Interaction between Atazanavir and Entrectinib
Major
Metabolism
| ID | DDInter129 and DDInter648 |
| Interaction | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of entrectinib, which is primarily metabolized by the isoenzyme. Increased exposure to entrectinib may increase the risk and/or severity of adverse effects such as cognitive impairment, mood disorders, dizziness, sleep disturbances, liver enzyme elevations, hyperuricemia, congestive heart failure, edema, myocarditis, QT prolongation, vision problems, anemia, and neutropenia. |
| Management | Concomitant use of entrectinib with potent (or moderate) CYP450 3A4 inhibitors should be avoided when possible. If coadministration is necessary, the dosage of entrectinib should be reduced to 100 mg once daily for adults and pediatrics patients (12 years and older) with a body surface area (BSA) greater than 1.5 m2. Following discontinuation, and after an appropriate washout period of the CYP450 3A4 inhibitor (i.e., 3 to 5 half-lives), the entrectinib dosage taken prior to initiating the CYP450 3A4 inhibitor may be resumed. For pediatric patients with a body surface area of 1.5 m2 or less, concomitant use of entrectinib with potent (or moderate) CYP450 3A4 inhibitors should be avoided. |
| References | |
| Alternative for Atazanavir |
J05A
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| Alternative for Entrectinib |
L01X
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.