Medicine guide

Bosentan

62.5 mg · Tablet, Film Coated

Prescription only
Endothelin Receptor Antagonist

Active substance: Bosentan
Made by: Sun Pharmaceutical Industries, Inc.
Source: Official label

Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.

At a glance

Quoted from the official label · 2025-12-22

What it is

Endothelin Receptor Antagonist

Used for

The label’s usual adult dose

Adults and pediatric patients >12 years and >40 kg , reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks.

Full directions ↓

Serious warning

RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY Because of the risk of hepatotoxicity, bosentan is available only through a restricted program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS).

All warnings ↓

Good to know

Prescription only
FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02

13other products contain Bosentan — compare makers, forms and strengths

Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed

What it is for

Bosentan is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1):

in
adults to improve exercise ability and to decrease clinical worsening.
Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) [see Clinical Studies (14.1)] . in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.
Bosentan is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1):
in
adults to improve exercise ability and to decrease clinical worsening.
Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) (1). in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability (1).

From the official label · 2025-12-22 · DailyMed

How it works

From this product’s own US prescribing label.

Bosentan is a specific and competitive antagonist at endothelin receptor types ET A and ET B.
Bosentan has a slightly higher affinity for ET A receptors than for ET B receptors.

Peak level after3–5 h

How the body breaks it down

Bosentan is eliminated by biliary excretion following metabolism in the liver.

With food

The absolute bioavailability of bosentan in normal volunteers is about 50% and is unaffected by food.

Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2025-12-22

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY Because of the risk of hepatotoxicity, bosentan is available only through a restricted program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS).
Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.2)].
Hepatotoxicity In clinical studies, bosentan caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases.
Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration (2.4), Warnings and Precautions (5.1)] .
In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with bosentan in patients with multiple comorbidities and drug therapies.
There have also been reports of liver failure.
The contribution of bosentan in these cases could not be excluded.
In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of bosentan.
This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping bosentan with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration (2.4)].
Elevations in aminotransferases require close attention [see Dosage and Administration (2.4)] .
Bosentan should generally be avoided in patients with elevated aminotransferases (> 3 x ULN) at baseline because monitoring for hepatotoxicity may be more difficult.
If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 x ULN, treatment with bosentan should be stopped.
There is no experience with the reintroduction of bosentan in these circumstances.
Embryo-Fetal Toxicity Bosentan is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant females based on animal data.
Therefore, for females of reproductive potential, exclude pregnancy before the start of treatment with bosentan.
Advise use of effective contraception before initiation, during treatment and for one month after stopping bosentan.
When pregnancy is detected, discontinue bosentan as soon as possible [see Dosage and Administration (2.1), Contraindications (4.1), Warnings and Precautions (5.3), Drug Interactions (7.2), Use in Specific Populations (8.1, 8.3)] .
WARNING:
RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning.
Bosentan is available only through a restricted distribution program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS) because of the risk of hepatotoxicity (5.2):
Elevations of liver aminotransferases (ALT, AST) and liver failure have been reported with bosentan (5.1).
Measure liver aminotransferases prior to initiation of treatment and then monthly (2.1, 5.1).
Discontinue bosentan if aminotransferase elevations are accompanied by signs or symptoms of liver dysfunction or injury or increases in bilirubin ≥2 x ULN (2.4, 5.1).
Based on animal data, bosentan may cause fetal harm if used during pregnancy (4.1, 5.3, 8.1).
Females of reproductive potential: Exclude pregnancy before initiating treatment.
Use effective contraception prior to initiation of treatment, during treatment and for one month after stopping bosentan (2.1, 4.1, 5.3, 8.1, 8.3).
When pregnancy is detected, discontinue bosentan as soon as possible (5.3).

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Pregnancy (4.1) Use with Cyclosporine A (4.2) Use with Glyburide (4.3) Hypersensitivity (4.4)
4.1 Pregnancy Use of bosentan is contraindicated in females who are pregnant. [see Boxed Warning, Dosage and Administration (2.1), Warnings and Precautions (5.3), Use in Specific Populations (8.1)] .
4.2 Use with Cyclosporine A Coadministration of cyclosporine A and bosentan resulted in markedly increased plasma concentrations of bosentan.
Therefore, concomitant use of bosentan and cyclosporine A is contraindicated [see Drug Interactions (7.1)].
4.3 Use with Glyburide An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan.
Therefore coadministration of glyburide and bosentan is contraindicated [see Drug Interactions (7.1)] .
4.4 Hypersensitivity Bosentan is contraindicated in patients who are hypersensitive to bosentan or any component of the product.
Observed reactions include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, rash, and angioedema [see Adverse Reactions (6.2), Description (11)] .

