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 abacavir would be possible from a pharmacokinetic standpoint. 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.

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp or possibly UGT when used for extended periods. African potato could potentially decrease rilpivirine exposure, but the effect on UGT1A1 and thereby cabotegravir exposure is unclear.

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 albuvirtide would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected. Cabotegravir and rilpivirine undergo hepatic metabolism whereas albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on P450 enzymes. 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.

Coadministration has not been studied but based on metabolism and clearance, a pharmacokinetic interaction is unlikely. Alfuzosin is metabolised mainly by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. A clinically relevant effect on rilpivirine concentrations is unlikely as alfuzosin does not inhibit CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with alfuzosin. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Alfuzosin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amiodarone inhibits intestinal P-gp but this is not relevant in the case of intramuscular administration of cabotegravir and rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with amiodarone. However, given the QT prolongation risk associated with amiodarone, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with apomorphine. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Apomorphine has a possible risk of QTc prolongation on the CredibleMeds.org website. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with aripiprazole. However, the product labels for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Aripiprazole has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, CYP2D6 (minor)). Cabotegravir and rilpivirine do not inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with asenapine. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Asenapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Astemizole is metabolized by CYP2D6, CYP2J2 and CYP3A4. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with astemizole. However, given the known QT prolongation risk associated with astemizole, caution is recommended.

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 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. Similarly, no significant effect is expected when cabotegravir is administered intramuscularly. Atazanavir may increase rilpivirine concentrations. However, 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. 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.

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/cobicistat 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 cabotegravir (30 mg once daily) exposure by 11% which is considered to be not clinically relevant. A comparable effect is expected with atazanavir/cobicistat. Similarly, no significant effect is expected when cabotegravir is administered intramuscularly. Atazanavir/cobicistat may increase rilpivirine concentrations. However, 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/cobicistat. 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.

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.

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of oral rilpivirine (150 mg once daily) and atorvastatin (40 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 9%, 10% and 10%, respectively. Atorvastatin Cmax and AUC increased by 35% and 4%; Cmin decreased by 15%. Cmax, AUC and Cmin of 2-hydroxy atorvastatin increased by 58%, 39% and 32%, whilst Cmax and AUC of 4-hydroxy atorvastatin increased by 28% and 23%. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug]. These effects are not considered to be clinically relevant. No effect is expected on cabotegravir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Cabotegravir and rilpivirine do not inhibit these transporters. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with azithromycin. However, given the known QT prolongation risk associated with azithromycin, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with bedaquiline. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bedaquiline has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and CYP3A4. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with bepridil. However, given the known QT prolongation risk associated with bepridil, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Cabotegravir and rilpivirine do not inhibit or induce P-gp. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with betrixaban. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Betrixaban has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Cabenuva (cabotegravir LA, rilpivirine LA) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and bictegravir) is unlikely to be of clinical benefit. 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.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. In vitro studies suggest black cohosh is unlikely to affect UGT1A1 or UGT1A9 at clinically relevant concentrations. No effect on rilpivirine is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate).

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYPs 3A4 and 2C19 and to a lesser extent CYPs 1A2, 2D6 and 2C9. Bortezomib is a weak inhibitor of CYP enzymes. Cabotegravir and rilpivirine do not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. A clinically relevant effect on rilpivirine concentrations is unlikely. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with bortezomib. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bortezomib has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Cabotegravir does not interfere with this metabolic pathway. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with capecitabine. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Capecitabine has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied with intramuscular cabotegravir and rilpivirine. Coadministration of rifampicin (600 mg once daily) and oral cabotegravir (30 mg once daily) decreased cabotegravir Cmax by 6%, AUC by 59% whereas oral clearance was increased by 2.4 fold. A similar effect is expected with carbamazepine, therefore coadministration is not recommended with intramuscular cabotegravir. In addition, carbamazepine is expected to substantially decrease rilpivirine exposure. Thus coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance.

Coadministration has not been studied. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (also known as methimazole). Despite this potential hepatic metabolism very few data exist on carbimazole drug interactions. Thiamazole has been shown to have inhibitory effects on CYP3A4 in vitro, however, the clinical relevance of this for rilpivirine is unclear.

