Bosentan is a medication primarily used in the treatment of pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). It belongs to a class of drugs called endothelin receptor antagonists, which work by blocking the effects of endothelin, a substance in the body that causes blood vessels to narrow and become tight.

In PAH, the blood vessels in the lungs become narrow and constricted, leading to increased blood pressure in the pulmonary arteries. Bosentan helps to widen these blood vessels, reducing the blood pressure and improving blood flow through the lungs, which can alleviate symptoms and improve exercise capacity in patients with PAH.

Bosentan is an endothelin receptor antagonist. It binds to the endothelin receptors and inhibits them resulting in vasodilation. It is used to treat the following conditions [Ref]:

• It is indicated in the treatment of pulmonary arterial hypertension WHO class 1 to improve exercise tolerance and prevent further deterioration.
• Idiopathic or congenital pulmonary arterial hypertension in children who are 3 years of age or older to improve vascular resistance.

Off-label uses of Bosentan include:

• Prevention of digital ulcers in patients with scleroderma.
• Raynaud's phenomenon.

Note: In patients with Pulmonary arterial hypertension and WHO functional class IV symptoms, it may be used as second-line therapy.

WHO Functional Classification for Pulmonary Hypertension
WHO Class 1	No limitation to the activity
WHO Class 2	Slight limitations to the activity. Ordinary activity may cause some symptoms
WHO Class 3	Marked limitation of activity. Less than ordinary activity causes symptoms
WHO Class 4	Severe limitation of physical activity. Any activity causes symptoms or patients with right heart failure.

Bosentan Dose in Adult

Bosentan dose in the treatment of Pulmonary artery hypertension:  

For people who weigh less than 40 kilograms:

• They typically start with a dose of 62.5 milligrams taken by mouth twice a day, and this dosage stays the same for maintenance.

For people who weigh 40 kilograms or more:

• Initially, they also start with 62.5 milligrams taken by mouth twice a day for 4 weeks.
• After 4 weeks, the dosage is increased to 125 milligrams taken by mouth twice a day for maintenance.
• It's usually not recommended to take more than 125 milligrams twice a day because higher doses don't seem to give extra benefits and may cause liver problems.

When stopping the medication, it's important to gradually reduce the dosage over 3 to 7 days to avoid worsening symptoms.

If someone is taking bosentan and also needs to take ritonavir, a different medication, there are some special instructions:

• If they're already taking ritonavir, they should start with a lower dose of bosentan, either 62.5 milligrams once daily or every other day, depending on how they tolerate it.
• If they're starting ritonavir while already on bosentan, they should stop taking bosentan 36 hours before starting ritonavir.
• After being on ritonavir for at least 10 days, they can start taking bosentan again at the lower dose of 62.5 milligrams once daily or every other day, depending on how they feel.

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Bosentan off-label use in the therapy of Prevention of digital ulcers in systemic sclerosis:  

• Typically started with a lower dose of 62.5 milligrams taken by mouth twice a day for 4 weeks, and then increased to a higher dose of 125 milligrams twice a day for maintenance.
• These trials lasted for up to 12 weeks to see how well bosentan worked in preventing these sores.

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Bosentan off-label use in the treatment of Raynaud phenomenon in systemic sclerosis:

• Started with 62.5 milligrams taken orally twice daily for 4 weeks, then increased to a maintenance dose of 125 milligrams twice daily.
• These studies, conducted over several weeks, aimed to assess the effectiveness of bosentan in managing Raynaud phenomenon associated with systemic sclerosis.

Bosentan Dose in Children

Bosentan Dose in the treatment of Pulmonary arterial hypertension:  

Infants and Children younger than 12 years:

• Start with 1 milligram per kilogram of body weight taken orally twice daily.
• Increase to a target dose of 2 milligrams per kilogram of body weight taken twice daily, up to a maximum of 125 milligrams per dose.

Children ≥12 years and Adolescents:

• For those weighing >20 to 40 kilograms: Begin with 31.25 milligrams orally twice daily, then increase to 62.5 milligrams twice daily.
• For those weighing >40 kilograms: Start with 62.5 milligrams orally twice daily, then increase to 125 milligrams twice daily.

