Odefsey (rilpivirine, 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. Based on metabolism and clearance a clinically significant interaction with abacavir and rilpivirine, emtricitabine or tenofovir alafenamide is unlikely.

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 rilpivirine 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this 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. No effect on emtricitabine exposure is expected. Rilpivirine does not interfere with acetazolamide elimination.

Coadministration has not been studied. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Rilpivirine does not interfere with acyclovir 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. 

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. Odefsey contains tenofovir (derived from tenofovir alafenamide) which 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.  Use with caution as African potato could decrease concentrations of rilpivirine (due to induction of CYP3A4) and absorption of tenofovir alafenamide (due to induction of intestinal P-gp). Therapeutic drug monitoring of rilpivirine is recommended. No effect on emtricitabine is expected.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly by CYP1A2. Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP 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. In vitro studies have shown that CYP3A4 and the flavine-containing monooxygenase system are involved in the formation of the active metabolite albendazole sulfoxide. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Odefsey (rilpivirine, 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. Rilpivirine is metabolized primarily by CYP3A with potential contribution from CYP2C19; tenofovir alafenamide and emtricitabine are eliminated renally. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on P450 enzymes. No interaction is expected with rilpivirine, emtricitabine and tenofovir alafenamide.

Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4. A clinically relevant drug-drug interaction is a priori not anticipated. 

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 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 relevant for tenofovir alafenamide as this prodrug results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Rilpivirine is unlikely to significantly inhibit alcuronium renal elimination. 

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 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Alfuzosin is metabolized by CYP3A. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. A clinically relevant effect on rilpivirine concentrations is unlikely as alfuzosin does not inhibit CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with alfuzosin. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Alfuzosin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration has not been studied but based on metabolism and clearance a 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 emtricitabine, tenofovir alafenamide and rilpivirine. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Rilpivirine, 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. Rilpivirine, 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. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYPs 2C9, 3A4 and 1A2. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with alprazolam 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. Rilpivirine is unlikely to significantly inhibit amantadine renal elimination. 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. Rilpivirine, 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 as amikacin is eliminated renally by glomerular filtration. 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 in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Rilpivirine is unlikely to significantly inhibit amiloride renal elimination. 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied. Amiodarone is metabolized by CYP2C8 and CYP3A4; in vitro data suggest it is only a weak inhibitor of CYP3A4. Rilpivirine, emtricitabine and tenofovir alafenamide are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with amiodarone. However, given the QT prolongation risk associated with amiodarone, caution is recommended. In addition, 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 Odefsey 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). Rilpivirine, 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. Rilpivirine, 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. Amlodipine is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with amlodipine 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. Rilpivirine, 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 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. Rilpivirine is unlikely to interfere with amoxicillin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolized by CYP2D6. Rilpivirine, 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 amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile. 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. Rilpivirine does not interfere with amphotericin B elimination pathway.

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion; it is reduced by probenecid. About 20 to 40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60-80% is excreted in the urine within 6 hours. Rilpivirine is unlikely to significantly inhibit ampicillin renal elimination. 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 when ampicillin is administered intravenously. When administered orally, there is little potential for significant interaction. 

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. Rilpivirine at a dose of 25 mg once daily does not inhibit or induce CYPs or UGTs. Emtricitabine and tenofovir alafenamide do not interact with anastrozole 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. 

Coadministration has not been studied. The combination of rilpivirine and antacids should be used with caution as coadministration may cause significant decreases in rilpivirine plasma concentrations due to an increase in gastric pH. Antacids should only be administered either at least 2 hours before or at least 4 hours after rilpivirine. Antacids do not interfere with emtricitabine and tenofovir alafenamide absorption.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with apixaban metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as apomorphine is metabolized by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with apomorphine. However, the product labels for rilpivirine indicate that rilpivirine/emtricitabine/tenofovir alafenamide should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Apomorphine has a possible risk of QTc prolongation on the CredibleMeds.org website. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4. Aprepitant could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. Emtricitabine and tenofovir alafenamide do not interact with aprepitant metabolic pathway. 

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 rilpivirine, emtricitabine or tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with aripiprazole metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with aripiprazole. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Aripiprazole has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYP3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolised via UGT1A9 and 2B7. A clinically significant effect of rilpivirine, emtricitabine or tenofovir alafenamide on artemisinins is unlikely. However, artemisinins induce CYP3A4 and/or CYP2C19 and could potentially decrease rilpivirine concentrations, but this is unlikely to be clinically relevant due to the short treatment duration for artemisinins. Emtricitabine and tenofovir alafenamide are unlikely to be impacted.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Significant interactions are not expected with vitamin C given alone or in multivitamins and rilpivirine, emtricitabine or tenofovir alafenamide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, 2D6 (minor). Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with asenapine metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with asenapine. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Asenapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a 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 and then further metabolized by glucuronidation (by several UGT, major UGT1A6). 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. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). 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 pharmacokinetic interaction is unlikely. Astemizole is metabolized by CYPs 2D6, 2J2 and 3A4 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with astemizole. However, given the known QT prolongation risk associated with astemizole, caution is recommended.

