Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134464 · Präparat HOS-097580

A clinical study utilising a cocktail of medicinal products that are metabolised by cytochromes CYP2C9, CYP2C19 and CYP2D6 demonstrated an increase in CYP2C9 and CYP2C19 activity and inhibition of CYP2D6 activity in the presence of darunavir/ritonavir, which may be attributed to the presence of low dose ritonavir. Co-administration of darunavir and ritonavir with medicinal products which are primarily metabolised by CYP2D6 (such as flecainide, propafenone, metoprolol) may result in increased plasma concentrations of these medicinal products, which could increase or prolong their therapeutic effect and adverse reactions. Co-administration of darunavir and ritonavir with medicinal products primarily metabolised by CYP2C9 (such as warfarin) and CYP2C19 (such as methadone) may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.

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): propafenone (HOS-084530) methadone (HOS-086198) flecainide (HOS-086203) ritonavir (HOS-084521) metoprolol (HOS-090094) warfarin (HOS-085950)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134465 · Präparat HOS-097580

Although the effect on CYP2C8 has only been studied in vitro, co-administration of darunavir and ritonavir and medicinal products primarily metabolised by CYP2C8 (such as paclitaxel, rosiglitazone, repaglinide) may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.

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): rosiglitazone (HOS-089664) paclitaxel (HOS-087959) ritonavir (HOS-084521) repaglinide (HOS-086935)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134469 · Präparat HOS-097580

Ritonavir inhibits the transporters P-glycoprotein, OATP1B1 and OATP1B3, and co-administration with substrates of these transporters can result in increased plasma concentrations of these compounds (e.g. dabigatran etexilate, digoxin, statins and bosentan; see the Interaction table below).

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): digoxin (HOS-086172) ritonavir (HOS-084521) bosentan (HOS-086291) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134470 · Präparat HOS-097580

Medicinal products that affect darunavir/ritonavir exposure Darunavir and ritonavir are metabolised by CYP3A. Medicinal products that induce CYP3A activity would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma concentrations of darunavir and ritonavir (e.g. rifampicin, St John’s wort, lopinavir). Co-administration of darunavir and ritonavir and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (e.g. indinavir, azole antifungals like clotrimazole). These interactions are described in the interaction table below.

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) clotrimazole (HOS-090574) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134472 · Präparat HOS-097580

Interaction table

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

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134473 · Präparat HOS-097580

Interactions between darunavir/ritonavir and antiretroviral and non-antiretroviral medicinal products are listed in the table below. The direction of the arrow for each pharmacokinetic parameter is based on the 90% confidence interval of the geometric mean ratio being within (↔), below (↓) or above (↑) the 80-125% range (not determined as “ND”).

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): ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134474 · Präparat HOS-097580

Several of the interaction studies (indicated by # in the table below) have been performed at lower than recommended doses of darunavir or with a different dosing regimen (see section 4.2 Posology). The effects on co-administered medicinal products may thus be underestimated and clinical monitoring of safety may be indicated.

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

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-134475 · Präparat HOS-097580

The below list of examples of drug -drug interactions is not comprehensive and therefore the label of each drug that is co-administered with darunavir should be consulted for information related to the

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

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-134476 · Präparat HOS-097580

9 route of metabolism, interaction pathways, potential risks, and specific actions to be taken with regards to co-administration.

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

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-134477 · Präparat HOS-097580

INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration HIV ANTIRETROVIRALS Integrase strand transfer inhibitors Dolutegravir dolutegravir AUC ↓ 22% dolutegravir Darunavir co-administered with low C24h ↓ 38% dolutegravir Cmax ↓ 11% dose ritonavir and dolutegravir can darunavir ↔* be used without dose adjustment. * Using cross-study comparisons to historical pharmacokinetic data Raltegravir Some clinical studies suggest At present the effect of raltegravir raltegravir may cause a modest on darunavir plasma concentrations decrease in darunavir plasma does not appear to be clinically concentrations. relevant. Darunavir co-administered with low dose ritonavir and raltegravir can be used without dose adjustments. Nucleo(s/t)ide reverse transcriptase inhibitors (NRTIs) Didanosine didanosine AUC ↓ 9% Darunavir co-administered with low 400 mg once daily didanosine Cmin ND dose ritonavir and didanosine can didanosine Cmax ↓ 16% be used without dose adjustments. darunavir AUC ↔ Didanosine is to be administered on darunavir Cmin ↔ an empty stomach, thus it should be darunavir Cmax ↔ administered 1 hour before or 2 hours after darunavir/ritonavir given with food. Tenofovir disoproxil tenofovir AUC ↑ 22% Monitoring of renal function may 245 mg once daily‡ tenofovir Cmin ↑ 37% be indicated when darunavir co- tenofovir Cmax ↑ 24% administered with low dose # darunavir AUC ↑ 21% ritonavir is given in combination # darunavir Cmin ↑ 24% with tenofovir disoproxil, # darunavir Cmax ↑ 16% particularly in patients with underlying systemic or renal (↑ tenofovir from effect on MDR-1 disease, or in patients taking transport in the renal tubules) nephrotoxic agents. Emtricitabine/tenofovir Tenofovir alafenamide ↔ The recommended dose of alafenamide Tenofovir ↑ emtricitabine/tenofovir alafenamide is 200/10 mg once daily when used with darunavir with low dose ritonavir. Abacavir Not studied. Based on the different Darunavir co-administered with low Emtricitabine elimination pathways of the other dose ritonavir can be used with Lamivudine NRTIs zidovudine, emtricitabine, these NRTIs without dose Stavudine stavudine, lamivudine, that are adjustment. Zidovudine primarily renally excreted, and abacavir for which metabolism is not mediated by CYP450, no interactions are expected for these medicinal compounds and darunavir co- administered with low dose ritonavir.

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): tenofovir (HOS-088083) tenofovir alafenamide (HOS-110476) stavudine (HOS-088080) dolutegravir (HOS-089992) tenofovir disoproxil (HOS-108843) lamivudine (HOS-085829) didanosine (HOS-085836) zidovudine (HOS-085837) raltegravir (HOS-086187) ritonavir (HOS-084521) abacavir (HOS-088077) emtricitabine (HOS-085840)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10–11

HOS-134481 · Präparat HOS-097580

10 INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration Non-nucleo(s/t)ide reverse transcriptase inhibitors (NNRTIs) Efavirenz efavirenz AUC ↑ 21% Clinical monitoring for central 600 mg once daily efavirenz Cmin ↑ 17% nervous system toxicity associated efavirenz Cmax ↑ 15% with increased exposure to # darunavir AUC ↓ 13% efavirenz may be indicated when # darunavir Cmin ↓ 31% darunavir co-administered with low # darunavir Cmax ↓ 15% dose ritonavir is given in combination with efavirenz. (↑ efavirenz from CYP3A inhibition) (↓ darunavir from CYP3A induction) 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 (see section 4.4). Etravirine etravirine AUC ↓ 37% Darunavir co-administered with low 100 mg twice daily etravirine Cmin ↓ 49% dose ritonavir and etravirine 200 mg etravirine Cmax ↓ 32% twice daily can be used without dose adjustments. darunavir AUC ↑ 15% darunavir Cmin ↔ darunavir Cmax ↔ Nevirapine nevirapine AUC ↑ 27% Darunavir co-administered with low 200 mg twice daily nevirapine Cmin ↑ 47% dose ritonavir and nevirapine can be nevirapine Cmax ↑ 18% used without dose adjustments. # darunavir: concentrations were consistent with historical data (↑ nevirapine from CYP3A inhibition) Rilpivirine rilpivirine AUC ↑ 130% Darunavir co-administered with low 150 mg once daily rilpivirine Cmin ↑ 178% dose ritonavir and rilpivirine can be rilpivirine C ↑ 79% used without dose adjustments. max darunavir AUC ↔ darunavir Cmin ↓ 11% darunavir Cmax ↔ HIV Protease inhibitors (PIs) - without additional co-administration of low dose ritonavir† Atazanavir atazanavir AUC ↔ Darunavir co-administered with low 300 mg once daily atazanavir Cmin ↑ 52% dose ritonavir and atazanavir can be atazanavir Cmax ↓ 11% used without dose adjustments. # darunavir AUC ↔ # darunavir Cmin ↔ # darunavir 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): atazanavir (HOS-086180) protease (HOS-085623) etravirine (HOS-088088) rilpivirine (HOS-088090) efavirenz (HOS-087947) nevirapine (HOS-088064) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-134483 · Präparat HOS-097580

Atazanavir: comparison of atazanavir/ritonavir 300/100 mg once daily vs. atazanavir 300 mg once daily in combination with darunavir/ritonavir 400/100 mg twice daily. Darunavir: comparison of darunavir/ritonavir 400/100 mg twice daily vs. darunavir/ritonavir 400/100 mg twice daily in combination with atazanavir 300 mg once daily.

