Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly affect ethinyl estradiol and levonorgestrel plasma concentrations to a clinically relevant extent. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau; levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively. No interaction is expected with intramuscular rilpivirine. No dose adjustment of oral contraceptives is necessary when coadministered with cabotegravir/rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Psilocybin is rapidly dephosphorylated to psilocin which is responsible for the hallucinogenic effects. Psilocin is deactivated to multiple metabolites by alcohol dehydrogenase and monoamine oxidase or glucuronidated to psilocin-O-glucuronide by UGT1A9 in the liver or UGT1A10 in the small intestine before excretion in the urine. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Rilpivirine is metabolized by CYP3A4. Cabotegravir/rilpivirine is unlikely to affect psilocybin or psilocin metabolism. Psilocybin and psilocin are unlikely to affect UGT1A1, UGT1A9 or CYP3A4.