Alternate dosing (per manufacturer's labeling):

• Children ≥3 years:
  • For weights:
    • 4 to 8 kilograms: 16 milligrams orally twice daily.
    • 8 to 16 kilograms: 32 milligrams orally twice daily.
    • 16 to 24 kilograms: 48 milligrams orally twice daily.
    • 24 to 40 kilograms: 64 milligrams orally twice daily.
• Adolescents:
  • For those weighing ≤40 kilograms: Take 62.5 milligrams orally twice daily.
  • For those weighing >40 kilograms: Initially, take 62.5 milligrams orally twice daily for 4 weeks, then increase to a target dose of 125 milligrams twice daily.

Dosage adjustment for concurrent use with ritonavir:

• When bosentan is taken with ritonavir:
  • There are no specific recommendations for children; dosage adjustment is suggested based on adult experience.
• When ritonavir is added to bosentan:
  • There are no specific recommendations for children; discontinue bosentan 36 hours before starting ritonavir. After at least 10 days on ritonavir, resume bosentan at an adjusted dose.

Pregnancy Risk Factor: X

[US Boxed Warning]

• Bosentan comes with a serious warning for pregnant women, as it can cause significant birth defects based on animal studies.
• Before starting treatment with bosentan, it's crucial to confirm that a woman isn't pregnant.
• Throughout treatment and for a month after stopping bosentan, women of childbearing age must use two reliable forms of birth control, unless they have an intrauterine device (IUD) or tubal sterilization.
• Hormonal contraceptives like pills or patches shouldn't be relied upon alone because they might not work effectively with bosentan.
• Monthly pregnancy tests are necessary during treatment.
• Even if a partner has had a vasectomy, an extra form of contraception is needed when using hormonal or barrier methods.
• When starting treatment, women should have a negative pregnancy test within the first 5 days of their menstrual cycle and at least 11 days after unprotected intercourse.
• Any missed periods or suspicion of pregnancy should be reported.

Bosentan Use during Breastfeeding:

• It's unclear if bosentan is present in breast milk, and because there's a risk of serious side effects in breastfed babies, the manufacturer advises against breastfeeding while taking bosentan.

Bosentan Dose in Renal Disease:

• No dosage adjustment is needed for people with kidney problems when taking bosentan, as the medication is unlikely to be removed effectively by dialysis.
• This is because bosentan has a high molecular weight and binds extensively to proteins in the blood.

Bosentan Dose in Liver Disease:

Liver dysfunction at treatment initiation:

• For mild impairment, no dosage adjustment is needed.
• But for moderate to severe impairment, or if baseline transaminase levels are over 3 times the upper limit of normal (ULN), bosentan should be avoided. In these cases, the drug's levels in the body can rise significantly.

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If liver problems develop during treatment, changes are made based on transaminase levels (enzymes indicating liver function):

• If transaminase levels rise along with symptoms like fatigue, nausea, or jaundice, or if bilirubin levels rise to 2 times ULN, treatment should be stopped.
• If AST/ALT levels rise to 3-5 times ULN, in patients over 40 kilograms, additional tests should confirm the rise. If confirmed, the dose is reduced or treatment is paused and monitored closely.
• If AST/ALT levels rise to 5-8 times ULN, treatment is stopped, and liver enzyme levels are monitored regularly.
• If AST/ALT levels rise above 8 times ULN, treatment is stopped without the possibility of reintroduction.

Common Side Effects of Bosentan Include:

• Central Nervous System:
  • Headache
• Cardiovascular:
  • Edema
• Respiratory:
  • Respiratory Tract Infection
• Hepatic:
  • Increased Serum ALT
  • Increased Serum AST

Less Common Side Effects of Bosentan Include:

• Endocrine & Metabolic:
  • Fluid Retention
• Cardiovascular:
  • Flushing
  • Chest Pain
  • Syncope
  • Hypotension
  • Palpitations
• Respiratory:
  • Sinusitis
• Hematologic & Oncologic:
  • Anemia
• Neuromuscular & Skeletal:
  • Arthralgia

Contraindications to Bosentan 

Bosentan should not be used in individuals with:

• Known hypersensitivity to bosentan or any of its ingredients.
• Concurrent use of certain medications like cyclosporine or glyburide.
• Pregnancy, as it can cause serious birth defects and should be avoided by women who are or may become pregnant.