Odefsey (rilpivirine, 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 atazanavir would be possible from a pharmacokinetic standpoint. Atazanavir may increase rilpivirine concentrations, though not to a clinically relevant extent. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for rilpivirine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir. Tenofovir alafenamide is dosed 25 mg in Odefsey whereas the recommended dose of tenofovir alafenamide is 10 mg with P-gp inhibitors such as atazanavir, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Odefsey (rilpivirine, 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 atazanavir/cobicistat would be possible from a pharmacokinetic standpoint. Atazanavir/cobicistat may increase rilpivirine concentrations but not to a clinically relevant extent. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for rilpivirine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir/cobicistat. Tenofovir alafenamide is dosed 25 mg in Odefsey whereas the recommended dose of tenofovir alafenamide is 10 mg with P-gp inhibitors such as atazanavir/cobicistat, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Odefsey (rilpivirine, 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 atazanavir/ritonavir would be possible from a pharmacokinetic standpoint. Atazanavir/ritonavir may increase rilpivirine concentrations but not to a clinically relevant extent. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for atazanavir; possible risk for rilpivirine). Although the product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval, there is no anticipated increased risk of QT prolongation when combining these drugs. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with atazanavir/ritonavir. Tenofovir alafenamide is dosed 25 mg in Odefsey whereas the recommended dose of tenofovir alafenamide is 10 mg with P-gp inhibitors such as atazanavir/ritonavir, 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 as atenolol is mainly eliminated unchanged in the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of rilpivirine (150 mg once daily) and atorvastatin (40 mg once daily) decreased rilpivirine Cmax, AUC and Cmin by 9%, 10% and 10%, respectively. Atorvastatin Cmax and AUC increased by 35% and 4%; Cmin decreased by 15%. Cmax, AUC and Cmin of 2-hydroxy atorvastatin increased by 58%, 39% and 32%, whilst Cmax and AUC of 4-hydroxy atorvastatin increased by 28% and 23%. No dose adjustment is needed for either drug. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.] Emtricitabine and tenofovir alafenamide do not interact with atorvastatin 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. Rilpivirine, 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 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 rilpivirine, 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Azathioprine is converted to 6-mercaptopurine which is metabolized analogously to natural purines. Rilpivirine, emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a 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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with beclometasone metabolism. 

Coadministration has not been studied. Bedaquiline is metabolised by CYP3A4, but rilpivirine, emtricitabine and tenofovir alafenamide are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with bedaquiline. However, bedaquiline has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website therefore caution is recommended. When bedaquiline is coadministered with other medicinal products that prolong the QTc interval, an additive or synergistic effect on QT prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including frequent electrocardiogram assessment is recommended. There are no clinical data on the safety and efficacy of bedaquiline when co-administered 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 relevant drug interaction is unlikely in the range of observed clinical concentrations with emtricitabine and tenofovir derived from tenofovir alafenamide. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes and therefore is unlikely to impact rilpivirine.

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 pharmacokinetic interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and CYP3A4. Rilpivirine, emtricitabine and tenofovir alafenamide are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with bepridil. However, given the known QT prolongation risk associated with bepridil, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a 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. Coadministration could significantly decrease rilpivirine concentrations particularly if betamethasone is administered orally or intravenously at high doses or for a long duration, in which case coadministration should be avoided. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with betamethasone metabolism. 

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

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 rilpivirine exposure. Perform TDM of rilpivirine if available. Emtricitabine and tenofovir alafenamide do not interfere with bexarotene 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. 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. 

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) and Odefsey (rilpivirine, 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.

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. 

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir are not expected to significantly interfere with bisoprolol elimination. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect on rilpivirine, emtricitabine or tenofovir alafenamide is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate) or digoxin (a P-gp substrate).

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase, and two thirds 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 pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent CYP1A2, 2D6 and 2C9. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. In addition, a clinically relevant effect on rilpivirine concentrations is unlikely as bortezomib is a weak inhibitor of CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with bortezomib metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with bortezomib. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Bortezomib has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Bosentan could potentially decrease rilpivirine exposure. Patients should be monitored carefully regarding their HIV infection. Bosentan does not impact 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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this bromazepam metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with budesonide metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is predominantly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. In addition, 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). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Rilpivirine at a dose of 25 mg once daily does not inhibit or induce CYPs or UGTs. 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. Bupropion is primarily metabolized by CYP2B6. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with buspirone metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolized by CYP1A2. Rilpivirine, 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.

