Coadministration has not been studied, but no interaction is expected. Etravirine can be used without dose adjustment.

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. Acetazolamide is primarily excreted unchanged via the kidneys, there is therefore little potential for interaction with etravirine 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. 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 etravirine via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied but based on metabolic data there is little potential for pharmacokinetic interactions. 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. However coadministration of African potato with efavirenz in healthy volunteers did not result in significant pharmacokinetic changes. Similarly, no significant effect is expected on the pharmacokinetics of etravirine.

Coadministration has not been studied. In vitro studies have demonstrated that CYP3A4 is involved in formation of the active metabolite albendazole sulfoxide. When antiepileptics (phenytoin, carbamazepine and phenobarbital) were coadministered with albendazole, significantly reduced levels of the active metabolite albendazole sulfoxide were observed, apparently due to induction of CYP3A4. Similarly, coadministration with etravirine could reduce albendazole exposure; however, the clinical relevance is unknown as the antihelmintic action is thought to be mainly intra-intestinal.

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. Etravirine is metabolized by CYPs 3A4, 2C9 and 2C19. 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. Induction of CYP3A4 by etravirine is unlikely to affect albuvirtide, a peptide which is eliminated by catabolism to its constituent amino acids.

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

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. 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. 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. Etravirine induces UGT1A1 but this is not involved in ambrisentan glucuronidation. Furthermore, induction of CYP3A4 by etravirine is unlikely to significantly impact ambrisentan exposure as CYP3A4 does not play a major role in 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.

Concentrations of amiodarone may be decreased when coadministered with etravirine. Drug concentration monitoring is recommended, if available.

Coadministration has not been studied. Amodiaquine is metabolised mainly by CYP2C8 to N-desethylamodiaquine. Based on a drug-drug interaction study with nevirapine, a limited decrease in amodiaquine exposure cannot be excluded with etravirine. No a priori dosage adjustment is required.

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

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. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Etravirine could potentially decrease apixaban exposure resulting in diminished efficacy.

Coadministration has not been studied. Apomorphine is metabolized by several pathways that include mainly glucuronidation and sulfation and to a lesser extent N-demethylation. Although some NNRTIs have the potential to induce glucuronidation, the clinical relevance of such an interaction is unknown considering the numerous pathways contributing to apomorphine metabolism. No a priori dosage adjustment is required.

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. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Erythromycin (a strong CYP3A4 inhibitor) had no effect on argatroban pharmacokinetics and pharmacodynamics and it is unlikely that etravirine will significantly reduce argatroban exposure due to induction of CYP3A4.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Etravirine could potentially decrease aripiprazole concentrations. Monitor therapeutic effect and adjust aripiprazole dosage if needed. The European SPC advises doubling the aripiprazole dose when given with potent inducers of CYP3A4, such as efavirenz or nevirapine.

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 etravirine via modulation of, or competition for metabolic pathways.

Coadministration has not been studied. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). Etravirine could potentially decrease asenapine concentrations by induction of CYP3A4, although to a moderate extent. No a priori dosage adjustment is recommended.

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. Astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. Etravirine, an inducer of CYP3A4, could potentially decrease astemizole exposure. Monitor clinical effect.

Coadministration has not been studied and is not recommended. Coadministration of atazanavir alone (400 mg once daily) and etravirine decreased atazanavir Cmax, AUC and Cmin by 3%, 17% and 47%, respectively. Etravirine Cmax, AUC and Cmin increased by 47%, 50% and 58%, respectively, but this is not considered clinically relevant. Atazanavir should only be used with etravirine in the presence of low dose ritonavir.

Coadministration has not been studied and is not recommended. Coadministration of etravirine and cobicistat is expected to decrease atazanavir and cobicistat plasma concentrations due to induction of CYP3A4 by etravirine. This may lead to loss of therapeutic effect and possible development of resistance to atazanavir.

