Coadministration has not been studied but should be avoided. Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent 3A4. Elvitegravir/cobicistat could potentially increase paclitaxel exposure (inhibition of CYP3A4) and thereby increase the risk of severe neutropenia. Avoid coadministration or consider switching to a non-CYP inhibiting antiretroviral regimen. If coadministration is unavoidable, reduce the dose of paclitaxel and monitor closely for paclitaxel induced toxicity. Emtricitabine and tenofovir alafenamide are unlikely to interact with this metabolic pathway.

Coadministration has not been studied. Quetiapine is primarily metabolized by CYP3A4 and coadministration with ketoconazole (a CYP3A4 inhibitor) increased quetiapine AUC by 5-8 fold. The European product label for quetiapine contraindicates quetiapine with CYP3A4 inhibitors (such as darunavir/cobicistat). However, the US product label recommends that quetiapine should be reduced to one sixth of the original dose if coadministered with a potent CYP3A4 inhibitor. [This interaction checker reflects the more cautious option.]

Coadministration is contraindicated as it is likely to increase amiodarone concentrations and the potential for serious and/or life threatening reactions such as cardiac arrhythmias.

Coadministration with darunavir/cobicistat has not been studied and is not recommended as it may substantially increase glecaprevir exposure. Medicinal products that inhibit OATP1B1/3 (e.g. darunavir) increase systemic concentrations of glecaprevir. Coadministration of darunavir/ritonavir (800/100 mg) increased glecaprevir AUC, Cmax and Cmin by 4.97-fold, 3.09-fold and 8.24-fold, respectively. A similar interaction may occur with darunavir/cobicistat.

Coadministration has not been studied but should be avoided. Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4. Ritonavir dosed as a pharmacokinetic booster is a weak inducer of CYP2C8 but a strong inhibitor of CYP3A4 and could potentially increase paclitaxel exposure. There have been several reports of severe, and occasionally life-threatening paclitaxel toxicity when coadministered with protease inhibitors, however, data on the effect of protease inhibitors on paclitaxel concentrations are limited. If coadministration is unavoidable, reduce the dose of paclitaxel and monitor closely for paclitaxel induced toxicity.

Coadministration has not been studied. Amiodarone is metabolized by CYP3A4 and 2C8 and elvitegravir/cobicistat could potentially increase amiodarone concentrations by inhibition of CYP3A4. Coadministration is contraindicated in the European SPC, but the US Prescribing Information recommends caution and therapeutic concentration monitoring if amiodarone if available.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., raltegravir and elvitegravir) is unlikely to be of clinical benefit.

Coadministration has not been studied. Quetiapine is primarily metabolized by CYP3A4 and coadministration with ketoconazole (a CYP3A4 inhibitor) increased quetiapine AUC by 5-8 fold. The European SPC for quetiapine contraindicates quetiapine with CYP3A4 inhibitors (such as cobicistat). However, the US Prescribing Information recommends that quetiapine should be reduced to one sixth of the original dose if coadministered with a potent CYP3A4 inhibitor. These interaction charts reflect the more cautious option.

Coadministration is not recommended. Concomitant use of glecaprevir/pibrentasvir with OATP1B inhibitors, such as ritonavir, may increase glecaprevir/pibrentasvir plasma concentrations.

Coadministration has not been studied.  Amiodarone is metabolized by CYP2C8 and 3A4 and exposure may increase due to CYP3A4 inhibition by darunavir/cobicistat causing potential cardiac arrhythmias. The European product label for darunavir/cobicistat contraindicates coadministration but the US product label for darunavir/cobicistat suggests caution and concentration monitoring of amiodarone.  [This interaction checker reflects the more cautious option.]

Coadministration has not been studied but should be avoided. Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent 3A4. Darunavir/cobicistat could potentially increase paclitaxel exposure (inhibition of CYP3A4) and thereby increase the risk of severe neutropenia. Avoid coadministration or consider switching to a non-CYP inhibiting antiretroviral regimen. If coadministration is unavoidable reduce dose of paclitaxel and monitor closely for paclitaxel induced toxicity.

Coadministration has not been studied. Quetiapine is primarily metabolised by CYP3A4 and coadministration with ketoconazole (a CYP3A4 inhibitor) increased quetiapine AUC by 5- 8 fold. The European SPCs for quetiapine and ritonavir contraindicate coadministration. However, the US Prescribing Information for quetiapine and ritonavir recommend that quetiapine should be reduced to one sixth of the original dose if coadministered. These interaction charts reflect the more cautious option.

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1. Cisplatin and emtricitabine could potentially compete for MATE1 which could slow their elimination. Close monitoring of renal function is recommended.