In Canada, additional contraindications include:

• Moderate to severe liver impairment, especially when liver enzyme levels (ALT or AST) are over 3 times the upper limit of normal (ULN), particularly if total bilirubin levels are over 2 times ULN.

Warnings and Precautions

Fluid retention and peripheral swelling:

• Bosentan treatment or the disease itself (pulmonary arterial hypertension) can lead to fluid buildup, causing swelling in the legs or other parts of the body.
• Some people may even require treatment for heart failure due to fluid retention.
• If significant swelling occurs, along with weight gain, it's important to get evaluated to find out the cause and decide on the right treatment, which might include stopping bosentan.
• Bosentan should be used cautiously in people with existing heart failure, as fluid retention can lead to complications.
• According to the American Heart Association, bosentan is recognized as a treatment that could worsen underlying heart muscle problems.

Hematologic effects

• When starting bosentan therapy, there might be a drop in hematocrit and hemoglobin levels, usually happening within the first few weeks.
• However, these levels typically stabilize within 4 to 12 weeks of treatment.
• It's important to check hemoglobin levels before starting treatment, then after 1 and 3 months, and every 3 months afterward.
• If there's a significant decrease in hemoglobin, it needs further evaluation to understand why and decide on the appropriate management.

Hepatotoxicity: [US Boxed Warning]

• Bosentan carries a serious warning for liver problems.
• Regular monitoring of liver enzymes (ALT or AST) is necessary, starting before treatment and continuing monthly thereafter.
• If liver enzyme levels rise without symptoms or elevated bilirubin, dosage adjustments may be made.
• Rare cases of unexplained liver cirrhosis and even liver failure have occurred after long-term use, especially in patients with multiple health issues and medications.
• Treatment should be stopped if liver enzymes rise significantly, with or without symptoms like fatigue or jaundice, or if bilirubin levels increase.
• It's not known if it's safe to restart treatment after stopping due to liver issues.
• Avoid using bosentan in patients with high baseline liver enzymes or severe liver problems.
• Elevated liver enzymes, usually without symptoms, can occur at any time during treatment but may reverse with dose changes or stopping treatment.
• When considering starting treatment in patients with less severe symptoms, weigh the benefits against the risk of liver problems.

Hypersensitivity

• Hypersensitivity reactions to bosentan are possible and can include severe conditions like Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, as well as rash and swelling (angioedema).

Spermatogenesis:

• Bosentan treatment can lead to reduced sperm counts in men and may affect sperm production negatively.

Pulmonary venoocclusive disease

• If signs of pulmonary edema develop, it's important to consider the possibility of pulmonary veno-occlusive disease, a rare condition where the veins in the lungs become blocked.
• This condition may require stopping bosentan treatment.

