Sorenafib is a substrate of CYP3A4 and contains secondary aminogroup seen in some mechanism-based CYP inhibitors. However it is only a moderately strong in-vitro inhibitor of CYP 2B6, 2C8 and 2C9, and no interactions have been reported that show this in clinical use. In-vitro studies show no induction of CYP3A4, and no reports of interactions pointing to induction in clinical use. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Sorafenib is an inhibitor of several serine/threonine and receptor tyrosine kinases. The polycyclic molecule contains secondary amino structures.

Sorafenib is an antineoplastic agent used in the treatment of liver cell cancer and advanced kidney cancer. It is administered orally. Common adverse reactions of sorafenib that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea and abdominal pain, as well as obstipation, arthalgia and myalgia. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Sorafenib is metabolised by the cytochrome P450 isoenzyme CYP3A4. In vitro studies have indicated that sorafenib itself inhibits the cytochrome P450 isoenzymes CYP3A4, CYP2C19, and CYP2D6, but use of sorafenib with midazolam, or omeprazole, or dextromethorphan did not alter the exposure to any of these drugs; interactions with drugs that are substrates of these enzymes are considered unlikely. Sorafenib inhibited CYP2B6, 2C8, and 2C9 activities (Ki = 5 - 6 µM, 1 - 2 µM, and 7 - 8 µM, respectively). Inhibition of CYP2C9, CYP2D6 and CYP3A5 was neither time- nor NADPH dependent, thus the inhibition is not irreversible. In vitro-studies found that CYPs 1A2 or 3A4 are not induced by sorenafib. (Scientific discussion, EMEA). Studies with CYP isoform-selective substrates indicated that sorafenib is unlikely to alter the metabolism of substrates of CYP2C19, CYP2D6 and CYP2C9 (including warfarin) (Rini, 2006).

Used uneventfully by elderly female patient (S. Thunell, Sweden).

Uneventful use reported in 1 patient with acute porphyria.