Coadministration has not been studied but is not recommended. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Bictegravir is equally metabolized by CYP3A4 and UGT1A1. Emtricitabine and tenofovir alafenamide are eliminated renally. Bictegravir is unlikely to affect phenytoin metabolism. No interaction is expected with emtricitabine. However, phenytoin is a strong CYP3A4 inducer and also induces UGT and is expected to significantly decrease bictegravir exposure. Phenytoin also induces P-gp which may decrease tenofovir alafenamide plasma concentrations. Both interactions may lead to a loss of therapeutic effect and development of virological resistance. Alternative anticonvulsants should be considered.

Coadministration has not been studied but is not recommended. Betamethasone is metabolized by CYP3A4 and is a moderate inducer of CYP3A4. No effect on betamethasone is expected as bictegravir does not inhibit or induce CYP450 enzymes and emtricitabine and tenofovir alafenamide do not interact with betamethasone’s metabolic pathway. However, bictegravir is metabolized equally by CYP3A4 and UGT1A and coadministration could potentially decrease bictegravir concentrations particularly if betamethasone is administered at high doses or for a long duration. Coadministration of bictegravir/emtricitabine/tenofovir alafenamide with rifabutin (a moderate inducer) decreased bictegravir Cmax, AUC and Cmin by 20%, 38% and 56%, respectively. Coadministration with moderate inducers is not recommended in the product labels for Biktarvy. Note, the inducing effect is expected to be modest when using lower doses of betamethasone and low dose betamethasone is unlikely to have a clinically significant effect on bictegravir.

Coadministration has not been studied but is not recommended. Thioridazine is metabolized by CYP2D6 and to a lesser extent by CYP3A4. No effect on thioridazine is expected as bictegravir does not inhibit or induce CYP450 enzymes and emtricitabine and tenofovir alafenamide do not interact with thioridazine’s metabolic pathway. However, thioridazine is a moderate inducer of CYP3A4 and coadministration could potentially decrease bictegravir concentrations as bictegravir is metabolized equally by CYP3A4 and UGT1A. Coadministration of bictegravir/emtricitabine/tenofovir alafenamide with rifabutin (a moderate inducer) decreased bictegravir Cmax, AUC and Cmin by 20%, 38% and 56%, respectively. Coadministration with moderate inducers is not recommended in the product labels for Biktarvy.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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., bictegravir and raltegravir is unlikely to be of clinical benefit.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. In addition, efavirenz is an inducer of CYP3A4 and is expected to decrease bictegravir exposure which may result in loss of therapeutic effect and development of resistance. 

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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, Biktarvy contains emtricitabine and should not be administered with lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Biktarvy should not be administered concomitantly with medicinal products containing lamivudine used for the treatment of HBV infection.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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, Biktarvy contains tenofovir alafenamide and should not be administered with tenofovir-DF. Biktarvy should not be administered concomitantly with medicinal products containing tenofovir used for the treatment of HBV infection.

Coadministration is contraindicated. Coadministration of rifampicin (600 mg once daily) and bictegravir alone (75 mg single dose) decreased bictegravir Cmax and AUC by 28% and 75%. Coadministration of rifampicin (600 mg once daily) and twice daily bictegravir/emtricitabine/tenofovir (50/200/25 mg, twice daily) decreased bictegravir AUC, Cmax and Ctrough by approximately 61%, 47% and 80%, respectively, and did not mitigate the enzyme inducing effect of rifampicin sufficiently to replicate the Ctrough concentrations seen in phase three bictegravir clinical trials. However, twice daily dosing with rifampicin did achieve intracellular tenofovir-DP concentrations similar to those with once-daily TAF alone.

Coadministration is not recommended. Carbamazepine is an inducer and is expected to decrease both bictegravir and tenofovir alafenamide exposures which may result in loss of therapeutic effect and development of resistance. Coadministration with bictegravir/emtricitabine/tenofovir alafenamide has not been studied. Coadministration of carbamazepine (300 mg twice a day) with emtricitabine/tenofovir alafenamide (200/25 mg once daily) decreased tenofovir Cmax and AUC by 57% and 54%. Alternative anticonvulsants should be considered.