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

Patients older than 12 years of age:
initiate at 62.5 mg orally twice daily; for patients weighing greater than 40 kg, increase to 125 mg orally twice daily after 4 weeks (2.2) Patients 12 years of age and younger:
dosage is based on weight, see Table 1 (2.2).
Reduce the dose and closely monitor patients developing aminotransferase elevations more than 3 X Upper Limit of Normal (ULN) (2.4).
2.1 Required Monitoring Healthcare professionals who prescribe bosentan must enroll in the Bosentan REMS Program and must comply with the required monitoring to minimize the risks associated with bosentan [see Warnings and Precautions (5.2)].
Measure liver aminotransferase levels prior to initiation of treatment and then monthly [see Boxed Warning, Warnings and Precautions (5.1, 5.2)].
Exclude pregnancy before initiating treatment with bosentan in females of reproductive potential [see Boxed Warning, Contraindications (4.1), Warnings and Precautions (5.3), Use in Specific Populations (8.1, 8.3)].
2.2 Recommended Dosage Administer bosentan tablet orally following the dosing recommendations in Table 1.
Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity.
Table 1:
Dosing Recommendations Initial 4 weeks Maintenance (after 4 weeks) Patients >12 years of age and >40 kg 62.5 mg twice daily 125 mg twice daily Patients >12 years of age and <40 kg 62.5 mg twice daily 62.5 mg twice daily Patients ≤12 years of age ≥4 to 8 kg 16 mg twice daily 16 mg twice daily ˃8 to 16 kg 32 mg twice daily 32 mg twice daily ˃16 to 24 kg 48 mg twice daily 48 mg twice daily ˃24 to 40 kg 64 mg twice daily 64 mg twice daily
2.3 Administration Bosentan film-coated tablets should be administered orally twice daily.
2.4 Dosage Adjustments for Aminotransferase Elevations If aminotransferase levels increase, adjust monitoring and treatment plan according to Table 2.
Discontinue bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or bilirubin ≥ 2 x Upper Limit of Normal (ULN).
There is no experience with the reintroduction of bosentan tablet in these circumstances.
Table 2:
Dosage Adjustment and Monitoring in Patients Developing Aminotransferase Elevations > 3 x ULN ALT/AST levels Treatment and monitoring recommendations > 3 and ≤ 5 x ULN Confirm by another aminotransferase test; if confirmed, - in
adults and pediatric patients >12 years and >40 kg , reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks.
If the aminotransferase levels return to pretreatment values, treatment may continue or be reintroduced at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 days. - in all other pediatric patients , interrupt treatment with no prior dose reduction.
If the aminotransferase levels return to pretreatment values, reintroduce at the dose used prior to treatment interruption, with reassessment of aminotransferase levels within 3 days. > 5 and ≤ 8 x ULN Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks.
Once the aminotransferase levels return to pretreatment values, -in
adults and pediatric patients >12 years and >40 kg , consider reintroduction of treatment at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 days. - in all other pediatric patients , consider reintroduction at the dose used prior to treatment interruption, with reassessment of aminotransferase levels within 3 days. > 8 x ULN Stop treatment permanently.
There is no experience with reintroduction of bosentan in these circumstances.
2.5 Use with Ritonavir Coadministration of Bosentan tablet in Patients on Ritonavir In patients who have been receiving ritonavir for at least 10 days, start bosentan tablet at the recommended initial dose once daily or every other day based upon individual tolerability [see Cytochrome P450 Drug Interactions (7.1)] .
Coadministration of Ritonavir in Patients on Bosentan tablet Discontinue use of bosentan tablet at least 36 hours prior to initiation of ritonavir.
After at least 10 days following the initiation of ritonavir, resume bosentan tablet at the recommended initial dose once daily or every other day based upon individual tolerability [see Cytochrome P450 Drug Interactions (7.1)] .
Use in Patients with Preexisting Hepatic Impairment
Avoid initiation of bosentan tablet in patients with aminotransferases >3 x ULN.
No dose adjustment is required in patients with mildly impaired liver function [see Warnings and Precautions (5.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Quoted from the official label, section “Dosage & Administration”.

Other warnings

Fluid retention: May require intervention (5.4).
Pulmonary veno-occlusive disease (PVOD):
If signs of pulmonary edema occur, consider the diagnosis of associated PVOD and consider discontinuing bosentan (5.5).
Decreased sperm counts (5.6).
Monitor hemoglobin levels after 1 and 3 months of treatment, then every 3 months thereafter (5.7).
5.1 Hepatotoxicity ALT or AST > 3 x ULN were observed in 11% of bosentan-treated patients (n = 658) compared to 2% of placebo-treated patients (n = 280).
Three-fold increases were seen in 12% of 95 pulmonary arterial hypertension (PAH) patients on 125 mg twice daily and 14% of 70 PAH patients on 250 mg twice daily.
Eight-fold increases were seen in 2% of PAH patients on 125 mg twice daily and 7% of PAH patients on 250 mg twice daily.
Bilirubin increases to ≥ 3 x ULN were associated with aminotransferase increases in 2 of 658 (0.3%) of patients treated with bosentan.
In a pooled analysis of four pediatric studies conducted in PAH (n =100), elevations in liver aminotransferases ≥3×ULN were observed in 2% of patients.
The combination of hepatocellular injury (increases in aminotransferases of > 3 x ULN) and increases in total bilirubin (≥ 2 x ULN) is a marker for potential serious hepatotoxicity.
Elevations of AST or ALT associated with bosentan are dose-dependent, occur both early and late in treatment, usually progress slowly, are typically asymptomatic, and usually have been reversible after treatment interruption or cessation.
Aminotransferase elevations also may reverse spontaneously while continuing treatment with bosentan.
Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly and therapy adjusted accordingly [see Dosage and Administration (2.1, 2.4)].
Discontinue bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 x ULN.
Avoid initiation of bosentan in patients with elevated aminotransferases (> 3 x ULN) prior to drug initiation because monitoring hepatotoxicity in these patients may be more difficult [see Boxed Warning, Dosage and Administration (2.6), Use in Specific Populations (8.6)].
In WHO Functional Class II patients, consider whether the benefits of bosentan are sufficient to offset the risk of hepatotoxicity, which may preclude future use as their disease progresses.
Bosentan is only available through a restricted program under REMS [see Warnings and Precautions (5.2)] .
5.2 Bosentan REMS Because of the risks of hepatotoxicity, bosentan is available only through a restricted program called the Bosentan REMS.
As a component of the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Boxed Warning, Warnings and Precautions (5.1)].
Required components of the Bosentan REMS are:
Healthcare professionals who prescribe bosentan must review the prescriber educational materials, enroll in the Bosentan REMS and comply with its requirements.
Healthcare professionals must (1) review serum aminotransferases (ALT/AST) and bilirubin, and agree to order and monitor these tests monthly.
To receive bosentan, all patients must understand the risks and benefits, and complete a patient enrollment form with their prescriber.
Pharmacies that dispense bosentan must enroll in the program and agree to comply with the Bosentan REMS requirements.
Further information about bosentan and the Bosentan REMS is available at www.BosentanREMSProgram.com or 1-866-359-2612.
5.3 Embryo-Fetal Toxicity Based on data from animal reproduction studies, bosentan may cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant.
The available human data for endothelin receptor antagonists do not establish the presence or absence of major birth defects related to the use of bosentan.
Advise females of reproductive potential about the potential risk to a fetus.
Exclude pregnancy prior to bosentan treatment.
Advise females of reproductive potential to use effective contraception prior to initiation of treatment with bosentan, during treatment, and for at least one month after the last dose.
When pregnancy is detected, discontinue bosentan as soon as possible [see Dosage and Administration (2.1), Contraindications (4.1), Drug Interactions (7.2), Use in Specific Populations (8.1, 8.3)] .
5.4 Fluid Retention Peripheral edema is a known clinical consequence of PAH and worsening PAH and is also a known effect of bosentan and other endothelin receptor antagonists.
In PAH clinical trials with bosentan, combined adverse events of fluid retention or edema were reported in 1.7% (placebo-corrected) of patients.
In addition, there have been numerous postmarketing reports of fluid retention in patients with pulmonary hypertension occurring within weeks after starting bosentan.
Patients required intervention with a diuretic, fluid management, or hospitalization for decompensating heart failure.
If clinically significant fluid retention develops, with or without associated weight gain, further evaluation should be undertaken to determine the cause, such as bosentan or underlying heart failure, and the possible need for treatment or discontinuation of bosentan [see Adverse Reactions (6.1), Clinical Studies (14.2)] .
5.5 Pulmonary Veno-Occlusive Disease If signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease and consider whether bosentan should be discontinued.
5.6 Decreased Sperm Counts Decreased sperm counts have been observed in patients receiving bosentan.
Preclinical data also suggest that bosentan, similar to other endothelin receptor antagonists, may have an adverse effect on spermatogenesis [see Adverse Reactions (6.1), Nonclinical Toxicology (13.1)].
5.7 Decreases in Hemoglobin and Hematocrit Treatment with bosentan can cause a dose-related decrease in hemoglobin and hematocrit.
There have been postmarketing reports of decreases in hemoglobin concentration and hematocrit that have resulted in anemia requiring transfusion.
If a marked decrease in hemoglobin concentration occurs, further evaluation should be undertaken to determine the cause and need for specific treatment [see Adverse Reactions (6.1)] .

