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 abacavir would be possible from a pharmacokinetic standpoint.

Coadministration has not been studied. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (renal transporter unknown, possibly OATs or OCTs). A clinically significant interaction with bictegravir is unlikely. Tenofovir alafenamide is unlikely to compete with acamprosate for renal transporters as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. However, acamprosate and emtricitabine may compete for tubular secretion, which could lead to increased concentrations of either drug. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with acenocoumarol’s metabolic pathway.

Coadministration has not been studied. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. In vitro studies have shown acetazolamide may competitively inhibit renal transporters OAT1, OAT3 and OAT4. Inhibition of these renal transporters is unlikely to lead to significant increase in tenofovir as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Emtricitabine and bictegravir do not interact with acetazolamide elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Bictegravir does not interfere with aciclovir elimination. Emtricitabine and tenofovir alafenamide are unlikely to compete with aciclovir 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 as acitretin undergoes isomerisation and glucuronidation. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with acitretin’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aclidinium bromide is rapidly and extensively hydrolyzed (non-enzymatic and enzymatic transformation by esterases and butylrylcholineesterases) to its pharmacologically inactive metabolites, with only a minor role for CYP metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adalimumab 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 and is contraindicated. Biktarvy, which contains tenofovir (derived from tenofovir alafenamide), should not be used concomitantly with adefovir dipivoxil.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). 

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. Bictegravir exposure could potentially be decreased as it partly metabolized by CYP3A4. Tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and its absorption may be decreased due to induction of intestinal P-gp by African potato. No effect on emtricitabine is expected.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with agomelatine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with albendazole’s metabolic pathway. 

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 albuvirtide would be possible from a pharmacokinetic standpoint. Bictegravir is metabolized by CYP3A and UGT1A1; tenofovir alafenamide and emtricitabine are eliminated renally. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on P450 enzymes. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. No interaction is expected with bictegravir, emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4, however, no clinically relevant effect is expected on bictegravir exposure. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied. Alcuronium is predominantly eliminated unchanged via the kidneys. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is some potential for exposure of alcuronium to be increased since bictegravir inhibits the renal transporters OCT2 and MATE1. Caution is advised as alcuronium has a narrow therapeutic index. In addition, competition with emtricitabine for active renal transport mechanisms cannot be excluded, which may lead to increased levels of either drug. This mechanism of interaction is unlikely to be relevant for tenofovir alafenamide as this prodrug results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

Coadministration has not been studied. If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product. 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. P-glycoprotein is a major determinant of aliskiren bioavailability. Significant interactions are not expected with bictegravir, emtricitabine and tenofovir alafenamide. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. 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. Almotriptan is partly eliminated unchanged in the urine and partly metabolized mainly via monoamine oxidase-A and to a lesser extent by CYP3A4, CYP2D6 and flavin monooxygenase. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with almotriptan’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. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs. No interaction with emtricitabine or tenofovir alafenamide is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYPs 2C9, 3A4 and 1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with alosetron’s metabolic pathway.

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

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. Bictegravir is unlikely to cause a clinically significant interaction via inhibition of OCT2. Emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to interfere with amantadine renal elimination as they are eliminated by different renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Bictegravir, emtricitabine and tenofovir alafenamide do not interfere with ambrisentan metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration therefore no interaction is expected with bictegravir or emtricitabine. 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. Amiloride is eliminated unchanged by the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Bictegravir inhibits OCT2 to some extent but is unlikely to cause a clinically relevant drug interaction with amiloride. Furthermore, emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to compete for renal elimination as they are eliminated by other renal transporters

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with aminophylline’s metabolic pathway.