Coadministration has not been studied. In vitro studies have demonstrated the ability of ifosfamide to both inhibit and induce CYP3A4. Clinical data with sunitinib suggests that ifosfamide can decrease sunitinib levels via CYP3A4 induction. Therefore there is potential for ifosfamide to alter levels of bictegravir via modulation of CYP3A4 activity. In addition, ifosfamide has been associated with serious nephrotoxicity including proximal and distal tubular damage, glomerular effects and Fanconi syndrome and therefore renal function should be closely monitored when coadministered with tenofovir (derived from tenofovir alafenamide) due to potential renal additive toxicity. 

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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 lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration may increase bictegravir concentrations due to inhibition of CYP3A4 by lopinavir/ritonavir but this is unlikely to require dose modification. Coadministration of lopinavir/ritonavir and emtricitabine/tenofovir alafenamide had no significant effect on lopinavir and increased exposure of tenofovir alafenamide. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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 of ritonavir-boosted darunavir (or indinavir) would be possible from a pharmacokinetic standpoint. Coadministration of bictegravir and darunavir/cobicistat increased bictegravir AUC by 74%. A comparable increase in bictegravir exposure is anticipated when coadministered with darunavir/ritonavir. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4-fold increase in bictegravir AUC. However, darunavir/ritonavir increases tenofovir alafenamide (the prodrug of tenofovir) due to inhibition of intestinal P-gp thereby increasing the systemic concentration. Coadministration of darunavir/ritonavir (800/100 mg once daily) and tenofovir alafenamide (10 mg once daily) increased tenofovir AUC and Cmax by 105% and 142%, respectively. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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. Coadministration of bictegravir and darunavir/cobicistat increased bictegravir AUC by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4-fold increase in bictegravir AUC. A comparable increase in bictegravir exposure is anticipated when coadministered with darunavir/ritonavir. However, coadministration of darunavir/ritonavir (800/100 mg once daily) and tenofovir alafenamide (10 mg once daily) increased tenofovir AUC and Cmax by 105% and 142%, respectively. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration of multiple dose of metformin (850 mg once daily followed by 500 mg twice daily and 500 mg once daily) was studied with bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg once daily) in 32 subjects. Coadministration increased metformin Cmax and AUC by 28% and 39% due to inhibition of renal OCT2 and MATE1 transporters by bictegravir. The pharmacodynamic characteristics of metformin (including glucose reduction, increases in active GLP-1 and plasma lactate) were not affected by coadministration with bictegravir, emtricitabine and tenofovir alafenamide relative to placebo. In addition, no significant differences were observed in fasted blood glucose or HbA1c values before and after initiating bictegravir in HIV+ people with either normal or mildly impaired renal function receiving metformin at daily doses of 500-3000 mg. The US product label for Biktarvy refers to the Prescribing Information of metformin for assessing the benefit and risk of concomitant use of Biktarvy and metformin. This is particularly important in patients with renal impairment. The European product label for Biktarvy indicates that no dose adjustment is required upon coadministration in patients with normal renal function, but for patients with moderate renal impairment, close monitoring should be considered when starting coadministration of bictegravir with metformin, due to increased risk for lactic acidosis in these patients and a dose adjustment of metformin should be considered if required.

Coadministration has not been studied. Bictegravir is metabolized equally by CYP3A4 and UGT1A1 and is a substrate of P-gp. Ketoconazole is a strong inhibitor of CYP3A4 and P-gp and is predicted to increase bictegravir concentrations but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. However, tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as ketoconazole are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. Clarithromycin is a strong inhibitor of CYP3A4 and P-gp and is predicted to increase bictegravir concentrations but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. However, tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as clarithromycin are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Bictegravir does not inhibit or induce CYP450 enzymes. Sulfadiazine has been associated with crystalluria leading to renal toxicity and in some cases renal failure, with case reports in immunocompromised patients suggesting that AIDS patients may be particularly prone to sulfadiazine-induced renal toxicity. The use of tenofovir alafenamide is unlikely to be problematic as it results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. However, monitoring of renal function is warranted as sulfadiazine may impair emtricitabine renal elimination. 

Coadministration has not been studied. A clinically significant effect on ranolazine is unlikely as it is primarily metabolized by CYP3A4. However, tenofovir-alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as ranolazine are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. Coadministration of ciclosporin, a potent P-gp inhibitor, is expected to increase bictegravir concentrations but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. However, tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as ciclosporin are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile. Note, the European product label for Biktarvy does not recommend coadministration with ciclosporin. If the combination is needed, clinical and biological monitoring, notably renal function, is recommended.

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1. OCT2 facilitates the entry of cisplatin in the tubular cell whereas MATE1 facilitates its elimination in the urine. Bictegravir is an inhibitor of OCT2 but causes no clinically significant inhibition of MATE1. Inhibition of OCT2 will lead to lower concentrations of cisplatin inside the tubular cell which represents an advantage as this may reduce the risk of cisplatin related nephrotoxicity. However, cisplatin may impair renal function which may alter the elimination of emtricitabine. Closely monitor creatinine clearance. No significant interaction is expected with tenofovir alafenamide.

Coadministration has not been studied. Orlistat should only be used with bictegravir, emtricitabine and tenofovir alafenamide if separated by 4-5 hours. Orlistat reduces dietary fat absorption and may affect the absorption of antiretrovirals (especially if lipophilic). [Note: this interaction is not specific for bictegravir, emtricitabine and tenofovir alafenamide, but for any medication taken with orlistat.]

Coadministration has not been studied. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Bictegravir, emtricitabine and tenofovir alafenamide are unlikely to affect clofazimine. However, clofazimine is a moderate inhibitor of CYP3A4 and may increase bictegravir concentrations, but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally (partly by OAT1) and is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily) and also has inducing effects on UGTs. Bictegravir is metabolized equally by CYP3A4 and UGT1A. A modest reduction in bictegravir concentrations may be observed but this is unlikely to be clinically relevant unless flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days). Emtricitabine and tenofovir alafenamide are unlikely to compete with flucloxacillin for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

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 bictegravir is unclear. No interaction is expected with emtricitabine and tenofovir alafenamide.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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 zidovudine would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied. 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. No effect on tamoxifen is expected as bictegravir does not inhibit or induce cytochromes and emtricitabine and tenofovir alafenamide do not interact with this pathway. Tamoxifen has been shown to have some inducing effects on CYP3A4 in vivo and in vitro, however, a clinically significant effect on bictegravir is unlikely as as bictegravir is metabolized equally by CYP3A4 and UGT1A1. 

