Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Viramune

Viramune 200 mg tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-088109 · Präparat HOS-083615

Nevirapine concentrations not measured, no effect is expected. INTEGRASE INHIBITORS Elvitegravir/cobicistat Interaction has not been studied. Coadministration of Viramune Cobicistat, a cytochrome P450 3A with elvitegravir in combination inhibitor significantly inhibits with cobicistat is not recommended hepatic enzymes, as well as other (see section 4.4). metabolic pathways. Therefore coadministration would likely result in altered plasma levels of cobicistat and Viramune. Raltegravir No clinical data available. Due to Raltegravir and Viramune can be 400 mg BID the metabolic pathway of co-administered without dose raltegravir no interaction is adjustments. expected. ANTIBIOTICS Clarithromycin Clarithromycin AUC  0.69 Clarithromycin exposure was 500 mg BID (0.62-0.76) significantly decreased, 14-OH Clarithromycin Cmin  0.44 metabolite exposure increased. (0.30-0.64) Because the clarithromycin active Clarithromycin Cmax  0.77 metabolite has reduced activity (0.69-0.86) against Mycobacterium avium- intracellulare complex overall Metabolite 14-OH clarithromycin activity against the pathogen may AUC  1.42 (1.16-1.73) be altered. Alternatives to Metabolite 14-OH clarithromycin clarithromycin, such as Cmin  0 (0.68-1.49) azithromycin should be considered. Metabolite 14-OH clarithromycin Close monitoring for hepatic Cmax  1.47 (1.21-1.80) abnormalities is recommended

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): cobicistat (HOS-088111) azithromycin (HOS-088112) clarithromycin (HOS-084517) raltegravir (HOS-086187) elvitegravir (HOS-088110)

Wechselwirkungen · Viramune

Viramune 50 mg/5 mL oral suspension · Abschnitt 4.5 · PDF-Seite 36

HOS-088207 · Präparat HOS-083615

INTEGRASE INHIBITORS Elvitegravir/ Interaction has not been studied. Coadministration of Viramune cobicistat Cobicistat, a cytochrome P450 3A with elvitegravir in combination inhibitor significantly inhibits with cobicistat is not recommended hepatic enzymes, as well as other (see section 4.4). metabolic pathways. Therefore coadministration would likely

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): cobicistat (HOS-088111) elvitegravir (HOS-088110)

Wechselwirkungen · Viramune

Viramune 400 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 62

HOS-088300 · Präparat HOS-083615

INTEGRASE INHIBITORS Elvitegravir/ Interaction has not been studied. Coadministration of Viramune cobicistat Cobicistat, a cytochrome P450 3A with elvitegravir in combination inhibitor significantly inhibits with cobicistat is not recommended hepatic enzymes, as well as other (see section 4.4). metabolic pathways. Therefore coadministration would likely result in altered plasma levels of cobicistat and Viramune.

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): cobicistat (HOS-088111) elvitegravir (HOS-088110)

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-118457 · Präparat HOS-094825

Medicinal product by Effects on active substance levels Recommendations therapeutic areas Geometric mean change if not concerning co- (dose of CELSENTRI stated otherwise administration in adults used in study) ANTI-INFECTIVES Antiretrovirals Pharmacokinetic Enhancers Cobicistat Interaction not studied. CELSENTRI dose should be decreased to 150 mg Cobicistat is a potent CYP3A twice daily when co- inhibitor. administered with cobicistat containing regimen. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) Lamivudine 150 mg BID Lamivudine AUC12: ↔ 1.13 No significant interaction (maraviroc 300 mg BID) Lamivudine Cmax: ↔ 1.16 seen/expected. Maraviroc concentrations not CELSENTRI 300 mg measured, no effect is expected. twice daily and NRTIs can Tenofovir 300 mg QD Maraviroc AUC12: ↔ 1.03 be co-administered (maraviroc 300 mg BID) Maraviroc Cmax: ↔ 1.03 without dose adjustment. Tenofovir concentrations not measured, no effect is expected. Zidovudine 300 mg BID Zidovudine AUC12: ↔ 0.98 (maraviroc 300 mg BID) Zidovudine Cmax: ↔ 0.92 Maraviroc concentrations not measured, no effect is expected. Integrase Inhibitors Elvitegravir/ritonavir Maraviroc AUC12: ↑ 2.86 (2.33-3.51) Elvitegravir as a single 150/100mg QD Maraviroc Cmax: ↑ 2.15 (1.71-2.69) agent is indicated only in (maraviroc 150 mg BID) Maraviroc C12: ↑ 4.23 (3.47-5.16) combination with certain ritonavir boosted PIs. Elvitegravir AUC24: ↔ 1.07 (0.96-1.18) Elvitegravir per se is not Elvitegravir Cmax: ↔ 1.01 expected to affect (0.89-1.15) maraviroc exposure to a Elvitegravir C24: ↔ 1.09 (0.95-1.26) clinically relevant degree and the observed effect is attributed to 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) cobicistat (HOS-088111) lamivudine (HOS-085829) zidovudine (HOS-085837) ritonavir (HOS-084521) elvitegravir (HOS-088110)

