Specific interaction studies have not been performed with efavirenz and abacavir. Clinically significant interactions would not be expected with abacavir since the NRTIs are metabolised via a different route than efavirenz and would be unlikely to compete for the same metabolic enzymes and elimination pathways. Abacavir had no effect on efavirenz pharmacokinetics when abacavir. efavirenz and indinavir were coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has been studied but is not recommended as it is expected to reduce the efficacy of abemaciclib. Abemaciclib is metabolized by CYP3A4 and is a substrate of P-gp and BCRP. Efavirenz (a moderate CYP3A4 inducer) has been predicted to reduce abemaciclib AUC by 69% and to reduce the AUC of abemaciclib’s active metabolites (sum of 3 metabolites) by 52%.

Coadministration has not been studied and is not recommended. Abiraterone is metabolized by CYP3A4 and SULT2A1. Efavirenz induces CYP3A4 and may significantly decrease abiraterone concentrations and consequently reduce its efficacy. It is recommended to use an alternative antiretroviral agent devoid of inducing properties. Abiraterone has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but is not recommended. Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Efavirenz is metabolized by CYP2B6 and CYP3A4. Abrocitinib is not expected to have a clinically relevant effect on these CYPs. Efavirenz inhibits CYP2C9 but induces CYP3A4 and CYP2B6. The net effect of the interaction is difficult to predict. The product label for abrocitinib does not recommend coadministration with efavirenz.

Coadministration should be avoided due to the risk for lack of efficacy as PBPK modelling predicted efavirenz would reduce acalabrutinib exposure by 61%. Note, the US product label does not provide dosage recommendations in presence of moderate inducers of CYP3A4, such as efavirenz. However, the label mentions that if a strong CYP3A4 inducer cannot be avoided, the dose of acalabrutinib should be increased to 200 mg twice daily.

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 may increase or decrease acenocoumarol concentrations. Monitor INR. A case report described an HIV-infected patient who required an increase in average acenocoumarol dose to maintain INR in the target range whilst on either an efavirenz-based or an atazanavir/ritonavir-based regimen; eventually the patient was stabilised on a raltegravir regimen.

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 efavirenz 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. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and efavirenz should be separated by 4 hours. [Note: this interaction is not specific for efavirenz, but for any oral medication taken with activated charcoal.]

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 efavirenz via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied. Afatinib is mainly eliminated unchanged in the faeces and is a substrate of P-gp and BCRP. Coadministration with rifampicin (a strong inducer) decreased afatinib exposure by approximately 34%. However, the decrease in afatinib exposure is expected to be lower with efavirenz given that it is a moderate inducer. No a priori dose adjustment of afatinib is needed.

The effect of multiple doses of an African potato preparation on a single dose of efavirenz (600 mg) was studied in 10 HIV-negative subjects. Coadministration had no significant effect on efavirenz AUC or Cmax.

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 efavirenz 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. Efavirenz is metabolized by CYP3A4 and CYP2B6. 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 efavirenz 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Alectinib does not inhibit CYP3A4 to a clinically relevant extent. Efavirenz is metabolized by CYP2B6 and CYP3A4 and induces CYP3A4 but is not expected to alter alectinib exposure to a significant extent. Coadministration with rifampicin (a strong CYP3A4 inducer) decreased the combined exposure of alectinib and M4 by only 18%.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Efavirenz is metabolized by CYP2B6 and CYP3A4. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

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. Alfuzosin is metabolised mainly by CYP3A4. Efavirenz, an inducer of CYP3A4, could potentially decrease alfuzosin exposure. Monitor clinical effect and increase dosage if needed. Alfuzosin has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Alogliptin was shown to have no inhibitory or inducing effect on CYPs at concentrations achieved with the recommended dose of 25 mg alogliptin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Efavirenz is metabolized by CYP2B6 and CYP3A4 and induces these CYPs but is not expected to cause a significant decrease in alpelisib exposure as CYP3A4 represents a minor pathway in alpelisib metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Efavirenz is metabolized by CYP2B6 and CYP3A4. Alprostadil is unlikely to affect CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amantadine is mainly eliminated renally by glomerular filtration and active secretion. A bicarbonate dependent organic cation transporter has been identified as the major uptake transporter of amantadine in the renal proximal tubule. Amantadine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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. Efavirenz induces UGT1A1 but this is not involved in ambrisentan glucuronidation. Furthermore, induction of CYP3A4 by efavirenz 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.

Coadministration has not been studied and the nature of the interaction is difficult to predict. Amiodarone is metabolized by CYP2C8 and 3A4. Efavirenz is an inducer of CYP3A4, but in vitro data suggest that it inhibits CYP2C8. Amiodarone concentrations could potentially decrease due to induction of CYP3A4 or increase due to inhibition of CYP2C8. Close monitoring of the therapeutic effect is recommended. Amiodarone has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As efavirenz has the potential to increase amiodarone exposure, this interaction reflects the more cautious option.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally. Amisulpride has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as amitriptyline is metabolized predominantly by CYP2D6 and CYP2C19. Amitriptyline has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile. Amphotericin B has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on efavirenz is expected and no a priori dose adjustment is required.

Coadministration of efavirenz with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption. Coadministration of an antacid containing aluminium hydroxide-magnesium hydroxide-simethicone (Maalox, 30 ml single dose) and efavirenz (400 mg single dose) did not alter the absorption of efavirenz. Coadministration with antacids containing calcium carbonate has not been studied. No dosage adjustment is recommended when efavirenz is given with antacids.

