Liverpool HIV Interactions

Do Not Coadminister

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

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration with intramuscular cabotegravir/rilpivirine has not been studied clinically and is not recommended in the product labels due to the potential for loss of therapeutic effect of rilpivirine and the development of resistance. Coadministration of rifabutin (300 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir Cmax by 17%, AUC by 21% and Ctrough by 26%. This reduction in cabotegravir exposure is not considered to be clinically relevant. Similarly, no clinically relevant interaction is expected when cabotegravir is administered intramuscularly. However, coadministration of oral rilpivirine (25 mg once daily) and rifabutin (300 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 31%, 42% and 48%, respectively. When compared to rilpivirine 25 mg once daily, coadministration of oral rifabutin and rilpivirine (50 mg once daily) had no effect on rilpivirine Cmin, and increased AUC and Cmax by 16% and 43%, respectively. Coadministration is contraindicated due to the potential for loss of therapeutic effect of rilpivirine and development of resistance. Using PBPK modelling, rifabutin was predicted to reduce the exposure of long-acting intramuscular cabotegravir by 16% and rilpivirine by 18% with a large proportion of individuals predicted to have concentrations at the end of the dosing interval below 664 ng/mL for cabotegravir and below 50 ng/mL for rilpivirine. The drug interaction with rifabutin or other moderate inducers is predicted to be overcome by administering intramuscular cabotegravir/rilpivirine monthly together with a daily oral rilpivirine dose of 25 mg. After dose adjustment, rilpivirine and cabotegravir concentrations are predicted to remain below their safety threshold.

Description:

Coadministration of rifabutin and oral cabotegravir decreased cabotegravir AUC, Cmax and Ctau by 21%, 17% and 8%. Rifabutin may decrease cabotegravir plasma concentration. Concomitant use should be avoided.

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

Coadministration of oral rilpivirine (25 mg once daily) and rifabutin (300 mg once daily) had no effect on the AUC, Cmin or Cmax of rifabutin or 25-O-desacetyl-rifabutin. Rilpivirine AUC, Cmin and Cmax decreased by 42%, 48% and 31%, respectively. When compared to 25 mg once daily rilpivirine, coadministration of rifabutin (300 mg once daily) and rilpivirine (50 mg once daily) increased rilpivirine AUC and Cmax by 16% and 43%, and had no effect on Cmin. Rekambys must not be used in combination with rifabutin as specific dosing recommendations have not been established. Co-administration is likely to result in loss of therapeutic effect of rilpivirine.

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

Coadministration is predicted to decrease concentrations of cabotegravir and rilpivirine, but have no effect on rifabutin. Coadministration is contraindicated with CABENUVA due to potential for loss of virologic response and development of resistance. Coadministration of rifabutin (300 mg once daily) and oral cabotegravir (30 mg once daily) was studied in 12 subjects. Cabotegravir Cmax, AUC and Ctau decreased by 17%, 23% and 26%, respectively. Coadministration of rifabutin (300 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 18 subjects. Rilpivirine Cmax, AUC and Cmin decreased by 31%, 42% and 48%, respectively. Coadministration of rifabutin (300 mg once daily) and oral rilpivirine (50 mg once daily) was studied in 18 subjects. When compared to rilpivirine 25 mg once daily administered alone, rilpivirine Cmax and AUC increased by 43% and 16% and Cmin decreased by 7%.

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

Coadministration of oral cabotegravir (30 mg once daily) and rifabutin (300 mg once daily) was studied in 12 subjects and was found to decrease cabotegravir AUC, Cmax and C24 by 21%, 17% and 26%, respectively. Rifabutin had a modest impact on plasma cabotegravir exposure and overall plasma cabotegravir trough exposures remained above the 10 mg oral dose shown to maintain viral suppression in HIV-1-infected subjects. Oral cabotegravir can be coadministered with rifabutin without dosage adjustment.

Effect of rifabutin on the pharmacokinetics of oral cabotegravir in healthy subjects. Ford SL, Lou Y, Lewis N, et al. Antivir Ther. 2019;24(4):301-308.

PBPK modelling was used to simulate the interaction between long-acting (LA) intramuscular cabotegravir/rilpivirine and the moderate inducer rifabutin. At steady-state, rifabutin was predicted to reduce the exposure of LA cabotegravir by 16% and rilpivirine by 18% with a large proportion of individuals predicted to have concentrations at the end of the dosing interval below 664 ng/mL (i.e., 4x PA-IC90) for cabotegravir and below 50 ng/mL for rilpivirine. The drug interaction with rifabutin or other moderate inducers is predicted to be overcome by administering LA cabotegravir/rilpivirine monthly together with a daily oral rilpivirine dose of 25 mg. After adjustment, rilpivirine and cabotegravir concentrations are predicted to remain below their safety threshold.

Management of drug-drug interactions between long-acting cabotegravir and rilpivirine and comedications with inducing properties: a modelling study. Bettonte S, Berton M, Stader F, et al. Clin Infect Dis, 2022, online ahead of print.

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