Coadministration has not been studied. Amiodarone is metabolized by CYPs 3A4 and 2C8, but bictegravir does not inhibit or induce CYP450 enzymes. Amiodarone is a P-gp inhibitor and coadministration 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 amiodarone 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT). Bictegravir, emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to significantly impair amisulpride elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with amitriptyline’s metabolic pathway.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Emtricitabine and tenofovir derived from tenofovir alafenamide are secreted by other renal transporters. In addition, bictegravir is unlikely to impair amoxicillin elimination.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile. 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. Renal clearance of ampicillin occurs partly by glomerular filtration and tubular secretion. Bictegravir is unlikely to cause a clinically relevant drug interaction. No interaction is expected with tenofovir alafenamide as it results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. However, as emtricitabine is eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased levels of either drug particularly when ampicillin is administered intravenously. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated via UGT1A4. 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 metabolism and clearance a clinically significant interaction is unlikely as anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature. 

Bictegravir should be taken at least 2 hours before or 6 hours after antacids containing aluminium/magnesium. Simultaneously administration of bictegravir with antacids containing aluminium/magnesium is not recommended. Bictegravir can be taken under fasting conditions 2 hours before antacids containing aluminium, magnesium or calcium. Fasted administration of bictegravir 2 hours before antacids decreased bictegravir AUC by 13%. When bictegravir was administered 2 hours after antacids, bictegravir AUC decreased by 52%. Simultaneous administration of bictegravir and antacids in fasted and fed conditions decreased bictegravir AUC by 79% and 47%, respectively. Emtricitabine and tenofovir alafenamide are not impacted by antacids.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thymoglobulins are cleared by the reticuloendothelial system.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with apixaban’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. 

Coadministration has not been studied. Aprepitant is mainly metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with aprepitant’s metabolic pathway. Bictegravir is metabolized equally by CYP3A4 and UGT1A1. Aprepitant is a moderate inhibitor of CYP3A4 and is unlikely to significantly increase bictegravir exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. Drug-drug interactions studies performed with substrates of different cytochromes and P-glycoprotein (i.e., acetaminophen, lidocaine, warfarin, digoxin) indicate that argatroban has a low potential to cause drug-drug interactions and therefore is unlikely to alter the exposure of bictegravir, emtricitabine or tenofovir alafenamide.

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

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolism via UGTs 1A9 and 2B7. A clinically significant effect of bictegravir, emtricitabine and tenofovir alafenamide on artemisins is unlikely. Bictegravir is metabolized equally by CYP3A4 and UGT1A1. Artemisinins induce CYP3A4 and/or CYP2C19 and may decrease bictegravir concentrations. However, this is unlikely to clinically relevant due to the short treatment duration for artemisinins. Emtricitabine and tenofovir alafenamide are unlikely to be impacted.

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. A pharmacokinetic interaction is unlikely with vitamin C itself as bictegravir, emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. However, vitamin C can be found in multivitamins preparations which may also contain calcium, iron, aluminium, magnesium. As the effect of cationic complexation with bictegravir cannot be excluded, it is recommended to administer bictegravir and multivitamins containing divalent cations simultaneously with food.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, CYP2D6 (minor)). Bictegravir does not inhibit or induce UGT or P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with asenapine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticulo-endothelial system. Less than 0.1% of a total injected dose is recovered in urine. 

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. 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 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. Astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with astemizole’s metabolic pathway.

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, coadministration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore coadministration is not recommended. Coadministration of bictegravir (75 mg) and atazanavir alone (400 mg once daily) increased bictegravir AUC by 315%.

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, coadministration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore coadministration is not recommended. Coadministration of bictegravir (75 mg) and atazanavir/cobicistat (300/150 mg once daily) increased bictegravir AUC by 306%.

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, coadministration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore coadministration is not recommended. Coadministration of bictegravir (75 mg) and atazanavir/cobicistat (300/150 mg once daily) or atazanavir alone (400 mg once daily) increased bictegravir AUC by 306% and 315%, respectively. A similar magnitude of increase could occur with atazanavir/ritonavir.

Coadministration has not been studied. Atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. Therefore there is potential for bictegravir to increase atenolol exposure via inhibition of OCT2 and MATE1. Based on the drug-drug interaction study with metformin (another drug transported by OCT2 and MATE1), the increase in atenolol exposure is expected to be ~40%. It is recommended to start atenolol at a lower dose and adjust dosage until the desired clinical effect is achieved.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atovaquone is mainly eliminated unchanged in the faeces. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with atovaquone’s metabolic pathway. 

Coadministration has not been studied. Based on the metabolism/elimination profiles of both drugs, there is little potential for interaction when atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. There is therefore little potential for clinically significant interactions with bictegravir, emtricitabine and tenofovir alafenamide via modulation of, or competition for metabolic pathways. 

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

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolized analogously to natural purines. 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. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-gp and MRP2. Bictegravir, emtricitabine and tenofovir alafenamide are not expected to interfere with azithromycin elimination. Azithromycin is not a significant inhibitor of CYP3A4 or P-gp and therefore is not expected to increase bictegravir (CYP3A4 and P-gp substrate) to a significant extent. Note: the European product label for Biktarvy indicates that coadministration of azithromycin may increase bictegravir plasma concentrations and recommends caution.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab 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. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with beclomethasone metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. There are no clinical data on the safety and efficacy of bedaquiline when coadministered with antiretroviral agents. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

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 as benserazide is hydrolysed to trihydroxybenzylhydrazine. 

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. Bepridil is metabolized by CYPs 2D6 (major) and 3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with bepridil’s metabolic pathway. 

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. 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, caution is required as bictegravir is metabolized equally by CYP3A4 and UGT1A and coadministration could potentially decrease bictegravir concentrations. Note: betamethasone is unlikely to cause a clinically significant interaction when administered topically (ointment, cream, foam, nasal drops) but caution is needed when administered orally or intravenously particularly when used at high doses or for a long duration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp and bictegravir, emtricitabine or tenofovir alafenamide do not inhibit or induce P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Coadministration has not been studied. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300 mg/m2/day). Bexarotene could potentially decrease bictegravir exposure and therefore caution is needed. Emtricitabine and tenofovir alafenamide do not interact with bexarotene’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as half of bezafibrate dose is eliminated unchanged in the urine. Significant interactions are not expected with bictegravir and emtricitabine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1 but a clinically relevant drug interaction with tenofovir derived from tenofovir alafenamide is unlikely in the observed range of clinical concentrations. 

Coadministration has not been studied but based on limited information concerning the metabolism and clearance of biperiden, there is little potential for clinically significant interaction. Limited human data suggest biperiden undergoes hydroxylation in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. 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. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with bisoprolol’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. No effect on bictegravir is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate) and in vitro studies suggest black cohosh is unlikely to affect UGT1A1 at clinically relevant concentrations. No effect on tenofovir alafenamide is expected as black cohosh had no significant effect on the pharmacokinetics of digoxin (a P-gp substrate).

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase. Furthermore, ~67% of the administered drug is excreted unchanged in urine probably by glomerular filtration. 

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

Coadministration has not been studied. Bosentan is a substrate and moderate inducer of CYP3A4 and could potentially decrease bictegravir exposure as bictegravir is metabolised equally by CYP3A4 and UGT1A1. Significant interactions are not expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with bromazepam’s metabolic pathway.

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. Bupivacaine is predominantly metabolized by CYP3A4, however, bictegravir does not induce or inhibit CYP3A4. Renal excretion of unchanged bupivacaine is thought to account for approximately 1% of a dose; therefore, there is little potential for interaction with emtricitabine and tenofovir derived from tenofovir alafenamide. 

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. 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 the metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with buspirone’s metabolic pathway.

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with caffeine citrate’s metabolic pathway.

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. In theory, calcium could chelate with bictegravir and potentially decrease the amount of bictegravir available to bind to the active site of the HIV integrase. However, given that the extent of chelation is dependent on the amount of calcium, this risk is predicted to be low when administering calcium folinate in small doses at frequent intervals. Since calcium is distributed rapidly, separating the intake of bictegravir from the IV administration of calcium folinate by 2 hours should eliminate any risk of chelation. No interaction is expected with emtricitabine or tenofovir alafenamide.

As with other HIV integrase inhibitors, bictegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced bictegravir concentrations. Bictegravir and calcium supplements can be coadministered simultaneously. The European product label for Biktarvy recommends they can be taken together without regard to food, but the US product label recommends to administer simultaneously with food. (The decision to administer with or without food should be decided on a case-by-case basis.) The simultaneous administration of calcium carbonate (1200 mg) and bictegravir with food did not significantly modify bictegravir exposure whereas exposure was decreased by 33% when coadministered in fasted conditions. No interaction is expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 which are not affected by bictegravir, emtricitabine or tenofovir alafenamide. Canagliflozin is a weak P-gp inhibitor but is unlikely to affect tenofovir alafenamide concentrations to a significant extent. Although an increased risk for bone fractures has been reported with canagliflozin (particularly in patients with a history of, or at high risk of, cardiovascular disease), coadministration with tenofovir alafenamide is unlikely to be problematic in terms of additive bone toxicity as tenofovir alafenamide results in 90% lower systemic exposure of tenofovir compared to tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit CYP3A4, UGT1A1 or intestinal transporters in the range of doses in clinical use. Bictegravir does not inhibit or induce P450 enzymes. Emtricitabine and tenofovir alafenamide do not interfere with cannabidiol elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetrahydrocannabinol (THC, the psychoactive component of cannabis) is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with cannabis’s metabolic pathway.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Bictegravir does not interfere with these metabolic pathways. However, nucleoside/tide analogues such as emtricitabine and tenofovir alafenamide may compete for these metabolic pathways. The clinical relevance of this interaction is unknown.

Coadministration has not been studied. Capreomycin is predominantly excreted via the kidneys as unchanged drug, partly by glomerular filtration and partly by tubular secretion. Bictegravir is unlikely to cause a significant interaction via inhibition of OCT2 and MATE1. 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. However, capreomycin may potentially compete with emtricitabine for renal elimination and levels of either drug may increase. Renal function should be monitored as clinically appropriate. 

Coadministration has not been studied. Captopril is largely excreted in the urine by OAT1. Bictegravir does not interact with captopril. Emtricitabine and tenofovir alafenamide are unlikely to compete with captopril 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 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Carbidopa is partly metabolized and partly eliminated unchanged (30% of the total urinary excretion). 

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.

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. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with carvedilol’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with caspofungin’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw is a strong inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. However, cat’s claw is unlikely to increase bictegravir to a clinically significant extent as bictegravir is metabolized equally by CYP3A4 and UGT1A1. No effect on emtricitabine or tenofovir alafenamide is expected.

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. 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. 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. 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. Chlorambucil is almost completely metabolized (little is known about chlorambucil metabolism in humans, most probably non-CYP mediated) and has extremely low urinary excretion. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolised via UDP-glucuronyltransferases, in particular UGT2B7. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. In vitro studies have shown that chloramphenicol can inhibit CYP3A4 but this is unlikely to be clinically significant as bictegravir is metabolized equally by CYP3A4 and UGT1A1.

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

Coadministration has not been studied. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). No effect on chloroquine is expected. Concentrations of bictegravir may increase due to inhibition of P-glycoprotein by chloroquine but this is unlikely to be clinically significant as clinical data have shown a good safety profile with up to a 2.4-fold increase in bictegravir AUC. However, concentrations of tenofovir may also increase and 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. No effect on emtricitabine 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. 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. Chlortalidone is mainly excreted unchanged in the urine and faeces. 

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. 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 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 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. 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. 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. 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. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature. 

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 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. 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 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. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Clobazam is a weak inducer and could potentially decrease bictegravir exposure although to a limited extent. 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. Clobetasol is a substrate of CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clobetasol’s metabolic pathway.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Tenofovir alafenamide is unlikely to compete with the elimination of clofibrate as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF and emtricitabine is eliminated by other renal transporters. Bictegravir does not interfere with clofibrate elimination 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. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clomipramine’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. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). Bictegravir does not interact with clonidine. Clonidine is a weak inhibitor of OCT2 but is unlikely to interact with emtricitabine and tenofovir derived from tenofovir alafenamide which are eliminated by different renal transporters. 