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

Coadministration has not been studied but is not recommended. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4. Apalutamide concentrations may significantly increase as efavirenz is a strong inhibitor of CYP2C8 and has been shown to significantly increase the exposure of amodiaquine, a CYP2C8 substrate. Apalutamide is a strong inducer of CYP3A4 and could reduce efavirenz exposure although to a limited extent based on the interaction study with rifampicin. Concurrent use is not recommended. If coadministration is necessary, closely monitor and consider a reduction of apalutamide dosage in case of adverse events. Apalutamide has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Efavirenz 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. Apomorphine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Coadministration with rifampicin (a strong CYP3A4 inducer) was shown to decrease substantially apremilast AUC by 72% and Cmax 43%. The product label for apremilast does not recommend coadministration with strong CYP3A4 inducers as it may reduce the efficacy of apremilast. Efavirenz is a moderate inducer and could potentially reduce apremilast exposure, although to a lower extent than rifampicin. Use with caution; monitoring of the clinical effect is warranted. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Coadministration has not been studied but should be avoided. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Efavirenz is metabolized by CYP2B6 and CYP3A4. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect from day 8 which is clinically insignificant by two weeks. Any transient change in efavirenz exposure is unlikely to be clinically significant. However, efavirenz is a moderate CYP3A4 inducer and could potentially decrease aprepitant concentrations. Coadministration of oral aprepitant and rifampicin (a strong CYP3A4 inducer) decreased aprepitant exposure by 91% and product labels for aprepitant advise to avoid coadministration with strong CYP3A4 inducers. Although a reduced effect is expected with a moderate CYP3A4 inducer such as efavirenz, coadministration with efavirenz should be avoided due to a potentially large decrease in aprepitant exposure leading to reduced efficacy.

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 efavirenz will significantly reduce argatroban exposure due to induction of CYP3A4.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Efavirenz could potentially decrease aripiprazole concentrations. Monitor therapeutic effect and adjust aripiprazole dosage if needed. The European SmPC advises doubling the aripiprazole dose when given with potent inducers of CYP3A4, such as efavirenz. Aripiprazole has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration of efavirenz and artemeter/lumefantrine has been investigated in two studies. Both studies showed decreases in artemether exposure (51% and 79%), dihydroartemisinin exposure (46% and 75%) and lumefantrine exposure by (21% and 56%). Lumefantrine had no significant effect on efavirenz exposure in either study. Use with caution as decreased concentrations of artemether, dihydroartemisinin, or lumefantrine may result in a decrease of antimalarial efficacy.

Coadministration has not been studied. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Efavirenz is metabolized by CYP2B6 and CYP3A4. Asciminib is a weak inhibitor of CYP3A4 but is unlikely to cause a clinically significant increase in efavirenz exposure. Efavirenz induces CYP3A4 and UGTs and may decrease asciminib exposure, although to a limited extent. Coadministration with rifampicin (a strong inducer) decreased asciminib exposure by 15%, although a more pronounced decrease is anticipated when asciminib is used at a higher dose. Use with caution. In addition, QT prolongation has been reported in patients receiving asciminib. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. There is therefore little potential for an interaction with efavirenz 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 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 efavirenz 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). Efavirenz has been shown to induce UGT1A4 and CYP3A4 and could potentially decrease asenapine exposure. Monitor the clinical effect and increase dosage if needed. Asenapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro.

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. Efavirenz, an inducer of CYP3A4, could potentially decrease astemizole exposure. However, the European SPC (but no longer the US Prescribing Information) for efavirenz contraindicates coadministration due to potential serious and/or life-threatening adverse events such as cardiac arrhythmias citing competition for CYP3A4 by efavirenz as a potential mechanism for inhibition of astemizole metabolism. Coadministration should be avoided or used with caution. Astemizole has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied. The European product label for atazanavir does not recommend coadministration, but if the combination is required suggests to consider increasing atazanavir/ritonavir to 400/200 mg once daily with close clinical monitoring. Based on historical comparison, atazanavir AUC, Cmax and Cmin were unchanged with coadministration of atazanavir/ritonavir (400/200 mg once daily) and efavirenz (600 mg once daily). The US Prescribing Information suggests atazanavir/ritonavir 400/100 mg for treatment naive patients, but advises not to coadminister to treatment experienced patients. Coadministration of atazanavir/ritonavir (400/100 mg once daily) and efavirenz (600 mg once daily) had no effect on atazanavir AUC, increased Cmax by 17% and decreased Cmin by 42%. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. Efavirenz has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration with atazanavir alone is not recommended as efavirenz decreases atazanavir exposure. Coadministration of atazanavir (400 mg once daily) and efavirenz (600 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 74%, 59% and 93%, respectively. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. Efavirenz has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration is not recommended. Coadministration of cobicistat (150 mg once daily) and efavirenz (600 mg single dose) had no significant effect on efavirenz (Cmax and AUC decreased by 13% and 7%, respectively). However, coadministration is expected to decrease cobicistat plasma concentrations and consequently those of atazanavir being boosted, leading to loss of therapeutic effect and possible development of resistance. The European SmPC and US Prescribing Information do not recommend coadministration of atazanavir/cobicistat with efavirenz. Furthermore, a prolongation of the QT interval may occur with efavirenz treatment in carriers of CYP2B6*6/*6. The product label for atazanavir advises caution when prescribing atazanavir with medicinal products which have the potential to increase the QT interval. Efavirenz 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 as atenolol is mainly eliminated unchanged by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied. Atogepant is metabolized primarily by CYP3A4 and is a substrate of OATP. Efavirenz is metabolized by CYP2B6 and CYP3A4. Atogepant is not expected to have a clinically relevant effect on drugs metabolized by CYP enzymes. Efavirenz is a moderate CYP3A4 inducer and may decrease atogepant exposure. Atogepant AUC decreased by 60% with rifampicin (a strong CYP3A4 inducer) and by 25% with topiramate (a weak CYP3A4 inducer). No dose recommendations are given for coadministration with CYP3A4 inducers in the European product label for atogepant. For the treatment of episodic migraine, the American product label for atogepant recommends a once daily dose of 30 mg or 60 mg with CYP3A4 inducers and recommends to avoid use with CYP3A4 inducers if treatment is for chronic migraine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Atomoxetine is metabolized by CYP2D6. Atomoxetine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration of atorvastatin (10 mg once daily) and efavirenz (600 mg once daily) decreased atorvastatin Cmax (14%), AUC (43%) and Cmin (69%). Total active drug (including metabolites) decreased by 15% (Cmax), 32% (AUC) and 48% (Cmin). There was no change in efavirenz Cmax, AUC or Cmin. Given the decrease in exposure of total active drug, an increase in atorvastatin dose might be needed in presence of efavirenz. Monitor lipid values and adjust the atorvastatin dose based on the clinical response.

