Coadministration is contraindicated with systemic dexamethasone (except as a single dose) as significant decreases in rilpivirine plasma concentrations may occur. Dexamethasone is metabolized by CYP3A4. Rilpivirine is primarily metabolized by CYP3A4 and has no inhibitory or inducing effects on drug metabolizing enzymes. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Coadministration may decrease rilpivirine concentrations due to induction of CYP3A4. Emtricitabine and tenofovir-DF are unlikely to interact with dexamethasone. In the specific case of patients being treated with short term dexamethasone for COVID-19 please refer to www.covid19-druginteractions.org for additional advice.