Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-215275 · Präparat HOS-155418

Table 1: Interactions between efavirenz and other medicinal products in adults Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) ANTI-INFECTIVES HIV antivirals Protease inhibitors (PI) Atazanavir/ritonavir/efavirenz Atazanavir (pm): Co-administration of efavirenz (400 mg once daily/100 mg once AUC: ↔* (↓ 9 to ↑ 10) with atazanavir/ritonavir is not daily/600 mg once daily, all Cmax: ↑ 17%* (↑ 8 to ↑ 27) recommended. If the administered with food) Cmin: ↓ 42%* (↓ 31 to ↓ 51) co-administration of atazanavir with an NNRTI is required, an Atazanavir/ritonavir/efavirenz Atazanavir (pm): increase in the dose of both (400 mg once daily/200 mg once AUC: ↔*/** (↓ 10 to ↑ 26) atazanavir and ritonavir to 400 mg daily/600 mg once daily, all Cmax: ↔*/** (↓ 5 to ↑ 26) and 200 mg, respectively, in administered with food) Cmin: ↑ 12%*/** (↓ 16 to ↑ 49) combination with efavirenz could (CYP3A4 induction) be considered with close clinical * When compared to atazanavir monitoring. 300 mg/ritonavir 100 mg once daily in the evening without efavirenz. This decrease in atazanavir Cmin might negatively impact the efficacy of atazanavir. ** Based on historical comparison Darunavir/ritonavir/efavirenz Darunavir: Efavirenz in combination with (300 mg twice daily*/100 mg AUC: ↓ 13% darunavir/ritonavir 800/100 mg twice daily/600 mg once daily) Cmin: ↓ 31% once daily may result in *lower than recommended doses, Cmax: ↓ 15% suboptimal darunavir Cmin. If similar findings are expected with (CYP3A4 induction) efavirenz is to be used in recommended doses Efavirenz: combination with AUC: ↑ 21% darunavir/ritonavir, the Cmin: ↑ 17% darunavir/ritonavir 600/100 mg Cmax: ↑ 15% twice daily regimen should be (CYP3A4 inhibition) used. This combination should be used with caution. See also ritonavir row below. Fosamprenavir/ritonavir/ No clinically significant No dose adjustment is necessary efavirenz pharmacokinetic interaction for any of these medicinal (700 mg twice daily/100 mg twice products. See also ritonavir row daily/600 mg once daily) below. Fosamprenavir/nelfinavir/ Interaction not studied No dose adjustment is necessary efavirenz for any of these medicinal products. Fosamprenavir/saquinavir/ Interaction not studied efavirenz

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atazanavir (HOS-086180) nelfinavir (HOS-084520) protease (HOS-085623) saquinavir (HOS-084522) darunavir (HOS-086181) fosamprenavir (HOS-086182) ritonavir (HOS-084521)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-215276 · Präparat HOS-155418

