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. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Dexamethasone has shown some inducing effects on UGT1A1 in vitro, however, the clinical relevance is unclear. Coadministration may decrease rilpivirine concentrations due to induction of CYP3A4. No significant effect is expected on cabotegravir as indicated by a drug-drug interaction study with rifabutin (a moderate inducer). 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.