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1 and in vitro data indicate that cobicistat is a moderate inhibitor of MATE1. Cobicistat could potentially slow down cisplatin renal elimination and thus increase the risk of nephrotoxicity. Close monitoring of renal function is recommended.

Coadministration has not been studied. Ifosfamide is metabolized by CYP3A4 and CYP2B6. Data with ketoconazole show that enzyme inhibitors such as darunavir/cobicistat may inhibit ifosfamide conversion to active metabolites, therefore decreasing its therapeutic effect.

Coadministration has not been studied but may potentially reduce the efficacy of tamoxifen as inhibition of CYPs 3A4 and 2D6 may reduce the amount of drug converted to endoxifen (a pharmacologically active metabolite). Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6>2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4. Tamoxifen may also induce CYP3A4. Coadministration of letrozole (CYP3A4 and CYP2D6 substrate) with tamoxifen decreased letrozole exposure by 38%. The clinical significance of this effect is unknown in the context of strong CYP3A4 inhibition by darunavir/cobicistat. Closely monitor for toxicity/efficacy or consider switching to an antiretroviral regimen with no effect on CYP3A4.

Coadministration has not been studied but may potentially reduce the efficacy of tamoxifen as inhibition of CYPs 3A4 and 2D6 may reduce the amount of drug converted to endoxifen (a pharmacologically active metabolite). Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4. Tamoxifen may also induce CYP3A4. Coadministration of letrozole (CYP3A4 and CYP2D6 substrate) with tamoxifen decreased letrozole exposure by 38%. The clinical significance of this effect is unknown in the context of strong CYP3A4 inhibition by ritonavir. Closely monitor for toxicity/efficacy or consider switching to an antiretroviral regimen with no effect on CYP3A4.

Coadministration has not been studied. Ifosfamide is metabolized by CYP3A4 and CYP2B6. Data with ketoconazole show that enzyme inhibitors such as ritonavir may inhibit ifosfamide conversion to active metabolites, therefore decreasing its therapeutic effect.

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1 and in vitro data indicate that ritonavir is a moderate inhibitor of MATE1. Ritonavir could potentially slow down cisplatin renal elimination and thus increase the risk of nephrotoxicity. Close monitoring of renal function is recommended.

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1 and in vitro data indicate that cobicistat is a moderate inhibitor of MATE1. Elvitegravir/cobicistat could potentially slow down cisplatin renal elimination and thus increase the risk of nephrotoxicity. In addition, cisplatin and emtricitabine could potentially compete for MATE1 which could slow their elimination. Close monitoring of renal function is recommended.

Coadministration has not been studied but may potentially reduce the efficacy of tamoxifen as inhibition of CYPs 3A4 and 2D6 may reduce the amount of drug converted to endoxifen (a pharmacologically active metabolite). Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6>2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4. Tamoxifen may also induce CYP3A4. Coadministration of letrozole (CYP3A4 and CYP2D6 substrate) with tamoxifen decreased letrozole exposure by 38%. The clinical significance of this effect is unknown in the context of strong CYP3A4 inhibition by elvitegravir/cobicistat. Closely monitor for toxicity/efficacy or consider switching to an antiretroviral regimen with no effect on CYP3A4. No interaction is expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Elvitegravir/cobicistat could potentially increase citalopram concentrations although to a moderate extent. No a priori dosage adjustment is recommended. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Ritonavir could potentially increase citalopram concentrations, although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Darunavir/cobicistat could potentially increase citalopram concentrations although to a limited extent. No a priori dosage adjustment is recommended.

Some clinical trials with darunavir/ritonavir suggest that raltegravir may cause a modest decrease in darunavir plasma concentrations however this effect does not appear to be clinically relevant. Raltegravir and darunavir/cobicistat can be administered without dose adjustments.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely.

Coadministration of raltegravir (400 mg single dose) and  low dose ritonavir had no significant effect on raltegravir pharmacokinetics (AUC decreased by 16%, Cmax decreased by 24%, no change in Cmin). No dose adjustment required for twice daily or once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%).

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for pharmacokinetic interaction. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6.

Coadministration of glecaprevir/pibrentasvir (300/120 mg once daily) and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide increased glecaprevir Cmax, AUC and Cmin by 2.50-fold, 3.05-fold and 4.58-fold, respectively; pibrentasvir Cmax, AUC and Cmin increased by 24%, 57% and 89% (n=24). However these increases were deemed to be within safety limits and no dose adjustment is required. There were no clinically significant changes in the pharmacokinetics of elvitegravir, cobicistat, emtricitabine or tenofovir.

Studies performed with emtricitabine showed no clinically significant interactions with glecaprevir/pibrentasvir. No dose adjustment is required when glecaprevir/pibrentasvir is co administered with emtricitabine.