjustment of bosentan is not required.

An increase in plasma concentrations of bosentan is also expected with the simultaneous use of itraconazole and ritonavir, despite the lack of confirmation in in vivo studies. However, when bosentan is combined with a CYP3A4 inhibitor, in patients with reduced metabolism of the CYP2C9 isoenzymethere is a risk of a significant increase in the concentration of bosentan, which may increase the frequency and severity of its side effects.

With simultaneous use in healthy volunteers for 7 days of bosentan at a dose of 125 mg 2 times / day and rifampicin, which is an inducer of CYP2C9 and CYP3A4 isoenzymes, the concentration of bosentan in blood plasma decreased by 58%, and in some patients by 90% . As a result, a clinically significant decrease in the effect of bosentan is possible when used together with rifampicin; this combination is not recommended. Data on the combined use with other inducers of the CYP3A4 isoenzyme, such as carbamazepine, phenobarbital, phenytoin, as well as drugs that include St. .

Co-administration of bosentan 125 mg twice daily with lopinavir + ritonavir 400 + 100 mg twice daily for 9.5 days in healthy volunteers resulted in an approximately 48-fold higher trough plasma concentration of bosentan compared to concentration when using only one bosentan. C _ss of bosentan in blood plasma on day 9 was 5 times higher than when taking bosentan alone. The mechanism of interaction is probably due to the inhibition of the CYP3A4 isoenzyme and the transport protein responsible for the transport of bosentan into hepatocytes by ritonavir, which leads to a decrease in the clearance of bosentan. In patients receiving concomitant treatment with bosentan and drugs containing lopinavir + ritonavir or other overactive protease inhibitors, it is necessary to monitor the tolerability of bosentan. When used together with bosentan for 9.