Composition
Tab: Bosentan 62.5 mg (as monohydrate).
Indications & Dosage
Pulmonary arterial hypertension: Adult: Initially 62.5 mg twice daily for 4 weeks, then increased to 125 mg twice daily (max. per dose 250 mg); max. 500 mg per day Children: Not recommended. Systemic sclerosis with ongoing digital ulcer disease to reduce number of new digital ulcers: Adult: Initially 62.5 mg twice daily for 4 weeks, then increased to 125 mg twice daily Children: Not recommended.
Contraindications
Hepatic impairment, hepatic aminotransferase levels >3x upper limit, acute porphyrias, not to be initiated if systemic systolic blood pressure is below 85mmHg
Precautions
Severe pulmonary arterial hypertension, raised liver enzymes; monitor prior to and at monthly intervals during therapy and two weeks after any increase in dose. Advise patients to report any signs suggestive of liver damage. Monitor haemoglobin prior to and at monthly intervals during therapy for first 4 months and quarterly thereafter. Monitor for signs of fluid retention. Women of childbearing po-tential should use non-hormonal contraception during treatment; perform monthly pregnancy test where appropriate. Avoid abrupt withdrawal; withdraw treatment gradually.
Interactions
CYP3A4 inhibitors (particularly potent inhibitors e.g. ketoconazole, itraconazole, ritonavir) or CYP3A4 inducers, CYP2C9 inhibitors (voriconazole, fluconazole), contraceptives, cyclosporin, rifampicin, glibenclamide, tacrolimus, sirolimus, sildenafil, simvastatin.
Pregnancy
Contraindicated in pregnancy.
Lactation
Not recommended.
Side Effects
Anaemia, diarrhea, flushing, gastro-oesophageal reflux, headache, hypotension, oedema, palpitation, syncope, leucopenia, neutropenia thrombocytopenia, urinary tract infection, dyspnoea, GI upset, erythema, dermatitis. Rare: Liver cirrhosis, liver failure