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Risk Summary Based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4.1)].
Available data from postmarketing reports and published literature over decades of use with endothelin receptor antagonists (ERA) in the same class as bosentan have not identified an increased risk of major birth defects; however, these data are limited.
Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data.
These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use.
In animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (MRHD) on a mg/m 2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see Animal Data] .
Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Bosentan was teratogenic in rats given oral doses two times the MRHD (on a mg/m 2 basis).
In an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels.
Bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the MRHD (on a mg/m 2 basis).
Although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat.
The similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs .
IN SPECIFIC POPULATIONS Nursing mothers: Choose breastfeeding or bosentan (8.2).
8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4.1)].
Available data from postmarketing reports and published literature over decades of use with endothelin receptor antagonists (ERA) in the same class as bosentan have not identified an increased risk of major birth defects; however, these data are limited.
Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data.
These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use.
In animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (MRHD) on a mg/m 2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see Animal Data] .
Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Bosentan was teratogenic in rats given oral doses two times the MRHD (on a mg/m 2 basis).
In an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels.
Bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the MRHD (on a mg/m 2 basis).
Although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat.
The similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs .
8.2 Lactation Risk Summary Data from a case report describe the presence of bosentan in human milk.
There is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan on milk production.
Because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan.
8.3 Females and Males of Reproductive Potential Based on data from animal reproductive toxicity studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1), Use in Specific Populations (8.1)] .
Pregnancy Testing Verify that females of reproductive potential are not pregnant prior to initiating bosentan.
The patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected.
If the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus [see Dosage and Administration (2.1), Contraindications (4.1), Warnings and Precautions (5.3)] .
Contraception Drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives.
Based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using bosentan and should not be used as a patient’s only contraceptive method [see Drug Interactions (7.2)] .
Females of reproductive potential using bosentan should use effective methods of contraception prior to initiation of treatment, during treatment, and for 1 month after treatment with bosentan [see Warnings and Precautions (5.3)] .
Patients may choose one highly effective form of contraception (intrauterine devices (IUD) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods).
If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method.
Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling .
Infertility Males Decreased sperm counts have been observed in patients receiving bosentan.
Based on these findings and findings in animals, bosentan may impair fertility in males of reproductive potential.
It is not known whether effects on fertility would be reversible [see Warnings and Precautions (5.6), Adverse Reactions (6.1), Nonclinical Toxicology (13.1)].
8.4 Pediatric Use The efficacy of bosentan in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with bosentan.
In this study, cardiopulmonary hemodynamic improvements were similar to those seen in
adults treated with bosentan [see Clinical Studies (14.1)] .
Safety in pediatric patients is supported by data from 100 pediatric patients treated with bosentan for a median of 17 months [see Adverse Reactions (6.1), Clinical Studies (14.1)] .
Juvenile Animal Toxicity Data In a juvenile rat toxicity study, rats were treated from Day 4 postpartum to adulthood (Day 69 postpartum).
Decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning.
No effect on testis histology or sperm morphology and function was seen.
The NOAEL was 4 times (at Day 4 postpartum) and 2 times (Day 69 postpartum) the human therapeutic exposure, respectively.
No effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with PAH.
8.5 Geriatric Use Clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.
8.6 Hepatic Impairment Because there is in vitro and in vivo evidence that the main route of excretion of bosentan is biliary, liver impairment could be expected to increase exposure (C max and AUC) of bosentan.
The pharmacokinetics of bosentan have not been evaluated in patients with severe liver impairment (Child-Pugh Class C).
In patients with moderate hepatic impairment (Child-Pugh Class B), the systemic exposures to bosentan and its active metabolite increased significantly.
Bosentan should generally be avoided in patients with moderate or severe liver impairment.
Pharmacokinetics of bosentan were not altered in patients with mild impairment of hepatic function (Child-Pugh Class A) [see Dosage and Administration (2.6), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)] .
8.7 Renal Impairment The effect of renal impairment on the pharmacokinetics of bosentan is small and does not require dosing adjustment [see Clinical Pharmacology (12.3)] .