Coadministration has not been studied. Cat’s claw was demonstrated to inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Similarly, Cat’s claw may increase rilpivirine exposure although to a limited extent. No dose adjustment is needed.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with chloroquine. However, given the known QT prolongation risk associated with chloroquine, caution is recommended. Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine. ECG monitoring is advised. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with chlorpromazine. However, given the known QT prolongation risk associated with chlorpromazine, caution is recommended

Ciprofloxacin is primarily eliminated unchanged through the kidneys (by glomerular filtration and tubular secretion via OAT3). Cabotegravir has been shown to inhibit OAT3 in vitro. The interaction between cabotegravir and ciprofloxacin was evaluated using a PBPK model. Coadministration was shown to cause a minimal effect on ciprofloxacin exposure thus dose adjustment is not needed. Rilpivirine does not inhibit OAT3. Ciprofloxacin is a moderate inhibitor of CYP3A4 and therefore could potentially increase rilpivirine exposure however to a limited extent, which does not require dose adjustment. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with ciprofloxacin. However, given the known QT prolongation risk associated with ciprofloxacin, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cisapride is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with cisapride. However, given the known QT prolongation risk associated with cisapride, caution is recommended

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with citalopram. However, given the known QT prolongation risk associated with citalopram, caution is recommended

Coadministration has not been studied. Clarithromycin is a strong inhibitor of CYP3A4. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, however, rilpivirine exposure may increase. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clarithromycin. However, given the known QT prolongation risk associated with clarithromycin, caution is recommended. Consider alternatives such as azithromycin.

Coadministration has not been studied. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Clofazimine is a moderate inhibitor of CYP3A4 and may increase rilpivirine concentrations but to a modest extent. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clofazimine. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes; clofazimine has a conditional risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clozapine. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clozapine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cocaine is metabolized by several non CYP mediated pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with cocaine. However, given the known QT prolongation risk associated with cocaine, caution is recommended

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 darunavir/cobicistat would be possible from a pharmacokinetic standpoint. 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration would be possible from a pharmacokinetic standpoint. 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.

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 darunavir/ritonavir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Induction of UGTs by ritonavir used to boost darunavir is unlikely to cause a clinically relevant decrease of cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Coadministration of oral rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) was studied in 14 subjects. Rilpivirine Cmax increased by 79% and AUC and Cmin increased by 130% and 178%, respectively. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug]. No dose adjustment of rilpivirine is required. 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.

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dasatinib is metabolized by CYP3A4 and is a weak inhibitor of this enzyme. No effect is expected on cabotegravir as it mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Dasatinib could increase rilpivirine exposure but not to an extent that is considered to be clinically relevant. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with dasatinib. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. However, QTc prolongation has been reported with delamanid (and is very closely correlated with the metabolite DM-6705). Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with delamanid. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Delamanid has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desipramine is metabolized by CYP2D6. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with desipramine. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, intramuscular cabotegravir is unlikely to alter ethinylestradiol and desogestrel exposures. Similarly, no interaction is expected with intramuscular rilpivirine.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The elimination of digoxin is dependent on P-glycoprotein which is not inhibited by cabotegravir or rilpivirine. Coadministration of digoxin (0.5 mg single dose) and oral rilpivirine (25 mg once daily) did not significantly alter digoxin pharmacokinetics (digoxin Cmax increased by 6% and AUC decreased by 2%).

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Cabotegravir and rilpivirine have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Diltiazem could increase rilpivirine concentrations although to a limited extent. No dose adjustment is needed. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with diltiazem. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Diltiazem has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) whereas 50% of the drug is eliminated unchanged in the urine (possibly via OCT2). Cabotegravir and rilpivirine do not cause clinically relevant inhibition of renal transporters and do not inhibit or induce CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with disopyramide. However, given the known QT prolongation risk associated with disopyramide, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Cabotegravir and rilpivirine do not cause clinically relevant inhibition of renal transporters. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with dofetilide. However, given the known QT prolongation risk associated with dofetilide, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Cabotegravir and rilpivirine do not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with dolasetron. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

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. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Triumeq (dolutegravir, lamivudine, abacavir) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Dovato (dolutegravir/lamivudine) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Juluca (dolutegravir, rilpivirine) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both products contain rilpivirine and, furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. 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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with domperidone. However, given the known QT prolongation risk associated with domperidone, caution is recommended

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. Furthermore, doravirine should not be administered with another NNRTI (i.e., rilpivirine). 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Delstrigo (doravirine, lamivudine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, doravirine should not be administered with another NNRTI (i.e., rilpivirine). 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.