Coadministration of atovaquone/proguanil (250/100 mg single dose) and efavirenz (600 mg once daily) decreased atovaquone AUC and Cmax by 75% and 44%. Proguanil AUC decreased by 44% but there was no change in Cmax. The clinical relevance of this interaction is unknown due to the lack of data on the minimal effective atovaquone plasma concentration in the setting of malaria prophylaxis. Concomitant administration of atovaquone/proguanil with efavirenz should be avoided whenever possible. If coadministration is judged necessary, consider taking atovaquone/proguanil with a high fat meal to increase its bioavailability and increase the dosage if required.

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 efavirenz 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 efavirenz.

Coadministration has not been assessed in clinical pharmacokinetic studies. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Efavirenz is metabolized by CYP2B6 and CYP3A4. Avapritinib was shown to inhibit and induce CYP3A4 in vitro but the net effect in vivo has not been studied. However, coadministration with efavirenz (a moderate CYP3A4 inducer) is predicted to decrease avapritinib exposure by 62% at steady-state. Coadministration should be avoided.

Coadministration has not been studied. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Efavirenz is metabolized by CYP2B6 and CYP3A4. Avatrombopag does not inhibit or induce these CYPs. However, efavirenz is a moderate inducer of CYP3A4 but in vitro data also suggest that it inhibits CYP2C9. The net effect on avatrombopag is unclear. Use with caution and monitor platelet counts and adjust dose as necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

Coadministration has not been studied but should be avoided. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Efavirenz is metabolized by CYP2B6 and CYP3A4. Axitinib does not inhibit or induce CYP3A4. However, efavirenz induces CYP3A4 and UGT1A1 and may significantly decrease concentrations of axitinib. Coadministration of rifampicin (a strong CYP3A4 inducer) and axitinib reduced axitinib AUC by 79%. Coadministration is not recommended. If coadministration is unavoidable, the dose of axitinib should be increased gradually with careful monitoring of tolerability.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Although in vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, this is unlikely to impact the exposure of efavirenz given that CYP3A4 is already induced by efavirenz.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Efavirenz is metabolised by CYP2B6 and CYP3A4. Azacitidine does not inhibit or induce CYP enzymes.

Coadministration has not been studied. Azilsartan is metabolized mainly by CYP2C9. In vitro data suggest that efavirenz inhibits CYP2C9 and could potentially increase azilsartan concentrations, however, the clinical relevance of this is unknown. No a priori dose adjustment is required.

Coadministration of azithromycin (600 mg single dose) with efavirenz (400 mg once daily) increased azithromycin Cmax by 22%, but had no effect on azithromycin AUC or efavirenz Cmax, AUC or Cmin. No dosage adjustment is necessary. Azithromycin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes. Efavirenz is moderate inducer of CYP3A4 but coadministration with rifampicin (a strong inducer) did not significantly alter baricitinib exposure.

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 with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration is predicted to decrease exposure of bazedoxifene and conjugated estrogens. Monitor for signs of hormone deficiency.

Coadministration of bedaquiline (400 mg single dose) and efavirenz (600 mg once daily) to 33 HIV/TB-negative subjects decreased bedaquiline AUC by 18% and had no effect on Cmax. Efavirenz pharmacokinetics were similar to historical data from HIV-infected subjects. A reduction in bedaquiline exposure may result in loss of activity and coadministration is not recommended. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents. Bedaquiline has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. In vitro data indicate that efavirenz is a substrate and inhibitor of UGT2B7 and could potentially increase bempedoic acid concentration, but to an extent that is unlikely to be clinically relevant based on other drug interaction data with UGT inhibitors.

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 pharmacokinetic interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Efavirenz is metabolized by CYP3A4 and CYP2B6 and is unlikely to inhibit or induce CYP1A2. Bendamustine does not inhibit or induce CYP enzymes. Bendamustine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. Bendroflumethiazide has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Efavirenz is metabolized by CYP2B6 and CYP3A4.

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 and is contraindicated. Bepridil is metabolised mainly by CYP2D6 and to a lesser extent by CYP3A4. Efavirenz, an inducer of CYP3A4, could potentially decrease bepridil exposure. However, the European SPC (but no longer the US Prescribing Information) for efavirenz contraindicates coadministration due to potential serious and/or life-threatening adverse events such as cardiac arrhythmias citing competition for CYP3A4 by efavirenz as a potential mechanism for inhibition of bepridil metabolism. Coadministration should be avoided or used with caution. Bepridil has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As efavirenz has the potential to increase bepridil exposure, this interaction reflects the more cautious option. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Efavirenz is metabolized by CYP2B6 and CYP3A4. Beta-alanine is unlikely to affect CYP2B6 or CYP3A4.

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

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of betamethasone (for example, ointment, cream, lotion, emollient, foam).

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. In vitro data indicate that efavirenz does not induce or inhibit P-gp in the range of clinical concentrations. Betrixaban has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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

Coadministration has not been studied. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Efavirenz is metabolized by CYP2B6 and CYP3A4. Bicalutamide is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on efavirenz. However, efavirenz is a moderate inducer of CYP3A4 and induces UGT and has the potential to decrease bicalutamide concentrations. Use with caution and monitor clinical effect. Bicalutamide has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Efavirenz is metabolized by CYP2B6 and CYP3A4. Bilastine is unlikely to affect CYP2B6 or CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Efavirenz is metabolized by CYP2B6 and CYP3A4. Binimetinib is unlikely to have a significant effect on these CYPs. However, efavirenz induces glucuronidation and may decrease binimetinib exposure. Use with caution.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Efavirenz is metabolized by CYP2B6 and CYP3A4. Bismuth subsalicylate is unlikely to affect CYPs.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Efavirenz 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 efavirenz 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 clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Efavirenz could potentially decrease bortezomib concentrations and thus potentially reduce the clinical effect. Bortezomib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Efavirenz, a CYP3A4 inducer, could potentially decrease bosentan exposure and the clinical effect of bosentan should be monitored.

Coadministration has not been studied but should be avoided. Bosutinib is metabolized by CYP3A4. Coadministration with rifampicin (a strong inducer) decreased bosutinib AUC by 94%. Increasing the dose of bosutinib when coadministering with strong or moderate CYP3A inducers, such as efavirenz, is unlikely to sufficiently compensate for the loss of exposure. Use an alternative antiretroviral drug with no inducing or inhibitory effects. Bosutinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Efavirenz is metabolized by CYP2B6 and CYP3A4. BCAAs are unlikely to affect CYP2B6 or CYP3A4.

