Imatinib CYP3A4 inducers

Sunirinib (Sutent) [Kinase Inhibitor] Uses Advanced GI stromal tumor refractory/intolerant of imatinib advanced RCC Action Kinase inhibitor Dose Adults. 50 mg PO daily x 4 wk, followed by 2 wk holiday = 1 cycle 4- to 37.5 mg w/ CYP3A4 inhibitors (Table VI-8), to T 87.5 mg w/ CYP3A4 inducers Contra w/ atazanavir Caution [D, -] Multiple interactions require dose modification (eg, St. John s wort) Disp Caps SE -l WBC pit, bleeding, T BP, -l ejection fraction, T QT interval, pancreatitis, DVT, Sz, adrenal insuff, N/V/D, skin discoloration, oral ulcers, taste perversion, hypothyroidism Interactions Multiple interactions require dose modification (eg, St. John s wort) EMS Monitor ECG for T QT interval grapefruit juice may T adverse effects may affect potassium level (hypo-/hyperkalemia) monitor for S/Sxs of heart failure drug can 4- ejection fraction OD May cause abd pain, muscle weakness, and chills symptomatic and supportive... 

Rifampicin (rifampin) and St John s wort Hypericum perforatum) lower serum imatinib levels other CYP3A4 inducers (such as carbamazepine, phenobarbital and phenytoin) are predicted to... 

No specific studies have been carried out with imatinib and other CYP3A4-inducing drugs, but the manufacturers suggest that carbamazepine, dexamethasone, phenobarbital, and phenytoin, may also reduce imatinib serum levels, and they have a possible case on file with phenytoin. The manufacturers therefore reasonably recommend caution, and suggest that concurrent use with these drugs should be avoided. However, if this is not possible it would be prudent to monitor the outcome of concurrent use, and increase the imatinib dose as necessary. 

Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Use aprepitant with caution in patients receiving concomitant medicinal products, including chemotherapy agents that are primarily metabolized through CYP3A4 (docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine). 

CYP3A4 is the major enzyme responsible for metabolism of imatinib. Other CYPs play a minor role in imatinib s metabolisrrL Imatinib increased the peak plasma concentration andAUC o/simvastatin by 2 and 3.5 times, respectively, and coadministration with rifampin, an inducer of CYP3A4, reduces plasma imatinib AUC by -70%. Elimination of imatinib occurs predominantly in the feces, mostly as metabolites. 

Rifampicin is a known potent inducer of many cytochrome P450 isoenzymes, including CYP3A4, by which imatinib is metabolised. Therefore rifampicin increases imatinib metabolism and decreases its levels. St John s wort induces intestinal CYP3A4 and it therefore also reduces imatinib levels. 

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