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and etravirine decreased atazanavir AUC, Cmin and Cmax by 14%, 38% and 3%, respectively. Etravirine AUC, Cmin and Cmax increased by 30%, 26% and 30%. The decrease in atazanavir Cmin is unlikely to be clinically significant and no dose adjustment is required.

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 had no significant effect on etravirine (Cmax decreased by 3%, and AUC and Cmin increased by 2% and 10%). Atorvastatin Cmax increased by 4% and AUC decreased by 37%; Cmax and AUC of 2-hydroxy atorvastatin increased by 76% and 27%. No dose adjustment of etravirine required. Given the decrease in atorvastatin exposure but the increase in exposure of an active metabolite, an a priori dose adjustment of atorvastatin might not needed when coadministered with etravirine. However, treatment with statins requires periodic monitoring of lipid values and the atorvastatin dose should be adjusted based on the clinical response.

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 etravirine via modulation of, or competition for metabolic pathways.

Coadministration has not been studied but is not recommended. Avanafil is primarily metabolized by CYP3A4 and concentrations (and efficacy) may decrease due to induction of CYP3A4 by etravirine.

Coadministration has not been studied, but no drug interactions are expected based on the biliary elimination pathway of azithromycin. No dose adjustments required.

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. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat. Benazeprilat is a substrate of UGTs (the specific UGTs have not been well described) and concentrations may decrease due to induction of UGTs by etravirine. Adjust benazepril dosage based on the clinical response.

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%), although the exact pathway is not known. It is unlikely that CYP enzymes are involved in this process and no transporter interactions have been described. 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. Bepridil is metabolised mainly by CYP2D6 and to a lesser extent by CYP3A4. Concentrations of bepridil may be decreased when coadministered with etravirine. Drug concentration monitoring is recommended, if available.

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. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Etravirine is a weak inhibitor of P-gp and therefore could increase the exposure of betrixaban although to a limited extent which unlikely to require a dose adjustment of betrixaban.

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 should not be administered with other antiretroviral products. In addition, etravirine is an inducer of CYP3A4 and is expected to decrease bictegravir exposure which may result in loss of therapeutic effect and development of resistance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although limited human data suggest biperiden undergoes hydroxylation in the liver, there are no known or documented interactions with other drugs that have an effect on metabolism or transport.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Etravirine could potentially decrease bisoprolol exposure, although to a moderate extent. No a priori dosage adjustment is required.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect on etravirine 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. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Etravirine, a CYP3A4 inducer, could potentially decrease bosentan exposure and the clinical effect of bosentan should be monitored.

Coadministration has not been studied. 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. Bromazepam does not inhibit CYP3A4. Etravirine could potentially decrease bromazepam concentrations although to a moderate extent. No a priori dosage adjustment is required.

Coadminsitration has not been studied. Bupivacaine is predominantly metabolized by CYP3A4. Etravirine may decrease levels of bupivacaine due to induction of CYP3A4 and potentially decrease its efficacy. The clinical relevance of this interaction is unknown.

No dose adjustments required, however, clinical monitoring for withdrawal symptoms is recommended. Maintenance therapy may need to be adjusted in some patients. Coadministration decreased buprenorphine Cmax, AUC and Cmin by 11%, 25% and 40%, respectively. Cmax of norbuprenorphine increased by 8%; AUC and Cmin decreased by 12% and 24%.

Coadministration has not been studied. Buspirone is metabolized by CYP3A4 but does not inhibit CYP3A4. Etravirine could potentially decrease buspirone concentrations. Monitor the clinical response and increase dosage of buspirone if needed.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 which are not affected by etravirine.

Coadministration has not been studied. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit or induce CYPs and therefore no effect is expected on etravirine. However, etravirine induces CYP3A4 which may decrease cannabidiol exposure. A careful dose increase in cannabidiol might be needed. In addition, a careful titration might be needed within the two weeks following cessation of etravirine.

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.

Etravirine should not be used in combination with carbamazepine as it is expected to decrease plasma concentrations of etravirine.