8 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Not recommended as the exposure to both PIs is expected to be significantly decreased. Indinavir/efavirenz Indinavir: While the clinical significance of (800 mg q8h/200 mg once daily) AUC: ↓ 31% (↓ 8 to ↓47) decreased indinavir Cmin: ↓ 40% concentrations has not been A similar reduction in indinavir established, the magnitude of the exposures was observed when observed pharmacokinetic indinavir 1000 mg q8h was given interaction should be taken into with efavirenz 600 mg daily. consideration when choosing a (CYP3A4 induction) regimen containing both efavirenz and indinavir. Efavirenz: No clinically significant pharmacokinetic interaction Indinavir/ritonavir/efavirenz Indinavir: No dose adjustment is necessary (800 mg twice daily/100 mg twice AUC: ↓ 25% (↓ 16 to ↓32) b for efavirenz when given with daily/600 mg once daily) Cmax: ↓ 17% (↓ 6 to ↓ 26) b indinavir or indinavir/ritonavir. Cmin: ↓ 50% (↓ 40 to ↓ 59) b Efavirenz: See also ritonavir row below. No clinically significant pharmacokinetic interaction The geometric mean Cmin for indinavir (0.33 mg/l) when given with ritonavir and efavirenz was higher than the mean historical Cmin (0.15 mg/l) when indinavir was given alone at 800 mg q8h. In HIV-1 infected patients (n=6), the pharmacokinetics of indinavir and efavirenz were generally comparable to these uninfected volunteer data. Lopinavir/ritonavir soft capsules Substantial decrease in lopinavir With efavirenz, an increase of the or oral solution/ efavirenz exposure. lopinavir/ritonavir soft capsule or oral solution doses by 33% should Lopinavir/ritonavir tablets/ be considered (4 capsules/ efavirenz ~6.5 ml twice daily instead of 3 (400/100 mg twice daily/ 600 mg Lopinavir concentrations: ↓ 30-40% capsules/5 ml twice daily). once daily) Caution is warranted since this (500/125 mg twice daily/ 600 mg Lopinavir concentrations: similar to dose adjustment might be once daily) lopinavir/ritonavir 400/100 mg twice insufficient in some patients. The daily without efavirenz dose of lopinavir/ritonavir tablets should be increased to 500/125 mg twice daily when co-administered with efavirenz 600 mg once daily. See also ritonavir row below. Nelfinavir/efavirenz Nelfinavir: No dose adjustment is necessary (750 mg q8h/600 mg once daily) AUC: ↑ 20% (↑ 8 to ↑ 34) for either medicinal product. Cmax: ↑ 21% (↑ 10 to ↑ 33) The combination was generally well tolerated. Ritonavir/efavirenz Ritonavir: When using efavirenz with (500 mg twice daily/600 mg once Morning AUC: ↑ 18% (↑ 6 to ↑ 33) low-dose ritonavir, the possibility daily) Evening AUC: ↔ of an increase in the incidence of Morning Cmax: ↑ 24% (↑ 12 to ↑ 38) efavirenz-associated adverse Evening Cmax: ↔ events should be considered, due

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): indinavir (HOS-084518) lopinavir (HOS-086269) nelfinavir (HOS-084520) ritonavir (HOS-084521)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-215277 · Präparat HOS-155418

9 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Morning Cmin: ↑ 42% (↑ 9 to ↑ 86) b to possible pharmacodynamic Evening Cmin: ↑ 24% (↑ 3 to ↑ 50) b interaction.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-215278 · Präparat HOS-155418

Efavirenz: AUC: ↑ 21% (↑ 10 to ↑ 34) Cmax: ↑ 14% (↑ 4 to ↑ 26) Cmin: ↑ 25% (↑ 7 to ↑ 46) b (Inhibition of CYP-mediated oxidative metabolism) When efavirenz was given with ritonavir 500 mg or 600 mg twice daily, the combination was not well tolerated (for example, dizziness, nausea, paraesthesia and elevated liver enzymes occurred). Sufficient data on the tolerability of efavirenz with low-dose ritonavir (100 mg, once or twice daily) are not available. Saquinavir/ritonavir/efavirenz Interaction not studied No data are available to make a dose recommendation. See also ritonavir row above. Use of efavirenz in combination with saquinavir as the sole protease inhibitor is not recommended. CCR5 antagonist Maraviroc/efavirenz Maraviroc: Refer to the Summary of Product (100 mg twice daily/600 mg once AUC12: ↓ 45% (↓ 38 to ↓ 51) Characteristics for the medicinal daily) Cmax: ↓ 51% (↓ 37 to ↓ 62) product containing maraviroc. Efavirenz concentrations not measured, no effect is expected. Integrase strand transfer inhibitor Raltegravir/efavirenz Raltegravir: No dose adjustment is necessary (400 mg single dose/ -) AUC: ↓ 36% for raltegravir. C12: ↓ 21% Cmax: ↓ 36% (UGT1A1 induction) NRTIs and NNRTIs NRTIs/efavirenz Specific interaction studies have not No dose adjustment is necessary been performed with efavirenz and for either medicinal product. NRTIs other than lamivudine, zidovudine and tenofovir disoproxil. Clinically significant interactions are not expected 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. NNRTIs/efavirenz Interaction not studied Since use of two NNRTIs proved not beneficial in terms of efficacy and safety, co-administration of efavirenz and another NNRTI is not recommended. Hepatitis C antivirals Boceprevir/efavirenz Boceprevir: Plasma trough concentrations of (800 mg 3 times daily/600 mg AUC: ↔ 19%* boceprevir were decreased when once daily) Cmax: ↔ 8% administered with efavirenz. The clinical outcome of this observed

