Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Endothelin Receptor Antagonist (ERA) — Pulmonary Arterial Hypertension / Digital Ulcers Pregnancy: CONTRAINDICATED IN PREGNANCY (SPC §4.3, §4.6). §4.6 (section cross-references omitted): 'Studies in animals have shown reproductive toxicity (teratogenicity, embryotoxicity). There are no reliable data on the use of bosentan in pregnant women. The potential risk for humans is still unknown. Bosentan is contraindicated in pregnancy.' WOMEN OF CHILD-BEARING POTENTIAL: 'Before the initiation of bosentan treatment in women of child-bearing potential, the absence of pregnancy should be checked, appropriate advice on reliable methods of contraception provided, and reliable contraception initiated... bosentan may render hormonal contraceptives ineffective. Therefore, women of child-bearing potential must not use hormonal contraceptives (including oral, injectable, transdermal or implantable forms) as the sole method of contraception but must use an additional or an alternative reliable method of contraception.' 'monthly pregnancy tests during treatment with bosentan are recommended to allow early detection of pregnancy.' BREAST-FEEDING: 'A risk to the breastfed infant cannot be excluded. Breast-feeding is not recommended during treatment.'

Bosentan

Brand names: Tracleer

Bosentan is a dual endothelin receptor antagonist licensed for pulmonary arterial hypertension to improve exercise capacity and symptoms, and for digital ulcers in systemic sclerosis.

Adult dose

Dose: Pulmonary arterial hypertension (PAH) in adults, and separately systemic sclerosis with ongoing digital ulcer disease (to reduce the number of new digital ulcers) - the same regimen for both: 62.5 mg twice daily for 4 weeks, then increased to the maintenance dose of 125 mg twice daily
Route: Oral - tablets taken morning and evening, with or without food, swallowed with water
Frequency: Twice daily (morning and evening)
SCOPE: UK SPC 4.1 (Bosentan 125 mg Film-coated Tablets, eMC product 821; the text calls the product 'Bosentan Mylan'): PAH 'to improve exercise capacity and symptoms in patients with WHO functional class III' (some improvement also shown in class II), and 'to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease'. VERBATIM 4.2 (PAH, adults): 'In adult patients, bosentan treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. The same recommendations apply to re-introduction of bosentan after treatment interruption.' Systemic sclerosis with digital ulcers, adults: 'Bosentan treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.' INITIATION: PAH - 'Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension'; digital ulcers - by 'a physician experienced in the treatment of systemic sclerosis'. A Patient Alert Card is included in the pack. NO MAXIMUM PRINTED: the SPC prints no maximum dose, so maxDose is blank. Under PAH clinical deterioration it states only: 'Some patients not responding well to 125 mg twice daily of bosentan may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily. A careful benefit/risk assessment should be made, taking into consideration that the liver toxicity is dose dependent.' That sentence appears only in the PAH section; the digital-ulcer section gives no escalation. DIGITAL ULCERS: 'Controlled clinical study experience in this indication is limited to 6 months. The patient's response to treatment and need for continued therapy should be re-evaluated on a regular basis.' 4.4: 'Bosentan has not been shown to have a beneficial effect on the healing of existing digital ulcers.' CLINICAL DETERIORATION IN PAH: 'In the case of clinical deterioration (e.g., decrease in 6-minute walk test distance by at least 10% compared with pre-treatment measurement) despite bosentan treatment for at least 8 weeks (target dose for at least 4 weeks), alternative therapies should be considered.' DISCONTINUATION: '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.' BEFORE STARTING (4.4): 'Bosentan should only be initiated if the systemic systolic blood pressure is higher than 85 mmHg.' 'The efficacy of bosentan has not been established in patients with severe pulmonary arterial hypertension' and 'The benefit/risk balance of bosentan has not been established in patients with WHO class I functional status of pulmonary arterial hypertension.' ELDERLY: 'No dose adjustment is required in patients over the age of 65 years.' TRUNCATION: UK SPC 4.4 ends at the source-fetch limit after the pulmonary veno-occlusive disease section; 4.8 is truncated too.