Bosentan: Drug Interaction

Risk Factor C (Monitor therapy)
Benzhydrocodone	CYP3A4 Inducers (Moderate) may lower the level of benzhydrocodone in the blood. More specifically, hydrocodone serum concentrations could be decreased.
CloZAPine	CloZAPine's serum levels may be lowered by moderate CYP3A4 inducers.
Codeine	The active metabolite(s) of codeine's serum concentrations may be lowered by CYP3A4 Inducers (Moderate).
CYP2C9 Inhibitors (Moderate)	may increase the amount of bosentan in the serum. Management: Because doing so would probably produce a considerable increase in the drug's blood concentrations, it is not recommended to use bosentan along with both a CYP2C9 inhibitor and a CYP3A inhibitor at the same time. Monograph for further details.
CYP3A4 Inhibitors (Moderate)	may increase the amount of bosentan in the serum. Management: Because doing so would probably produce a considerable increase in the drug's blood concentrations, it is not recommended to use bosentan along with both a CYP2C9 inhibitor and a CYP3A inhibitor at the same time. Monograph for further details.
CYP3A4 Inhibitors (Strong)	may increase the amount of bosentan in the serum. Management: Because doing so would probably produce a considerable increase in the drug's blood concentrations, it is not recommended to use bosentan along with both a CYP2C9 inhibitor and a CYP3A inhibitor at the same time. Monograph for further details.
CYP3A4 Substrates (High risk with Inducers)	The amount of CYP3A4 substrates in the blood may be reduced by bosentan (High risk with Inducers).
Doravirine	The serum concentration of doravirine may drop in response to CYP3A4 Inducers (Moderate).
Eltrombopag	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.
Estriol (Systemic)	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic).
Estriol (Topical)	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical).
FentaNYL	CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL.
Gemfibrozil	may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Agents indicated as exceptions should be examined in separate drug interaction monographs.
Glecaprevir and Pibrentasvir	Glecaprevir and Pibrentasvir's serum concentrations may be affected by CYP3A4 Inducers (Moderate).
HYDROcodone	The serum levels of HYDROcodone may drop in response to CYP3A4 Inducers (Moderate).
Ibrutinib	Ibrutinib's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Ifosfamide	Ifosfamide's active metabolite may be seen at lower blood concentrations while using CYP3A4 Inducers (Moderate) (s). Ifosfamide's active metabolite may be present in higher blood quantities while using CYP3A4 Inducers (Moderate) (s).
Macimorelin	Bosentan may lessen Macimorelin's ability to serve as a diagnostic aid.
Mirodenafil	The serum concentration of Mirodenafil may be decreased by CYP3A4 Inducers (Moderate).
Naldemedine	The serum concentration of naldemedine may drop in response to CYP3A4 Inducers (Moderate).
NiMODipine	NiMODipine's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Phosphodiesterase 5 Inhibitors	The blood concentration of phosphodiesterase 5 inhibitors may be reduced by bosentan. Taking phosphodiesterase 5 inhibitors may cause the serum levels of Bosentan to increase.
RifAMPin	may lower the level of bosentan in the serum. This effect is most likely to occur after the initial few weeks of concomitant rifampin use. Bosentan's serum levels may rise when RifAMPin is present. Most likely, this impact will be felt within the first several weeks of concurrent therapy (and maybe the greatest immediately following initiation of the combination). The first four weeks of concurrent therapy should include weekly monitoring of liver function tests, and thereafter, as necessary, weekly monitoring should resume.
Rolapitant	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant.
Simvastatin	Bosentan may decrease the serum concentration of Simvastatin.
Teriflunomide	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.
Vitamin K Antagonists (eg, warfarin)	Bosentan may hasten the metabolism of vitamin K antagonists.
Zolpidem	CYP3A4 Inducers (Moderate) may cause zolpidem levels in the blood to drop.
Risk Factor D (Consider therapy modification)
Atazanavir	Atazanavir's serum levels might decrease if you take bosentan. The serum levels of bosentan may rise when atazanavir is used. Bosentan and atazanavir (without ritonavir) should not be used together. When taken in conjunction with atazanavir/ritonavir, modifications to the dosage of bosentan are necessary.
Brigatinib	Response to CYP3A4 Inducers may result in a reduction in the serum concentration of Brigatinib (Moderate). Management: Whenever possible, refrain from using brigatinib with weak CYP3A4 inducers. Increase the daily dose of brigatinib by 30 mg increments after seven days of therapy, up to a maximum of twice the dose.
Clarithromycin	The active metabolite(s) of clarithromycin's serum concentrations may rise when taken with bosentan. In particular, 14-hydroxyclarithromycin concentrations may rise in response to bosentan. Bosentan may decrease the level of clarithromycin in the serum. The serum levels of bosentan may rise when clarithromycin is used. Management: If at all feasible, consider using a different antibiotic. Bosentan toxicity might rise and clarithromycin's clinical activity could change.
Cobicistat	might raise the serum level of bosentan. For further information, see the entire medication interaction monograph.
Daclatasvir	The blood level of Daclatasvir may decrease when CYP3A4 Inducers (Moderate) are present. Treatment: If daclatasvir is used with a moderate CYP3A4 inducer, increase the dosage to 90 mg once day.
Darunavir	Bosentan may lower the level of Darunavir in the serum. Bosentan's serum levels may rise in response to darunavir. Bosentan 62.5 mg should be used everyday or every other day in people receiving darunavir that has been cobicistat- or ritonavir-boosted for at least 10 days. Before beginning boosted darunavir, stop taking bosentan for at least 36 hours. Then, please wait at least 10 days before starting it again.
Estrogen Derivatives (Contraceptive)	Bosentan may reduce oestrogen derivative levels in the blood (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception rather than only relying on hormonal contraceptives for all women of reproductive potential who are taking bosentan.