Coadministration has not been studied. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with efavirenz. However, MMAE is a substrate of CYP3A4 and P-gp, therefore efavirenz may decrease concentrations of MMAE. Coadministration of brentuximab vedotin and the strong inducer rifampicin decreased MMAE AUC by 46%. A less pronounced interaction is expected with efavirenz. No a priori dose adjustment of brentuximab vedotin is necessary as the contribution of free MMAE to efficacy is minimal.

Coadministration has not been studied. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Efavirenz is metabolized by CYP2B6 and CYP3A4. Brexpiprazole is unlikely to have a clinically relevant effect on drugs metabolised by CYP enzymes. However, efavirenz is a moderate inducer of CYP3A4 and may decrease brexpiprazole exposure. Use with caution. Product labels for brexpiprazole recommend to double the brexpiprazole dose over 1 to 2 weeks when coadministered with a strong CYP3A4 inducer. A dose adjustment could also be considered, based on clinical response, when brexpiprazole is coadministered with efavirenz.

Coadministration has not been studied but should be avoided. Brigatinib is metabolised by CYP2C8 and CYP3A4. Efavirenz is a moderate inducer of CYP3A4 and is predicted to decrease brigatinib exposure by ~50%. Avoid coadministration. The US product label for brigatinib mentions that if coadministration with a moderate CYP3A4 inducer is needed, the brigatinib once daily dose can be increased in 30 mg increments after 7 days of treatment with the current brigatinib dose as tolerated, up to a maximum of twice the brigatinib dose that was tolerated prior to initiating the moderate CYP3A4 inducer. After discontinuation of a moderate CYP3A4 inducer, resume the brigatinib dose that was tolerated prior to initiating the moderate CYP3A4 inducer.

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

Coadministration has not been studied. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Brincidofovir inhibits CYP2B6, the main enzyme involved in efavirenz metabolism and could increase efavirenz exposure. However, the clinical relevance of this is unknown considering the short treatment course of brincidofovir.

Coadministration has not been studied. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Efavirenz is metabolized by CYP2B6 and CYP3A4. Brinzolamide does not inhibit or induce CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and may decrease brinzolamide concentrations. The clinical relevance of this potential interaction is unknown and patients should be monitored for clinical effect.

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. Efavirenz could potentially decrease bromazepam concentrations although to a moderate extent. No a priori dosage adjustment is required.

Coadministration has not been studied. Bromocriptine is metabolised by CYP3A4. Efavirenz is metabolized by CYP2B6 and CYP3A4. Bromocriptine is unlikely to affect CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and may decrease bromocriptine concentrations. Monitor patients for clinical effect.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration of efavirenz (600 mg once daily) significantly decreased buprenorphine AUC by 50% in HIV- subjects; however, no subject developed an opioid withdrawal syndrome. Efavirenz concentrations remained in the therapeutic range. Dose adjustments are unlikely to be required, but consider monitoring for withdrawal symptoms. Buprenorphine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration of efavirenz and a single dose of bupropion decreased bupropion AUC (55%) and Cmax (34%). The AUC of an active metabolite, hydroxybupropion, was unchanged, but Cmax increased by 50% and half life decreased from 24 h to 16 h. The 55% decrease in bupropion exposure may be clinically significant. Increases in bupropion dosage should be guided by clinical response, but the maximum recommended dose of bupropion should not be exceeded. No dose adjustment is necessary for efavirenz.

Coadministration has not been studied. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Efavirenz is metabolized by CYP2B6 and CYP3A4. Busulfan is unlikely to affect CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and may decrease busulfan concentrations. Monitor patients for busulfan efficacy and adjust dose if necessary.

Coadministration has not been studied and should be used with caution. Cabazitaxel is metabolized by CYP3A4. Coadministration with rifampicin (a strong CYP3A4 inducer) decreased cabazitaxel exposure by 17%. Efavirenz is a moderate inducer and, therefore, may cause less reduction in cabazitaxel exposure. Coadministration should be avoided but, if required, should be done with caution and monitoring of cabazitaxel efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and is a substrate of P-gp. In vitro data indicate that efavirenz does not induce or inhibit P-gp in the range of clinical concentrations. No effect on efavirenz is expected as cabergoline does not inhibit or induce drug metabolizing enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and is a substrate of P-gp. In vitro data indicate that efavirenz does not induce or inhibit P-gp in the range of clinical concentrations. No effect on efavirenz is expected as cabergoline does not inhibit or induce drug metabolizing enzymes.

Coadministration with intramuscular cabotegravir has not been studied but based on the drug-drug interaction study with oral cabotegravir and rifabutin (another moderate inducer), efavirenz has the potential to cause a modest reduction in cabotegravir exposure. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Efavirenz is a moderate inducer. Based on drug-drug interaction studies with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure is expected not to be clinically relevant. Cabotegravir is not expected to alter concentrations of other antiretroviral products. No dose adjustment is required with oral cabotegravir.

Coadministration is contraindicated due to the potential for loss of therapeutic effect and development of resistance. Efavirenz is a moderate inducer of CYP3A. Based on the drug-drug interaction study with rifabutin (also a moderate inducer), the decrease in cabotegravir exposure after intramuscular administration is expected not to be clinically relevant. However, efavirenz has the potential to significantly reduce rilpivirine exposure. 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. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs. Note, a physiologically based pharmacokinetic modelling study indicates that switching from an efavirenz-containing regimen to intramuscular cabotegravir/rilpivirine does not create a risk of having a time window with suboptimal drug levels.

Coadministration has not been studied. Coadministration with rifampicin (a strong inducer) reduced cabozantinib AUC by 77%. Efavirenz is expected to reduce cabozantinib concentrations, but to a lesser extent than rifampicin. Avoid coadministration is possible and consider a non-inducing/inhibiting antiretroviral regimen. If coadministration with efavirenz is unavoidable, consider increasing the cabozantinib dose by 20 mg as tolerated (do not exceed a daily dose of 80 mg). The US product label for cabozantinib recommends to resume the dose that was used prior to initiating the CYP3A4 inducer 2 to 3 days after discontinuation of the strong inducer. Cabozantinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Efavirenz is metabolized by CYP2B6 and CYP3A4 and does not affect CYP1A2. Caffeine is unlikely to affect CYP2B6 or CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolized via proteolysis in the kidney. Efavirenz does not interfere with this pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 and efavirenz has been shown to inhibit UGT1A9 in vitro. The clinical relevance of this inhibition is unknown but a significant interaction is unlikely as UGT1A9 contributes only partly to canagliflozin metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on efavirenz is expected and no a priori dose adjustment is required.