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): protease (HOS-085623) tenofovir disoproxil (HOS-108843) lamivudine (HOS-085829) saquinavir (HOS-084522) boceprevir (HOS-090617) maraviroc (HOS-086186) zidovudine (HOS-085837) raltegravir (HOS-086187) ritonavir (HOS-084521)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10–11

HOS-215280 · Präparat HOS-155418

10 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Cmin: ↓ 44% reduction of boceprevir trough Efavirenz: concentrations has not been AUC: ↔ 20% directly assessed. Cmax: ↔ 11% (CYP3A induction - effect on boceprevir) *0-8 hours No effect (↔) equals a decrease in mean ratio estimate of ≤20% or increase in mean ratio estimate of ≤25% Telaprevir/efavirenz Telaprevir (relative to If efavirenz and telaprevir are co- (1,125 mg q8h/600 mg once 750 mg q8h): administered, telaprevir 1,125 mg daily) AUC: ↓ 18% (↓ 8 to ↓ 27) every 8 hours should be used. Cmax: ↓ 14% (↓ 3 to ↓ 24) Cmin: ↓ 25% (↓ 14 to ↓ 34)% Efavirenz: AUC: ↓ 18% (↓ 10 to ↓ 26) Cmax: ↓ 24% (↓ 15 to ↓ 32) Cmin: ↓ 10% (↑ 1 to ↓ 19)% (CYP3A induction by efavirenz) Simeprevir/efavirenz Simeprevir: Concomitant administration of (150 mg once daily /600 mg once AUC: ↓71% (↓67 to ↓74) simeprevir with efavirenz resulted daily) Cmax: ↓51% (↓46 to ↓56) in significantly decreased plasma concentrations of simeprevir due Cmin: ↓91% (↓88 to ↓92) to CYP3A induction by efavirenz, Efavirenz: which may result in loss of AUC: ↔ therapeutic effect of simeprevir. Cmax: ↔ Co-administration of simeprevir Cmin: ↔ with efavirenz is not No effect (↔) equals a decrease in recommended. mean ratio estimate of ≤20% or increase in mean ratio estimate of ≤25% (CYP3A4 enzyme induction) Sofosbuvir/velpatasvir ↔sofosbuvir Concomitant administration of ↓velpatasvir sofosbuvir/velpatasvir with efavirenz resulted in a ↔efavirenz reduction (approximately 50%) in the systemic exposure of velpatasvir. The mechanism of the effect on velpatasvir is induction of CYP3A and CYP2B6 by efavirenz. Coadministration of sofosbuvir/velpatasvir with efavirenz is not recommended. Refer to the prescribing information for sofosbuvir/velpatasvir for more information.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sofosbuvir (HOS-108928) telaprevir (HOS-090618) boceprevir (HOS-090617) velpatasvir (HOS-108929) simeprevir (HOS-086302)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-215282 · Präparat HOS-155418