Coadministration has not been studied. Echinacea has a selective effect on CYP3A4 activity (inhibition of intestinal CYP3A4 and induction of hepatic CYP3A4) and its effect on the net exposure of a CYP3A4 substrate will depend on the extraction of the drug at the intestinal and hepatic sites. Echinacea could potentially cause a modest reduction in bictegravir plasma concentrations as bictegravir is metabolized equally by CYP3A4 and UGT1A1. No effect is expected on emtricitabine and tenofovir alafenamide.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Bictegravir is unlikely to cause a clinically significant interaction via inhibition of MATE1. Emtricitabine and tenofovir alafenamide are unlikely to compete with cephalexin for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. This renal transporter does not play a major role in tenofovir and emtricitabine renal elimination. In addition, bictegravir is unlikely to interfere with cefazolin elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolized by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Emtricitabine and tenofovir derived from tenofovir alafenamide are eliminated by other renal transporters. In addition, bictegravir is unlikely to interfere with cefotaxime elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolized and partially cleared through the bile and intestine. Bictegravir, emtricitabine and tenofovir derived from tenofovir alafenamide do not interfere with ciprofloxacin’s elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolized (likely non CYP mediated pathway) and excreted in the urine by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clindamycin’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent. As total renal elimination is approximately 35% of a dose, there is little potential for significant interactions with emtricitabine or tenofovir (derived from tenofovir alafenamide) via competition for renal transporters or with bictegravir via inhibition of OCT2 and MATE1. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Between 40%-60% of an administered dose can be accounted for in the urine. There is little potential for a clinically significant interaction with emtricitabine and tenofovir (derived from tenofovir alafenamide) via competition for renal elimination transport mechanisms or with bictegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gentamicin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with bictegravir or emtricitabine. There is little potential for interaction with tenofovir alafenamide via competition for active renal transport mechanisms. Note, coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Bictegravir is unlikely to cause a clinically significant interaction with levofloxacin via inhibition of OCT2. Emtricitabine and tenofovir derived from tenofovir alafenamide are eliminated by other renal transporters and therefore no pharmacokinetic interaction is expected. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Bictegravir does not inhibit or induce UGT1A1; emtricitabine and tenofovir alafenamide do not interfere with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Bictegravir inhibits OCT2 and MATE1 but is unlikely to cause a clinically relevant drug interaction with ofloxacin. Emtricitabine is not transported by OCT2 and therefore is unlikely to be impacted by ofloxacin. Tenofovir alafenamide is unlikely to be problematic as it results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Bictegravir does not inhibit OAT. Emtricitabine and tenofovir alafenamide are unlikely to compete with penicillins for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracyclines are eliminated unchanged primarily by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vancomycin is excreted unchanged via renal glomerular filtration. Note, coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clopidogrel’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is not metabolized by CYP450 enzymes and is mainly cleared by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with prasugrel’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clonazepam’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacosamide is metabolized to O-desmethyl-lacosamide mainly by CYP2C19 (~30% of the dose) and is eliminated unchanged through the kidneys (~40% of the dose). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topiramate is mainly eliminated by renal elimination in unchanged form (up to 60% of the dose) and partly by oxidation. Weak induction of CYP isozymes has been observed with higher doses of topiramate but this is unlikely to be of clinical relevance with bictegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pregabalin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zonisamide is metabolized partly by CYP3A4 and also by N-acetyl-transferases and conjugation. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with zonisamide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with bupropion’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with citalopram’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with duloxetine’s metabolic pathway.

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. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fluvoxamine’s metabolic pathway.

Coadministration has not been studied. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate therefore no pharmacokinetic interaction is expected. Note: coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with mirtazapine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYP2D6 and CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with paroxetine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolized mainly by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with trimipramine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolized by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with tolbutamide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is a moderate inhibitor of CYP3A4 but is unlikely to significantly change bictegravir exposure as bictegravir is metabolised equally by CYP3A4 and UGT1A1. Emtricitabine and tenofovir alafenamide are unlikely to be impacted by fluconazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Bictegravir inhibits OCT2 and MATE1 but is unlikely to cause a clinically relevant drug interaction with cetirizine. Emtricitabine and tenofovir derived from tenofovir alafenamide are not transported by OCT2 and therefore no pharmacokinetic interaction is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with chlorphenamine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with loratadine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with promethazine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ergotamine is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ergotamine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with chlorpromazine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clozapine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fluphenazine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, CYP2D6). Bictegravir does not inhibit or induce UGT or P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with haloperidol’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with levomepromazine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolized mainly by CYP1A2, but also by glucuronidation (UGT1A4). Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with olanzapine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Bictegravir, emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to significantly impair paliperidone’s elimination or metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with risperidone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ziprazidone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolized by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4) and glucuronidation. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1, OAT3. Note: coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as foscarnet is cleared mainly by glomerular filtration. Note: coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oseltamivir is converted to oseltamivir carboxylate by esterases. The latter is excreted in the urine by glomerular filtration and tubular secretion by OAT1. Bictegravir does not interfere with oseltamivir elimination. Emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely interact significantly with oseltamivir. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ribavirin is partly metabolized (non CYP mediated) and partly excreted in the urine. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Bictegravir does not inhibit or induce P450 and UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. A small amount of the orally inhaled zanamivir is systemically absorbed. Absorbed zanamivir is excreted unchanged in the urine whereas unabsorbed zanamivir is excreted in the faeces. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with diazepam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with estazolam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with flurazepam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant drug-drug interaction is unlikely. Lorazepam is mainly glucuronidated (by UGTs 2B15, 2B4, 2B7, 1A7, 1A10). Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with lorazepam’s metabolic pathway. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated (possibly by UGTs 2B15, 1A9 and 2B7). Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with lormetazepam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with temazepam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with triazolam’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9 and CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with zolpidem’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with zopiclone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with metoprolol’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiotropium bromide is predominantly excreted unchanged in the urine. Metabolism by CYP2D6 and CYP3A4 is only a minor role in its elimination. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with tiotropium’s metabolic pathway.