Coadministration has not been studied. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit or induce CYP2B6 and therefore no effect is expected on efavirenz. However, efavirenz induces both CYP3A4 and CYP2C19, which may decrease cannabidiol exposure. A careful dose increase of cannabidiol might be needed. In addition, a careful titration might be needed within the two weeks following cessation of efavirenz.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Capecitabine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied and should be avoided. Capmatinib is primarily metabolized by CYP3A4. Efavirenz induces CYP3A4 and coadministration was predicted to decrease capmatinib exposure by 44% and Cmax by 34%. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. Efavirenz is metabolized by CYP2B6 and CYP3A4, but capmatinib is unlikely to have a clinically relevant effect on CYP3A4.

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 of carbamazepine (400 mg once daily) and efavirenz (600 mg once daily) decreased carbamazepine Cmax (20%), AUC (27%) and Cmin (35%); carbamazepine epoxide Cmin decreased by 13%, but there was no change in Cmax or AUC. Efavirenz Cmax, AUC and Cmin decreased by 21%, 36% and 47%, respectively. There are no data from coadministration of higher doses of either drug. No dose recommendation can be made and alternative anticonvulsant treatment should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbocisteine is metabolized in the liver via acetylation, decarboxylation and sulfoxidation with up to 60% excreted unchanged in the urine. The likelihood of a clinically significant drug interaction is low and no studies have been performed. Efavirenz is metabolized by CYP2B6 and CYP3A4.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolized, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Efavirenz is metabolized by CYP2B6 and CYP3A4 and is a moderate inducer of CYP3A4. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs and is unlikely to be affected by inhibitors and inducers of CYPs and P-gp.

Coadministration has not been studied and is not recommended. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Efavirenz is metabolized by CYP2B6 and CYP3A4. Cariprazine is unlikely to affect CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and is expected to decrease cariprazine exposure. Cariprazine and its metabolites have very long elimination half-lives and changes in dose may not be fully reflected in plasma for several weeks. The European product label for cariprazine contraindicates coadministration with strong and moderate CYP3A4 inducers, whereas the American product label does not recommend coadministration with CYP3A4 inducers. Refer to the cariprazine product labels for more information.

Coadministration has not been studied. Carvedilol undergoes glucuronidation and additional metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Efavirenz 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 efavirenz. Coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Efavirenz is metabolised by CYP2B6 and CYP3A4. Cedazuridine does not inhibit or induce 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. 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. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration has not been studied. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Efavirenz is metabolized by CYP2B6 and CYP3A4. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate is unlikely to alter efavirenz exposure significantly as rifampicin (a strong inducer) had only a modest effect on efavirenz exposure. Efavirenz induces UGT but is not expected to cause a significant decrease in cenobamate exposure based on drug interaction studies between cenobamate and various anticonvulsants.

Coadministration has not been studied. Ceritinib is metabolized by CYP3A4. Efavirenz induces CYP3A4 and can reduce ceritinib exposure. Coadministration is not recommended. Ceritinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration of a single dose of cetirizine (10 mg) with efavirenz (600 mg) decreased cetirizine Cmax by 24% but caused no change in AUC. Efavirenz Cmax, AUC and Cmin were unaltered. No dosage adjustment is necessary.

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 efavirenz 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 with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but is expected to reduce the contraceptive efficacy of chlormadinone and ethinylestradiol and therefore a reliable method of barrier contraception must be used in addition to hormonal contraceptives. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Efavirenz has been shown to reduce the exposure of progestogens and unintended pregnancies have been observed when used with levonorgestrel or etonogestrel containing implants. In addition, coadministration of efavirenz and a desogestrel-containing COC decreased etonogestrel exposure by 61% and an increased risk of contraceptive failure (evaluated by measuring serum progesterone) was observed.

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%). Efavirenz could potentially increase chloroquine exposure (inhibition CYP2C8) or decrease chloroquine exposure (induction CYP3A4) although to a moderate extent due to the multiple elimination pathways. No dosage adjustment is recommended but monitor toxicity and efficacy of the antimalarial. Chloroquine has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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 CYP1A2. Chlorpromazine has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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

Coadministration may decrease ciclosporin concentration. Case reports have shown efavirenz concentrations to be similar to historical data, but ciclosporin concentrations to be lower when coadministered. Close monitoring is recommended with appropriate dose adjustment of ciclosporin.

Co-administration of efavirenz with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption. Cimetidine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Efavirenz is metabolized by CYP2B6 and CYP3A4. Cinacalcet does not inhibit or induce these CYPs. However, concentrations of cinacalcet may decrease due to induction of CYP3A4 by efavirenz. A dose adjustment of cinacalcet may be required to achieve the desired clinical effect. Monitoring of iPTH serum phosphorus and serum calcium is recommended when starting or discontinuing efavirenz. In addition, decreases in serum calcium may prolong the QT interval. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. 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. Ciprofloxacin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Cisapride is metabolised mainly by CYP3A4. Efavirenz, an inducer of CYP3A4, could potentially decrease cisapride exposure. However, the European SmPC (but no longer the US Prescribing Information) for efavirenz contraindicates coadministration due to potential serious and/or life-threatening adverse events such as cardiac arrhythmias citing competition for CYP3A4 by efavirenz as a potential mechanism for inhibition of cisapride metabolism. Coadministration should be avoided or used with caution. Cisapride has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Efavirenz could potentially decrease citalopram concentrations, although to a moderate extent. No a priori dosage adjustment is recommended. Citalopram has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration of clarithromycin (500 mg every 12 hours) and efavirenz (400 mg once daily) decreased clarithromycin Cmax (26%), AUC (39%) and Cmin (53%) and increased 14-OH clarithromycin Cmax (49%), AUC (34%) and Cmin (26%). Efavirenz Cmax increased by 11%, but AUC and Cmin were unaltered. The clinical significance of the decreases in clarithromycin is unknown. In uninfected individuals, 46% developed rash while receiving efavirenz and clarithromycin. No dose adjustment of efavirenz is recommended when given with clarithromycin. Alternatives to clarithromycin, such as azithromycin, should be considered. Clarithromycin has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Clindamycin is metabolized by CYP3A4 and some metabolites have antibacterial activity. Efavirenz 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. Efavirenz induces CYP3A4, CYP2B6 and CYP2C19 which may decrease clobazam exposure. Monitor for anticonvulsant effect and adjust clobazam dosage if needed. Clobazam is unlikely to affect efavirenz.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Clofazimine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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 efavirenz 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. Efavirenz could potentially decrease clomipramine concentrations but increase the formation of the active metabolite. The clinical relevance is unknown. Monitor clinical effect. Clomopramine has a conditional of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Clopidogrel is a prodrug and is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2. 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). Since efavirenz is an inhibitor of CYP2C19, a similar effect cannot be excluded, therefore coadministration is not recommended. Furthermore, clopidogrel is an inhibitor of CYP2B6 and has been shown to increase efavirenz exposure (17% increase in AUC, 31% increase in Cmax).