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 the metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with clorazepate’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. 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. Cocaine is metabolized by several pathways (CYP and non CYP mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with cocaine’s metabolic pathway.

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. Colchicine is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with colchicine’s metabolic pathway.

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for an interaction with bictegravir via modulation of, or competition for, metabolic pathways. No interaction is expected with vitamin D when given as a single agent (i.e. not with calcium or in a multivitamin preparation) or as an injection. However, colecalciferol can be found in multivitamin preparations which may also contain calcium, iron, aluminium, magnesium. As the effect of cationic complexation cannot be excluded, it is recommended to administer bictegravir and multivitamins containing divalent cations simultaneously with food.

Coadministration has not been studied. Several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, however this is unlikely to increase bictegravir exposure to a clinically significant extent as bictegravir is metabolized equally by CYP3A4 and UGT1A1. Piperine, a component of Piper cubeba, inhibits intestinal P-gp however the clinical significance of this effect is unclear and does not necessitate a lower dose of tenofovir alafenamide. No effect on emtricitabine exposure is expected.

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with vitamin B12 when given as a single agent (i.e. not in a multivitamin preparation) or as an injection. However, vitamin B12 can be found in multivitamins preparations which may also contain calcium, iron, aluminium, magnesium. As the effect of cationic complexation with bictegravir cannot be excluded, it is recommended to administer bictegravir and multivitamins containing divalent cations simultaneously with food.

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. Cycloserine is predominantly excreted renally via glomerular filtration. 

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. Cytarabine is metabolized by cytidine deaminase. 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. 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. 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 the metabolism and clearance a clinically significant interaction is unlikely. No dose adjustment of daclatasvir is required. 

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. Dalteparin is excreted largely unchanged via the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9 which is not affected by bictegravir, emtricitabine or tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Bictegravir does not inhibit or induce CYP enzymes; emtricitabine and tenofovir alafenamide do not interact with dapsone’s metabolic pathway.

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

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/cobicistat 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. However, coadministration with darunavir/cobicistat (800/150 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir AUC and Cmax by 224% and 216%, 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) and Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, both products contain emtricitabine and tenofovir alafenamide and must not be administered with other products containing 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 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 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. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Bictegravir/FTC/TAF does not affect CYP enzymes.

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. Desflurane is almost exclusively eliminated unchanged by the lungs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with desipramine’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 a desogestrel-containing progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes. Emtricitabine and tenofovir alafenamide do not interact with desogestrel’s 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 as dextropropoxyphene is mainly metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with dextropropoxyphene’s metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then 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 diamorphine’s metabolic pathway. 

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 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. Diethylcarbamazine is mainly excreted unchanged in the urine. There is little potential for interaction with bictegravir or emtricitabine. A clinically significant interaction is not expected with 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. 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. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. Bictegravir does not inhibit or induce CYP450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with dihydrocodeine’s metabolic pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and subsequently glucuronidated. No clinically significant drug interactions are known, and significant interactions with antiretrovirals are unlikely. 

Coadministration has not been studied. Diltiazem is a strong inhibitor of CYP3A4 and is predicted to increase bictegravir concentrations but to a modest extent as bictegravir is metabolized equally by CYP3A4 and UGT1A1. 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. Emtricitabine and tenofovir alafenamide do not interfere with diltiazem’s metabolic pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with dipyridamole’s metabolic pathway.

Coadministration has not been studied. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine possibly via OCT2. Bictegravir inhibits OCT2 and therefore could potentially reduce the renal elimination of disopyramide to some extent. Caution is warranted if coadministered. Emtricitabine and tenofovir derived from tenofovir alafenamide are not transported by OCT2 and therefore are unlikely to affect disopyramide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disulfiram is reduced to diethyldithiocarbamic acid, is conjugated with glucuronic acid, oxidised to sulphate, methylated and decomposed to diethylamine and carbon disulphide. 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 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 and is contraindicated. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Bictegravir is an inhibitor of OCT2 and therefore can increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias. No interaction is expected with emtricitabine or tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Bictegravir does not inhibit or induce CYP450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with dolasetron’s metabolic pathway.