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) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-134484 · Präparat HOS-097580

11 INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration Indinavir indinavir AUC ↑ 23% When used in combination with 800 mg twice daily indinavir Cmin ↑ 125% darunavir co-administered with low indinavir Cmax ↔ dose ritonavir, dose adjustment of # darunavir AUC ↑ 24% indinavir from 800 mg twice daily to 600 mg twice daily may be # darunavir Cmin ↑ 44% warranted in case of intolerance. # darunavir Cmax ↑ 11%

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) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-134485 · Präparat HOS-097580

Indinavir: comparison of indinavir/ritonavir 800/100 mg twice daily vs. indinavir/darunavir/ritonavir 800/400/100 mg twice daily. Darunavir: comparison of darunavir/ritonavir 400/100 mg twice daily vs. darunavir/ritonavir 400/100 mg in combination with indinavir 800 mg twice daily. Saquinavir # darunavir AUC ↓ 26% It is not recommended to combine 1,000 mg twice daily # darunavir Cmin ↓ 42% darunavir co-administered with low # darunavir Cmax ↓ 17% dose ritonavir with saquinavir. saquinavir AUC ↓ 6% saquinavir Cmin ↓ 18% saquinavir Cmax ↓ 6%

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) saquinavir (HOS-084522) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-134486 · Präparat HOS-097580

Saquinavir: comparison of saquinavir/ritonavir 1,000/100 mg twice daily vs. saquinavir/darunavir/ritonavir 1,000/400/100 mg twice daily. Darunavir: comparison of darunavir/ritonavir 400/100 mg twice daily vs. darunavir/ritonavir 400/100 mg in combination with saquinavir 1,000 mg twice daily. HIV Protease inhibitors (PIs) - with co-administration of low dose ritonavir† Lopinavir/ritonavir 400/100 lopinavir AUC ↑ 9% Due to a decrease in the exposure mg twice daily lopinavir Cmin ↑ 23% (AUC) of darunavir by 40%, lopinavir Cmax ↓ 2% appropriate doses of the combination have not been darunavir AUC ↓ 38% ‡ established. Hence, concomitant use darunavir Cmin ↓ 51%‡ of darunavir co-administered with darunavir Cmax ↓ 21%‡ low dose ritonavir and the Lopinavir/ritonavir lopinavir AUC ↔ combination product 533/133.3 mg twice daily lopinavir Cmin ↑ 13% lopinavir/ritonavir is lopinavir Cmax ↑ 11% contraindicated (see section 4.3). darunavir AUC ↓ 41% darunavir Cmin ↓ 55% darunavir Cmax ↓ 21% ‡ based upon non dose normalised values CCR5 ANTAGONIST Maraviroc maraviroc AUC ↑ 305% The maraviroc dose should be 150 mg twice daily maraviroc Cmin ND 150 mg twice daily when co- maraviroc Cmax ↑ 129% administered with darunavir with darunavir, ritonavir concentrations low dose ritonavir. were consistent with historical data α1-ADRENORECEPTOR ANTAGONIST

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): lopinavir (HOS-086269) protease (HOS-085623) saquinavir (HOS-084522) maraviroc (HOS-086186) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12–13

HOS-134488 · Präparat HOS-097580

12 INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration Alfuzosin Based on theoretical considerations Co-administration of darunavir with darunavir is expected to increase low dose ritonavir and alfuzosin is alfuzosin plasma concentrations. contraindicated (see section 4.3). (CYP3A inhibition) ANAESTHETIC Alfentanil Not studied. The metabolism of The concomitant use with darunavir alfentanil is mediated via CYP3A, and and low dose ritonavir may require may as such be inhibited by darunavir to lower the dose of alfentanil and co-administered with low dose requires monitoring for risks of ritonavir. prolonged or delayed respiratory depression. ANTIANGINA/ANTIARRHYTHMIC Disopyramide Not studied. Darunavir is expected to Caution is warranted and Flecainide increase these antiarrhythmic plasma therapeutic concentration Lidocaine concentrations. monitoring, if available, is (systemic) (CYP3A and/or CYP2D6 inhibition) recommended for these Mexiletine antiarrhythmics when co- Propafenone administered with darunavir with low dose ritonavir.