Coadministration has not been studied. Calcium is eliminated through faeces, urine and sweat. Coadministration with calcium supplements containing calcium carbonate may decrease rilpivirine concentrations due to reduced absorption due to gastric pH increase. Calcium supplements containing calcium carbonate should be administered at least 2 h before or 4 h after rilpivirine. Calcium carbonate is unlikely to interfere with emtricitabine and tenofovir alafenamide absorption.

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 rilpivirine, 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 or intestinal transporters in the range of doses in clinical use. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolized by CYP enzymes.

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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Rilpivirine 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. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with capecitabine. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Capecitabine has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Capreomycin is predominantly excreted via the kidneys as unchanged drug. As capreomycin may potentially compete with emtricitabine for renal elimination transport mechanisms, levels of either drug may increase. Renal function should be monitored as clinically appropriate. 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. In addition, rilpivirine does not interfere with capreomycin renal elimination.

Coadministration has not been studied. Captopril is largely excreted in the urine by OAT1. 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. Rilpivirine does not interfere with captopril elimination.

Coadministration is contraindicated as it may cause significant decreases in the plasma concentrations of rilpivirine (induction of CYP3A4) and tenofovir alafenamide (induction of P-glycoprotein).

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 rilpivirine 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. Rilpivirine and emtricitabine do not interfere with carboplatin elimination pathway. 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 additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. 

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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied. Cat’s claw is an 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. Similarly, concentrations of rilpivirine may also increase, but to a limited extent and no dose adjustment is required for rilpivirine. No effect on emtricitabine or tenofovir alafenamide is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Rilpivirine does not interfere with cefalexin renal elimination. 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. Rilpivirine does not interfere with cefazolin renal elimination. OAT3 does not play a major role in tenofovir and emtricitabine renal 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. Rilpivirine does not interfere with cefixime renal elimination.

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. Rilpivirine does not interfere with cefotaxime renal elimination. Emtricitabine and tenofovir derived from tenofovir alafenamide are eliminated by other renal transporters. 

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. In vitro data indicate that cetirizine inhibits OCT2. Rilpivirine is unlikely to significantly inhibit cetirizine renal elimination. 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 UGTs (in particular UGT2B7) which are not affected by rilpivirine; emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. Rilpivirine is metabolized by CYP3A4. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 but this is unlikely to cause a clinically significant interaction with rilpivirine.

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 but does not inhibit cytochromes and therefore does not impact rilpivirine exposure. Emtricitabine and tenofovir alafenamide do not interfere with chlordiazepoxide metabolic pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver by CYP2D6. Rilpivirine, emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to interact with chlorphenamine. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with chlorpromazine. However, given the known QT prolongation risk associated with chlorpromazine, caution is recommended.

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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with ciclesonide metabolism.

Coadministration has not been studied and is not recommended in the European Summary of Product Characteristics. Rilpivirine is metabolised mainly by CYP3A4 and is transported by OATP1B1. Ciclosporin inhibits CYP3A4 and OATP1B1 and is a potent inhibitor of P-gp. Coadministration could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. Although, ciclosporin can impair renal function this is unlikely to be problematic as tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. However, coadministration is expected to increase plasma concentrations of tenofovir alafenamide due to inhibition of P-gp. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Odefsey 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 the metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1, OAT3. Rilpivirine does not interfere with cidofovir elimination. Tenofovir alafenamide is unlikely to compete with cidofovir for renal transporters or to be of concern when coadministered with nephrotoxic agents such as cidofovir 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. Cilazapril is mainly eliminated unchanged by the kidneys. 

Coadministration has not been studied. Use with caution as coadministration may decrease rilpivirine concentrations. Only H2-receptor antagonists that can be dosed once daily should be used. Administer at least 12 h before or 4 h after Odefsey. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. No interaction is expected with tenofovir derived from tenofovir alafenamide or emtricitabine. 

Coadministration has not been studied. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolized and partially cleared through the bile and intestine. Rilpivirine, emtricitabine and tenofovir derived from tenofovir alafenamide do not interfere with ciprofloxacin elimination. Ciprofloxacin is a moderate inhibitor of CYP3A4 and could increase rilpivirine exposure but to a limited extent and no dose adjustment is required for rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with ciprofloxacin. However, given the known QT prolongation risk associated with ciprofloxacin, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cisapride is metabolized by CYP3A4. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with cisapride metabolism. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cisapride. However, given the known QT prolongation risk associated with cisapride, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a 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. Rilpivirine does not interfere with cisplatin elimination pathway. Tenofovir alafenamide is unlikely to cause a pharmacokinetic interaction as it is eliminated renally by other renal transporters. However, cisplatin and emtricitabine could potentially compete for MATE1 which could slow their elimination. Close monitoring of renal function is recommended. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with citalopram. However, given the known QT prolongation risk associated with citalopram, caution is recommended.

Coadministration has not been studied and is not recommended. Where possible, alternatives such as azithromycin should be considered. Clarithromycin may increase rilpivirine concentrations due to inhibition of CYP3A4. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clarithromycin. However, given the known QT prolongation risk associated with clarithromycin, caution is recommended. In addition, 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. 

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with this 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 rilpivirine exposure although to a limited extent. Emtricitabine and tenofovir alafenamide do not interfere with these metabolic pathways.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Rilpivirine does not interfere with clofibrate elimination.

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. Renal excretion of clomifene is thought to account for approximately 8% of an oral dose therefore there is little potential for an interaction with rilpivirine, emtricitabine and tenofovir derived from tenofovir alafenamide. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYP3A4, 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. Rilpivirine, 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. Clonazepam is metabolized by CYP3A4 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with clonazepam 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). 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. Rilpivirine does not interfere with clonidine elimination.

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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. There is little potential for significant interactions with rilpivirine or emtricitabine and tenofovir (derived from tenofovir alafenamide) via competition for renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with clozapine. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Clozapine has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cocaine is metabolized by several pathways (CYP and non CYP mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with cocaine. However, given the known QT prolongation risk associated with cocaine, caution is recommended.

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. Rilpivirine at a dose of 25 mg once daily does not inhibit or induce CYPs or UGTs. 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 colchicine is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with colchicine metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with vitamin D when given with calcium or in a multivitamin preparation. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. Significant interactions are not expected with rilpivirine, emtricitabine or tenofovir alafenamide.

Coadministration has not been studied. Several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, and could potentially increase the exposure of rilpivirine, but to a limited extent and no dose adjustment is required for rilpivirine. Piperine, a component of Piper cubeba, inhibits intestinal P-gp. Tenofovir alafenamide is a substrate of P-gp and absorption of tenofovir alafenamide could potentially increase. No effect on emtricitabine exposure is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with cyanocobalamin when given alone or in multivitamins. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with cyclophosphamide 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 and does not inhibit CYPs when used at doses lower than 100 mg three times per day. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Cytarabine is metabolized by cytidine deaminase. Rilpivirine, emtricitabine and tenofovir alafenamide do not interfere with this metabolic pathway. 

Coadministration has not been studied. Increases in dabigatran plasma concentrations due to inhibition of intestinal P-gp cannot be excluded.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. In vitro data indicate that dacarbazine is a substrate of the renal transporter OAT1. However, emtricitabine and tenofovir are unlikely to compete for active renal transport as emtricitabine is eliminated by different renal transporters and tenofovir alafenamide results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6 but rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir do not interfere with darifenacin metabolism.

Odefsey (rilpivirine, 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. Darunavir/cobicistat is expected to increase rilpivirine concentrations, but the expected increase in rilpivirine concentrations is not considered clinically relevant and no dose adjustment is required. Coadministration with emtricitabine/tenofovir alafenamide has not been studied, but no interaction with emtricitabine is expected. Coadministration with darunavir/cobicistat (800/150 mg once daily) and tenofovir alafenamide alone (25 mg once daily) increased tenofovir AUC and Cmax by 224% and 216%, respectively. Tenofovir alafenamide is dosed 25 mg in Odefsey whereas the recommended dose of tenofovir alafenamide is 10 mg with P-gp inhibitors such as darunavir/cobicistat, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) and Odefsey (rilpivirine, 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.

Odefsey (rilpivirine, 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 darunavir/ritonavir would be possible from a pharmacokinetic standpoint. No dose adjustment is required when rilpivirine is co-administered with darunavir/ritonavir. Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) increased rilpivirine Cmax by 79% and AUC and Cmin increased by 2.3- and 2.78-fold, respectively. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively. Coadministration of darunavir/ritonavir (800/100 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 105% and 142% (n-10). No significant effects were observed on darunavir pharmacokinetics relative to historical controls. Tenofovir alafenamide is dosed 25 mg in Odefsey whereas the recommended dose of tenofovir alafenamide is 10 mg with P-gp inhibitors such as darunavir/ritonavir, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. Dasatinib is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Dasatinib is a weak inhibitor of CYP3A4 and therefore could potentially increase rilpivirine exposure although to a moderate extent. Emtricitabine and tenofovir alafenamide do not interact with dasatinib metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with dasatinib. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. An in vitro study has shown that daunorubicin was able to inhibit metabolism mediated by CYP3A4, but was unlikely to cause clinically significant drug interactions via this mechanism. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with daunorubicin metabolic pathway. However, damage to the myocardium is one of the major risks of daunorubicin treatment and may include: dose-independent supraventricular arrhythmias (sinus tachycardia, premature ventricular contractions, AV-block) and/or non-specific ECG abnormalities. 