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. Clozapine is metabolized by CYPs 1A2, 2C19 and 3A4. Efavirenz may decrease clozapine concentrations, leading to reduced efficacy. No a priori dosage adjustment is recommended, but monitor therapeutic effect.Clozapine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but should be avoided. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Efavirenz induces CYP3A4 and glucuronidation and may significantly decrease concentrations of cobimetinib thereby potentially reducing its efficacy. Cobimetinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied. Cocaine is metabolized by several pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Norcocaine is further transformed to a hepatotoxic metabolite. Efavirenz could potentially increase the serum level of the hepatotoxic metabolite. Cocaine has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but efavirenz 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Efavirenz is metabolised by CYP2B6 and CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Colchicine is a substrate of CYP3A4 and P-gp. Coadministration with efavirenz (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. 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 efavirenz) may increase metabolism of vitamin D and therefore reduce its effect. Various observational studies have reported increased risk for vitamin D deficiency in patients taking efavirenz containing regimens. However, no effect of efavirenz on the response to vitamin D supplementation was observed in a clinical study nor found in a PK modelling study.

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 efavirenz) may increase metabolism of vitamin D and therefore reduce its effect. Various observational studies have reported increased risk for vitamin D deficiency in patients taking efavirenz containing regimens. However, no effect of efavirenz on the response to vitamin D supplementation was observed in a clinical study nor found in a PK modelling study.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Efavirenz is metabolised by CYP2B6 and CYP3A4. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after efavirenz to minimize the risk of reduced absorption.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for efavirenz, but for any medication taken with colestyramine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Efavirenz is metabolized by CYP2B6 and CYP3A4. Collagen hydrolysate is unlikely to affect CYP2B6 or CYP3A4.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration is predicted to decrease exposure of conjugated estrogens. In addition, exposure of progestogens administered as part of HRT may also decrease. Monitor for signs of hormone deficiency. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied but should be avoided. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Efavirenz is metabolized by CYP2B6 and CYP3A4. Copanlisib does not inhibit or induce CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and may decrease copanlisib concentrations. Coadministration of copanlisib (60 mg i.v. infusion) and a strong CYP inducer (rifampicin, 600 mg once daily for 12 days) decreased copanlisib AUC and Cmax by 60% and 12%, respectively. Avoid coadministration if possible.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Efavirenz is metabolized by CYP2B6 and CYP3A4. Creatine is unlikely to affect CYP2B6 or CYP3A4.

Coadministration has not been studied but should be avoided. Crizotinib is mainly metabolized by CYP3A4. Efavirenz induces CYP3A4 and therefore can reduce crizotinib exposure and potentially its efficacy. Crizotinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

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 efavirenz is required.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Efavirenz is metabolized by CYP2B6 and CYP3A4 and is unlikely to inhibit or induce CYP2D6.

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. Efavirenz could either potentially increase the conversion to the active metabolite or 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 efavirenz. A dose adjustment of cyproterone may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Efavirenz is metabolised by CYP2B6 and CYP3A4.

Coadministration has not been studied. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Efavirenz is metabolized by CYP2B6 and CYP3A4 and is a moderate inducer of CYP3A4 and could potentially decrease dabrafenib exposure. Use with caution. In addition, dabrafenib is a strong inducer of CYP3A4 and induces CYP2B6 and has the potential to decrease efavirenz exposure, although to a modest extent which does not warrant a dose adjustment (based on the rifampicin drug interaction study). Dabrafenib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Efavirenz is metabolized by CYP2B6 and CYP3A4. Dacomitinib does not inhibit or induce these CYPs. Efavirenz induces CYP3A4 and may decrease dacomitinib concentrations. However, this is unlikely to be clinically significant as CYP3A4 contributes to dacomitinib metabolism only to a small degree.

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. Efavirenz has been shown to inhibit this enzyme in vitro, but a clinically relevant effect is not expected as coadministration of dapagliflozin with mefenamic acid (which is also an inhibitor of UGT1A9), increased dapagliflozin systemic exposure by 55%, but had no clinically meaningful effect on 24-hour urinary glucose excretion. No dose adjustment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Efavirenz is metabolized by CYP2B6 and CYP3A4. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Coadministration has not been studied. Dapoxetine is metabolized by CYP2D6, CYP3A4 and flavin monooxygenase 1. Efavirenz could reduce dapoxetine exposure due to CYP3A4 induction although to a limited extent given that multiple metabolic pathways are involved in dapoxetine elimination. No a priori dose adjustment of dapoxetine is needed.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Efavirenz is metabolized by CYP2B6 and CYP3A4.

Coadministration of daridorexant and efavirenz decreased daridorexant exposure. Daridorexant is mainly metabolised by CYP3A4. Efavirenz is metabolized by CYP2B6 and CYP3A4. Daridorexant is unlikely to significantly affect CYP2B6 and is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on efavirenz. However, efavirenz is a moderate CYP3A4 inducer and coadministration of daridorexant (50 mg single dose) and efavirenz (600 mg once daily) decreased daridorexant AUC and Cmax by 61% and 35%, respectively. Decreases in daridorexant exposure may lead to reduced efficacy and patients should be monitored for clinical effect. A reduction in daridorexant exposure may be more clinically relevant for patients receiving the lower (25 mg) daridorexant dose than those receiving the higher dose (50 mg).

