Liverpool HIV Interactions

Potential Weak Interaction

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

Fostemsavir (FTR)

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 fostemsavir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine is metabolized by CYP3A4 and does not inhibit or induce CYP enzymes at clinically relevant concentrations. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Temsavir does not inhibit or induce CYP enzymes. Fostemsavir and rilpivirine have been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration. However, the product labels indicate that these antiretroviral drugs should be used with caution in combination with drugs with a known risk of Torsade de Pointes. 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:

A supratherapeutic dose (at a Cmax approximately 4.2-fold the therapeutic dose) of fostemsavir has been shown to significantly prolong the QTc interval of the electrocardiogram. Fostemsavir should be used with caution in patients with a history of QT interval prolongation, when co-administered with a medicine with a known risk of Torsade de Pointes or in patients with relevant pre-existing cardiac disease. Elderly patients may be more susceptible to drug-induced QT interval prolongation.

Rukobia Summary of Product Information, ViiV Healthcare, June 2021.

Fostemsavir at 2,400 mg twice daily, 4 times the recommended daily dose, has been shown to significantly prolong the QTc interval of the electrocardiogram. Fostemsavir should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation.

Rukobia US Prescribing Information, ViiV Healthcare, July 2020.

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.

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. 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.

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