Coadministration has not been studied. 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. No pharmacokinetic interaction is expected as rilpivirine, emtricitabine and tenofovir alafenamide do not affect CYP enzymes. However, QTc prolongation has been reported with delamanid (and is very closely correlated with the metabolite DM-6705). Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with delamanid. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Delamanid has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway.

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 pharmacokinetic interaction is unlikely as desipramine is metabolized by CYP2D6. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with desipramine. However, the product labels for rilpivirine indicate that rilpivirine/emtricitabine/tenofovir alafenamide should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics. Emtricitabine and tenofovir alafenamide do not interact with the desogestrel or ethinylestradiol metabolic pathways.

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 which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with desogestrel 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). Rilpivirine, 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. Dextropropoxyphene is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. 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). Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. 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. A clinically significant interaction is not expected with tenofovir alafenamide which results in 90% lower systemic levels of tenofovir compared to tenofovir-DF. Also, there is little potential for interaction with emtricitabine or rilpivirine. 

Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of digoxin and rilpivirine had no significant effect on digoxin pharmacokinetics. No effect is expected on emtricitabine or tenofovir alafenamide as 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 undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Rilpivirine at a dose of 25 mg once daily does not inhibit or induce CYPs or UGTs. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied. Dihydroergotamine is a substrate and inhibitor of CYP3A4 and could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. Emtricitabine and tenofovir alafenamide do not interact with dihydroergotamine elimination.

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 metabolized by CYP3A4 and CYP2D6. Diltiazem is an inhibitor of CYP3A4 and could potentially increase rilpivirine exposure, but to a limited extent and no dose adjustment is required for rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with diltiazem. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Diltiazem has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. 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. Diphenhydramine is mainly metabolized by CYP2D6. Rilpivirine, 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. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Rilpivirine, emtricitabine and tenofovir alafenamide are unlikely to interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. In vitro data suggest that disopyramide weakly inhibits the renal transporter OCT2 in rats. Rilpivirine, emtricitabine and tenofovir derived from tenofovir alafenamide are not transported by OCT2 and therefore are unlikely to be affected by disopyramide. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with disopyramide. However, given the known QT prolongation risk associated with disopyramide, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a 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. 

Coadministration has not been studied. Some European product labels for docetaxel warn in vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which are metabolised by cytochrome P450 3A (and thus may inhibit the enzyme competitively). As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction. Emtricitabine and tenofovir alafenamide are not expected to interfere with docetaxel metabolism. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as dofetilide is mainly excreted unchanged in urine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with dofetilide. However, given the known QT prolongation risk associated with dofetilide, caution is recommended.

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

Odefsey (rilpivirine, 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 dolutegravir would be possible from a pharmacokinetic standpoint. No clinically relevant drug-drug interaction is expected between dolutegravir and rilpivirine, emtricitabine or tenofovir alafenamide. Coadministration of dolutegravir (50 mg once daily) and rilpivirine (25 mg once daily) increased dolutegravir Cmax, AUC and Ctrough by 13%, 12% and 22%, respectively. Rilpivirine Cmax, AUC and Ctrough increased by 10%, 6% and 21%, respectively. Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls.

Triumeq (dolutegravir, abacavir, lamivudine) and Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be co-administered with other antiretroviral medicinal products. Furthermore, 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.

Dovato (dolutegravir/lamivudine) and Odefsey (rilpivirine, 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.

Juluca (dolutegravir/rilpivirine) and Odefsey (rilpivirine, 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 rilpivirine and should not be administered with additional rilpivirine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with domperidone metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with domperidone. However, given the known QT prolongation risk associated with domperidone, caution is recommended.

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. There is little potential for dopamine to affect disposition of antiretrovirals, or to be affected if co-administered with antiretrovirals.

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with another NNRTI.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Odefsey (rilpivirine, 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. 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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

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

Coadministration 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 therefore little potential for a clinically significant interaction with rilpivirine or with emtricitabine and tenofovir (derived from tenofovir alafenamide) via competition for renal elimination transport mechanisms. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Droloxifene is mainly glucuronidated. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with droloxifene 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with dronabinol metabolic pathway. 

Coadministration with a drospirenone-containing combined oral contraceptive (COC) 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. Ethinylestradiol is mainly metabolized by hydroxylation. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics. Emtricitabine and tenofovir alafenamide do not interact with the drospirenone or ethinylestradiol metabolic pathways.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied. Dulaglutide is degraded by general protein catabolism pathways therefore no metabolic interaction is expected. Dulaglutide delays gastric emptying but interaction studies showed no clinically significant effect on the absorption of concomitantly orally administered drugs. No clinically significant interaction is expected with emtricitabine and tenofovir alafenamide. However, caution is needed when coadministering rilpivirine and GLP-1 agonists such as dulaglutide due to their potential to inhibit gastric secretion and thereby reduce the absorption of rilpivirine. Consider monitoring virological response after initiating dulaglutide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Rilpivirine, 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. Dutasteride is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this 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). Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this 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 rilpivirine plasma concentrations. Echinacea is unlikely to affect emtricitabine and tenofovir alafenamide exposure. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolized mainly by CYP2D6. Rilpivirine, 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. Edoxaban is a substrate for P-gp but rilpivirine does not inhibit or induce P-gp. In addition emtricitabine and tenofovir alafenamide are unlikely to interfere with edoxaban elimination.

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be co-administered with other antiretroviral medicinal products. In addition, efavirenz could potentially decrease rilpivirine exposure and thereby result in loss of efficacy. Furthermore, rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with efavirenz. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Efavirenz has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Eflornithine 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 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. Rilpivirine is unlikely to significantly inhibit eflornithine renal elimination.

Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied. Coadministration of rilpivirine (25 mg daily) and elbasvir + grazoprevir (50 + 200 mg once daily) had no clinically meaningful effect on exposures of grazoprevir, elbasvir, or rilpivirine. No dose adjustments are required. Coadministration of rilpivirine (25 mg once daily) and elbasvir + grazoprevir (50 + 200 mg once daily) to 19 subjects increased elbasvir AUC, Cmax and C24 by 7%, 7% and 4%, respectively; grazoprevir AUC and Cmax decreased by 2% and 3%, with no change in C24. Rilpivirine AUC, Cmax and Ctrough increased by 13%, 7% and 16%, respectively. Emtricitabine and tenofovir alafenamide do not interfere with elbasvir/grazoprevir elimination.

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). Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) and Odefsey (rilpivirine, 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.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) and Odefsey (rilpivirine, 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, 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. 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. Rilpivirine is unlikely to affect the metabolism of empagliflozin and empagliflozin is unlikely to affect rilpivirine concentrations as it does not inhibit or induce CYPs and does not inhibit UGTs. 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.

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) contains emtricitabine and should not be administered with additional emtricitabine.

Odefsey (rilpivirine, 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.

Odefsey (rilpivirine, 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, Odefsey 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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enflurane is predominantly metabolized by CYP2E1. Rilpivirine, 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. 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 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. Rilpivirine is unlikely to significantly inhibit entecavir renal elimination. Emtricitabine and tenofovir alafenamide are unlikely to significantly interact with entecavir. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2. Rilpivirine is unlikely to significantly inhibit ephedrine elimination via inhibition of OCT2. 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 pharmacokinetic interaction is unlikely as epirubicin is glucuronidated by UGT2B7. Emtricitabine and tenofovir alafenamide do not interfere with epirubicin metabolic pathway. Epirubicin may lead to cardiotoxicity consisting of tachycardia and/or ECG abnormalities. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with epirubicin. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Epirubicin has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. 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, but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied. Ergotamine is a substrate and inhibitor of CYP3A4 and could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine. Emtricitabine and tenofovir alafenamide do not interact with ergotamine elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Erlotinib is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with erlotinib metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant drug interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role. 

Coadministration has not been studied. Emtricitabine and tenofovir alafenamide (the prodrug of tenofovir) are unlikely to be impacted by erythromycin (erythromycin did not alter P-gp mediated efflux of digoxin, a P-gp substrate). Erythromycin is considered to be a moderate inhibitor of CYP3A4 and may increase rilpivirine concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur with erythromycin. However, given the known QT prolongation risk associated with erythromycin, caution is recommended. Consider alternatives such as azithromycin. Note, the European Summary of Product Characteristics for Odefsey mentions a potential increase in the absorption of tenofovir alafenamide via inhibition of intestinal P-gp.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with escitalopram. However, given the known QT prolongation risk associated with escitalopram, caution is recommended.

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. Eslicarbazepine was shown to reduce simvastatin (CYP3A4 substrate) exposure by 50%. A similar effect is expected on rilpivirine, 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 is contraindicated as significant decreases in rilpivirine plasma concentrations may occur.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with estazolam 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with the estradiol metabolic pathways.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with estramustine metabolic 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 rilpivirine/emtricitabine/tenofovir alafenamide has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and an oral contraceptive containing ethinylestradiol/norethindrone (0.035/1.0 mg once daily) had no effect on rilpivirine Cmax, AUC and Cmin. Ethinylestradiol Cmax, AUC and Cmin increased by 17%, 14% and 9%: norethisterone Cmax, AUC and Cmin decreased by 6%, 11% and 1%. Coadministration of ethinylestradiol (0.025 mg once daily), norgestimate (0.180/0.215/0.250 mg once daily) and emtricitabine/tenofovir alafenamide (200/25 mg once daily) had no effect on the AUC, Cmin and Cmax of norelgestromin, norgestrel or ethinylestradiol. No dose adjustment is required. No dose adjustment is needed for any of the drugs. Emtricitabine and tenofovir alafenamide do not interact with ethinylestradiol metabolic pathway. 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 metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver with animal studies suggesting involvement of flavin-containing monooxygenases. Rilpivirine, 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. Ethosuximide is mainly oxidized by CYP3A4 and does not induce cytochromes. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with ethosuximide 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 rilpivirine, emtricitabine and tenofovir alafenamide do not inhibit or induce drug metabolizing enzymes.