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 has not been studied. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Efavirenz is metabolized by CYP2B6 and CYP3A4. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on efavirenz. However, efavirenz is a moderate inducer of CYP3A4 and induces UGT and has the potential to decrease darolutamide concentrations. Use with caution and monitor clinical effect. In addition, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Efavirenz in combination with darunavir/ritonavir 800/100 mg once daily may result in sub-optimal darunavir Cmin. If efavirenz is to be used in combination with darunavir/ritonavir, the darunavir/ritonavir 600/100 mg twice daily regimen should be used. Coadministration of efavirenz (600 mg once daily) and darunavir/ritonavir at a dose lower than that licensed (300/100 mg twice daily) decreased darunavir Cmax (15%), AUC (13%) and Cmin (31%). Efavirenz Cmax, AUC and Cmin increased by 15%, 21% and 17%, respectively. The clinical significance has not been established. Coadministration of efavirenz and once daily darunavir/ritonavir (900/100 mg once daily) decreased darunavir AUC (14%), Cmax (8%) and Ctrough (57%). Ritonavir AUC and Ctrough were significantly reduced, but there was no significant effect on efavirenz AUC, Cmax or Ctrough. The combination should be used with caution. Clinical monitoring for CNS toxicity associated with increased efavirenz exposure may be indicated.

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, efavirenz is expected to decrease darunavir/cobicistat exposure which may result in loss of therapeutic effect and development of resistance to darunavir.

Coadministration has not been studied and is not recommended because it is expected to decrease darunavir/cobicistat exposure which may result in loss of therapeutic effect and development of resistance to darunavir. 

This interaction has not been studied. Dasatinib is metabolized by CYP3A4 and coadministration could potentially decrease dasatinib concentrations. Consider alternatives, but if coadministration is unavoidable, monitoring of dasatinib therapeutic effect is recommended. Dasatinib has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. 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. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Efavirenz is metabolised by CYP2B6 and CYP3A4. Decitabine does not inhibit or induce CYP enzymes.

Coadministration has not been studied. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Efavirenz is metabolized by CYP2B6 and CYP3A4. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease efavirenz concentrations. Deferasirox is unlikely to affect CYP2B6. However, efavirenz induces UGT1A1 and may decrease deferasirox concentrations leading to a possible decrease in efficacy. Monitor serum ferritin levels and clinical responses to determine if a deferasirox dose increase is necessary.

Coadministration has not been studied but should be avoided. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Efavirenz is metabolized by CYP2B6 and CYP3A4. Deflazacort and 21-desdeflazacort do not inhibit or induce CYP2B6 or CYP3A4. However, efavirenz is a moderate CYP3A4 inducer and may decrease concentrations of 21-desdeflazacort. Coadministration of deflazacort with rifampicin (a strong CYP3A4 inducer) significantly decreased the exposure of 21-desdeflazacort by ~95%. The US product label for deflazacort recommends to avoid concomitant use of strong or moderate CYP3A4 inducers with deflazacort. The European product label recommends to increase the maintenance dose of deflazacort if coadministered with enzyme inducers.

No clinically significant interaction was observed when efavirenz (600 mg daily) and delamanid (100 mg twice daily) were coadministered. There was no change in delamanid Cmax and a 3% decrease in AUC; efavirenz Cmax and AUC both decreased by 6%. However, the overall incidence of adverse effects was higher during concomitant dosing with delamanid and efavirenz compared to either medication alone. A higher rate of neuropsychiatric adverse effects (e.g., euphoric mood and abnormal dreams) was observed with delamanid plus efavirenz compared to either drug alone, but no subject discontinued the study because of neuropsychiatric events or had serious neuropsychiatric adverse effects. Delamanid has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as desipramine is metabolized by CYP2D6. Desipramine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Efavirenz is metabolized by CYP2B6 and CYP3A4. Desloratadine does not inhibit CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Efavirenz is metabolized by CYP2B6 and CYP3A4. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

Coadministration is expected to reduce the contraceptive efficacy of desogestrel and therefore a reliable method of barrier contraception must be used in addition to hormonal contraceptives. 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 efavirenz and desogestrel was administered as a COC to HIV+ women (n=16). An increased risk of contraceptive failure (evaluated by measuring serum progesterone) was observed and efavirenz C12 concentrations decreased by 22% and were below the target of 1000 ng/ml in 3/16 subjects. When compared to values obtained from administration without efavirenz to HIV-negative women (n=14), etonogestrel trough concentrations decreased by 61% in HIV+ women administered desogestrel/ethinylestradiol and efavirenz (n=16). In addition, efavirenz has been shown to reduce the exposure of progestogens and unintended pregnancy have been observed when used with levonorgestrel or etonogestrel containing implants.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but is expected to reduce the contraceptive efficacy of desogestrel and therefore a reliable method of barrier contraception must be used in addition to hormonal contraceptives. 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. Efavirenz has been shown to reduce the exposure of progestogens and unintended pregnancies have been observed when used with levonorgestrel or etonogestrel containing implants. In addition, an increased risk of contraceptive failure (evaluated by measuring serum progesterone) was observed when efavirenz was coadministered with a combined oral contraceptive containing desogestrel and ethinylestradiol.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4 and concentrations may decrease due to the inducing effect of efavirenz. Efavirenz is metabolized by CYP2B6 and CYP3A4. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. However, dexamethasone is unlikely to alter efavirenz exposure significantly as rifampicin (a strong inducer) had only a modest effect on efavirenz exposure. Monitor steroid effect.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4 and concentrations may decrease due to the inducing effect of efavirenz. Efavirenz is metabolized by CYP2B6 and CYP3A4. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on efavirenz.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Efavirenz is metabolized by CYP2B6 and CYP3A4. In vitro data suggests that efavirenz is an inhibitor of CYP2C8/9 although it is unlikely to significantly increase dexketoprofen concentrations. Dexketoprofen is unlikely to affect CYP2B6 or CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption.