Fosamprenavir	When utilising bosentan, the serum concentration of fosamprenavir may decrease. The use of fosamprenavir may cause an increase in the blood levels of bosentan. Treatment: Administer bosentan 62.5 mg once day or every other day to adult patients who have been taking fosamprenavir for at least 10 days. Bosentan should be temporarily stopped before starting fosamprenavir (for at least 36 hours). After that, give it a 10-day break before beginning again.
GuanFACINE	CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with moderate CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if moderate CYP3A4 inducer therapy is just beginning.
Indinavir	may increase the amount of bosentan in the serum. If you use bosentan, your serum concentration of indinavir can decrease. In patients on indinavir, bosentan should be started at 62.5 mg once day or every other day, and then modified based on tolerability (see ritonavir fordosing if that agent is used). Watch out for any possible indinavir side effects as well.
Lopinavir	may increase the amount of bosentan in the serum. If you use bosentan, your serum levels of lopinavir can decrease. Treatment: Administer bosentan 62.5 mg once or every other day to adult patients who have been taking lopinavir/ritonavir for at least 10 days. Bosentan must be temporarily stopped (for at least 36 hours) and at least 10 days must pass before commencing lopinavir or ritonavir.
Lorlatinib	Lorlatinib's hepatotoxic effects might be made worse by CYP3A4 inducers (Moderate). By CYP3A4 Inducers, lorlatinib's serum levels could be reduced (Moderate). Combining lorlatinib with low-dose CYP3A4 inducers is not recommended. If such a combination is required, the levels of AST, ALT, and bilirubin should be assessed within 48 hours after starting the combination and at least three times throughout the first week of treatment.
Lurasidone	Lurasidone's serum levels may be reduced by moderate CYP3A4 inducers. Management: If provided with moderate CYP3A4 inducers for seven or more days, watch for any diminished effects of the lurasidone and consider raising the dosage.
Nelfinavir	may increase the amount of bosentan in the serum. If you use bosentan, your serum levels of nelfinavir can decrease. In patients on nelfinavir, bosentan should be begun at a dose of 62.5 mg once day or every other day, and then modified based on tolerability. Watch out for any potential changes in the clinical response to nelfinavir as well.
Palbociclib	Palbociclib's serum levels may be decreased by moderate CYP3A4 inducers. Management: The Canadian label advises against using mild CYP3A4 inducers, however the US label makes no specific advice on their usage.
Perampanel	The serum concentration of Perampanel may be decreased by CYP3A4 Inducers (Moderate). When using perampanel alongside strong and moderate CYP3A4 inducers, the beginning dosage should be increased to 4 mg/day.
Progestins (Contraceptive)	Bosentan may reduce the serum concentration of progestins (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception rather than only relying on hormonal contraceptives for all women of reproductive potential who are taking bosentan.
Ritonavir	May increase the serum concentration of Bosentan. Management: Use bosentan 62.5 mg daily or every other day in adult patients who have been on ritonavir for at least 10 days. Temporarily stop bosentan (for at least 36 hrs) before starting ritonavir; wait until at least 10 days on ritonavir before restarting.
Saquinavir	Bosentan may decrease the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Bosentan. Management: Use bosentan 62.5 mg/day or every other day in adult patients taking saquinavir/ritonavir for at least 10 days. Temporarily stop bosentan (for at least 36 hrs) before starting saquinavir/ritonavir; wait at least 10 days before restarting bosentan.
Tipranavir	Tipranavir levels in the serum might be decreased by bosentan. When tipranavir is administered, the serum levels of bosentan may increase. Treatment: Administer bosentan 62.5 mg once day or every other day to adult patients who have been taking tipranavir/ritonavir for at least 10 days. Temporarily stop taking bosentan before starting tipranavir/ritonavir (for at least 36 hours). Then, before starting it again, kindly wait at least 10 days.
Tolvaptan	may raise the level of OATP1B1/1B3 (SLCO1B1/1B3) Substrates in the serum.
Risk Factor X (Avoid combination)
Antihepaciviral Combination Products	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products.
Asunaprevir	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir.
Axitinib	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
Bedaquiline	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline.
Bosutinib	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib.
Cobimetinib	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib.
CycloSPORINE (Systemic)	May increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of CycloSPORINE (Systemic).
Dasabuvir	CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir.
Deflazacort	The serum concentrations of the active metabolite(s) of Deflazacort may be lowered by CYP3A4 Inducers (Moderate).
Elbasvir	Elbasvir's serum levels may be reduced by moderate CYP3A4-inducing drugs.
Encorafenib	Encorafenib's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Flibanserin	Flibanserin's serum levels may drop if CYP3A4 Inducers (Moderate) are used.
GlyBURIDE	may intensify Bosentan's hepatotoxic effects. Bosentan's serum concentration might drop because to GlyBURIDE. Bosentan may lower the level of GlyBURIDE in the blood.
Grazoprevir	The serum concentration of Grazoprevir may fall in response to CYP3A4 Inducers (Moderate).
Neratinib	Neratinib's serum levels may be reduced by CYP3A4 Inducers (Moderate).
Nisoldipine	The serum concentration of nisoldipine may fall in response to CYP3A4 Inducers (Moderate).
Olaparib	Olaparib's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Ranolazine	Ranolazine's serum levels may be reduced by moderate CYP3A4 inducers.
Simeprevir	Simeprevir's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Sonidegib	Sonidegib's serum levels may be decreased by CYP3A4 Inducers (Moderate).
Ulipristal	Ulipristal's serum concentration might drop if you take bosentan.
Velpatasvir	The serum concentration of Velpatasvir may fall in response to CYP3A4 Inducers (Moderate).
Venetoclax	Venetoclax serum levels may be decreased by CYP3A4 Inducers (Moderate).