11 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Velpatasvir/sofosbuvir/voxilap ↓velpatasvir Concomitant administration of revir ↓voxilaprevir velpatasvir/sofosbuvir/ voxilaprevir with efavirenz is not recommended, as it may decrease concentrations of velpatasvir and voxilaprevir. Refer to the prescribing information for velpatasvir/sofosbuvir/ voxilaprevir for more information. Protease inhibitor : ↓elbasvir Concomitant administration of Elbasvir/grazoprevir ↓grazoprevir efavirenz with elbasvir/grazoprevir is ↔efavirenz contraindicated because it may lead to loss of virologic response to elbasvir/grazoprevir. This loss is due to significant decreases in elbasvir and grazoprevir plasma concentrations caused by CYP3A4 induction. Refer to the prescribing information for elbasvir/grazoprevir for more information. Glecaprevir/pibrentasvir ↓glecaprevir Concomitant administration of ↓ pibrentasvir glecaprevir/pibrentasvir with efavirenz may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect. Coadministration of glecaprevir/pibrentasvir with efavirenz is not recommended. Refer to the prescribing information for glecaprevir/pibrentasvir for more information. Antibiotics Azithromycin/efavirenz No clinically significant No dose adjustment is necessary (600 mg single dose/400 mg once pharmacokinetic interaction for either medicinal product. daily) Clarithromycin/efavirenz Clarithromycin: The clinical significance of these (500 mg q12h/400 mg once daily) AUC: ↓ 39% (↓ 30 to ↓ 46) changes in clarithromycin plasma Cmax: ↓ 26% (↓ 15 to ↓ 35) levels is not known. Alternatives to clarithromycin (e.g. Clarithromycin azithromycin) may be considered. 14-hydroxymetabolite: No dose adjustment is necessary AUC: ↑ 34% (↑ 18 to ↑ 53) for efavirenz. Cmax: ↑ 49% (↑ 32 to ↑ 69)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): elbasvir (HOS-108814) sofosbuvir (HOS-108928) protease (HOS-085623) pibrentasvir (HOS-086298) glecaprevir (HOS-086297) azithromycin (HOS-088112) lead (HOS-085592) voxilaprevir (HOS-108930) grazoprevir (HOS-108815) clarithromycin (HOS-084517) velpatasvir (HOS-108929)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-215285 · Präparat HOS-155418

Efavirenz:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12–13

HOS-215286 · Präparat HOS-155418

12 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) AUC: ↔ Cmax: ↑ 11% (↑ 3 to ↑19) (CYP3A4 induction) Rash developed in 46% of uninfected volunteers receiving efavirenz and clarithromycin. Other macrolide antibiotics (e.g. Interaction not studied No data are available to make a erythromycin)/efavirenz dose recommendation. Antimycobacterials Rifabutin/efavirenz Rifabutin: The daily dose of rifabutin should (300 mg once daily/600 mg once AUC: ↓ 38% (↓ 28 to ↓ 47) be increased by 50% when daily) Cmax: ↓ 32% (↓ 15 to ↓ 46) administered with efavirenz. Cmin: ↓ 45% (↓ 31 to ↓ 56) Consider doubling the rifabutin dose in regimens where rifabutin Efavirenz: is given 2 or 3 times a week in AUC: ↔ combination with efavirenz. The Cmax: ↔ clinical effect of this dose Cmin: ↓ 12% (↓ 24% to ↑ 1%) adjustment has not been (CYP3A4 induction) adequately evaluated. Individual tolerability and virological response should be considered when making the dose adjustment (see section 5.2). Rifampicin/efavirenz Efavirenz: When taken with rifampicin in (600 mg once daily/600 mg once AUC: ↓ 26% (↓ 15 to ↓ 36) patients weighing 50 kg or daily) Cmax: ↓ 20% (↓ 11 to ↓ 28) greater, increasing efavirenz daily Cmin: ↓ 32% (↓ 15 to ↓ 46) dose to 800 mg may provide (CYP3A4 and CYP2B6 induction) exposure similar to a daily dose of 600 mg when taken without rifampicin. The clinical effect of this dose adjustment has not been adequately evaluated. Individual tolerability and virological response should be considered when making the dose adjustment (see section 5.2). No dose adjustment is necessary for rifampicin, including 600 mg. Antifungals Itraconazole/efavirenz Itraconazole: Since no dose recommendation (200 mg q12h/600 mg once daily) AUC: ↓ 39% (↓ 21 to ↓ 53) for itraconazole can be made, Cmax: ↓ 37% (↓ 20 to ↓ 51) alternative antifungal treatment Cmin: ↓ 44% (↓ 27 to ↓ 58) should be considered. (Decrease in itraconazole concentrations: CYP3A4 induction)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rifabutin (HOS-086262) itraconazole (HOS-084516) clarithromycin (HOS-084517) erythromycin (HOS-084514)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13