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. Carvedilol undergoes glucuronidation and additional metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Etravirine could potentially increase carvedilol concentrations via CYP2C9 inhibition or decrease carvedilol concentrations via induction of glucuronidation (UGT1A1). The net effect on carvedilol concentrations is difficult to predict but likely to be moderate in magnitude. No a priori dosage adjustment is required.

Coadministration has not been studied. Cat’s claw is a strong inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Similar increases would be expected for other CYP3A4 substrates, such as etravirine. Coadministration should be avoided.

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

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

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. Cefotaxime is predominantly eliminated unchanged via the kidneys.

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. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4. Coadministration of chloramphenicol may potentially increase levels of etravirine via this mechanism, increasing the risk of adverse events. The clinical significance of this interaction is unknown. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

Coadministration has not been studied. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Etravirine could potentially decrease chloroquine exposure due to induction CYP3A4, although to a moderate extent due to the multiple elimination pathways. No dosage adjustment is recommended but monitor the efficacy of the antimalarial.

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 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. Etravirine is unlikely to have clinically significant effect on ciclesonide metabolism.

Administer with caution. Plasma concentrations of ciclosporin may be decreased.

Etravirine can be coadministered with H2 receptor antagonists without dose adjustments.

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

Etravirine decreased clarithromycin Cmax, AUC and Cmin by 34%, 39% and 53%, but increased the Cmax, AUC and Cmin of the active metabolite (14-hydroxy clarithromycin) by 33%, 21% and 5%, respectively. Etravirine Cmax, AUC and Cmin increased by 46%, 42% and 46% respectively. Because 14-hydroxy clarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered. Consider alternatives to clarithromycin, such as azithromycin, for the treatment of MAC.

Coadministration has not been studied. Clindamycin is metabolized by CYP3A4 and some metabolites have antibacterial activity. Etravirine could potentially decrease clindamycin exposure which could impact efficacy.

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. Etravirine induces CYP3A4 which may decrease clobazam exposure but is a weak inhibitor of CYP2C19 which may increase clobazam exposure. The literature reports the case of a patient coadministered etravirine and clobazam who experienced clobazam toxicity. The authors hypothesized an increased exposure to N-desmethylclobazam due to induction of CYP3A4 and inhibition of CYP2C19 by etravirine. Monitor for clobazam toxicity and consider a dose reduction of clobazam if indicated. Clobazam is unlikely to affect etravirine. 

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. In vitro studies have suggested that CYP3A4 does not affect conversion of clomifene to its active metabolite, and that this transformation is likely to be mediated via CYP2D6. There is therefore little potential for etravirine to affect this metabolic pathway.

Coadministration has not been studied. 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. Etravirine could potentially decrease clomipramine concentrations but increase the formation of the active metabolite. The clinical relevance is unknown. Monitor clinical effect.

Clopidogrel is a prodrug and is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2. Etravirine may decrease activation of clopidogrel to its active metabolite and therefore impair clopidogrel effect. Coadministration is not recommended. Recurrent drug-eluting in-stent restenosis was described in a HIV patient treated concurrently with etravirine and clopidogrel, possibly due to inhibition of CYP2C19 and thereby decreased conversion of clopidogrel to its active metabolite.

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 etravirine could potentially decrease codeine exposure and increase the conversion to norcodeine, a metabolite that does not have analgesic properties. Codeine is converted to morphine (active metabolite) via CYP2D6 and inactivated to codeine-6-glucuronide via glucuronidation (major pathway) as well as to norcodeine via CYP3A4. No a priori dosage adjustment is recommended but monitoring the analgesic effect may be considered.

Colchicine is a substrate of CYP3A4 and P-gp. Coadministration with etravirine (an inducer of CYP3A4) has not been studied but may reduce colchicine concentrations. The clinical relevance of this potential interaction is unknown.

Coadministration has not been studied. No interaction is expected 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. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. These studies suggest that inducers of CYP3A4 (such as etravirine) may increase metabolism of vitamin D and therefore reduce its effect. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study.

