Bosentan is an active pharmaceutical ingredient in the Antihypertensives For Pulmonary Arterial Hypertension group (C02KX). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
CAOfficial regulatory label· revised March 22, 2025[1]
2 Breast-feeding 02/2025 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .............................................................................................
2 TABLE OF CONTENTS ............................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION .......................................................................
EUOfficial regulatory label· revised October 25, 2024[2]
Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III. 1). 1). 3
How to take
EU
USUnited States· FDA
1 product
1 product on record with this regulator. Detailed label text (uses, dosage, side effects) is being ingested — the original document is linked under Sources [3].
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 704 reports total. [4]
Off Label Use 122
Hospitalisation 63
Dyspnoea 53
Death 41
Diarrhoea 41
Product Dose Omission Issue 41
Fatigue 40
Headache 40
Drug Ineffective 34
Pneumonia 33
Product Use Issue 30
Drug interactions
Known interactions involving Bosentan. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 513. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]Health Canada (DPD) · 02483130 · revised March 22, 2025
[2]European Medicines Agency · EMEA/H/C/000401 · revised October 25, 2024
[3]FDA DailyMed · 02892f47-0d59-42… · revised November 25, 2024 [PDF]
[4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
31 12 SPECIAL HANDLING INSTRUCTIONS ................................................................................ 31 PART II: SCIENTIFIC INFORMATION ........................................................................................
32 13 PHARMACEUTICAL INFORMATION […]
How to take
CAOfficial regulatory label· revised March 22, 2025[1]
2 Breast-feeding 02/2025 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .............................................................................................
2 TABLE OF CONTENTS ............................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION .......................................................................
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[1]
) associated with the use of bosentan could potentially occur in the breastfed infant, breast- feeding is not recommended during treatment with Taro-Bosentan. 7. 1. 3 Pediatrics Pediatrics (3-18 years of age): The safety and efficacy of bosentan in children was studied in a group of 19 patients ages 3-15 years with PAH either primary or secondary to various congenital heart defects, in WHO functional class II or III.
Of the 19 patients, 10 were receiving concomitant epoprostenol. After 12 weeks of treatment with bosentan, efficacy could not be demonstrated based on increased exercise capacity. However, statistically significant improvements in certain hemodynamic indices were noted (mean pulmonary artery pressure, mean systemic artery pressure, pulmonary vascular resistance and pulmonary vascular resistance index, systemic vascular resistance and systemic vascular resistance index, cardiac output and stroke index).
No statistically significant improvement in respiratory parameters (oxygen and CO2) or cardiac index was present. By treatment end, five patients had improved by one functional class and one deteriorated. No new safety concerns arose during the study, though one patient was withdrawn from treatment due to increased liver transaminases.
The dosing regimen used in the study was based on body-weight with a recommended target dose of 2 mg/kg, morning and evening. There is extremely limited clinical experience in Taro-Bosentan Product Monograph Page 12 of 52 children below 1 year of age.
d. d. d. d. d. d. 7. 1. 4 Geriatrics Geriatrics (> 65 years of age): Limited clinical experience with bosentan in patients aged 65 years or older has not identified any difference in response between elderly and younger patients, but the possibility of decreased hepatic function in the elderly should be considered (see 4.
2 Recommended Dose and Dosage Adjustment). 8 ADVERSE REACTIONS 8. 1 Adverse Reaction Overview Safety data on bosentan were obtained from placebo-controlled and open-label studies in 677 patients with pulmonary arterial hypertension or other conditions.
Doses up to 8 times the currently recommended maintenance dose for pulmonary arterial hypertension were administered. 1 years. In the placebo- controlled studies, the adverse events that occurred more frequently in patients treated with bosentan than those treated with placebo were flushing, leg edema, abnormal hepatic function, headache and anemia.
Treatment with bosentan has been associated with dose- dependent elevations in liver aminotransferases and decreases in hemoglobin concentration. 8. 2 Clinical Trial Adverse Drug Reactions Clinical trials are conducted under very specific conditions.
The adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
In placebo-controlled studies 258 were patients with pulmonary arterial hypertension. They received bosentan at doses of 250 mg (n=188) or 500 mg (n=70) per day. ) in placebo-controlled studies in pulmonary arterial hypertension System Organ Class / Adverse Events (AEs) Bosentan n=188 Placebo n=172 n (%) N (%) All system Organ Classes Total patients with at least one AE 155 (82) 135 (79) Total number of AEs 504 548 Infections and infestations Nasopharyngitis 16 (9) 14 (8) Upper respiratory tract infection 15 (8) 11 (6) Sinusitis 7 (4) 4 (2) Bronchitis 6 (3) 12 (7) Urinary tract infection 5 (3) 6 (4) Respiratory tract infection 5 (3) 5 (3) Influenza 4 (2) 8 (5) Lower respiratory tract infection 3 (2) 4 (2) Pharyngitis 3 (2) 1 (1) Ear infection 3 (2) Gastrointestinal disorders Nausea 15 (8) 19 (11) Diarrhea 8 (4) 13 (8) Abdominal pain 5 (3) 7 (4) Vomiting 4 (2) 10 (6) Dyspepsia 4 (2) 4 (2) Abdominal distension 4 (2) 3 (2) Rectal hemorrhage 4 (2) Constipation 3 (2) 4 (2) Dry mouth 3 (2) 2 (1) Mouth ulceration 3 (2) Nervous system disorders Headache 24 (13) 25 (15) Dizziness 18 (10) 23 (13) Syncope 8 (4) 7 (4) General disorders and administration site conditions Edema peripheral 15 (8) 13 (8) Chest pain 10 (5) 8 (5) Edema 5 (3) 4 (2) Influenza like illness 4 (2) 2 (1) Respiratory, thoracic and mediastinal disorders Cough 9 (5) 14 (8) Taro-Bosentan Product Monograph Page 14 of 52 Pulmonary hypertension 8 (4) 23 (13) Dyspnea 6 (3) 7 (4) Epistaxis 6 (3) 7 (4) Hemoptysis 4 (2) 4 (2) Dyspnea exacerbated 3 (2) 6 (4) Dyspnea exertional 3 (2) 1 (1) Musculoskeletal and connective tissue disorders Back pain 7 (4) 6 (4) Arthralgia 6 (3) 3 (2) Muscle spasms 5 (3) 6 (4) Shoulder pain 4 (2) 4 (2) Investigations Liver function test abnormal 8 (4) 3 (2) Hepatic enzyme increased 3 (2) Vascular disorders Flushing 8 (4) 5 (3) Hypotension 6 (3) 3 (2) Cardiac disorders Palpitations 6 (3) 3 (2) Eye disorders Vision blurred 3 (2) 2 (1) Blood and lymphatic system disorders Anemia 6 (3) Injury, poisoning and procedural complications Contusion 4 (2) 1 (1) In placebo-controlled studies of bosentan in the treatment of pulmonary arterial hypertension and other diseases, a total of 677 patients were treated with bosentan and 288 patients were treated with placebo, with doses ranging from 100 mg to 2,000 mg per day.
The duration of treatment ranged from […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[1]
2 Breast-feeding 02/2025 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .............................................................................................
2 TABLE OF CONTENTS ............................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION .......................................................................
6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ...................................... 7 7 WARNINGS AND PRECAUTIONS ........................................................................................ 7 7. 1 Special Populations .....................................................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[1]
Taro-Bosentan is contraindicated in patients: • who are hypersensitive to bosentan or to any excipient in the formulation. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • who are pregnant, or of childbearing potential unless adequate contraceptive measures are taken.
1 Pregnant Women). , aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), greater than 3 times the upper limit of normal (ULN), particularly when the total bilirubin is increased to greater than 2 times the ULN (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic).
• concomitant use of cyclosporine A • concomitant use of glyburide. Taro-Bosentan Product Monograph Page 5 of 52
This is not medical advice. Consult a qualified healthcare professional.
Method of administration Tablets are to be taken orally morning and evening, with or without food. The film-coated tablets are to be swallowed with water. Patients should be advised not to swallow the desiccant found in the white high-density polyethylene bottles.