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 metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes. Bictegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. Emtricitabine and tenofovir alafenamide do not interact with desogestrel’s metabolic pathway. 

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). Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with dydrogesterone’s metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with estradiol’s metabolic pathway. No significant interactions have been observed when estradiol was administered as feminizing hormone therapy (FHT) to trans women with HIV taking FHT and integrase inhibitors (bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir/abacavir/lamivudine).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 or UGT enzymes. Emtricitabine and tenofovir alafenamide do not interact with levonorgestrel’s metabolic pathway. 

Coadministration with levonorgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 or UGT enzymes. Emtricitabine and tenofovir alafenamide do not interact with levonorgestrel’s metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with a levonorgestrel progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 or UGT enzymes. Emtricitabine and tenofovir alafenamide do not interact with levonorgestrel’s metabolic pathway.

Coadministration with a levonorgestrel intra-uterine device (IUD) has not been studied but there is little potential for an interaction given the local mechanism of action of levonorgestrel.

Coadministration with a levonorgestrel progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 or UGT enzymes. Emtricitabine and tenofovir alafenamide do not interact with levonorgestrel’s metabolic pathway.

Coadministration with norgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 enzymes. Emtricitabine and tenofovir alafenamide do not interact with norgestrel’s metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration and therefore there is little potential for a pharmacokinetic interaction. Note: coadministration with nephrotoxic agents is unlikely to be of concern for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is metabolized by two pathways. Activation (major pathway) to 4-hydroxycyclophosphamide is catalyzed by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with cyclophosphamide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. In vitro data indicate that dacarbazine is a substrate of the renal transporter OAT1. Bictegravir does not inhibit or induce P450 enzymes. Emtricitabine and tenofovir are unlikely to compete for active renal transport as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolized. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is metabolized by CYP3A4 and is a weak inhibitor of CYP3A4. Dasatinib is unlikely to significantly increase bictegravir exposure. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with dasatinib’s metabolic pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as docetaxel is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with docetaxel’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with droloxifene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erlotinib is mainly metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with erlotinib’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemcitabine is metabolized in the liver by cytidine deaminase to an inactive metabolite. Bictegravir, emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mercaptopurine is predominantly metabolised by xanthine oxidase. Bictegravir, emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance there is little potential for interaction. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion (OAT1, OAT3 mediate methotrexate transport in the kidney whereas MRP4 and BCRP mediate methotrexate efflux in the urine). Bictegravir does not impact these renal transporters. In addition, there is no risk for competition for active renal transport mechanisms as emtricitabine is eliminated by other renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Methotrexate can cause tubular toxicity, however, coadministration of both drugs is unlikely to be of concern as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rituximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Toremifene is mainly metabolized by CYP3A4 to N-demethyltoremifene. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with toremifene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolised by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly CYP2A6). Bictegravir does not inhibit or induce CYP450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with desmedetomidine’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with cisapride’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is metabolized by CYP3A4 and CYP2C8. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with loperamide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolized to N-acetyl-mesalazine by N-acetyltransferase. Bictegravir, emtricitabine and tenofovir alafenamide do not interfere with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ondansetron’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bictegravir is metabolized equally by CYP3A4 and UGT1A1. Menthol is a moderate inhibitor of CYP3A4 but is not expected to significantly impact bictegravir exposure. Emtricitabine and tenofovir alafenamide are not affected by menthol.