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 dolutegravir) 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 must not be administered with other antiretroviral products. In addition, Triumeq (dolutegravir, abacavir, lamivudine) should not be taken with any other medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Dovato (dolutegravir/lamivudine) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

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

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

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. 

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, the coadministration with doravirine would be possible from a pharmacokinetic standpoint. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Bictegravir is equally metabolized by CYP3A4 and UGT1A1. None of these antiretroviral drugs has any inhibitory or inducing effects on P450 or UGT enzymes therefore no significant interactions are expected between doravirine, bictegravir, emtricitabine, and tenofovir alafenamide. 

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, products containing tenofovir-DF should not be coadministered with products containing tenofovir alafenamide.

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. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with doxepin’s metabolic pathway.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

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. 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. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with dronabinol’s metabolic pathway.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Bictegravir does not inhibit or induce P450 enzymes. Emtricitabine and tenofovir alafenamide do not interact with drospirenone’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 with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with drospirenone 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 as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is eliminated primarily as unchanged drug in urine and is minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%). 

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. 

Coadministration has not been studied. Eflornithine is predominantly eliminated unchanged via the kidneys. There are no available data determining whether excretion is via active tubular secretion or glomerular filtration. However bictegravir is unlikely to cause a clinically significant interaction with eflornithine via inhibition of the renal transporters OCT2 and MATE1. However, there is potential for competition with emtricitabine for active renal transport mechanisms, which may lead to increased levels of either drug. This mechanism of interaction is unlikely to be problematic 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. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with eltrombopag’s metabolic pathway. 

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both products contain emtricitabine and tenofovir alafenamide and must not be administered with other products containing emtricitabine and tenofovir alafenamide. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and elvitegravir) is unlikely to be of clinical benefit.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Bictegravir does not inhibit or induce UGT enzymes. Although an increased risk for bone fractures and decreased bone mineral density has been reported for other sodium glucose cotransporter 2 inhibitors, coadministration with tenofovir alafenamide is unlikely to be problematic in terms of additive bone toxicity as tenofovir alafenamide results in 90% lower systemic exposure of tenofovir compared to tenofovir disoproxil.

Biktarvy (bictegravir, 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 or with additional emtricitabine.

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, both products contain emtricitabine and tenofovir alafenamide and must not be administered with other products containing emtricitabine and tenofovir alafenamide.

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 emtricitabine and should not be administered with tenofovir-DF or additional emtricitabine (both components of Truvada).

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. Enflurane is predominantly metabolized by CYP2E1. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with enflurane’s metabolic pathway. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is excreted predominantly renally. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Bictegravir, emtricitabine and TAF are unlikely to significantly interact with entecavir. 

Coadministration has not been studied. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2, therefore there is potential for bictegravir to increase ephedrine exposure. Emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to interact as they are not transported by OCTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with epirubicin’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4 but bictegravir/emtricitabine/tenofovir alafenamide does not inhibit or induce CYP3A4.

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 as eprosartan is largely excreted in bile and urine as unchanged drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ergometrine is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with ergometrine’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. 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. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor component. 

Coadministration has not been studied. Erythromycin is a moderate inhibitor of CYP3A4 and P-gp 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with escitalopram’s metabolic pathway.

Coadministration has not been studied and is not recommended. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4 and UGTs and therefore is expected to reduce bictegravir exposure, leading to loss of therapeutic effect and possible development of resistance. An alternative anticonvulsant should be considered. Eslicarbazepine was shown to have no clinically significant effect on digoxin (a P-glycoprotein substrate) therefore no significant effect is expected on tenofovir alafenamide. No interaction is expected with emtricitabine.

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 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 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 interaction was observed in a pilot study when estradiol was administered as feminizing hormone therapy (FHT) to trans women with HIV taking FHT and integrase inhibitors (bictegravir/emtricitabine/tenofovir alafenamide, n=8; dolutegravir/abacavir/lamivudine, n=2) and trans women without HIV taking FHT (n=7).