HOS-215287 · Präparat HOS-155418

Hydroxyitraconazole: AUC: ↓ 37% (↓ 14 to ↓ 55) Cmax: ↓ 35% (↓ 12 to ↓ 52) Cmin: ↓ 43% (↓ 18 to ↓ 60)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13

HOS-215288 · Präparat HOS-155418

Efavirenz: No clinically significant pharmacokinetic change. Posaconazole/efavirenz Posaconazole: Concomitant use of posaconazole (--/400 mg once daily) AUC: ↓ 50% and efavirenz should be avoided Cmax: ↓ 45%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): posaconazole (HOS-085622)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13–14

HOS-215289 · Präparat HOS-155418

13 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) (UDP-G induction) unless the benefit to the patient outweighs the risk. Voriconazole/efavirenz Voriconazole: When efavirenz is (200 mg twice daily/400 mg once AUC: ↓ 77% co-administered with daily) Cmax: ↓ 61% voriconazole, the voriconazole maintenance dose must be Efavirenz: increased to 400 mg twice daily AUC: ↑ 44% and the efavirenz dose must be Cmax: ↑ 38% reduced by 50%, i.e. to 300 mg once daily. When treatment with Voriconazole/efavirenz Voriconazole: voriconazole is stopped, the initial (400 mg twice daily/300 mg once AUC: ↓ 7% (↓ 23 to ↑ 13) * dose of efavirenz should be daily) Cmax: ↑ 23% (↓ 1 to ↑ 53) * restored.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): voriconazole (HOS-084524)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 14

HOS-215290 · Präparat HOS-155418

Efavirenz: AUC: ↑ 17% (↑ 6 to ↑ 29) ** Cmax: ↔** *compared to 200 mg twice daily alone ** compared to 600 mg once daily alone (Competitive inhibition of oxidative metabolism) Fluconazole/efavirenz No clinically significant No dose adjustment is necessary (200 mg once daily/400 mg once pharmacokinetic interaction for either medicinal product. daily) Ketoconazole and other imidazole Interaction not studied No data are available to make a antifungals dose recommendation. Antimalarials Artemether/lumefantrine/efaviren Artemether: Since decreased concentrations of z AUC: ↓ 51% artemether, dihydroartemisinin, or (20/120 mg tablet, 6 doses of 4 Cmax: ↓ 21% lumefantrine may result in a decrease of antimalarial efficacy, tablets each over 3 days/600mg Dihydroartemisinin: caution is recommended when once daily) AUC: ↓ 46% efavirenz and Cmax: ↓ 38% artemether/lumefantrine tablets Lumefantrine: are coadministered. AUC: ↓ 21% Cmax: ↔ Efavirenz: AUC: ↓ 17% Cmax: ↔ (CYP3A4 induction) Atovaquone and proguanil Atovaquone: Concomitant administration of hydrochloride/efavirenz AUC: ↓ 75% (↓ 62 to ↓ 84) atovaquone/proguanil with (250/100 mg single dose/600 mg Cmax: ↓ 44% (↓ 20 to ↓ 61) efavirenz should be avoided. once daily) Proguanil: AUC: ↓ 43% (↓ 7 to ↓ 65) Cmax: ↔