Coadministration has not been studied. Bictegravir is metabolized equally by CYP3A4 and UGT1A1. Coadministration of valerian with probe substrates for CYP3A4 (alprazolam) and CYP2D6 (dextromethorphan) modestly increased alprazolam Cmax and AUC (~20%) and had no effect on dextromethorphan. A clinically significant interaction is unlikely with drugs metabolised by CYP3A4 or CYP2D6. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically significant interaction is unlikely in the range of observed clinical concentrations. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bictegravir does not interact with digoxin. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-glycoprotein, whereas emtricitabine and tenofovir alafenamide are excreted by different renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with doxazosin’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Coadministration of bictegravir, emtricitabine and tenofovir alafenamide is unlikely to result in a clinically relevant drug interaction. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolyzed in the blood.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). Bictegravir does not inhibit or induce UGTs enzymes. A large proportion of furosemide is also eliminated unchanged renally (via OATs). In vitro data indicate that furosemide is an inhibitor of the renal transporters OAT1/OAT3 but this is unlikely to significantly impact tenofovir concentration as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Emtricitabine is unlikely to interact as it is eliminated by different renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolized and is cleared by the kidneys via OAT1. In vitro data indicate that hydrochlorothiazide is unlikely to inhibit OAT1 in the range of clinically relevant drug concentrations and therefore is unlikely to affect the renal elimination of tenofovir derived from tenofovir alafenamide. Emtricitabine and bictegravir do not interact with hydrochlorothiazide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolized to other inactive metabolites. Elimination occurs predominantly via the urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Bictegravir, emtricitabine and tenofovir alafenamide are not expected to interfere with these metabolic pathways. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is primarily metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with sildenafil’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with telmisartan’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolized mainly by CYP2C9. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with torasemide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valsartan is eliminated unchanged mostly through biliary excretion. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Methamphetamine is mainly metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with methamphetamine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with simvastatin’s metabolic pathway.

Coadministration with bictegravir/emtricitabine/tenofovir alafenamide has not been studied but a clinically significant interaction is unlikely. Coadministration of bictegravir/tenofovir alafenamide (50/25 mg once daily) and midazolam (2 mg single dose) increased midazolam Cmax and AUC by 3% and 15%. These changes are not considered as clinically significant.

Coadministration of a combined oral contraceptive (COC) containing norgestrel/ethinylestradiol has not been studied. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Bictegravir does not inhibit or induce P450 or UGT enzymes. Emtricitabine and tenofovir alafenamide do not interact with norgestrel’s metabolic pathway. Ethinylestradiol is mainly metabolized by hydroxylation. Bictegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 at concentrations much higher than the observed clinical concentrations and therefore no interaction is expected with tenofovir derived from tenofovir alafenamide or emtricitabine. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by cimetidine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by esomeprazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by lansoprazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by omeprazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by pantoprazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by rabeprazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Studies have shown no evidence that bictegravir solubility is impacted by changes in pH and therefore can be coadministered with PPIs or H2-antagonists without dose adjustment or separation. Emtricitabine and tenofovir alafenamide are not impacted by ranitidine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with timolol’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clomifene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with cyproterone acetate’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway. (Note, caution is required if given with calcium supplements as bictegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced bictegravir concentrations. It is recommended to administer bictegravir and calcium supplements simultaneously with food )

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with dutasteride’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolised by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with finasteride’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goserelin is mainly hydrolyzed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Leuprorelin acetate is a peptide that is primarily degraded by peptidases.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with levothyroxine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Multiple mechanisms are thought to be involved in sulfasalazine metabolism including acetylation, hydroxylation, and glucuronidation. Significant interactions are not expected with bictegravir, emtricitabine and tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as thalidomide is cleared by non-enzymatic hydrolysis. 

Coadministration has not been studied. Varenicline is eliminated unchanged by the kidneys via glomerular filtration and active tubular secretion by OCT2. Bictegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with varenicline. Emtricitabine and tenofovir alafenamide are unlikely to significantly interact with varenicline. 

Coadministration has not been studied. Zoledronic acid is eliminated unchanged renally and has been associated with reports of renal dysfunction. Concurrent use of a nephrotoxic agent is unlikely to be problematic as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. (Note, caution is required if given with calcium supplements as bictegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced bictegravir concentrations. It is recommended to administer bictegravir and calcium supplements simultaneously with food).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as benserazide is hydrolysed to trihydroxybenzylhydrazine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with budesonide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism. Bictegravir does not inhibit or induce P450 or UGT enzymes. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with prednisone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with testosterone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamcinolone is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with triamcinolone’s metabolic pathway.

