Darunavir and cobicistat and Lorlatinib interaction

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided.

Strong CYP3A Inhibitors Avoid concomitant use of LORBRENA with a strong CYP3A inhibitor.

Concomitant use with a strong CYP3A inhibitor increased lorlatinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the incidence and severity of adverse reactions of LORBRENA.

Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance.

Anticonvulsants with CYP3A induction effects that are NOT contraindicated: e.g. eslicarbazepine, oxcarbazepine ↓ cobicistat darunavir: effect unknown Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures.

Initiation of medications that inhibit or induce CYP3A may respectively increase or decrease concentrations of PREZCOBIX or PREZCOBIX PED.

Co-administration of PREZCOBIX or PREZCOBIX PED and drugs that induce CYP3A activity are expected to increase the clearance of darunavir and cobicistat, resulting in lowered plasma concentrations of darunavir and cobicistat which may lead to loss of therapeutic effect and development of resistance.

…metabolized by CYP3A: e.g. betamethasone budesonide ciclesonide fluticasone methylprednisolone mometasone triamcinolone ↓ darunavir ↓ cobicistat ↑ corticosteroids Co-administration with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to PREZCOBIX or PREZCOBIX PED.