Cobimetinib Fumarate and Fedratinib Hydrochloride

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer information for this interaction is not currently available.GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cobimetinib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers given a single 10 mg dose of cobimetinib with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 14 days), mean cobimetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 6.7-fold, respectively, compared to cobimetinib administered alone. The risk and/or severity of adverse effects such as diarrhea, nausea, vomiting, stomatitis, hemorrhage, cardiomyopathy, rash, photosensitivity, retinopathy, retinal vein occlusion, liver enzyme abnormalities, and rhabdomyolysis may be increased. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that steady-state concentrations of cobimetinib given at a reduced dose of 20 mg with short-term (less than 14 days) use of a moderate CYP450 3A4 inhibitor would be similar to steady-state concentrations observed following a 60 mg dose given alone. MANAGEMENT: Concomitant use of cobimetinib with moderate CYP450 3A4 inhibitors should be avoided whenever possible. If short-term (14 days or less) use of a moderate CYP450 3A4 inhibitor is required during treatment with cobimetinib 60 mg once daily, the manufacturer suggests reducing the cobimetinib dose to 20 mg. Following discontinuation of the moderate CYP450 3A4 inhibitor, the previous dose of 60 mg may be resumed. An alternative to the moderate CYP450 3A4 inhibitor should be used in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). References "Product Information. Cotellic (cobimetinib)." Genentech, South San Francisco, CA.

GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cobimetinib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers given a single 10 mg dose of cobimetinib with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 14 days), mean cobimetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 6.7-fold, respectively, compared to cobimetinib administered alone. The risk and/or severity of adverse effects such as diarrhea, nausea, vomiting, stomatitis, hemorrhage, cardiomyopathy, rash, photosensitivity, retinopathy, retinal vein occlusion, liver enzyme abnormalities, and rhabdomyolysis may be increased. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that steady-state concentrations of cobimetinib given at a reduced dose of 20 mg with short-term (less than 14 days) use of a moderate CYP450 3A4 inhibitor would be similar to steady-state concentrations observed following a 60 mg dose given alone.

MANAGEMENT: Concomitant use of cobimetinib with moderate CYP450 3A4 inhibitors should be avoided whenever possible. If short-term (14 days or less) use of a moderate CYP450 3A4 inhibitor is required during treatment with cobimetinib 60 mg once daily, the manufacturer suggests reducing the cobimetinib dose to 20 mg. Following discontinuation of the moderate CYP450 3A4 inhibitor, the previous dose of 60 mg may be resumed. An alternative to the moderate CYP450 3A4 inhibitor should be used in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily).

Cobimetinib Fumarate

Generic Name: cobimetinib

Brand name: Cotellic

Synonyms: Cobimetinib

What is Cobimetinib Fumarate?

Fedratinib Hydrochloride

Generic Name: fedratinib

Brand name: Inrebic

Synonyms: Fedratinib

What is Fedratinib Hydrochloride?