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): alfentanil (HOS-109375) alfuzosin (HOS-086139) propafenone (HOS-084530) flecainide (HOS-086203) lidocaine (HOS-108866) mexiletine (HOS-086341) disopyramide (HOS-085595) ritonavir (HOS-084521)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13

HOS-134490 · Präparat HOS-097580

Amiodarone Darunavir co-administered with low Bepridil dose ritonavir and amiodarone, Dronedarone bepridil, dronedarone, ivabradine, Ivabradine, quinidine, or ranolazine is Quinidine contraindicated (see section 4.3). Ranolazine Digoxin digoxin AUC ↑ 61% Given that digoxin has a narrow 0.4 mg single dose digoxin Cmin ND therapeutic index, it is digoxin Cmax ↑ 29% recommended that the lowest (↑ digoxin from probable inhibition of possible dose of digoxin should P-gp) initially be prescribed in case digoxin is given to patients on darunavir/ritonavir therapy. The digoxin dose should be carefully titrated to obtain the desired clinical effect while assessing the overall clinical state of the subject. ANTIBIOTIC clarithromycin AUC ↑ 57% Clarithromycin 500 mg Caution should be exercised when twice daily clarithromycin Cmin ↑ 174% clarithromycin is combined with clarithromycin Cmax ↑ 26% darunavir co-administered with low # darunavir AUC ↓ 13% dose ritonavir. # darunavir Cmin ↑ 1% # darunavir Cmax ↓ 17% For patients with renal impairment the Summary of Product 14-OH-clarithromycin concentrations Characteristics for clarithromycin were not detectable when combined should be consulted for the with darunavir/ritonavir. recommended dose. (↑ clarithromycin from CYP3A inhibition and possible P-gp inhibition) ANTICOAGULANT/PLATELET AGGREGATION INHIBITOR Apixaban Not studied. Co-administration of The use of boosted darunavir with a Rivaroxaban boosted darunavir with these direct anticoagulant (DOAC) that is anticoagulants may increase metabolized by CYP3A4 and concentrations of the anticoagulant. transported by P-gp is not (CYP3A and/or P-gp inhibition). recommended as this may lead to an increased bleeding risk.

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): dronedarone (HOS-086144) bepridil (HOS-085612) quinidine (HOS-085593) digoxin (HOS-086172) rivaroxaban (HOS-086236) lead (HOS-085592) clarithromycin (HOS-084517) apixaban (HOS-112091) ivabradine (HOS-109426) ritonavir (HOS-084521) amiodarone (HOS-085596) ranolazine (HOS-086141)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13–14

HOS-134491 · Präparat HOS-097580

13 INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration Dabigatran etexilate dabigatran etexilate (150 mg): Darunavir/ritonavir: Edoxaban darunavir/ritonavir 800/100 mg Clinical monitoring and/or dose single dose: reduction of the DOAC should be dabigatran AUC ↑ 72% considered when a DOAC dabigatran Cmax ↑ 64% transported by P-gp but not metabolised by CYP3A4, including darunavir/ritonavir 800/100 mg dabigatran etexilate and edoxaban, once daily: is co-administered with dabigatran AUC ↑ 18% Darunavir/rtv. dabigatran Cmax ↑ 22% Ticagrelor Based on theoretical considerations, Concomitant administration of co-administration of boosted darunavir boosted darunavir with ticagrelor is with ticagrelor may increase contraindicated (see section 4.3). concentrations of ticagrelor (CYP3A and/or P-glycoprotein inhibition).

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): ticagrelor (HOS-112065) dabigatran (HOS-112096) edoxaban (HOS-086234) ritonavir (HOS-084521) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 14

