European Union summary of product characteristics(SPC) algorithm for the management of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations
| Liver function | Treatment and monitoring recommendations |
| Before treatment | Liver ALT/AST levels must be measured prior to initiation of treatment and subsequently at monthly intervals. In addition, levels must be measured 2 weeks after any dose increase |
| ALT/AST levels | |
| >3–≤5×ULN | Confirm by another liver test; if confirmed, reduce daily dose or stop treatment and monitor ALT/AST levels at least every 2 weeks. If ALT/AST levels return to pre-treatment values, consider continuing or re-introducing bosentan according to re-introduction conditions¶ |
| 5–≤8×ULN | Confirm by another liver test; if confirmed, stop treatment and monitor ALT/AST levels at least every 2 weeks. If ALT/AST levels return to pre-treatment values, consider continuing or re-introducing bosentan according to re-introduction conditions¶ |
| >8×ULN | Treatment must be stopped and re-introduction of bosentan is not to be considered |
| Associated clinical symptoms of injury# | Treatment must be stopped and re-introduction of bosentan is not to be considered |
ULN: upper limit of normal. #: i.e. nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue or flu-like syndromes (arthralgia, myalgia, fever); ¶: re-introduction of treatment with bosentan should only be considered if the potential benefits outweigh the potential risks and when liver ALT/AST levels are within pre-treatment values. The advice of a hepatologist is recommended. Re-introduction must follow the prescribing guidelines detailed in the SPC. ALT/AST levels must be checked within 3 days of re-introduction, again after a further 2 weeks and thereafter according to the above recommendations.