Paediatric dose

Dose: 2 mg/kg
Route: Oral
Frequency: Twice daily, morning and evening (2 mg/kg per dose)
PAH ONLY, children aged 1 year and older. UK SPC 4.2: 'when used in children with PAH 1 year and older, the recommended starting and maintenance dose is 2 mg/kg morning and evening.' The SPC adds that paediatric plasma concentrations 'were not increased by increasing the dose of bosentan above 2 mg/kg body weight or by increasing the dosing frequency from twice daily to three times daily' and that 'Increasing the dose or the dosing frequency will likely not result in additional clinical benefit.' No recommendation on a posology can be made for neonates with persistent pulmonary hypertension of the newborn. Systemic sclerosis with digital ulcers: 'There are no data on the safety and efficacy in patients under the age of 18 years.' The SPC states the dose in mg/kg only and does not describe how it is measured out with this 125 mg film-coated tablet product - verify the dose and a suitable formulation against a children's formulary and a specialist paediatric pulmonary hypertension service.

Dose adjustments

Renal

SPC §4.2, verbatim: 'No dose adjustment is required in patients with renal impairment. No dose adjustment is required in patients undergoing dialysis (see section 5.2).'

Hepatic

CONTRAINDICATED in moderate to severe liver dysfunction (Child-Pugh class B or C) and where baseline AST and/or ALT are greater than 3 times the upper limit of normal (§4.3). SPC §4.2: 'No dose adjustment is needed in patients with mild hepatic impairment (i.e., Child-Pugh class A).' §4.4: 'Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with bosentan. In addition, liver aminotransferase levels must be measured 2 weeks after any dose increase.' ALT/AST >3 and ≤5 x ULN — confirm with a second liver test; if confirmed, decide individually whether to continue (possibly at a reduced dose) or stop, and continue monitoring at least every 2 weeks. >5 and ≤8 x ULN — confirm with a second liver test; if confirmed, stop treatment and monitor at least every 2 weeks. >8 x ULN — 'Treatment must be stopped and re-introduction of bosentan is not to be considered.' Liver enzyme elevations are dose dependent and 'typically occur within the first 26 weeks of treatment but may also occur late in treatment'.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

PAH ONLY, children aged 1 year and older. UK SPC 4.2: 'when used in children with PAH 1 year and older, the recommended starting and maintenance dose is 2 mg/kg morning and evening.' The SPC adds that paediatric plasma concentrations 'were not increased by increasing the dose of bosentan above 2 mg/kg body weight or by increasing the dosing frequency from twice daily to three times daily' and that 'Increasing the dose or the dosing frequency will likely not result in additional clinical benefit.' No recommendation on a posology can be made for neonates with persistent pulmonary hypertension of the newborn. Systemic sclerosis with digital ulcers: 'There are no data on the safety and efficacy in patients under the age of 18 years.' The SPC states the dose in mg/kg only and does not describe how it is measured out with this 125 mg film-coated tablet product - verify the dose and a suitable formulation against a children's formulary and a specialist paediatric pulmonary hypertension service.

Verify in a children's formulary

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (SPC §4.3)
  • Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C (SPC §4.3)
  • Baseline values of liver aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT), greater than 3 times the upper limit of normal (SPC §4.3)
  • Concomitant use of ciclosporin A (SPC §4.3)
  • Pregnancy (SPC §4.3)
  • Women of child-bearing potential who are not using reliable methods of contraception (SPC §4.3)

