Apretude Drug Interactions

Effect of cabotegravir on the pharmacokinetics of other agents: In vivo, cabotegravir did not have an effect on midazolam, a CYP3A4 probe. Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17, P-gp, breast cancer resistance protein (BCRP), Bile salt export pump (BSEP), organic cation transporter (OCT)1, OCT2, OATP1B1, OATP1B3, multidrug and toxin extrusion transporter (MATE) 1, MATE 2-K, multidrug resistance protein (MRP) 2 or MRP4.
Cabotegravir inhibited the organic anion transporters (OAT) 1 (IC₅₀=0.81 μM) and OAT3 (IC₅₀=0.41 μM) in vitro, however, based on physiologically based pharmacokinetic (PBPK) modelling, no interaction with OAT substrates is expected at clinically relevant concentrations.
In vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4.
Based on these data and the results of drug interaction studies, cabotegravir is not expected to affect the pharmacokinetics of drugs that are substrates of these enzymes or transporters.
Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other anti-retroviral medications, including protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors, and ibalizumab.
Effect of other agents on the pharmacokinetics of cabotegravir: Cabotegravir is primarily metabolised by UGT1A1 with some contribution from UGT1A9. Medicinal products which are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations, leading to lack of efficacy (see Contraindications).
Simulations using PBPK show that no clinically significant interaction is expected following co-administration of cabotegravir with drugs that inhibit UGT enzymes.
In vitro, cabotegravir was not a substrate of OATP1B1, OATP1B3, OATP2B1 or OCT1.
Cabotegravir is a substrate of P-gp and BCRP, however, because of its high permeability, no alteration in absorption is expected when co-administered with either P-gp or BCRP inhibitors.
No drug interaction studies have been performed with APRETUDE injection. The drug interaction data provided in Table 12 is obtained from studies with oral cabotegravir. (See Table 12.)

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