Coadministration of rilpivirine/emtricitabine/tenofovir alafenamide with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of an etonogestrel-containing progestogen-only implant (68 mg) in HIV-positive women on a rilpivirine-based regimen did not significantly alter etonogestrel concentrations (18% increase at week 24; 15% decrease at week 48) compared to HIV-negative women receiving the same contraceptive in the absence of antiretroviral therapy. No interaction is expected with emtricitabine and tenofovir alafenamide. The etonogestrel implant represents a suitable contraceptive option for women receiving rilpivirine-based antiretroviral regimens.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with the etonogestrel or ethinylestradiol metabolic pathways.

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. Rilpivirine at a dose of 25 mg once daily does not inhibit or induce CYPs or UGTs. Emtricitabine and tenofovir alafenamide do not interact with this etoposide metabolism. 

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be co-administered with other antiretroviral medicinal products. Furthermore, etravirine could potentially decrease rilpivirine exposure and thereby result in loss of efficacy.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eucalyptus is only a weak inhibitor of CYP3A4 and is unlikely to impact the exposure of rilpivirine. There is no evidence to suggest that eucalyptus impacts UGTs or P-gp and therefore is unlikely to impact tenofovir alafenamide absorption. No effect on emtricitabine is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Everolimus is mainly metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with the everolimus 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with exemestane metabolic pathway. 

Coadministration has not been studied. Exenatide is primarily eliminated by glomerular filtration therefore no interaction is expected at the level of drug elimination. However, caution is needed when coadministering rilpivirine and GLP-1 agonists such as exenatide due to their potential to inhibit gastric secretion and thereby reduce the absorption of rilpivirine. Furthermore, exenatide has the potential to slow gastric emptying. Consider taking rilpivirine 4 hours before the GLP-1 agonist.

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. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied but based on 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. Rilpivirine 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 with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied. Use with caution as coadministration may decrease rilpivirine concentrations. Only H2-receptor antagonists that can be dosed once daily should be used. Administer at least 12 h before or 4 h after Odefsey. Coadministration of rilpivirine (150 mg single dose) and famotidine (40 mg single dose) administered 2 hours before rilpivirine, decreased rilpivirine Cmax and AUC by 85% and 76%. Coadministration of famotidine 12 hours before rilpivirine decreased rilpivirine Cmax and AUC by 1% and 9%; coadministration of famotidine 4 hours after rilpivirine increased rilpivirine Cmax and AUC by 21% and 13%. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.] Famotidine does not impair emtricitabine and tenofovir alafenamide absorption. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with felodipine 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. 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. Rilpivirine does not interfere with fenofibrate elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir do not interfere with fesoterodine metabolism.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Rilpivirine, emtricitabine and tenofovir alafenamide are not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with flecainide. However, given the known QT prolongation risk associated with flecainide, caution is recommended.

Coadministration has not been studied. Flibanserin is primarily metabolized by CYP3A4 and has been shown to moderately increase the exposure of simvastatin, a CYP3A4 substrate. Flibanserin could potentially increase rilpivirine exposure, but to a limited extent and no dose adjustment is required for rilpivirine. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally, partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily). Flucloxacillin could decrease rilpivirine concentrations to a significant extent. Use with caution particularly if flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days). 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 may increase plasma concentrations of rilpivirine (inhibition of CYP3A4) and tenofovir alafenamide (inhibition of P-gp). The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Odefsey 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, coadministration is not recommended in the European Summary of Product Characteristics due to the increase in rilpivirine and tenofovir alafenamide concentrations, whereas the US Prescribing Information recommends no dose adjustment for Odefsey when coadministered with azole antifungal agents and recommends clinical monitoring for breakthrough fungal infections when azole antifungals are coadministered with Odefsey. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with fluconazole. However, given the known QT prolongation risk associated with fluconazole, caution is recommended.