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.) However, rilpivirine should be used with caution when coadministered with a drug that has a potential risk to prolong the QT interval. In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QT interval. Possible cardiac toxicities (ECG abnormalities and sometimes arrhythmias) have been reported with doxorubicin. Use with caution. ECG monitoring is recommended.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, intramuscular cabotegravir is unlikely to alter ethinylestradiol and drospirenone exposures. Likewise, no interaction is expected with intramuscular rilpivirine.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance. Efavirenz is a moderate inducer of CYP3A. Based on the drug-drug interaction study with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure after intramuscular administration is expected not to be clinically relevant. However, efavirenz has the potential to significantly reduce rilpivirine exposure. Furthermore, rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with efavirenz. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Efavirenz has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. 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. Note, a physiologically based pharmacokinetic modelling study indicates that switching from an efavirenz-containing regimen to intramuscular cabotegravir/rilpivirine does not create a risk of having a time window with suboptimal drug levels.

Cabenuva (cabotegravir LA, rilpivirine LA) and Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. 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.

Cabenuva (cabotegravir LA, rilpivirine LA) and Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and elvitegravir) is unlikely to be of clinical benefit. 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.

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 emtricitabine would be possible from a pharmacokinetic standpoint. 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.

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 emtricitabine and tenofovir alafenamide would be possible from a pharmacokinetic standpoint. When given with Cabenuva, the recommended dose of Descovy (emtricitabine/tenofovir alafenamide) is 200/25 mg once daily. 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.

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 emtricitabine and tenofovir-DF would be possible from a pharmacokinetic standpoint. Coadministration with cabotegravir LA or rilpivirine LA has not been studied. Coadministration of oral rilpivirine (150 mg once daily) and tenofovir-DF (300 mg once daily) decreased rilpivirine Cmax and Cmin by 4% and 1%, and increased AUC by 1%. Tenofovir Cmax, AUC and Cmin increased by 19%, 23% and 24%. No dose adjustment is necessary. 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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Cabotegravir and rilpivirine do not inhibit or induce UGT enzymes at clinically relevant concentrations. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Epirubicin may lead to cardiotoxicity consisting of tachycardia and/or ECG abnormalities. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with epirubicin. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Epirubicin has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erlotinib is mainly metabolized by CYP3A4, but cabotegravir and rilpivirine do not inhibit or induce CYP450 enzymes at clinically relevant concentrations. Erlotinib is a strong inhibitor of UGT1A1. However, based on the drug interaction study with atazanavir (another strong inhibitor of UGT1A1), this is unlikely to alter intramuscular cabotegravir exposure to a clinically significant extent. Erlotinib does not affect rilpivirine as it is metabolized by CYP3A4.

Coadministration has not been studied. Erythromycin is a moderate inhibitor of CYP3A. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, however, rilpivirine exposure may increase. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with erythromycin. However, given the known QT prolongation risk associated with erythromycin, caution is recommended. Consider alternatives such as azithromycin.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with escitalopram. However, given the known QT prolongation risk associated with escitalopram, caution is recommended