Coadministration has not been studied. Piperine, a constituent of piper cubeba was shown to inhibit nevirapine metabolism, increasing nevirapine AUC and Cmin by 170% and 146%, respectively, however, the treatments were well tolerated. No a priori dose adjustment of etravirine is required.

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 and is difficult to predict. Cyclophosphamide is activated to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9, and 3A4. The inactivation pathway (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is mainly by CYP3A4. Etravirine could potentially increase the amount of drug converted to the inactive neurotoxic metabolite. Careful monitoring of cyclophosphamide efficacy and toxicity 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. Cycloserine is predominantly excreted renally via glomerular filtration.

Coadministration has not been studied. Cyproterone acetate is metabolized by CYP3A4 and concentrations may decrease due to induction of CYP3A4 by etravirine. A dose adjustment of cyproterone may be required.

Coadministration has not been studied. The prodrug of dabigatran is a substrate of P-gp. Etravirine is a weak inhibitor of P-gp and could potentially increase the exposure of dabigatran although to a limited extent. Use with caution.

Coadministration has not been studied but is expected to decrease daclatasvir concentrations due induction of CYP3A4 by etravirine. Coadministration is not recommended in the European product labels for etravirine and daclatasvir, but the US product labels advise to increase the daclatasvir dose to 90 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.

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 etravirine.

Coadministration has not been studied. Darifenacin is metabolized by CYP3A4 and CYP2D6 and could potentially decrease darifenacin exposure due to induction of CYP3A4. Monitor the effect.

Coadministration is not recommended. Coadministration of etravirine and darunavir/cobicistat decreased cobicistat AUC, Cmax and Cmin by 30%, 14% and 66%, respectively. Darunavir AUC and Cmax were not changed significantly but Cmin was decreased by 56%. On the other hand, darunavir/cobicistat had no significant effects on etravirine exposure. Boosting of darunavir with cobicistat is not recommended in presence of etravirine due to the marked decrease in cobicistat exposure and in darunavir Cmin. However, boosting of darunavir with ritonavir may constitute an option if darunavir has to be coadministered with etravirine.

Symtuza (darunavir, cobicistat, 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, boosting of darunavir with cobicistat is not recommended in the presence of etravirine due to the marked decrease in cobicistat exposure and in darunavir Cmin.

Etravirine and darunavir/ritonavir can be coadministered without any dose adjustments. Etravirine exposures from Phase 3 trials with darunavir/ritonavir as part of the background regimen were determined to be safe and effective. Coadministration decreased etravirine Cmax, AUC and Cmin by 32%, 37% and 49%, respectively; darunavir Cmax, AUC and Cmin increased by 11%, 15% and 2%, respectively. When etravirine was added to raltegravir/darunavir/ritonavir, raltegravir AUC, Cmax and Cmin increased by 29%, 21% and 54%, respectively and darunavir AUC, Cmax and Cmin increased by 14%, 6%, and 29%, respectively.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. No clinically relevant decrease in delamanid exposure was observed with efavirenz (a moderate inducer of CY3A4). As etravirine is also a moderate inducer of CYP3A4, a clinically relevant decrease in delamanid exposure is not expected.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but is not expected to affect contraceptive efficacy. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration of etravirine and a norethisterone-containing COC decreased norethisterone Cmin by 22% whereas ethinylestradiol exposure was increased by 22%. These small pharmacokinetic changes did not impact the efficacy of the contraceptive. Similarly, etravirine is not expected to significantly impair desogestrel pharmacokinetics and efficacy when administered as COC.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but is not expected to affect the contraceptive efficacy of desogestrel. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration of etravirine and combined oral contraceptive containing norethisterone/ethinylestradiol resulted in a 22% decrease in norethisterone Cmin. This small pharmacokinetic change did not impact the efficacy of the contraceptive. Similarly, etravirine is not expected to significantly impair desogestrel pharmacokinetics and contraceptive efficacy when administered as a POP.