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estramustine phosphate undergoes rapid dephosphorylation to estramustine which is then oxidized by 17beta-hydroxysteroid dehydrogenases to estromustine. Estramustine and estromustine are subsequently hydrolyzed to estradiol and estrone, respectively. Estradiol is then hydroxylated by CYP1A1, 1A2 and 3A4. 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. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%). 

Coadministration with ethinylestradiol alone has not been studied but a clinically significant interaction is unlikely. Coadministration of bictegravir (75 mg once daily) or emtricitabine/tenofovir alafenamide (200/25 mg once daily) with a combined oral contraceptive (COC) containing ethinylestradiol/norgestimate did not significantly impair ethinylestradiol, norelgestromin (active metabolite of norgestimate) and norgestrel exposures. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver and animal studies suggest involvement of flavin-containing monooxygenases. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etidocaine is metabolized by CYP3A4, but bictegravir, emtricitabine and tenofovir alafenamide do not inhibit or induce drug metabolizing enzymes.

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with etonogestrel’s metabolic pathway.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Bictegravir does not inhibit or induce P450 or UGT 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 etonogestrel’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoposide is partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. Furthermore, etoposide is partly glucuronidated by UGT1A1. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with etoposide’s metabolic pathway. 

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, etravirine is an inducer of CYP3A4 and is expected to decrease bictegravir exposure which may result in loss of therapeutic effect and development of resistance.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that eucalyptus impacts UGTs or P-gp.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with ezetimibe’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Famciclovir is converted to penciclovir by aldehyde oxydase. Penciclovir is secreted in the urine possibly by OAT1. Bictegravir does not interfere with famciclovir elimination. No significant interactions were observed when emtricitabine (200 mg single dose) and famciclovir (500 mg single dose) was studied in 12 HIV-negative subjects. There was no change in the AUC or Cmax values for emtricitabine or famciclovir. Tenofovir alafenamide is unlikely to compete with famciclovir for renal transporters 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. 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. Furthermore, famotidine is eliminated by renal excretion via OAT3 (65-70%) and therefore is unlikely to interact with emtricitabine or tenofovir alafenamide as they are eliminated by other renal transporters.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolyzed to an active metabolite, fenofibric acid. Significant interactions are not expected with bictegravir. In vitro data suggest that fenofibric acid inhibits OAT3 but this is unlikely to impact emtricitabine or tenofovir derived from tenofovir alafenamide as they are eliminated by other renal transporters. 

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. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fesoterodine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine undergoes negligible metabolism and is mainly eliminated unchanged in the faeces. 

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. 

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. Flibanserin is primarily metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with flibanserin’s metabolic pathway. Flibanserin has been shown to moderately increase the exposure of simvastatin (a CYP3A4 substrate), but is unlikely to cause a clinically significant increase in bictegravir exposure. 

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 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. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase. This enzyme is also involved in the catabolic pathway of pyrimidine analogs and competition could potentially increase haematological toxicity. This mechanism of interaction is unlikely to be problematic for tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF but could be relevant for emtricitabine. Monitor haematological parameters and consider dose reduction if required. Bictegravir does not interfere with flucytosine metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludarabine phosphate is rapidly hydrolyzed to 2F-ara-A, the principal metabolite (non CYP mediated metabolism) which is then eliminated renally. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fludrocortisone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Bictegravir, emtricitabine and tenofovir alafenamide do not interact with flunisolide metabolism.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and CYP2C19. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with flunitrazepam’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of fluocinolone.

Coadministration has not been studied. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. Bictegravir does not interfere with this metabolic pathway and an interaction is unlikely with tenofovir alafenamide as it results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. However, emtricitabine may compete for this metabolic pathway. The clinical relevance of this interaction is unknown. 

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. 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 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 metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fluticasone’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolized by CYP2C9. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with fluvastatin’s 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

Coadministration has not been studied. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. A pharmacokinetic interaction is unlikely with folic acid itself. However, folic acid may be administered in a multivitamin preparation which may also contain calcium, iron, aluminium and/or magnesium. As the effect of cationic complexation cannot be excluded, it is recommended to administer bictegravir and multivitamins containing divalent cations simultaneously with food.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. Bictegravir does not inhibit or induce P450 or UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with formoterol’s metabolic pathway.