Posology Pulmonary arterial hypertension Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. A Patient Alert Card providing important safety information that patients need to be aware of before and during treatment with Tracleer is included in the pack.
5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. 4). 2). Increasing the dose or the dosing frequency will likely not result in additional clinical benefit. Based on these pharmacokinetic results, when used in children with PAH aged 1 year and older, the recommended starting and maintenance dose is 2 mg/kg morning and evening.
In neonates with persistent pulmonary hypertension of the newborn (PPHN), the benefit of bosentan has not been shown in the standard-of-care treatment. 2). , decrease in 6-minute walk test distance by at least 10% compared with pre-treatment measurement) despite Tracleer treatment for at least 8 weeks (target dose for at least 4 weeks), alternative therapies should be considered.
However, some patients who show no response after 8 weeks of treatment with Tracleer may respond favourably after an additional 4 to 8 weeks of treatment. , after several months of treatment), the treatment should be re-assessed. Some patients not responding well to 125 mg twice daily of Tracleer may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily.
1). 4 Discontinuation of treatment There is limited experience with abrupt discontinuation of Tracleer in patients with PAH. No evidence for acute rebound has been observed. However, to avoid the possible occurrence of harmful clinical deterioration due to potential rebound effect, gradual dose reduction (halving the dose for 3 to 7 days) should be considered.
Intensified monitoring is recommended during the discontinuation period. If the decision to withdraw Tracleer is taken, it should be done gradually while an alternative therapy is introduced. Systemic sclerosis with ongoing digital ulcer disease Treatment should only be initiated and monitored by a physician experienced in the treatment of systemic sclerosis.
A Patient Alert Card providing important safety information that patients need to be aware of before and during treatment with Tracleer is included in the pack. 5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
4). 1). The patient’s response to treatment and need for continued therapy should be re-evaluated on a regular basis. 8). Paediatric population There are no data on the safety and efficacy in patients under the age of 18 years. Pharmacokinetic data are not available for Tracleer in young children with this disease.
2). 2). Renal impairment No dose adjustment is required in patients with renal impairment. 2). Elderly No dose adjustment is required in patients over the age of 65 years.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised October 25, 2024[2]
In 20 placebo-controlled studies, conducted in a variety of therapeutic indications, a total of 2 486 patients were treated with bosentan at daily doses ranging from 100 mg to 2 000 mg and 1 838 patients were treated with placebo. The mean treatment duration was 45 weeks.
5% more than on placebo. 9%). 4). Adverse reactions observed in 20 placebo-controlled studies and post-marketing experience with bosentan are ranked according to frequency using the following convention: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1 000 to < 1/100); rare ( 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. No clinically relevant differences in adverse reactions were observed between the overall dataset and the approved indications. 4) Rare Liver cirrhosis, liver failure1 Skin and subcutaneous disorders Common Erythema General disorders and administration site conditions Very common Oedema, fluid retention5 1 Data derived from post-marketing experience, frequencies based on statistical modelling of placebo-controlled clinical trial data.
1% of patients on placebo. 8% of patients on placebo. 4 These types of reactions can also be related to the underlying disease. 9% of patients on placebo. In the post-marketing period rare cases of unexplained hepatic cirrhosis were reported after prolonged therapy with Tracleer in patients with multiple co-morbidities and therapies with medicinal products.
There have also been rare reports of liver failure. 4). Paediatric population Uncontrolled clinical studies in paediatric patients The safety profile in the first paediatric uncontrolled study performed with the film-coated tablet (BREATHE-3: n = 19, median age 10 years [range 3–15 years], open-label bosentan 2 mg/kg twice daily; treatment duration 12 weeks) was similar to that observed in the pivotal trials in adult patients with PAH.
In BREATHE-3, the most frequent adverse reactions were flushing (21%), headache, and abnormal liver function test (each 16%). A pooled analysis of uncontrolled paediatric studies conducted in PAH with the bosentan 32 mg dispersible tablet formulation (FUTURE 1/2, FUTURE 3/Extension) included a total of 100 children treated with bosentan 2 mg/kg twice daily (n = 33), 2 mg/kg three times daily (n = 31), or 4 mg/kg twice daily (n = 36).