Coadministration has not been studied. 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. Rilpivirine does not interfere with flucytosine elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic 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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide are unlikely to interact with fludrocortisone. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Rilpivirine, 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 2C19. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interfere with flunitrazepam metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug 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. Rilpivirine 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. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with fluorouracil. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Fluorouracil has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by 2C19 and 3A4 to form norfluoxetine. Rilpivirine, emtricitabine and tenofovir do not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. However, rilpivirine should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval. Fluphenazine may prolong the QT interval and some European product labels have advised against concurrent use of drugs that prolong the QT interval.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. 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. Fluticasone is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide are unlikely to interact with fluticasone. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as fluvastatin is mainly metabolized by CYP2C9. Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Rilpivirine, 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. 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 but based on metabolism and clearance a clinically significant interaction is unlikely when folic acid is administered in a multivitamin preparation. 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 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 pharmacokinetic interaction is unlikely. Formestane undergoes reductive metabolism by hepatic hydroxysteroid dehydrogenase and glucuronidation. 

Coadministration has not been studied. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction is low. Emtricitabine and tenofovir alafenamide do not interfere with formoterol elimination. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with formoterol. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Formoterol may induce prolongation of the QT interval and the product label for formoterol advises caution in patients treated with drugs affecting the QT interval.

Coadministration 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. Rilpivirine and emtricitabine do not interfere with foscarnet elimination. 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. Dose Descovy according to the concomitant antiretroviral.

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). 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. Rilpivirine does not interfere with furosemide elimination.

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. Rilpivirine 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%. Similarly, concentrations of rilpivirine could be decreased via induction of CYP3A4 and/or P-gp. In addition, 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. No effect on emtricitabine is expected as its metabolism is not CYP-mediated. 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 2D6. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with gefitinib 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. Rilpivirine, 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. Rilpivirine, 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. Gentamicin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with rilpivirine or emtricitabine. There is little potential for interaction with tenofovir alafenamide via competition for active renal transport mechanisms. 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. Ethinylestradiol is mainly metabolized by hydroxylation. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Compared to historical controls, coadministration of rilpivirine (25 mg once daily) and a COC containing ethinylestradiol/norethindrone had no significant effect on rilpivirine or ethinylestradiol pharmacokinetics. Emtricitabine and tenofovir alafenamide do not interact with the gestodene 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 but rilpivirine is unlikely to affect gamma hydroxybutyrate metabolism. Similarly, emtricitabine and tenofovir alafenamide do not interfere with gamma-hydroxybutyrate elimination.

Coadministration has not been studied. Gingerols moderately inhibit CYP3A4 in vitro and could potentially increase the exposure of rilpivirine, but to a limited extent and no dose adjustment is required for rilpivirine. No effect on absorption of tenofovir alafenamide is expected as gingerols are unlikely to cause clinically significant inhibition of P-gp. No effect on emtricitabine exposure is expected.

Coadministration has not been studied. Inconsistent findings have been reported from clinical drug interaction studies with CYP3A4 substrates, but could reduce exposure of non-boosted protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Use with caution and monitor patients carefully regarding their HIV infection. Ginkgo is unlikely to affect emtricitabine and tenofovir alafenamide exposure. 

Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of rilpivirine and glecaprevir/pibrentasvir increased rilpivirine Cmax, AUC and Cmin by 105%, 84% and 77%, respectively (n=12). This was deemed within safety limits. Studies performed with emtricitabine or tenofovir alafenamide showed no clinically significant interactions with glecaprevir/pibrentasvir. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with rilpivirine/emtricitabine/tenofovir alafenamide.

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. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with glibenclamide 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. Rilpivirine, 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. Glimepiride is mainly metabolized by CYP2C9. Rilpivirine, 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. Rilpivirine, 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. 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. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Granisetron is metabolized by CYP3A4. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Emtricitabine and tenofovir alafenamide do not interact with granisetron metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with granisetron. However, the product labels for rilpivirine/emtricitabine/tenofovir alafenamide indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Granisetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but may increase rilpivirine concentrations through inhibition of CYP3A4 and possibly P-gp. The magnitude of this potential interaction is difficult to predict as the effect of grapefruit juice is concentration, dose and preparation dependent and varies widely across brands. No a priori dose adjustment is recommended for rilpivirine. Grapefruit juice is unlikely to affect emtricitabine and tenofovir alafenamide exposure. 

Coadministration has not been studied. Griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels (and therefore reduce the efficacy) of concomitantly administered medicinal products that are metabolized by CYP3A4, such as rilpivirine. As less than 1% of a griseofulvin dose is excreted unchanged via the kidneys, emtricitabine and tenofovir derived from tenofovir alafenamide are unlikely to interact. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4 but rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with halofantrine. However, given the known QT prolongation risk associated with halofantrine, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Rilpivirine, emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with haloperidol. However, given the known QT prolongation risk associated with haloperidol, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Halothane undergoes both oxidative and reductive metabolism by cytochromes. Rilpivirine, 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. Heparin is thought to be eliminated via the reticuloendothelial system.