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. Fosinopril is hydrolysed by esterases in the GI mucosa and liver. Fosinopril does not inhibit or induce CYP450 enzymes.

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 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. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Bictegravir does not interfere with ganciclovir elimination. Emtricitabine and tenofovir alafenamide are unlikely to compete with ganciclovir 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. Garlic supplements have been shown to decrease unboosted saquinavir AUC by 50% in a clinical trial and there is a case report of treatment failure due to garlic cloves (six garlic cloves three times weekly) decreasing ritonavir-boosted atazanavir trough concentrations by ~70%. This effect has been attributed to the induction of intestinal CYP3A4 and/or P-gp by garlic. Tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and its absorption could decrease due to induction of intestinal P-gp by garlic. Furthermore, garlic could also decrease the absorption of bictegravir as it is metabolized equally by CYP3A4 and UGT1A1. Patients should be advised against the use of garlic supplements.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gefitinib is metabolized by CYP3A4 and CYP2D6. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with gefitinib’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. Gemfibrozil is metabolised by UGT2B7. Bictegravir does not inhibit or induce UGT enzymes; emtricitabine and tenofovir alafenamide do not interact with gemfibrozil’s metabolic pathway.

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 with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Bictegravir does not inhibit or induce P450 or UGT 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 gestodene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gamma-hydroxybutyrate undergoes first pass metabolism. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with GHB’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Gingerols moderately inhibit CYP3A4 in vitro but this is unlikely to cause a significant effect on bictegravir as bictegravir is metabolised equally by CYP3A4 and UGT1A1. There is no evidence that ginger inhibits or induces UGTs. No effect on absorption of tenofovir alafenamide is expected as gingerols are unlikely to cause clinically significant inhibition of P-gp. No interaction with emtricitabine is expected.

Coadministration has not been studied. Bictegravir is metabolized equally by CYP3A4 and UGT1A1. Ginkgo biloba may decrease bictegravir concentrations through induction of CYP3A4 but the magnitude and clinical relevance of this potential interaction is difficult to predict as inconsistent findings have been reported from clinical drug interaction studies with CYP3A4 substrates. 

Coadministration has not been studied. Bictegravir is a substrate of P-gp and concentrations may increase, but to a modest extent, as glecaprevir/pibrentasvir inhibits P-gp. 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. Studies performed with emtricitabine or tenofovir alafenamide showed no clinically significant interactions with glecaprevir/pibrentasvir. Note, the European product label for Biktarvy indicates that coadministration of glecaprevir may increase bictegravir plasma concentrations and recommends caution.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C19. Bictegravir does not inhibit or induce P450 enzymes; emtricitabine and tenofovir alafenamide do not interact with gliclazide’s metabolic pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2. Glyceryl trinitrate is not known to induce or inhibit CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Bictegravir, emtricitabine and tenofovir alafenamide are unlikely to significantly change glycopyrronium bromide exposure.  

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. Goldenseal has been shown to inhibit CYP3A4 in vitro, however, no significant effect of golden seal root on indinavir pharmacokinetics was observed in a study in HIV-negative subjects. Interactions with other drugs metabolized by CYP3A4 are unlikely. No interaction with emtricitabine or tenofovir alafenamide is expected.

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. Granisetron is metabolized by CYP3A4. Bictegravir does not inhibit or induce CYP450 enzymes; emtricitabine and tenofovir alafenamide do not interact with granisetron’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. Grapefruit juice is unlikely to increase bictegravir exposure to a clinically significant extent. No interaction with emtricitabine or tenofovir alafenamide is expected.

Coadministration has not been studied. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys and no interaction is expected with emtricitabine and tenofovir alafenamide. However, bictegravir is metabolized equally by CYP3A4 and UGT1A1 and griseofulvin is a liver microsomal enzyme inducer. Use with caution as coadministration could potentially decrease bictegravir exposure.