Bosentan is contra-indicated in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C). Liver-aminotransferase concentrations should be measured before starting therapy, at monthly intervals during therapy, and 2 weeks after any increase in dose; bosentan should not be given to patients with concentrations greater than 3 times the upper limit of normal, and the dose should be reduced or treatment withdrawn if abnormalities occur during treatment or if there are clinical signs of hepatotoxicity. Haemoglobin concentrations should be monitored every 3 months during therapy, more frequently at the start.

Bosentan should not be given to patients with hypotension. Although there is no evidence of rebound effects after discontinuation of bosentan, it is recommended that therapy should be withdrawn gradually.

Bosentan is teratogenic in animals and the manufacturers advise that it should not be used in pregnancy or in women of child-bearing potential who are not using a reliable method of contraception; hormonal contraceptives alone may not be adequate and additional measures may be required.

Bosentan is metabolised by the cytochrome P450 isoenzymes CYP2C9 and CYP3A4 and is also an inducer of the same isoenzymes. It may also possibly induce CYP2C19. Interactions may therefore occur with other drugs that are either metabolised by, or inhibit, these isoenzymes. Use with ciclosporin is contra-indicated since plasma concentrations of bosentan are significantly increased. There is an increased risk of hepatotoxicity if bosentan is given with glibenclamide and such use should be avoided; the hypoglycaemic effect of glibenclamide may also be reduced. Bosentan has reduced the plasma concentrations of some hormonal contraceptives and additional contraceptive measures are advised.