Coadministration has not been studied. 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). Etravirine does not induce UGT2B7 but is a weak inhibitor of P-gp and could potentially increase the amount of morphine and morphine-6-glucuronide entering the CNS.

Coadministration has not been studied. Diazepam is metabolized to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Based on this metabolic pathway, a decrease in diazepam exposure is expected as the effect of induction of CYP3A4 by etravirine is predicted to be greater than inhibition of CYP2C19 by etravirine. Note: the etravirine product labels state that coadministration may increase plasma concentrations of diazepam (likely due to inhibition of CYP2C19 by etravirine).

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 etravirine.

Coadministration of digoxin (0.5 mg single dose) alone and with etravirine (200 mg twice daily increased digoxin Cmax and AUC by 19% and 18% respectively. No change in the urinary excretion of digoxin was observed. Etravirine AUC and Cmax were comparable to historical controls. No initial dose adjustments are needed, however, consider starting on the lowest dose. Standard monitoring of digoxin plasma concentrations is recommended.

Coadministration has not been studied but etravirine could potentially decrease dihydrocodeine exposure. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. The analgesic effect appears to be primarily due to the parent compound. Monitoring for analgesic effect and for signs of opiate toxicity may be required as clinically indicated.

Coadministration has not been studied. Dihydroergotamine is a substrate and inhibitor of CYP3A4. Etravirine is metabolized by CYP3A4, CYP2C9 and CYP2C19. Dihydroergotamine is unlikely to have a clinically significant effect on etravirine. However, etravirine is a moderate inducer of CYP3A4 and could potentially decrease dihydroergotamine exposure. If coadministration is necessary, use with caution and monitor for clinical effect.

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. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Etravirine induces UGT1A1 and could potentially decrease dipyridamole exposure, thereby reducing the antiplatelet effect.

Concentrations of disopyramide may be decreased when coadministered with etravirine. Drug concentration monitoring is recommended, if available.

Coadministration with CYP3A inducers (i.e. efavirenz, etravirine, nevirapine) may decrease concentrations of docetaxel.

Coadministration has not been studied. Dofetilide is metabolized to a small degree by CYP3A4 and therefore etravirine could potentially decrease dofetilide exposure. Dose adjustment may be needed and should be done with caution due to the narrow therapeutic index of dofetilide.

Etravirine significantly reduced plasma concentrations of dolutegravir, but the effect of etravirine was mitigated by coadministration of lopinavir/ritonavir or darunavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. The etravirine product labels and the US Prescribing Information for dolutegravir do not recommend the use of dolutegravir and etravirine without coadministration of atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. However, the European SPC for dolutegravir suggests a dose of dolutegravir of 50 mg twice daily when coadministered with etravirine without boosted protease inhibitors to patients without INSTI resistance, but recommends dolutegravir and etravirine should be administered with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir in INSTI-resistant patients. Coadministration of etravirine (200 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 52%, 71% and 88%, respectively. When the same doses were coadministered in the presence of ritonavir-boosted darunavir or lopinavir, dolutegravir Cmax, AUC and Ctrough decreased by 12%, 25% and 37%, respectively, with darunavir/lopinavir and increased by 7%, 11% and 28%, respectively, with lopinavir/ritonavir. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of etravirine.