How to take Bosentan?

• With or Without Food: Bosentan can be taken with or without food.
• Tablets for Oral Suspension (Dispersible Tablets):
  • Before Taking: Disperse the tablet in a small amount of water right before taking it.
  • Dosage: The 32 mg dispersible tablet can be split into halves but should not be broken into quarters.

Mechanism of action of Bosentan:

• Bosentan is an endothelin receptor antagonist that works by blocking endothelin receptors found on both the endothelium (the inner lining of blood vessels) and vascular smooth muscle (the muscle in the walls of blood vessels).
• These receptors, when stimulated, typically cause blood vessels to constrict, leading to increased blood pressure.
• By blocking both types of endothelin receptors, Bosentan helps to prevent this vasoconstriction.
• It has a slightly stronger affinity for the A subtype of endothelin receptors.

Distribution:

• Volume of Distribution: Approximately 18 liters, but it doesn't distribute into red blood cells.

Protein Binding:

• Plasma Protein Binding: Over 98%, primarily to albumin.

Metabolism:

• Route: Metabolized in the liver via enzymes CYP2C9 and 3A4 to three metabolites, one of which is active and contributes to about 10% to 20% of its pharmacological activity.
• Autoinduction: Steady-state plasma concentrations are 50% to 65% of those reached after a single dose, likely due to the drug's ability to induce liver enzymes. Steady-state is typically reached within 3 to 5 days.

Bioavailability:

• Approximately 50%.

Half-life:

• Elimination: Around 5 hours, but it may be prolonged in conditions like heart failure, and possibly in pulmonary arterial hypertension (PAH).

Time to Peak:

• Plasma Concentration: It takes 3 to 5 hours to reach peak plasma concentration after administration.

Excretion:

• Feces: Excreted primarily in the feces as metabolites.
• Urine: Less than 3% is excreted unchanged in urine.

International Brands of Bosentan:

• ACT Bosentan
• APO-Bosentan
• BIO-Bosentan
• MYLAN-Bosentan
• PMS-Bosentan
• SANDOZ Bosentan
• TEVA-Bosentan
• Tracleer
• Bosencard
• Bosentadin
• Bosentadine
• Bosentas
• Boxtel
• Lupibose
• Pahsentan
• Pulmiprove
• Pulmofirst
• Pulmonat
• Pulmoten
• Stayveer
• Tracleer
• Trasentan
• Usenta
• Zuxtana

Bosentan Brands in Pakistan:

Bosentan [Tabs 125 mg]
Bosmon	Hilton Pharma (Pvt) Limited

Bosentan [Tabs 62.5 mg]
Bosmon	Hilton Pharma (Pvt) Limited