At enrolment, six patients were between 3 months and 1 year old, 15 children were between 1 and less than 2 years old, and 79 were between 2 and 12 years old. 4–258 weeks). 3%). 4 weeks). The most frequent adverse events were upper respiratory tract infections (25%), pulmonary (arterial) hypertension (20%), nasopharyngitis (17%), pyrexia (15%), vomiting (13%), bronchitis (10%), abdominal pain (10%), and diarrhoea (10%).
There was no relevant difference in adverse event frequencies between patients above and below the age of 2 years; however, this is based on only 21 children less than 2 years, including 6 patients between 3 months to 1 year of age.
Adverse events of liver abnormalities and anaemia/haemoglobin decrease occurred in 9% and 5% of patients, respectively. In a randomised placebo-controlled study, conducted in PPHN patients (FUTURE-4), a total of 13 neonates were treated with the bosentan dispersible tablet formulation at a dose of 2 mg/kg twice daily (8 patients were on placebo).
5 days). The most frequent adverse events in the bosentan- and placebo-treated […]
EUOfficial regulatory label· Warnings and precautions· revised October 25, 2024[2]
The efficacy of Tracleer has not been established in patients with severe PAH. 2). The benefit/risk balance of bosentan has not been established in patients with WHO class I functional status of PAH. Tracleer should only be initiated if the systemic systolic blood pressure is higher than 85 mmHg.
Tracleer has not been shown to have a beneficial effect on the healing of existing digital ulcers. , aspartate and alanine aminotransferases (AST and/or ALT), associated with bosentan are dose dependent. 8). These increases may be partly due to competitive inhibition of the elimination of bile salts from hepatocytes but other mechanisms, which have not been clearly established, are probably also involved in the occurrence of liver dysfunction.
The accumulation of bosentan in hepatocytes leading to cytolysis with potentially severe damage of the liver, or an immunological mechanism, are not excluded. 5), are co-administered with bosentan, but limited data are available. Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with Tracleer.
In addition, liver aminotransferase levels must be measured 2 weeks after any dose increase. 2). Monitoring of aminotransferase levels should be continued at least every 2 weeks. If the aminotransferase levels return to pre-treatment values continuing or re- introducing Tracleer according to the conditions described below should be considered.
> 5 and 8 ULN The result should be confirmed by a second liver test; if confirmed, treatment should be stopped and aminotransferase levels monitored at least every 2 weeks. If the aminotransferase levels return to pre-treatment values re- introducing Tracleer according to the conditions described below should be considered.
6 > 8 ULN Treatment must be stopped and re-introduction of Tracleer is not to be considered. , nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome (arthralgia, myalgia, fever), treatment must be stopped and re-introduction of Tracleer is not to be considered.
Re-introduction of treatment Re-introduction of treatment with Tracleer should only be considered if the potential benefits of treatment with Tracleer outweigh the potential risks and when liver aminotransferase levels are within pre-treatment values.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised October 25, 2024[2]
6)
This is not medical advice. Consult a qualified healthcare professional.
31 12 SPECIAL HANDLING INSTRUCTIONS ................................................................................ 31 PART II: SCIENTIFIC INFORMATION ........................................................................................
32 13 PHARMACEUTICAL INFORMATION ................................................................................. 32 14 CLINICAL TRIALS..............................................................................................................
33 14. 3 COMPARATIVE BIOAVAILABILITY STUDY […]
The advice of a hepatologist is recommended. 2. Aminotransferase levels must then be checked within 3 days after re-introduction, then again after a further 2 weeks, and thereafter according to the recommendations above. 8). In placebo-controlled studies, bosentan-related decreases in haemoglobin concentration were not progressive, and stabilised after the first 4–12 weeks of treatment.
It is recommended that haemoglobin concentrations be checked prior to initiation of treatment, every month during the first 4 months, and quarterly thereafter. If a clinically relevant decrease in haemoglobin concentration occurs, further evaluation and investigation should be undertaken to determine the cause and need for specific treatment.