Coadministration with intramuscular cabotegravir and rilpivirine has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of oral cabotegravir (30 mg once daily) with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) did not significantly affect ethinylestradiol and levonorgestrel plasma concentrations to a clinically relevant extent. Ethinylestradiol Cmax decreased by 8%, AUC increased by 2% and there was no change in Ctau; levonorgestrel Cmax, AUC and Ctau increased by 5%, 12% and 7%, respectively. Coadministration of ethinylestradiol/norethindrone (0.035/1 mg once daily) and oral rilpivirine (25 mg once daily) had no effect on rilpivirine Cmax, AUC or Cmin when compared to historic controls (n=15). Ethinylestradiol Cmax, AUC and Cmin increased by 17%, 14% and 9%, respectively. Norethindrone Cmax, AUC and Cmin decreased by 6%, 11% and 1%, respectively. Similarly, no interaction is expected with intramuscular cabotegravir/rilpivirine. No dose adjustment of oral contraceptives is necessary when coadministered with cabotegravir/rilpivirine. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance. Etravirine is a moderate inducer of CYP3A. Coadministration of etravirine (200 mg twice daily) and oral cabotegravir (30 mg once daily) did not significantly alter cabotegravir AUC, Cmax and Cmax. Similarly, no significant effect is expected on cabotegravir when administered intramuscularly. However, etravirine has the potential to significantly reduce rilpivirine exposure. 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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion of the parent drug also eliminated unchanged renally. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with flecainide. However, given the known QT prolongation risk associated with flecainide, caution is recommended.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Cabotegravir does not cause clinically relevant inhibition of OAT1. Likewise, rilpivirine does not inhibit OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily) and also has inducing effects on UGTs. Flucloxacillin is unlikely to cause a significant decrease in cabotegravir exposure. However, flucloxacillin could decrease rilpivirine concentrations to a significant extent. Use with caution particularly if flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days).

Coadministration has not been studied. Fluconazole is a moderate inhibitor of CYP3A4. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9, however, rilpivirine exposure may increase. No dose adjustment is required for rilpivirine when co-administered with azole antifungal agents, but clinical monitoring for breakthrough fungal infections is recommended when azole antifungals are co-administered with rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with fluconazole. However, given the known QT prolongation risk associated with fluconazole, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is therefore little potential for an interaction with cabotegravir or rilpivirine via modulation of, or competition for, metabolic pathways. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with fluorouracil. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Fluorouracil has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Cabotegravir and rilpivirine do not inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with fluphenazine. However, the product label for Cabenuva indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Fluphenazine may prolong the QT interval and some European product labels have advised against concurrent use of drugs that prolong the QT interval.

Coadministration has not been studied but based on metabolism and clearance, a pharmacokinetic interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. Cabotegravir and rilpivirine do not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with formoterol. Note: the product label indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Formoterol may induce prolongation of the QT interval and the product label for formoterol advises caution in patients treated with drugs affecting the QT interval.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is metabolized by hydroxylation and glucuronidation. Coadministration of oral cabotegravir (30 mg once daily) with ethinylestradiol (0.03 mg) + levonorgestrel (0.15 mg) did not significantly affect the hormones levels. Similarly, intramuscular cabotegravir is unlikely to alter ethinylestradiol and gestodene exposures. No interaction is expected with intramuscular rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goserelin is mainly hydrolyzed. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Granisetron is metabolized by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Likewise, rilpivirine does not inibit or induce CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with granisetron. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Granisetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4. Cabotegravir was shown to have no effect on midazolam (a sensitive CYP3A4 substrate) in healthy subjects. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with halofantrine. However, given the known QT prolongation risk associated with halofantrine, caution is recommended

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, CYP2D6). Cabotegravir and rilpivirine do not inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Rilpivirine does not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur when coadministered with haloperidol. However, given the known QT prolongation risk associated with haloperidol, caution is recommended.

Coadministration has not been studied. In vitro data indicate that extracts of hops activate PXR and induce expression of CYP3A4, CYP2B6 and MDR1 genes to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). Based on these results, hop extracts are unlikely to have a clinically significant effect on rilpivirine. No effect is expected on cabotegravir as it is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Cabotegravir was shown to have no impact on midazolam (a sensitive CYP3A4 substrate) in healthy volunteers. Rilpivirine does not inhibit or induce CYP3A4 at clinically relevant concentrations.

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 ibalizumab would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Cabotegravir and rilpivirine undergo hepatic metabolism whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Dose modifications of ibalizumab are not required when administered with any other antiretroviral. 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.