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lumefantrine (HOS-114826) atovaquone (HOS-086266) artemether (HOS-116383) ketoconazole (HOS-084513) imidazole (HOS-117862) proguanil (HOS-138707) fluconazole (HOS-087945)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 14

HOS-215294 · Präparat HOS-155418

Antiparasitics Praziquantel Significant decrease in plasma Concomitant use with concentrations of praziquantel with praziquantel is not recommended. risk of treatment failure due to In case the combination is needed,

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): praziquantel (HOS-132858)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 14–15

HOS-215296 · Präparat HOS-155418

14 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) increased hepatic metabolism by an increased dose of praziquantel efavirenz. could be considered. ACID-REDUCING AGENTS Aluminium hydroxide- Neither aluminium/magnesium Co-administration of efavirenz magnesium hydroxide- hydroxide antacids nor famotidine with medicinal products that alter simethicone antacid/efavirenz altered the absorption of efavirenz. gastric pH would not be expected (30 ml single dose/400 mg single to affect efavirenz absorption. dose)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): praziquantel (HOS-132858) famotidine (HOS-112087) magnesium (HOS-085165) simethicone (HOS-118210)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 15

HOS-215298 · Präparat HOS-155418

Famotidine/efavirenz (40 mg single dose/400 mg single dose) ANTIANXIETY AGENTS Lorazepam/efavirenz Lorazepam: No dose adjustment is necessary (2 mg single dose/600 mg once AUC: ↑ 7% (↑ 1 to ↑ 14) for either medicinal product. daily) Cmax: ↑ 16% (↑ 2 to ↑ 32) These changes are not considered clinically significant. ANTICOAGULANTS Warfarin/efavirenz Interaction not studied. Plasma Dose adjustment of warfarin or Acenocoumarol/efavirenz concentrations and effects of warfarin acenocoumarol may be required. or acenocoumarol are potentially increased or decreased by efavirenz. ANTICONVULSANTS Carbamazepine/efavirenz Carbamazepine: No dose recommendation can be (400 mg once daily/600 mg once AUC: ↓ 27% (↓ 20 to ↓ 33) made. An alternative daily) Cmax: ↓ 20% (↓ 15 to ↓ 24) anticonvulsant should be Cmin: ↓ 35% (↓ 24 to ↓ 44) considered. Carbamazepine plasma levels should be Efavirenz: monitored periodically. AUC: ↓ 36% (↓ 32 to ↓ 40) Cmax: ↓ 21% (↓ 15 to ↓ 26) Cmin: ↓ 47% (↓ 41 to ↓ 53) (decrease in carbamazepine concentrations: CYP3A4 induction; decrease in efavirenz concentrations: CYP3A4 and CYP2B6 induction)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): carbamazepine (HOS-085618) lorazepam (HOS-085981) famotidine (HOS-112087) acenocoumarol (HOS-109456) warfarin (HOS-085950)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 15

HOS-215300 · Präparat HOS-155418

The steady-state AUC, Cmax and Cmin of the active carbamazepine epoxide metabolite remained unchanged. Co-administration of higher doses of either efavirenz or carbamazepine has not been studied. Phenytoin, phenobarbital, and Interaction not studied. There is a When efavirenz is other anticonvulsants that are potential for reduction or increase in co-administered with an substrates of CYP450 isoenzymes the plasma concentrations of anticonvulsant that is a substrate phenytoin, phenobarbital and other of CYP450 isoenzymes, periodic anticonvulsants that are substrates of monitoring of anticonvulsant CYP450 isoenzymes when levels should be conducted. co-administered with efavirenz. Valproic acid/efavirenz No clinically significant effect on No dose adjustment is necessary (250 mg twice daily/600 mg once efavirenz pharmacokinetics. Limited for efavirenz. Patients should be daily) data suggest there is no clinically monitored for seizure control. significant effect on valproic acid pharmacokinetics.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) valproic acid (HOS-088515) carbamazepine (HOS-085618) phenytoin (HOS-084531)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 15–16