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Cytochrome P450:
Coadministration of bosentan with drugs metabolized by CYP2C9 and CYP3A can increase exposure to bosentan and/or the coadministered drug (4.2, 4.3, 7.1).
Hormonal contraceptives:
Bosentan use decreases contraceptive exposure and reduces effectiveness (7.2).
7.1 Cytochrome P450 Drug Interactions Bosentan is metabolized by CYP2C9 and CYP3A.
Inhibition of these enzymes may increase the plasma concentration of bosentan [see Clinical Pharmacology (12.3)] .
Concomitant administration of both a CYP2C9 inhibitor (such as fluconazole or amiodarone) and a strong CYP3A inhibitor (e.g., ketoconazole, itraconazole) or a moderate CYP3A inhibitor (e.g., amprenavir, erythromycin, fluconazole, diltiazem) with bosentan will likely lead to large increases in plasma concentrations of bosentan.
Coadministration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with bosentan is not recommended.
Bosentan is an inducer of CYP3A and CYP2C9.
Consequently plasma concentrations of drugs metabolized by these two isozymes will be decreased when bosentan is coadministered.
Bosentan had no relevant inhibitory effect on any CYP isozyme in vitro (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A).
Consequently, bosentan is not expected to increase the plasma concentrations of drugs metabolized by these enzymes.
Figure 1.
CYP3A induction-mediated effect of bosentan on other drugs Figure 2.
Effect of other drugs on bosentan spl-bosentan-figure-1 spl-bosentan-figure-2
7.2 Hormonal Contraceptives Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when bosentan is coadministered.
Females should practice additional methods of contraception and not rely on hormonal contraception alone when taking bosentan [see Use in Specific Populations (8.3)].
An interaction study demonstrated that coadministration of bosentan and a combination oral hormonal contraceptive produced average decreases of norethindrone and ethinyl estradiol levels of 14% and 31%, respectively.
However, decreases in exposure were as much as 56% and 66%, respectively, in individual subjects.

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

Bosentan has been given as a single dose of up to 2,400 mg in normal volunteers, or up to 2,000 mg/day for 2 months in patients, without any major clinical consequences.
The most common side effect was headache of mild to moderate intensity.
In the cyclosporine A interaction study, in which doses of 500 mg and 1,000 mg twice daily of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events.
Mild decreases in blood pressure and increases in heart rate were observed.
In the postmarketing period, there was one reported overdose of 10,000 mg of bosentan taken by an adolescent male patient.
He had symptoms of nausea, vomiting, hypotension, dizziness, sweating, and blurred vision.
He recovered within 24 hours with blood pressure support.
Bosentan is unlikely to be effectively removed by dialysis due to the high molecular weight and extensive plasma protein binding.

Quoted from the official label, section “Overdosage”.

Use in children

The efficacy of bosentan in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with bosentan.
In this study, cardiopulmonary hemodynamic improvements were similar to those seen in
adults treated with bosentan [see Clinical Studies (14.1)] .
Safety in pediatric patients is supported by data from 100 pediatric patients treated with bosentan for a median of 17 months [see Adverse Reactions (6.1), Clinical Studies (14.1)] .
Juvenile Animal Toxicity Data In a juvenile rat toxicity study, rats were treated from Day 4 postpartum to adulthood (Day 69 postpartum).
Decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning.
No effect on testis histology or sperm morphology and function was seen.
The NOAEL was 4 times (at Day 4 postpartum) and 2 times (Day 69 postpartum) the human therapeutic exposure, respectively.
No effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with PAH.

