Continuous co-administration of sorafenib and rifampicin resulted in an average 37% reduction of sorafenib AUC. Other inducers of CYP3A4 activity (for example, St. John’s wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone) may also increase metabolism of sorafenib and thus decrease sorafenib concentrations.
CYP3A4 Inhibitors and CYP Isoform Substrates
In vitro and in vivo data suggest that: 1) sorafenib is unlikely to be altered by CYP3A inhibitors, and 2) sorafenib is unlikely to alter the metabolism of substrates of CYP2C19, CYP2D6, and CYP3A4
Sorafenib prolongs the QT interval, hence, concomitant administration with patients taking certain anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, e.g. certain anti-arrhythmic drugs, should be used with caution
Sorafenib and Neoplastic Agents
When used concomitantly with carboplatin and paclitaxel, sorafenib has been observed to increase the AUC of paclitaxel, and the AUC of sorafenib also increased. Sorafenib can also cause increases in plasma concentrations of doxorubicin, irinotecan, docetaxel, fluorouracil, and paclitaxel.1,2,5 Sorafenib is contraindicated in patients with squamous cell lung cancer, as a result of observed increased mortality with the addition of sorafenib.
Sorafenib and CYP Inhibitors and Substrates
Sorafenib inhibits CYP2B6 and CYP2C8 in vitro. Systemic exposure to substrates of CYP2B6 and CYP2C8 is therefore expected to increase when co-administered with sorafenib.