Liverpool HIV Interactions

Do Not Coadminister

Rilpivirine (RPV)

Pantoprazole

Quality of Evidence: Moderate

Summary:

Coadministration is contraindicated as significant decreases in rilpivirine plasma concentrations may occur.

Description:

Coadministration with pantoprazole has not been studied. Significant decreases in rilpivirine plasma concentrations are expected due to reduced absorption due to gastric pH increase. Rilpivirine must not be used in combination with proton pump inhibitors as co-administration is likely to result in loss of therapeutic effect of rilpivirine.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

Coadministration is contraindicated due to the potential for significant decreases in rilpivirine plasma concentrations due to gastric pH increase, which may result in loss of virologic response.

Edurant US Prescribing Information, Janssen Therapeutics, May 2019.

Potential Interaction

Rilpivirine (RPV)

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

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 and should not be administered with other antiretroviral products. However, if a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (cabotegravir 30 mg and rilpivirine 25 mg once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly visit). The first dose of oral therapy should be taken approximately 1 month (or two months if administered at two-monthly intervals) after the last injection dose of cabotegravir/rilpivirine. Injection dosing should be resumed on the day oral dosing completes. Based on drug interaction study results, rilpivirine can be given after discontinuation of cabotegravir without a dose adjustment.

Description:

Coadministration of rilpivirine and oral cabotegravir increased cabotegravir AUC, Cmax and Ctau by 12%, 5% and 14%, respectively; rilpivirine AUC, Cmax Ctau decreased by 1%, 4% and 8%. Rilpivirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria injection is necessary when co-administered with rilpivirine. If a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (one 30 mg cabotegravir tablet and one 25 mg rilpivirine tablet once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly injection visit). For oral therapy durations greater than two months, an alternative oral regimen is recommended. The first dose of oral therapy should be taken one month (or approximately two months), +/- 7 days, after the last injection doses of cabotegravir and rilpivirine. Injection dosing should be resumed on the day oral dosing completes.

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

Coadministration of cabotegravir and oral rilpivirine had no effect on cabotegravir AUC, Cmin or Cmax. There was no change in rilpivirine AUC or Cmax, but Cmin decreased by 8%. No dose adjustment is required.

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

Based on drug interaction study results, rilpivirine can be coadministered with cabotegravir or given after discontinuation of cabotegravir without a dose adjustment. Coadministration of rilpivirine (25 mg once daily) and oral cabotegravir (30 mg once daily) was studied in 11 subjects. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively. Rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. If a patient plans to miss a scheduled injection visit by more than 7 days, take daily oral therapy to replace up to 2 consecutive monthly injection visits. The recommended oral daily dose is one 30-mg tablet of Vocabria (cabotegravir) and one 25-mg tablet of Edurant (rilpivirine). The first dose of oral therapy should be taken approximately 1 month after the last injection dose of Cabenuva and continued until the day injection dosing is restarted.

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

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 11 subjects. Cabotegravir AUC, Cmax and C24 increased by 12%, 5% and 14%; rilpivirine AUC, Cmax and C24 decreased by 1%, 4% and 8%, respectively. These results support coadministration of rilpivirine with cabotegravir as either oral or long-acting depot injection regimens.

Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Ford SL, Gould E, Chen S, et al. Antimicrob Agents Chemother. 2013;57(11):5472-7.

Potential Interaction

Cabotegravir [oral] (CAB oral)

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

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 and should not be administered with other antiretroviral products. However, if a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (cabotegravir 30 mg and rilpivirine 25 mg once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly visit). The first dose of oral therapy should be taken approximately 1 month (or two months if administered at two-monthly intervals) after the last injection dose of cabotegravir/rilpivirine. Injection dosing should be resumed on the day oral dosing completes.

Description:

If a patient plans to miss a scheduled injection visit by more than 7 days, oral therapy (one 30 mg cabotegravir tablet and one 25 mg rilpivirine tablet once daily) may be used to replace up to 2 consecutive monthly injection visits (or one 2-monthly injection visit). For oral therapy durations greater than two months, an alternative oral regimen is recommended. The first dose of oral therapy should be taken one month (or approximately two months), +/- 7 days, after the last injection doses of cabotegravir and rilpivirine. Injection dosing should be resumed on the day oral dosing completes.

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

If a patient plans to miss a scheduled injection visit by more than 7 days, take daily oral therapy to replace up to 2 consecutive monthly injection visits. The recommended oral daily dose is one 30-mg tablet of Vocabria (cabotegravir) and one 25-mg tablet of Edurant (rilpivirine). The first dose of oral therapy should be taken approximately 1 month after the last injection dose of Cabenuva and continued until the day injection dosing is restarted.

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

No Interaction Expected

Rilpivirine (RPV)

Cabotegravir [oral] (CAB oral)

Quality of Evidence: Low

Summary:

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) did not significantly alter cabotegravir and rilpivirine pharmacokinetics (n=11). Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively; rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively. No dose adjustment is required.

Description:

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. Coadministration of rilpivirine and oral cabotegravir increased cabotegravir AUC, Cmax and Ctau by 12%, 5% and 14%, respectively; rilpivirine AUC, Cmax Ctau decreased by 1%, 4% and 8%. Rilpivirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria tablets is necessary when co-administered with rilpivirine.

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

Based on drug interaction study results, rilpivirine can be coadministered with cabotegravir without a dose adjustment. Coadministration of rilpivirine (25 mg once daily) and cabotegravir (30 mg once daily) was studied in 11 subjects. Cabotegravir Cmax, AUC and Ctau increased by 5%, 12% and 14%, respectively. Rilpivirine Cmax, AUC and Ctau decreased by 4%, 1% and 8%, respectively.

Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021.

Coadministration of oral cabotegravir (30 mg once daily) and oral rilpivirine (25 mg once daily) was studied in 11 subjects. Cabotegravir AUC, Cmax and C24 increased by 12%, 5% and 14%; rilpivirine AUC, Cmax and C24 decreased by 1%, 4% and 8%, respectively. These results support coadministration of rilpivirine with cabotegravir as either oral or long-acting depot injection regimens.

Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Ford SL, Gould E, Chen S, et al. Antimicrob Agents Chemother. 2013;57(11):5472-7.

No Interaction Expected

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

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with intramuscular cabotegravir and rilpivirine. Pantoprazole is mainly metabolized by CYP2C19. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Furthermore, rilpivirine absorption is not impacted by pantoprazole when administered intramuscularly.

Description:

(See Summary)

No Interaction Expected

Cabotegravir [oral] (CAB oral)

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolized by CYP2C19. Cabotegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Solubility of cabotegravir is unlikely to be influenced by changes in gastric pH. Cabotegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation.

Description:

(See Summary)

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