Triumeq (dolutegravir, abacavir, 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 etravirine would be possible from a pharmacokinetic standpoint, but only if also coadministered with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir. Etravirine significantly reduced plasma concentrations of dolutegravir, but the effect of etravirine was mitigated by coadministration of lopinavir/ritonavir or darunavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. Coadministration of etravirine (200 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 52%, 71% and 88%, respectively. When the same doses were coadministered in the presence of ritonavir-boosted darunavir or lopinavir, dolutegravir Cmax, AUC and Ctrough decreased by 12%, 25% and 37%, respectively, with darunavir/lopinavir and increased by 7%, 11% and 28%, respectively, with lopinavir/ritonavir. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of etravirine. 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 etravirine would be possible from a pharmacokinetic standpoint. The European product label for Dovato recommends an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato, during coadministration with etravirine without boosted protease inhibitors but no dose adjustment is necessary for etravirine with boosted protease inhibitors. Coadministration of dolutegravir and etravirine (without boosted protease inhibitors) decreased dolutegravir AUC, Cmax and Cmin by 71%, 52% and 88%, respectively. There was no change in etravirine pharmacokinetics. Coadministration of etravirine (with lopinavir/ritonavir) increased dolutegravir AUC, Cmax and Cmin by 11%, 7% and 28%, respectively; there was no change in lopinavir, ritonavir or etravirine pharmacokinetics. Coadministration of etravirine (with darunavir/ritonavir) decreased dolutegravir AUC, Cmax and Cmin by 25%, 12% and 36%, respectively; there was no change in darunavir, ritonavir or etravirine pharmacokinetics. 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. Furthermore, coadministration may decrease dolutegravir and rilpivirine concentrations and combining two NNRTIs (i.e., etravirine and rilpivirine) has not been shown to be beneficial. Coadministration of etravirine (200 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 52%, 71% and 88%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of etravirine. 

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. Furthermore, coadministration is expected to decrease doravirine exposure.

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, coadministration is expected to decrease doravirine exposure.

Coadministration has not been studied. Doxazosin is metabolised mainly by CYP3A4 and concentrations may decrease due to induction of CYP3A4 by etravirine. Monitor clinical effect. For the treatment of benign prostatic hyperplasia (BPH), depending on the patient’s urodynamics and BPH symptomatology, doxazosin dose may be increased from 1 mg/day to 2 mg/day and thereafter 4 mg/day with a maximum recommended dose of 8 mg/day. The recommended titration interval is 1-2 weeks with routine blood pressure monitoring.

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

Coadministration has not been studied. Although metabolism of doxycycline is thought to be minimal and the mechanisms are not fully elucidated, metabolic enzyme inducers such as barbiturates, carbamazepine, and phenytoin have been found to decrease the half-life of doxycycline, which may result in sub-therapeutic concentrations. As etravirine induces metabolism mediated by some CYP450 enzymes, an interaction with doxycycline can not be ruled out.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied but is not expected to impair the contraceptive efficacy of drospirenone/ethinylestradiol. Coadministration of etravirine and combined oral contraceptive containing norethisterone/ethinylestradiol resulted in a 22% decrease in norethisterone Cmin. This small pharmacokinetic change did not impact the efficacy of the contraceptive. Similarly, etravirine is not expected to significantly impair drospirenone pharmacokinetics and contraceptive efficacy when administered as a COC.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied. CYP3A4 contributes to drospirenone metabolism. Coadministration is predicted to decrease drospirenone exposure. In addition, exposure of estrogens/estradiol administered as part of HRT may also decrease. Monitor for signs of hormone deficiency.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Coadministration is predicted to decrease drospirenone exposure. In addition, exposure of estrogens/estradiol administered as part of HRT may also decrease. Monitor for signs of hormone deficiency.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is a substrate for P-gp. Etravirine is a weak inhibitor of P-gp and therefore could increase the exposure of edoxaban, although to a limited extent.

Coadministration decreased etravirine AUC by 41% and Cmax by 18%. Coadministration is contraindicated as it significantly decreases etravirine concentrations. Combining two NNRTIs has not been shown to be beneficial. If switching from efavirenz to etravirine, the inducing effect of efavirenz has been shown to persist up to 14 days after stopping drug intake, resulting in decreases in etravirine AUC, Cmax and Cmin (32%, 22% and 42% for once daily; 26%, 19% and 34% for twice daily). The decrease in etravirine is comparable to that determined in the presence of darunavir/ritonavir and is not considered clinically significant.

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

Coadministration is not recommended. Coadministration of elbasvir/grazoprevir with etravirine, a moderate CYP3A inducer, may decrease grazoprevir and elbasvir concentrations, leading to reduced therapeutic effect of elbasvir/grazoprevir.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Genvoya should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir and/or the coadministered antiretroviral products.