Quoted from the official label, section “Pediatric Use”.

Use in older people

Clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

Quoted from the official label, section “Geriatric Use”.

Side effects

The following important adverse reactions are described elsewhere in the labeling:
Hepatotoxicity [see Boxed Warning, Warnings and Precautions (5.1)] Embryo-fetal Toxicity [see Boxed Warning, Warnings and Precautions (5.3)] Fluid Retention [see Warnings and Precautions (5.4)] Common adverse reactions (≥3% more than placebo) for the film-coated tablet are respiratory tract infection and anemia (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Safety data on bosentan were obtained from 13 clinical studies (9 placebo-controlled and 4 open-label) in 870 adult patients with PAH and other diseases.
Doses up to 8 times the currently recommended clinical dose (125 mg twice daily) were administered for a variety of durations.
The exposure to bosentan in these trials ranged from 1 day to 4.1 years (n=94 for 1 year; n=61 for 1.5 years; and n=39 for more than 2 years).
Exposure of PAH patients (n=328) to bosentan ranged from 1 day to 1.7 years (n=174 more than 6 months and n=28 more than 12 months).
Treatment discontinuations due to adverse events other than those related to pulmonary hypertension during the clinical trials in adult patients with PAH were more frequent on bosentan (6%; 15/258 patients) than on placebo (3%; 5/172 patients).
In this database the only cause of discontinuations > 1% and occurring more often on bosentan was abnormal liver function.
The adverse drug events that occurred in ≥ 3% of the bosentan-treated patients and were more common on bosentan in placebo-controlled trials in PAH at doses of 125 mg or 250 mg twice daily are shown in Table 3:
Table 3.
Adverse Events* Occurring in ≥3% of Patients Treated with Bosentan 125 mg to 250 mg Twice Daily and More Common on Bosentan in Placebo-Controlled Studies in Pulmonary Arterial Hypertension Adverse Event Bosentan n = 258 Placebo n = 172 No. % No. % Respiratory Tract Infection ** 56 22% 30 17% Headache 39 15% 25 14% Edema 28 11% 16 9% Chest Pain 13 5% 8 5% Syncope 12 5% 7 4% Flushing 10 4% 5 3% Hypotension 10 4% 3 2% Sinusitis 9 4% 4 2% Arthralgia 9 4% 3 2% Serum Aminotransferases, abnormal 9 4% 3 2% Palpitations 9 4% 3 2% Anemia 8 3% - - *Note:
only AEs with onset from start of treatment to 1 calendar day after end of treatment are included.
All reported events (at least 3%) are included except those too general to be informative, and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population. ** Respiratory Tract Infection combines the terms "Nasopharyngitis", "Upper Respiratory Tract Infection" and "Respiratory Tract Infection".
Combined data from Study 351, BREATHE-1 and EARLY Bosentan was evaluated for safety in 119 pediatric patients in uncontrolled studies.
The safety profile was similar to that observed in adult patients with PAH.
Decreased Sperm Counts An open-label, single-arm, multicenter, safety study evaluated the effect on testicular function of bosentan 62.5 mg twice daily for 4 weeks, followed by 125 mg twice daily for 5 months.
Twenty-five male patients with WHO functional class III and IV PAH and normal baseline sperm count were enrolled.
Twenty-three completed the study and 2 discontinued due to adverse events not related to testicular function.
There was a decline in sperm count of at least 50% in 25% of the patients after 3 or 6 months of treatment with bosentan.
Sperm count remained within the normal range in all 22 patients with data after 6 months and no changes in sperm morphology, sperm motility, or hormone levels were observed.
One patient developed marked oligospermia at 3 months and the sperm count remained low with 2 follow-up measurements over the subsequent 6 weeks.
Bosentan was discontinued and after 2 months the sperm count had returned to baseline levels.
Based on these findings and preclinical data from endothelin receptor antagonists, it cannot be excluded that endothelin receptor antagonists such as bosentan have an adverse effect on spermatogenesis.
Decreases in Hemoglobin and Hematocrit Treatment with bosentan can cause a dose-related decrease in hemoglobin and hematocrit.
It is recommended that hemoglobin concentrations be checked after 1 and 3 months, and every 3 months thereafter.
If a marked decrease in hemoglobin concentration occurs, further evaluation should be undertaken to determine the cause and need for specific treatment.
The overall mean decrease in hemoglobin concentration for adult bosentan-treated patients was 0.9 g/dL (change to end of treatment).
Most of this decrease of hemoglobin concentration was detected during the first few weeks of bosentan treatment and hemoglobin levels stabilized by 4 to 12 weeks of bosentan treatment.
In placebo-controlled studies of all uses of bosentan, marked decreases in hemoglobin (> 15% decrease from baseline resulting in values < 11 g/dL) were observed in 6% of bosentan-treated patients and 3% of placebo-treated patients.
In patients with PAH treated with doses of 125 mg and 250 mg twice daily, marked decreases in hemoglobin occurred in 3% compared to 1% in placebo-treated patients.
A decrease in hemoglobin concentration by at least 1 g/dL was observed in 57% of bosentan-treated patients as compared to 29% of placebo-treated patients.
In 80% of those patients whose hemoglobin decreased by at least 1 g/dL, the decrease occurred during the first 6 weeks of bosentan treatment.
During the course of treatment, the hemoglobin concentration remained within normal limits in 68% of bosentan-treated patients compared to 76% of placebo patients.
The explanation for the change in hemoglobin is not known, but it does not appear to be hemorrhage or hemolysis.
In a pooled analysis of pediatric patients (N=100) with PAH treated with bosentan, a decrease in hemoglobin levels to <10 g/dL from baseline was reported in 11% of patients.
There was no decrease to <8 g/dL.
6.2 Postmarketing Experience There have been several postmarketing reports of angioedema associated with the use of bosentan.
The onset of the reported cases occurred within a range of 8 hours to 21 days after starting therapy.
Some patients were treated with an antihistamine and their signs of angioedema resolved without discontinuing bosentan.
The following additional adverse reactions have been reported during the post approval use of bosentan.
Because these adverse reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to bosentan exposure:
Unexplained hepatic cirrhosis [see Boxed Warning] Liver failure [see Boxed Warning] Hypersensitivity, DRESS, and anaphylaxis [see Contraindications (4.4)] Thrombocytopenia Rash Jaundice Anemia requiring transfusion Neutropenia and leukopenia Nasal congestion Autoimmune hepatitis

