Liverpool HIV Interactions

Potential Interaction

Cabotegravir/rilpivirine [long acting] (CAB/RPV LA)

Atazanavir + ritonavir (ATV/r)

Quality of Evidence: Very Low

Summary:

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir/ritonavir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Coadministration with the strong UGT1A1 inhibitor atazanavir was predicted to increase oral cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant. A comparable effect is expected with atazanavir/ritonavir. Similarly, no significant effect is expected when cabotegravir is administered intramuscularly. Atazanavir/ritonavir may increase rilpivirine concentrations, but no dose adjustment of rilpivirine is required. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with atazanavir/ritonavir. However, the product label for Cabenuva indicates that rilpivirine should be used with caution in combination with drugs with a risk of QT interval prolongation. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Description:

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. No dosing adjustments for Vocabria are recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir).

Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021.

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. Rekambys should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes. At supra-therapeutic doses (75 and 300 mg once daily), oral rilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram (ECG). Oral rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Plasma rilpivirine concentrations after Rekambys injections are comparable to those during such oral rilpivirine therapy.

Rekambys (rilpivirine prolonged release injection) European Summary of Product Characteristics, Janssen-Cilag, January 2021.

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. Based on drug interaction study results, atazanavir/ritonavir can be given after discontinuation of rilpivirine. At mean steady-state Cmax values 4.4-fold and 11.6-fold higher than those with the recommended 600-mg dose of rilpivirine extended-release injectable suspension, rilpivirine may prolong the QTc interval. Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes.

Cabenuva (cabotegravir/rilpivirine extended release injection) US Prescribing Information, ViiV Healthcare, January 2021.

A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of atazanavir (an inhibitor of UGT1A1) and mefenamic acid (an inhibitor of UGT1A9) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 11% increase in oral cabotegravir exposure when coadministered with atazanavir or mefenamic acid, suggesting no restriction being required with these classes of inhibitors.

Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18.

View all available interactions with Cabotegravir/rilpivirine [long acting] (CAB/RPV LA) by clicking here.