Stribild (elvitegravir, cobicistat, emtricitabine, 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. Stribild should not be used in conjunction with non-nucleoside reverse transcriptase inhibitors due to potential drug-drug interactions including altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the coadministered antiretroviral products.

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. Empagliflozin does not inhibit or induce CYPs and does not inhibit UGTs. There is no evidence that etravirine induces the UGTs involved in empagliflozin metabolism or interacts to a significant level with the transporters involved in empagliflozin disposition.

Coadministration has not been studied, but no interaction is expected. Etravirine can be used without dose adjustment.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The recommended dose of Descovy 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 with tenofovir-DF (300 mg once daily) decreased etravirine Cmax and AUC (both by 19%) and Cmin by 18%. Tenofovir Cmax and AUC both increased by 15% and Cmin increased by 19%.  No dose adjustment needed for emtricitabine/tenofovir-DF or etravirine. 

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. Eplerenone is metabolized by CYP3A4. Etravirine could potentially decrease eplerenone exposure due to induction of CYP3A4 and thereby reduce the efficacy of eplerenone.

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. Ergometrine is metabolized by CYP3A4. Etravirine is metabolized by CYP3A4, CYP2C9 and CYP2C19. Ergometrine is unlikely to affect CYPs. However, etravirine is a moderate inducer of CYP3A4 and could potentially decrease ergometrine exposure. If coadministration is necessary, use with caution and monitor for clinical effect.

Coadministration has not been studied. Ergotamine is metabolized by CYP3A4. Etravirine is metabolized by CYP3A4, CYP2C9 and CYP2C19. Ergotamine is unlikely to affect CYPs. However, etravirine is a moderate inducer of CYP3A4 and could potentially decrease ergotamine exposure. If coadministration is necessary, use with caution and monitor for clinical effect.

Coadministration has not been studied but may increase etravirine concentrations. Due to its favourable safety profile, no a priori dosage adjustment is recommended for etravirine.

Coadministration has not been studied. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Etravirine could potentially decrease escitalopram concentrations although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4 and therefore could decrease etravirine concentrations although to a limited extent. No a priori dose adjustment is recommended but HIV infection (e.g. viral load, CD4 count) should be monitored.

Etravirine can be coadministered with proton pump inhibitors without dose adjustments.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Etravirine, an inducer of CYP3A4, could potentially decrease estradiol exposure. Monitor for signs of estrogen deficiency.

No dose adjustment needed for either drug. Coadministration increased ethinyl estradiol Cmax, AUC and Cmin by 33%, 22% and 9%, respectively, Norethindrone Cmax increased by 5%, and AUC and Cmin decreased by 5% and 22%. 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. Etidocaine is metabolized by CYP3A4. Inducers of CYP3A4, such as etravirine, may decrease concentrations of etidocaine and potentially decrease its efficacy. The clinical relevance of this interaction is unknown.

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied. Etonogestrel is metabolized by CYP3A4. Although efavirenz has been shown to impair the contraceptive efficacy of both etonogestrel and levonorgestrel containing implants, nevirapine did not have significant effect on levonorgestrel concentrations (another progestogen metabolized by CYP3A4) following use with a levonorgestrel implant and there were no report of unintended pregnancies. Etravirine has been shown to modestly impact the pharmacokinetics of norethisterone (another progestogen metabolized by CYP3A4). Taken together, these findings suggest that etravirine is likely to maintain the contraceptive efficacy of etonogestrel when administered as an implant.

Coadministration with the etonogestrel as a combined vaginal ring (CVR) has not been studied but is not expected to impair the contraceptive efficacy of etonogestrel/ethinylestradiol. Etonogestrel is metabolized by CYP3A4.  Coadministration of etravirine and norethisterone/ethinylestradiol administered as a COC decreased norethisterone Cmin by 22% but increased ethinylestradiol exposure by 22%. These small pharmacokinetic changes did not impact the efficacy of the contraceptive. Similarly, etravirine is not expected to significantly impair etonogestrel and ethinylestradiol pharmacokinetics and contraceptive efficacy when administered as a CVR.

