Endothelin Receptor Antagonist (ERA) — Pulmonary Arterial Hypertension / Digital Ulcers Pregnancy: Contraindicated — Category X; teratogenic in animal studies; mandatory pregnancy prevention programme

Bosentan

Brand names: Tracleer

Adult dose

Dose: 62.5 mg twice daily for 4 weeks, then 125 mg twice daily

Route: Oral

Frequency: Twice daily (morning and evening)

Max: 250 mg twice daily (in PAH — not shown superior to 125 mg BD in most)

Mandatory REMS programme (Tracleer REMS) — monthly liver function monitoring and pregnancy test. Dual ERA: blocks both ET-A and ET-B receptors. Strong CYP inducer — numerous drug interactions. Hepatotoxic — LFTs must be checked monthly. Licensed for digital ulcer prevention in systemic sclerosis.

Paediatric dose

Route:

Seek specialist opinion — paediatric PAH: weight-based dosing used in specialist centres

Dose adjustments

Renal

No dose adjustment required

Hepatic

Contraindicated in moderate-severe hepatic impairment (Child-Pugh B/C) — hepatotoxic and extensively hepatically metabolised

Clinical pearls

Strong CYP3A4, CYP2C9, and P-gp inducer — reduces plasma levels of many co-medications including warfarin and contraceptives
BREATHE-1 trial: bosentan improved 6MWD and delayed clinical worsening in PAH
RAPIDS-1/2 trials: reduced new digital ulcers in systemic sclerosis — licensed for this indication
Pregnancy testing and reliable contraception mandatory — two methods required (hormonal alone insufficient due to CYP induction)
Macitentan has replaced bosentan in many centres — fewer drug interactions, once-daily dosing, better outcome data (SERAPHIN trial)

Contraindications

Pregnancy (teratogenic — Category X)
Moderate-severe hepatic impairment
Concurrent cyclosporine A
Concurrent glyburide (glibenclamide)
Women of childbearing potential without highly reliable contraception

Side effects

Hepatotoxicity (dose-dependent — LFTs >3× ULN in 10%)
Flushing
Headache
Peripheral oedema
Anaemia (reduces haemoglobin ~1 g/dL)
Teratogenicity
Male infertility (reduced sperm count)

Interactions

Cyclosporine — absolute contraindication (marked increase in bosentan levels)
Glibenclamide — contraindicated (additive hepatotoxicity)
Warfarin — reduces INR (CYP2C9 induction)
Sildenafil — reduces sildenafil levels, increases bosentan levels — monitor
Hormonal contraceptives — bosentan reduces efficacy — additional contraception mandatory
Statins (simvastatin, atorvastatin) — reduced statin levels

Monitoring

LFTs monthly (mandatory)
Haemoglobin at 1 and 3 months then 3-monthly
Pregnancy test monthly (women of childbearing age)
Blood pressure
6MWD

Reference: BNFc; BNF 90; BREATHE-1 Trial; RAPIDS-2 Trial; NICE TA258 (Bosentan for PAH); ESC/ERS PAH Guidelines 2022. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways