Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with abacavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. Rilpivirine does not interfere with acetazolamide elimination.

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). There is therefore little potential for interaction with rilpivirine via modulation of, or competition for metabolic or elimination pathways.

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. Therapeutic drug monitoring of rilpivirine is recommended.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system.

Coadministration has not been studied but based on metabolism and clearance, as well as limited drug-drug interaction data, a clinically significant interaction is unlikely. Rilpivirine is metabolized primarily by CYP3A with potential contribution from CYP2C19. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcuronium is predominantly excreted unchanged via the kidneys. 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 pharmacokinetic interaction is unlikely. Alfuzosin is metabolized mainly 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. 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. 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 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.

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 does not interfere with ambrisentan metabolism.

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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amiodarone is metabolized by CYP2C8 and CYP3A4; in vitro data suggest it is only a weak inhibitor of 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. 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.

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 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.

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

Coadministration has not been studied and may decrease rilpivirine concentrations. Antacids should be administered at least 2 h before or 4 h after rilpivirine.

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.

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 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. 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. Aprepitant could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine.

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.

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. A clinically relevant effect on rilpivirine concentrations is unlikely as aripiprazole 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 aripiprazole. 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. 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 on artemisins 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with vitamin C when given alone or in multivitamins. 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. There is therefore little potential for interaction with rilpivirine via modulation of, or competition for metabolic pathways.

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 (mainly CYP1A2, with minor contributions from 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. A clinically relevant effect on rilpivirine concentrations is unlikely as asenapine 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 asenapine. 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. Asenapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

This interaction has not been studied. Based on the metabolic profiles of both drugs, there is little potential for pharmacokinetic interaction. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial system.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6).

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.

Coadministration with atazanavir has not been studied but may increase rilpivirine concentrations. No dose adjustment of rilpivirine is required as the expected increase in rilpivirine concentrations is not considered clinically relevant. Rilpivirine is not expected to affect concentrations of atazanavir. 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.

Coadministration has not been studied. Coadministration is expected to increase rilpivirine concentrations but is not expected to affect cobicistat concentrations. No dose adjustment of rilpivirine is required when atazanavir/cobicistat is used concomitantly with rilpivirine as the expected increase in rilpivirine concentrations is not considered clinically relevant. Rilpivirine is not expected to affect concentrations of atazanavir. 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.

Coadministration with atazanavir/ritonavir has not been studied but may increase rilpivirine concentrations. No dose adjustment of rilpivirine is required as the expected increase in rilpivirine concentrations is not considered clinically relevant. Rilpivirine is not expected to affect concentrations of atazanavir. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

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.]

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

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. 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. Bedaquiline is metabolised 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 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 eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes.

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

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 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 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. 

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and is not recommended in the Biktarvy product label. However, in specific clinical situations where an intensification of HIV treatment is needed, the coadministration of rilpivirine would be possible from a pharmacokinetic standpoint.

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. No effect on rilpivirine 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 metabolism and clearance a pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent by CYPs 1A2, 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. A clinically relevant effect on rilpivirine concentrations is unlikely as bortezomib is a weak inhibitor of CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with bortezomib. 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. Bortezomib has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

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

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.

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.

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. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with capecitabine. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Capecitabine has a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Capreomycin is predominantly excreted via the kidneys as unchanged drug.

Coadministration is contraindicated as significant decreases in rilpivirine plasma concentrations may occur.

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

Coadministration has not been studied 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.

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Approximately 50% of the absorbed dose is excreted unchanged in the urine; there is no evidence of metabolism of cefixime in vivo. In vitro studies have shown that cefixime does not inhibit/induce major cytochrome P450 metabolic enzymes, and would not be expected to cause clinically significant interactions with other drugs, which are metabolized by CYP450 enzymes.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ceftazidime is predominantly eliminated unchanged via renal glomerular filtration.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ceftriaxone is eliminated mainly as unchanged drug; approximately 60% of the dose being excreted in the urine, almost exclusively 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. 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. Chloramphenicol is predominantly metabolised via UGTs (in particular UGT2B7) which are not affected by rilpivirine. 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 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 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 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 via CYP2D6.

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 does not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur 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. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Rilpivirine does not interact with ciclesonide metabolism.

Coadministration has not been studied. Rilpivirine is metabolised mainly by CYP3A4 and is transported by OATP1B1. Ciclosporin inhibits CYP3A4 and OATP1B1 and could potentially increase rilpivirine concentrations, but to a limited extent and no dose adjustment is required for rilpivirine.

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 rilpivirine.

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 does 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, 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 cisapride. However, given the known QT prolongation risk associated with cisapride, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). 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 citalopram. However, given the known QT prolongation risk associated with citalopram, caution is recommended.

Coadministration has not been studied but 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 clarithromycin. However, given the known QT prolongation risk associated with clarithromycin, caution is recommended. Consider alternatives such as azithromycin.

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.

Coadministration has not been studied. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Clofazimine is a moderate inhibitor of CYP3A4 and may increase rilpivirine concentrations but to a modest extent. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with clofazimine. However, the product labels for rilpivirine 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. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. 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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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.

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 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 clozapine. 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. 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 relevant drug 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.

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.

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.

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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.

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

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction.

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.

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.

Coadministration has not been studied. Coadministration of rilpivirine and darunavir/cobicistat is expected to increase the plasma concentration of rilpivirine. However since the expected increase in rilpivirine concentrations is not considered clinically relevant, no dose adjustment is required when coadministering rilpivirine with darunavir/cobicistat. 

Symtuza (darunavir, cobicistat, 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 rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration of rilpivirine and 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. No interaction is expected with rilpivirine and emtricitabine or tenofovir alafenamide.

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) was studied in 14 subjects. Rilpivirine Cmax increased 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. [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.]

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. 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 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.

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. 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 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. 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 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 pharmacokinetic interaction is unlikely as desipramine is metabolized by 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. 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 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.

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.

This interaction has not been studied. Based on limited data concerning the metabolism/elimination and toxicity profile of diethylcarbamazine, there is little potential for interaction with rilpivirine.

In a clinical study, coadministration of digoxin (0.5 mg single dose) and rilpivirine (25 mg once daily) had no significant effect on digoxin pharmacokinetics (Cmax increased by 6%, AUC decreased by 2%). No dose adjustment is required.

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Coadministration has not been studied. In vitro data suggest that diltiazem inhibits CYP3A4 and could potentially increase rilpivirine concentrations, 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.

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 does not inhibit or induce these UGTs.

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. 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 disopyramide. However, given the known QT prolongation risk associated with disopyramide, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely 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 is not expected to inhibit or induce CYP and UGT enzymes at clinically relevant concentrations. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but these are unlikely to occur with dolasetron. 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. Dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

No clinically significant pharmacokinetic interaction was observed between rilpivirine and dolutegravir. Coadministration of rilpivirine (25 mg once daily) and dolutegravir (50 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. No dosage adjustment is necessary. [Dolutegravir is available coformulated with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.]

Triumeq (dolutegravir, abacavir, lamivudine) is indicted 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 rilpivirine would be possible from a pharmacokinetic standpoint. No clinically significant pharmacokinetic interaction was observed between rilpivirine and dolutegravir. Coadministration of rilpivirine (25 mg once daily) and dolutegravir (50 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. No interaction is expected with abacavir or lamivudine.

Dovato (dolutegravir/lamivudine) 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 rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration of rilpivirine (25 mg once daily) and dolutegravir (50 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. No interaction is expected with lamivudine.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Juluca should not be taken with any other medicinal product containing rilpivirine, except in case of co-administration with rifabutin.

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. 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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. 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.

Doravirine should not be administered with another NNRTI.

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

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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. No significant metabolism of doxycycline occurs, it is cleared intact by renal and biliary mechanisms.

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.

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. 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. 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.

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. 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.

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.

Coadministration has not been studied and is not recommended as it may decrease rilpivirine concentrations. Combining two NNRTIs has not been shown to be beneficial. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Eflornithine is predominantly eliminated unchanged via the kidneys but rilpivirine is unlikely to significantly inhibit eflornithine renal elimination.