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

Advise the patient to read the FDA-approved patient labeling (Medication Guide) Restricted Access Advise the patient that bosentan is only available through a restricted access program called the Bosentan REMS and that bosentan is available only from certified pharmacies enrolled in the Bosentan REMS..
As a component of the Bosentan REMS, prescribers must review the contents of the bosentan Medication Guide with the patient before initiating bosentan and patients must sign the Patient Enrollment Form to confirm that they understand the risks of bosentan.
Instruct patients that the risks associated with Bosentan include hepatotoxicity.
Discuss with the patient the requirement to measure serum aminotransferases monthly [see Dosage and Administration (2.1, 2.4), Warnings and Precautions (5.1, 5.2)] .
Embryo-Fetal toxicity Counsel female patients of reproductive potential about the need to use effective contraception prior to treatment, during treatment with bosentan and for one month after treatment discontinuation.
Females of reproductive potential should have a negative pregnancy test prior to treatment [see Dosage and Administration (2.1), Warnings and Precautions (5.3), Drug Interactions (7.2), Use in Specific Populations (8.1, 8.3)] .
Patients should be instructed to immediately contact their physician if they suspect they may be pregnant.
Patients should seek additional contraceptive advice from a gynecologist or similar expert as needed.
Educate and counsel females of reproductive potential on the use of emergency contraception in the event of unprotected sex or contraceptive failure.
Advise pre-pubertal females to report any changes in their reproductive status immediately to her prescriber.
Lactation Advise women not to breastfeed during treatment with bosentan [see Use in Specific Populations (8.2)].
Infertility Advise males of reproductive potential that bosentan may impair fertility [see Warnings and Precautions (5.6), Adverse Reactions (6.1), Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].
Other Risks Associated with Bosentan Instruct patients that the risks associated with bosentan also include the following:
Decreases in hemoglobin and hematocrit – advise patients of the importance of hemoglobin testing Decreases in sperm count Fluid retention Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512 Manufactured by: Sun Pharmaceutical Industries Ltd.
Survey No. 1012, Dadra-396 193, U.T. of D & NH and Daman & Diu, India.