HOS-134492 · Präparat HOS-097580

Clopidogrel Not studied. Co-administration of Co-administration of clopidogrel clopidogrel with boosted darunavir is with boosted darunavir is not expected to decrease clopidogrel active recommended. metabolite plasma concentration, which may reduce the antiplatelet Use of other antiplatelets not activity of clopidogrel. affected by CYP inhibition or induction (e.g. prasugrel) is recommended. Warfarin Not studied. Warfarin concentrations It is recommended that the may be affected when co-administered international normalised ratio (INR) with darunavir with low dose ritonavir. be monitored when warfarin is combined with darunavir co- administered with low dose ritonavir. ANTICONVULSANTS Phenobarbital Not studied. Phenobarbital and Darunavir co-administered with low Phenytoin phenytoin are expected to decrease dose ritonavir should not be used in plasma concentrations of darunavir and combination with these medicines. its pharmacoenhancer. (induction of CYP450 enzymes) Carbamazepine carbamazepine AUC ↑ 45% No dose adjustment for 200 mg twice daily carbamazepine Cmin ↑ 54% darunavir/ritonavir is carbamazepine Cmax ↑ 43% recommended. If there is a need to darunavir AUC ↔ combine darunavir/ritonavir and darunavir Cmin ↓ 15% carbamazepine, patients should be darunavir Cmax ↔ monitored for potential carbamazepine-related adverse events. Carbamazepine concentrations should be monitored and its dose should be titrated for adequate response. Based upon the findings, the carbamazepine dose may need to be reduced by 25% to 50% in the presence of darunavir/ritonavir. Clonazepam Not studied. Co-administration of Clinical monitoring is boosted darunavir with clonazepam recommended when co- may increase concentrations of administering boosted darunavir clonazepam. (CYP3A inhibition) with clonazepam.

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) carbamazepine (HOS-085618) clonazepam (HOS-116372) clopidogrel (HOS-087927) prasugrel (HOS-112066) ritonavir (HOS-084521) phenytoin (HOS-084531) warfarin (HOS-085950)

Wechselwirkungen · Darunavir Viatris (previously Darunavir Mylan)

Darunavir Viatris 75 mg film-coated tablets Darunavir Viatris 150 mg film-coated tablets Darunavir Viatris 300 mg film-coated tablets Darunavir Viatris 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 14–15

HOS-134494 · Präparat HOS-097580

14 INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS Medicinal products by Interaction Geometric mean change Recommendations concerning co- therapeutic areas (%) administration ANTIDEPRESSANTS Paroxetine paroxetine AUC ↓ 39% If antidepressants are co- 20 mg once daily paroxetine Cmin ↓ 37% administered with darunavir with paroxetine Cmax ↓ 36% low dose ritonavir, the recommended approach is a dose # darunavir AUC ↔ titration of the antidepressant based # darunavir Cmin ↔ on a clinical assessment of # darunavir Cmax ↔ antidepressant response. In addition, Sertraline sertraline AUC ↓ 49% patients on a stable dose of these 50 mg once daily sertraline Cmin ↓ 49% antidepressants who start treatment sertraline Cmax ↓ 44% with darunavir with low dose # darunavir AUC ↔ ritonavir should be monitored for # darunavir Cmin ↓ 6% antidepressant response. # darunavir Cmax ↔ Clinical monitoring is recommended when co- Concomitant use of darunavir co- administering darunavir with low administered with low dose ritonavir dose ritonavir with these and these antidepressants may increase antidepressants and a dose concentrations of the antidepressant. adjustment of the antidepressant (CYP2D6 and/or CYP3A inhibition) may be needed. Amitriptyline Desipramine Imipramine Nortriptyline Trazodone ANTIEMETICS Domperidone Not studied. Co-administration of domperidone with boosted darunavir is contraindicated. ANTIFUNGALS Voriconazole Not studied. Ritonavir may decrease Voriconazole should not be plasma concentrations of voriconazole. combined with darunavir co- (induction of CYP450 enzymes) administered with low dose ritonavir unless an assessment of the benefit/risk ratio justifies the use of voriconazole. Fluconazole Not studied. Darunavir may increase Caution is warranted and clinical Isavuconazole antifungal plasma concentrations and monitoring is recommended. When Itraconazole posaconazole, isavuconazole, co-administration is required the Posaconazole itraconazole, or fluconazole may daily dose of itraconazole should increase darunavir concentrations. not exceed 200 mg. (CYP3A and/or P-gp inhibition)

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) isavuconazole (HOS-085186) nortriptyline (HOS-086245) amitriptyline (HOS-085911) desipramine (HOS-086249) imipramine (HOS-085907) domperidone (HOS-114656) voriconazole (HOS-084524) itraconazole (HOS-084516) trazodone (HOS-086251) fluconazole (HOS-087945) sertraline (HOS-086247) ritonavir (HOS-084521) posaconazole (HOS-085622)