Side effects

  • Most frequent adverse reactions across 20 placebo-controlled studies (SPC §4.8): headache (11.5%), oedema/fluid retention (13.2%), abnormal liver function test (10.9%) and anaemia/haemoglobin decrease (9.9%)
  • Very common (≥1/10): headache; abnormal liver function test; oedema, fluid retention
  • Common (≥1/100 to <1/10): anaemia, haemoglobin decrease; hypersensitivity reactions (including dermatitis, pruritus and rash); syncope; palpitations; flushing, hypotension; nasal congestion; gastro-oesophageal reflux disease; diarrhoea; erythema
  • Uncommon (≥1/1,000 to <1/100): thrombocytopenia; neutropenia, leukopenia; aminotransferase elevations associated with hepatitis (including possible exacerbation of underlying hepatitis) and/or jaundice
  • Rare (≥1/10,000 to <1/1,000): anaphylaxis and/or angioedema; liver cirrhosis, liver failure, autoimmune hepatitis
  • Not known: blurred vision; anaemia or haemoglobin decreases requiring red blood cell transfusion
  • 'Treatment with bosentan has been associated with dose-dependent elevations in liver aminotransferases and decreases in haemoglobin concentration' (SPC §4.8/§4.4)
  • Male fertility (SPC §4.6): '8 out of 24 patients showed a decreased sperm concentration from baseline of at least 42% after 3 or 6 months of treatment with bosentan'

Interactions

  • Ciclosporin A - contraindicated with bosentan (UK SPC 4.3, 4.4)
  • Bile salt export pump inhibitors (UK SPC 4.4, section cross-references omitted): 'Liver dysfunction risk may also be increased when medicinal products that are inhibitors of the bile salt export pump, e.g., rifampicin, glibenclamide and ciclosporin A, are co-administered with bosentan, but limited data are available.'
  • Hormonal contraceptives (UK SPC 4.6): 'bosentan may render hormonal contraceptives ineffective'; women of child-bearing potential 'must not use hormonal contraceptives (including oral, injectable, transdermal or implantable forms) as the sole method of contraception but must use an additional or an alternative reliable method of contraception'
  • This interaction list may be incomplete — check the full SPC.

Monitoring

  • LIVER (§4.4): 'Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with bosentan. In addition, liver aminotransferase levels must be measured 2 weeks after any dose increase.'
  • Act on ALT/AST elevations per the §4.4 thresholds (>3-5 x ULN confirm and decide individually, monitoring at least every 2 weeks; >5-8 x ULN confirm and stop; >8 x ULN stop permanently).
  • PREGNANCY (§4.6): monthly pregnancy tests in women of child-bearing potential.
  • HAEMOGLOBIN (§4.4): '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 occurs, further evaluation and investigation should be undertaken to determine the cause and need for specific treatment.
  • BEFORE INITIATION (§4.4): systemic systolic blood pressure must be higher than 85 mmHg.
  • DISCONTINUATION (§4.2): 'Intensified monitoring is recommended during the discontinuation period.'
  • PAH RESPONSE (§4.2): reassess at 8 weeks (target dose for at least 4 weeks) using the 6-minute walk test.
  • NOTE: §4.4 was truncated at the source-fetch limit after the pulmonary veno-occlusive disease section, so any later §4.4 monitoring advice (for example on left ventricular failure) was NOT retrieved and is not stated here.

Clinical monograph

How it works

It blocks endothelin-1 at both ETA and ETB receptors on vascular smooth muscle and endothelium, reducing the vasoconstriction and proliferation that drive raised pulmonary vascular resistance.

Prescribing in practice

  • Bosentan is hepatotoxic and teratogenic: liver transaminases must be monitored and reliable contraception used, with pregnancy excluded before and during treatment.
  • It induces CYP3A4 and CYP2C9, reducing the efficacy of hormonal contraceptives and interacting with ciclosporin, glibenclamide and warfarin.
  • Avoid co-administration with ciclosporin and glibenclamide, and use with caution alongside other potentially hepatotoxic drugs.

Monitoring

Liver transaminases should be measured before starting and at regular intervals throughout treatment, with haemoglobin also checked periodically as anaemia can occur.

Counselling the patient

  • Women must use reliable non-hormonal contraception and report a missed period.
  • Attend for regular blood tests to monitor the liver.
  • Report jaundice, dark urine, nausea or undue tiredness promptly.

Evidence & guidelines

Randomised placebo-controlled trials in pulmonary arterial hypertension demonstrated improved exercise capacity and haemodynamics, supporting its established place in specialist treatment pathways.

Reference: BREATHE-1 Trial; RAPIDS-2 Trial; NICE TA258 (Bosentan for PAH); ESC/ERS PAH Guidelines 2022; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways