Vocabria and rilpivirine injections are intended for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral medicinal products for the treatment of HIV. Based on the in vitro and clinical drug interaction profile, cabotegravir is not expected to alter concentrations of other antiretroviral medications including protease inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, integrase inhibitors, entry inhibitors or ibalizumab.

Rekambys should not be administered with other antiretroviral medicinal products, except for cabotegravir injection for the treatment of HIV-1 infection. From a drug interaction perspective, there are no limitations on the use of other antiretroviral medicinal products after discontinuing Rekambys.

Because Cabenuva is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of Cabenuva.

Intramuscular cabotegravir and rilpivirine (IM CAB/RPV) are used once viral load suppression is achieved on another antiretroviral regimen. CAB/RPV are substrates of UGT1A1/CYP3A4 which are induced by efavirenz. This study simulated the initial IM CAB/RPV concentrations after stopping efavirenz using physiologically based pharmacokinetic (PBPK) modelling. The verified PBPK model was applied to simulate IM CAB/RPV concentrations over time when administering CAB/RPV (600/900 mg) 12 hours after the last dose efavirenz (600 mg). IM CAB/RPV concentrations during the switch period were compared to those in absence of residual efavirenz concentrations. Initiating IM CAB/RPV 12 hours after the last dose of efavirenz was predicted to have a minimal effect as IM CAB concentrations were reduced by 11%, 13% and 8% at days 1, 7 and 14 after discontinuing efavirenz. For all time points, CAB trough was above the 4-fold PA-IC90. Similarly, efavirenz was predicted to have a modest effect on IM RPV concentrations with the lowest reduction being 10% and occurring 7 days after the last dose of efavirenz. Residual efavirenz concentrations were predicted to have a less pronounced effect on IM RPV compared to the observed switch data with oral RPV (e.g. IM RPV reduced by 8% vs 28% for oral RPV at day 14 post efavirenz). In summary, switching from an efavirenz-containing regimen to IM CAB/RPV does not put a risk of having a time window with suboptimal drug levels.