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

FORMS AND STRENGTHS 62.5 mg tablets:
Orange white, round, biconvex film-coated tablet debossed with “945” on one side and plain on the other side. 125 mg tablets:
Orange white, oval, biconvex film-coated tablet debossed with “946” on one side and plain on the other side.
Film-coated tablet: 62.5 mg and 125 mg (3)

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

62.5 mg film-coated, orange white, round, biconvex tablet debossed with “945” on one side and plain on the other side.
Bottles of 60 with Child Resistant Closure.............................................................................NDC 47335-038-86 Blister pack of 30 (10 × 3) Tablets.........................................................................................NDC 47335-038-64 125 mg film-coated, orange white, oval, biconvex tablet debossed with “946” on one side and plain on the other side.
Bottles of 60 with Child Resistant Closure............................................................................NDC 47335-039-86 Blister pack of 30 (10 × 3) Tablets.........................................................................................NDC 47335-039-64
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). [See USP Controlled Room Temperature].
Keep out of reach of children.

Quoted from the official label, section “How Supplied”.

What is in it

Bosentan is an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives, with no chiral centers. It is designated chemically as 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2’]-bipyrimidin-4-yl]-benzenesulfonamide monohydrate and has the following structural formula:
Bosentan has a molecular weight of 569.63 and a molecular formula of C 27 H 29 N 5 O 6 S
H 2 O. Bosentan is a white to off-white crystalline powder. It is poorly soluble in water. In the solid state, bosentan is very stable, is not hygroscopic and is not light sensitive. Bosentan is available as 62.5 mg and 125 mg film-coated tablets for oral administration, and contains the following excipients:
corn starch, ethylcellulose, glyceryl behenate, hydroxypropylmethylcellulose, iron oxide red, iron oxide yellow, magnesium stearate, povidone, pregelatinized maize starch, sodium starch glycolate, talc, titanium dioxide, and triacetin. Each bosentan 62.5 mg tablet contains 64.541 mg of bosentan monohydrate, equivalent to 62.5 mg of anhydrous bosentan. Each bosentan 125 mg tablet contains 129.082 mg of bosentan monohydrate, equivalent to 125 mg of anhydrous bosentan. spl-bosentan-structure

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

The stored label for this product has no list of inactive ingredients. The list on the pack is the one to check.

Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.

Every version of this medicine (5)

The same active substance, strength and kind of form, from every company that sells it — with what each label lists.

Showing 5 of 5

Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

Medicine passport: one printable page to show a pharmacist abroad

European UnionNo exact match for this strength and form

Every strength and form (2)

Details

Made by	Sun Pharmaceutical Industries, Inc.
Active substance	Bosentan
Strength	62.5 mg
Form	Tablet, Film Coated
Route	Oral
Packs	10 BLISTER PACK in 1 CARTON / 3 TABLET, FILM COATED in 1 BLISTER PACK · 60 TABLET, FILM COATED in 1 BOTTLE
NDC	47335-038

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

11 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Tablet, Film Coated4 products
- 62.5 mg2
  62.5 mg · 2 companies
  - Actavis Pharma, Inc.
  - Sun Pharmaceutical Industries, Inc. · this page
- 125 mg2
  125 mg · 2 companies
  - Actavis Pharma, Inc.
  - Sun Pharmaceutical Industries, Inc.
Tablet, for Suspension3 products
- 32 mg3
  32 mg · 3 companies
Tablet, Coated2 products
- 62.5 mg
- 125 mg
Tablet2 products
- 62.5 mg
- 125 mg

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

Bosentan62.5 mgPrescription onlyTablet, Film Coated Actavis Pharma, Inc. · Bosentan Bosentan125 mgPrescription onlyTablet, Film Coated Actavis Pharma, Inc. · Bosentan Bosentan125 mgPrescription onlyTablet, Film Coated Sun Pharmaceutical Industries, Inc. · Bosentan Bosentan32 mgPrescription onlyTablet, for Suspension Lupin Pharmaceuticals, Inc. · Bosentan Bosentan62.5 mgPrescription onlyTablet, Coated Zydus Pharmaceuticals USA Inc. · Bosentan Bosentan125 mgPrescription onlyTablet, Coated Zydus Pharmaceuticals USA Inc. · Bosentan

See every product with Bosentan