Coadministration has not been studied. Dexmedetomidine undergoes extensive hepatic biostranformation through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly 2A6). Efavirenz has been shown to decrease exposure of another UGT1A4 substrate (posaconazole) and could potentially decrease dexmedetomidine concentrations. The clinical relevance of this interaction is unknown. Dexmedetomidine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Efavirenz is metabolized by CYP2B6 and CYP3A4. Efavirenz does not inhibit or induce CYP2D6. Dextromethorphan does not inhibit or induce CYP2B6 or CYP3A4.

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 efavirenz.

Coadministration has not been studied and the net effect of this interaction is difficult to predict. 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. Efavirenz could potentially increase the formation of nordihydrocodeine (via induction CYP3A4) and reduce the conversion to dihydrocodeine-6-glucuronide (via competition or inhibition of UGT2B7). No a priori dose adjustment is required, but 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. Efavirenz, an inducer of CYP3A4, could potentially decrease dihydroergotamine exposure. However, coadministration is contraindicated in the European SmPC (but no longer the US Prescribing Information) for efavirenz due to potential serious and/or life-threatening adverse events, such as acute ergot toxicity, citing competition for CYP3A4 by efavirenz as a potential mechanism for inhibition of dihydroergotamine metabolism. Coadministration should be avoided or used with caution.

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 of diltiazem (240 mg once daily) and efavirenz (600 mg for 14 days) decreased diltiazem Cmax (60%), AUC (69%) and Cmin (63%). Reductions in Cmax, AUC and Cmin were also observed for the metabolites desacetyl diltiazem (64%, 75%, 62%, respectively) and N-monodesmethyl diltiazem (28%, 37%, 37%, respectively). Efavirenz Cmax, AUC and Cmin increased by 16%, 11% and 13%, respectively. Diltiazem dose adjustments should be guided by clinical response but no dose adjustment of efavirenz is necessary. Diltiazem has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Efavirenz is metabolised by CYP2B6 and CYP3A4. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6 which is not inhibited or induced by efavirenz. Diphenhydramine has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Efavirenz induces UGT1A1 and could potentially decrease dipyridamole exposure, thereby reducing the antiplatelet effect.

Coadministration has not been studied but efavirenz may decrease disopyramide concentrations. Caution is warranted and therapeutic concentration monitoring is recommended for the antiarrhythmic if available. Disopyramide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration of disulfiram (62.5 mg or 250 mg once daily) with efavirenz (600 mg once daily) had no significant effect on efavirenz pharmacokinetics at either dose. Disulfiram is converted to an active metabolite by CYP3A4 and UGT. Coadministration with efavirenz (an inducer of CYP3A4) was associated with a moderate increase in disulfiram‐associated inhibition of ALDH activity. No dose adjustments for efavirenz or disulfiram are necessary.

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 efavirenz could potentially decrease dofetilide exposure. Dose adjustment may be needed and should be done with caution due to the narrow therapeutic index of dofetilide. Dofetilide has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Dolasetron has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration decreases dolutegravir exposure and a dose increase of dolutegravir is recommended. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. In treatment-naïve or INSTI-naïve patients, a dose adjustment of dolutegravir to 50 mg twice daily is recommended. Alternative combinations that do not include metabolic inducers should be considered where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks  in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Dolutegravir/lamivudine/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 with efavirenz would be possible from a pharmacokinetic standpoint. Product labels for dolutegravir/lamivudine/tenofovir-DF fixed dose combination recommend that an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after the fixed dose combination, during coadministration with efavirenz. Coadministration of dolutegravir and efavirenz decreased dolutegravir AUC, Cmax and Cmin by 57%, 39% and 75%, respectively. There was no change in efavirenz when compared to historical controls. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after dolutegravir/lamivudine/tenofovir-DF) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with efavirenz is expected to decrease dolutegravir exposure. The European product label for Triumeq does not recommend coadministration with efavirenz. However, the US product label for Triumeq recommends that an additional dolutegravir 50 mg tablet, separated by 12 hours from Triumeq, should be taken. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. Abacavir had no effect on efavirenz pharmacokinetics when abacavir, efavirenz and indinavir were coadministered. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after Triumeq) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

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 efavirenz 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 efavirenz. Coadministration of dolutegravir and efavirenz decreased dolutegravir AUC, Cmax and Cmin by 57%, 39% and 75%, respectively. There was no change in efavirenz when compared to historical controls. Coadministration of lamivudine (150 mg twice daily) with efavirenz (600 mg once daily) increased lamivudine Cmin by 265%, but had no effect on lamivudine Cmax or AUC. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks (as an additional 50 mg tablet of dolutegravir administered approximately 12 hours after Dovato) in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

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., efavirenz and rilpivirine) has not been shown to be beneficial. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. 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. Domperidone is metabolised mainly by CYP3A4. Efavirenz, an inducer of CYP3A4, could potentially decrease domperidone exposure. A dose adjustment may be needed. Domperidone has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered.

Coadministration has not been studied. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Efavirenz has inducing properties and therefore has the potential to reduce donepezil exposure. Adjust donepezil dosage if needed. Donepezil has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

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. Note: switching from efavirenz to doravirine resulted in a transient decrease in doravirine exposure (doravirine AUC, Cmax and Cmin decreased by 52%, 35% and 85%, respectively, one day after stopping efavirenz and by 32%, 14% and 50%, respectively, 14 days after stopping efavirenz). Dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in a virologically suppressed individual.

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. Note: switching from efavirenz to doravirine resulted in a transient decrease in doravirine exposure (doravirine AUC, Cmax and Cmin decreased by 52%, 35% and 85%, respectively, one day after stopping efavirenz and by 32%, 14% and 50%, respectively, 14 days after stopping efavirenz). Dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in a virologically suppressed individual.

Coadministration has not been studied. Doxazosin is metabolised mainly by CYP3A4 and concentrations may decrease due to induction of CYP3A4 by efavirenz. 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 pharmacokinetic interaction is unlikely. Doxepin is metabolized mainly by CYP2C19 to nordoxepin, an active metabolite. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Doxepin has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for a pharmacokinetic interaction. 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, possible cardiac toxicities (ECG abnormalities and sometimes arrhythmias) have been reported with doxorubicin. Use with caution. ECG monitoring is recommended. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.