HOS-215301 · Präparat HOS-155418

15 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Vigabatrin/efavirenz Interaction not studied. Clinically No dose adjustment is necessary Gabapentin/efavirenz significant interactions are not for any of these medicinal expected since vigabatrin and products. gabapentin are exclusively eliminated unchanged in the urine and are unlikely to compete for the same metabolic enzymes and elimination pathways as efavirenz. ANTIDEPRESSANTS Selective Serotonin Reuptake Inhibitors (SSRIs) Sertraline/efavirenz Sertraline: Sertraline dose increases should (50 mg once daily/600 mg once AUC: ↓ 39% (↓ 27 to ↓ 50) be guided by clinical response. daily) Cmax: ↓ 29% (↓ 15 to ↓ 40) No dose adjustment is necessary Cmin: ↓ 46% (↓ 31 to ↓ 58) for efavirenz.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): vigabatrin (HOS-115599) gabapentin (HOS-090745) serotonin (HOS-085477) sertraline (HOS-086247)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16

HOS-215304 · Präparat HOS-155418

Efavirenz: AUC: ↔ Cmax: ↑ 11% (↑ 6 to ↑ 16) Cmin: ↔ (CYP3A4 induction) Paroxetine/efavirenz No clinically significant No dose adjustment is necessary (20 mg once daily/600 mg once pharmacokinetic interaction for either medicinal product. daily) Fluoxetine/efavirenz Interaction not studied. Since No dose adjustment is necessary fluoxetine shares a similar metabolic for either medicinal product. profile with paroxetine, i.e. a strong CYP2D6 inhibitory effect, a similar lack of interaction would be expected for fluoxetine. Norepinephrine and dopamine reuptake inhibitor Bupropion/efavirenz Bupropion: Increases in bupropion dosage [150 mg single dose (sustained AUC: ↓ 55% (↓ 48 to ↓ 62) should be guided by clinical release)/600 mg once daily] Cmax: ↓ 34% (↓ 21 to ↓ 47) response, but the maximum recommended dose of bupropion Hydroxybupropion: should not be exceeded. No dose AUC: ↔ adjustment is necessary for Cmax: ↑ 50% (↑ 20 to ↑ 80) efavirenz. (CYP2B6 induction) ANTIHISTAMINES Cetirizine/efavirenz Cetirizine: No dose adjustment is necessary (10 mg single dose/600 mg once AUC: ↔ for either medicinal product. daily) Cmax: ↓ 24% (↓ 18 to ↓ 30) These changes are not considered clinically significant.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): paroxetine (HOS-086246) norepinephrine (HOS-090547) bupropion (HOS-086329) dopamine (HOS-085948) fluoxetine (HOS-085946) cetirizine (HOS-215305)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16

HOS-215306 · Präparat HOS-155418

Efavirenz: No clinically significant pharmacokinetic interaction CARDIOVASCULAR AGENTS Calcium Channel Blockers Diltiazem/efavirenz Diltiazem: Dose adjustments of diltiazem (240 mg once daily/600 mg once AUC: ↓ 69% (↓ 55 to ↓ 79) should be guided by clinical daily) Cmax: ↓ 60% (↓ 50 to ↓ 68) response (refer to the Summary of Cmin: ↓ 63% (↓ 44 to ↓ 75) Product Characteristics for diltiazem). No dose adjustment is Desacetyl diltiazem: necessary for efavirenz. AUC: ↓ 75% (↓ 59 to ↓ 84)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): diltiazem (HOS-086288) calcium (HOS-085615)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16–17

HOS-215307 · Präparat HOS-155418

16 Medicinal product by Effects on drug levels Recommendation concerning therapeutic areas Mean percent change in AUC, co-administration with (dose) Cmax, Cmin with confidence efavirenz intervals if availablea (mechanism) Cmax: ↓ 64% (↓ 57 to ↓ 69) Cmin: ↓ 62% (↓ 44 to ↓ 75)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.