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 etravirine given that CYP3A4 is already induced by etravirine.

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.

Etravirine can be coadministered with H2 receptor antagonists without dose adjustments.

Coadministration has not been studied. Fentanyl undergoes extensive CYP3A4 metabolism. Coadministration could decrease fentanyl concentrations due to induction of CYP3A4, which could decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to fentanyl. When using fentanyl with CYP3A4 inducers, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur. Discontinuation of a concomitantly used CYP3A4 inducer may increase in fentanyl concentrations which could result in a fatal overdose of fentanyl. When discontinuing CYP3A4 inducers in fentanyl-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of fentanyl until stable drug effects are achieved. 

Coadministration has not been studied. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4. Concentrations of the active metabolite of fesoterodine are likely to decrease due to induction of CYP3A4. Monitor the effect.

Coadministration has not been studied. Fexofenadine does not undergo CYP-mediated metabolism but is a substrate of P-gp and OATP. Etravirine is a weak inhibitor of P-gp and could potentially increase the exposure of fexofenadine, although to a moderate extent. Due to the large therapeutic index of fexofenadine, no a priori dosage adjustment is recommended.

Concentrations of flecainide may be decreased when coadministered with etravirine. Drug concentration monitoring is recommended, if available.

Flibanserin is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19. Coadministration with etravirine (a moderate inducer of CYP3A4) decreased flibanserin exposure by approximately 21%.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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), but is unlikely to alter etravirine exposure significantly as etravirine itself is a moderate inducer.

Coadministration significantly increased etravirine exposures (AUC by 86%, Cmax by 75%, Cmin by 2.09-fold) and had no significant effect on fluconazole exposure. Although no dose adjustments are needed, etravirine and fluconazole should be coadministered with caution as there are limited safety data on increased etravirine exposure.

Coadministration has not been studied. Flunisolide undergoes CYP3A4-mediated metabolism and coadministration may decrease flunisolide concentrations. Monitor steroid effect and adjust dosage if needed. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 etravirine 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. Fluphenazine is metabolised by CYP2D6.

Coadministration with etravirine may increase plasma concentrations of fluvastatin. Dose adjustments for fluvastatin may be necessary.

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 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 etravirine 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 is not expected to impair the contraceptive efficacy of gestodene/ethinylestradiol. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Coadministration of etravirine and combined oral contraceptive containing norethisterone/ethinylestradiol resulted in a 22% decrease in norethisterone Cmin. This small pharmacokinetic change did not impact the efficacy of the contraceptive. Similarly, etravirine is not expected to significantly impair gestodene pharmacokinetics and contraceptive efficacy when administered as a COC.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Although gingerols moderately inhibit CYP3A4 in vitro this is unlikely to impact the exposure of etravirine.

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. No a priori dose adjustment is recommended, but monitor etravirine concentrations (if available).

Coadministration has not been studied and is not recommended. Concentrations of glecaprevir/pibrentasvir may decrease due to CYP3A4 induction by etravirine which may lead to reduced therapeutic effect.

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.

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 etravirine.

Coadministration has not been studied. Haloperidol undergoes glucuronidation (UGT2B7 > 1A4, 1A9), carbonyl reduction and oxidative metabolism (CYP3A4, CYP2D6). Etravirine could potentially decrease haloperidol exposure. No a priori dosage adjustment 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 etravirine.

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 etravirine via these mechanisms.

Coadministration has not been studied but may decrease hydrocortisone concentrations. A dose adjustment of hydrocortisone may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea undergoes metabolism via non-CYP mediated metabolism and is not a substrate of P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Induction of metabolism by etravirine is unlikely to affect ibalizumab, a monoclonal antibody binding to the CD4 receptor, which is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Dose modifications of ibalizumab are not required when administered with any other antiretroviral.