Coadministration has not been studied but based on limited data available an interaction appears unlikely. Potassium is eliminated renally. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetuximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with ciclesonide metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piperacillin is eliminated renally via glomerular filtration and active renal secretion by OAT1/3. Bictegravir does not interfere with piperacillin elimination. Emtricitabine and tenofovir alafenamide are unlikely to compete with piperacillin for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is only minimally metabolised and is eliminated renally via glomerular filtration and active renal secretion by OAT1/3. Bictegravir does not interfere with tazobactam elimination. Emtricitabine and tenofovir alafenamide are unlikely to compete with tazobactam for renal transporters as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iodine is converted to iodide, which is trapped in the thyroid gland. Iodides are excreted mainly in the urine with smaller amounts excreted in the faeces, sweat and saliva.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Most inhaled nitrous oxide is rapidly eliminated unchanged through the lungs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propofol is glucuronidated via UGT1A9, UGT1A8 and is oxidized mainly via CYP2B6. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with propofol’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rocuronium is mostly cleared in the bile although up to 30% may be excreted renally. P-glycoprotein was shown to mediate biliary excretion of rocuronium in a rat model. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with rocuronium’s elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Suxamethonium is hydrolysed by plasma cholinesterase. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although pentobarbital (a potent inducer of hepatic microsomal drug metabolism) is formed during thiopental metabolism, levels do not reach the therapeutic range. Therefore, bictegravir pharmacokinetics are unlikely to be affected significantly by coadministration with thiopental. Furthermore, renal excretion of unchanged thiopental is thought to be minimal so there is little potential for an interaction with emtricitabine or tenofovir alafenamide due to competition for renal elimination pathways. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Bictegravir and emtricitabine do not interfere with this metabolic pathway. Coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Bictegravir does not inhibit or induce CYP450 or UGTs enzymes; emtricitabine and tenofovir alafenamide do not interact with buprenorphine’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolized by CYP2C9. Bictegravir does not inhibit or induce CYP450 enzymes. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine undergoes predominantly direct glucuronidation with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism. Bictegravir does not inhibit or induce CYP450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with codeine’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. Bictegravir does not inhibit or induce CYP450 or UGT enzymes. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fentanyl’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Bictegravir does not inhibit or induce CYP450 or UGT enzymes. In addition, coadministration with an NSAID is unlikely to be of concern for nephrotoxicity as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with morphine’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation. Bictegravir does not inhibit or induce CYP450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with paracetamol’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with oxycodone’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolized by CYPs 3A4, 2B6, and 2D6. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with tramadol’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivermectin is predominantly metabolised by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ivermectin’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism and elimination of levamisole has not been well characterized. Based on limited information, and single dose use of levamisole, a clinically significant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mebendazole is predominantly metabolized in the liver. Bictegravir does not inhibit or induce CYP450 or UGT enzymes. In addition, renal excretion of unchanged mebendazole appears to be minimal and therefore there is little potential for interaction with emtricitabine or tenofovir derived from tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After oral administration, absorption of niclosamide is considered minimal. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxamniquine is thought to be predominantly metabolized by CYP2D6, however, bictegravir is not expected to inhibit or induce CYP450 enzymes. In addition, renal excretion of unchanged drug is minimal therefore there is little potential for interaction with emtricitabine or tenofovir derived from tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrantel is metabolized by CYP2D6 in vitro, however, absorption of an oral dose is minimal and over 50% of a dose is excreted unchanged in the faeces. 

Coadministration has not been studied. In vitro, triclabendazole and its active sulfoxide metabolite are inhibitors of CYP3A4, and therefore may increase bictegravir exposure. However, due to short term dosing of triclabendazole (usually single dose), the clinical relevance of this interaction is low. Furthermore, renal excretion of unchanged triclabendazole appears to be minimal (<10%); therefore there is little potential for interaction with emtricitabine or tenofovir derived from tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with flecainide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with lidocaine’s metabolic pathway.