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.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infections. However, in specific clinical situations where an intensification of HIV treatment is needed, the coadministration of rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration is expected to increase rilpivirine concentrations however no dose adjustment is required.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration of rilpivirine would be possible from a pharmacokinetic standpoint. Coadministration is expected to increase rilpivirine concentrations however no dose adjustment is required.

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. 

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with emtricitabine.

Coadministration of rilpivirine (25 mg once daily) and tenofovir alafenamide (25 mg once daily) had no significant effect on the pharmacokinetics of rilpivirine and tenofovir alafenamide. The recommended dose of Descovy for HIV-1 treatment is 200/25 mg once daily.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of rilpivirine (150 mg once daily) and tenofovir-DF (300 mg once daily) decreased rilpivirine Cmax and Cmin by 4% and 1%, and increased AUC by 1%. Tenofovir Cmax, AUC and Cmin increased by 19%, 23% and 24%. No dose adjustment is necessary. [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.]

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ephedrine is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as epirubicin is glucuronidated by UGT2B7. 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.

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. 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.

Coadministration has not been studied and may increase rilpivirine concentration as erythromycin is considered to be a moderate inhibitor 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 erythromycin. However, given the known QT prolongation risk associated with erythromycin, caution is recommended.  Consider alternatives such as azithromycin.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. 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 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. 

Coadministration is contraindicated as significant decreases in rilpivirine plasma concentrations may occur.

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.

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%. No dose adjustment is needed for any of the drugs. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ethionamide is extensively metabolized in the liver, animal studies suggest involvement of flavin-containing monooxygenases. Ethionamide does not affect metabolism mediated by CYP450 enzymes in vitro.

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

Rilpivirine (25 mg once daily) had no significant effect on etonogestrel concentrations when administration of an etonogestrel-containing progestogen-only implant (68 mg) in HIV-positive women on a rilpivirine-based regimen (n=30) was compared to HIV-negative women receiving the same contraceptive in the absence of antiretroviral therapy (n=20). Etonogestrel concentrations in the rilpivirine group were not statistically different compared with the control group (18% increase at week 24; 15% decrease at week 48). These results suggest an 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.

Coadministration is not recommended as it may decrease rilpivirine concentrations. Combining two NNRTIs has not been shown to be beneficial.

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.

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.

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. 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.

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 rilpivirine. 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.]

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.

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 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 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.

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).

Coadministration has not been studied but may increase rilpivirine concentrations. No dose adjustment is required for rilpivirine when co-administered with azole antifungal agents, but clinical monitoring for breakthrough fungal infections is recommended when azole antifungals are co-administered with rilpivirine. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with fluconazole. However, given the known QT prolongation risk associated with fluconazole, caution is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Rilpivirine does not interact with flunisolide metabolism.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolized by CYP2D6 and 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. 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. Fluphenazine may prolong the QT interval and some European product labels have advised against concurrent use of drugs that prolong the QT interval.

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

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. Patients should be advised against the use of garlic supplements.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Gentamicin is predominantly eliminated unchanged via the kidneys.

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.

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.

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.

Coadministration of rilpivirine and glecaprevir/pibrentasvir increased rilpivirine Cmax, AUC and Cmin by 105%, 84% and 77%, respectively (n=24). This was deemed within safety limits and no dose adjustment is required when glecaprevir/pibrentasvir is coadministered with rilpivirine. There were no significant changes in the pharmacokinetics of glecaprevir or pibrentasvir. Glecaprevir Cmax, AUC and Ctrough decreased by 13%, 10% and 8%, respectively; pibrentasvir Cmax and AUC decreased by 3% and4%, and there was no change in Ctrough.

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.

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. 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 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.

This interaction 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 cytochrome P450 3A4, such as rilpivirine.

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 does not interact with this metabolic pathway. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur 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. Heparin is thought to be eliminated via the reticuloendothelial system.

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

This interaction has not been studied. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. There is little potential for clinically significant interactions with rilpivirine via these mechanisms.