Wechselwirkungen · Celsentri

CELSENTRI 20 mg/mL oral solution · Abschnitt 4.5 · PDF-Seite 35

HOS-118502 · Präparat HOS-094825

Medicinal product by Effects on active substance levels Recommendations therapeutic areas Geometric mean change if not concerning co- (dose of CELSENTRI stated otherwise administration in adults used in study) ANTI-INFECTIVES Antiretrovirals Pharmacokinetic Enhancers Cobicistat Interaction not studied. CELSENTRI dose should be decreased to 150 mg twice Cobicistat is a potent CYP3A daily when co-administered inhibitor. with cobicistat containing regimen. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) Lamivudine 150 mg BID Lamivudine AUC12: ↔ 1.13 No significant interaction (maraviroc 300 mg BID) Lamivudine Cmax: ↔ 1.16 seen/expected. CELSENTRI Maraviroc concentrations not 300 mg twice daily and measured, no effect is expected. NRTIs can be Tenofovir 300 mg QD Maraviroc AUC12: ↔ 1.03 co-administered without dose (maraviroc 300 mg BID) Maraviroc Cmax: ↔ 1.03 adjustment. Tenofovir concentrations not measured, no effect is expected. Zidovudine 300 mg BID Zidovudine AUC12: ↔ 0.98 (maraviroc 300 mg BID) Zidovudine Cmax: ↔ 0.92 Maraviroc concentrations not measured, no effect is expected. Integrase Inhibitors Elvitegravir/ritonavir Maraviroc AUC12: ↑ 2.86 (2.33-3.51) Elvitegravir as a single agent 150/100mg QD Maraviroc Cmax: ↑ 2.15 (1.71-2.69) is indicated only in (maraviroc 150 mg BID) Maraviroc C12: ↑ 4.23 (3.47-5.16) combination with certain ritonavir boosted PIs. Elvitegravir AUC24: ↔ 1.07 (0.96-1.18) Elvitegravir per se is not Elvitegravir Cmax: ↔ 1.01 (0.89-1.15) expected to affect maraviroc Elvitegravir C24: ↔ 1.09 (0.95-1.26) exposure to a clinically relevant degree and the observed effect is attributed to 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) cobicistat (HOS-088111) lamivudine (HOS-085829) zidovudine (HOS-085837) ritonavir (HOS-084521) elvitegravir (HOS-088110)

Wechselwirkungen · Harvoni

Harvoni 90 mg/400 mg film-coated tablets Harvoni 45 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16–17

HOS-132258 · Präparat HOS-097208

16  Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b Elvitegravir/ cobicistat/ Interaction not studied. When given with elvitegravir/ cobicistat/ emtricitabine/ tenofovir Expected: emtricitabine/ tenofovir disoproxil fumarate, disoproxil fumarate ↔ Emtricitabine Harvoni is expected to increase the concentration of (150 mg/ 150 mg/ 200 mg/ ↑ Tenofovir tenofovir. 300 mg once daily)/ ledipasvir (90 mg once Observed: The safety of tenofovir disoproxil fumarate in the daily)c/ sofosbuvir (400 mg Elvitegravir setting of Harvoni and a pharmacokinetic enhancer once daily)c ↔ Cmax 0.88 (0.82, 0.95) (e.g. ritonavir or cobicistat) has not been ↔ AUC 1.02 (0.95, 1.09) established. ↑ Cmin 1.36 (1.23, 1.49) The combination should be used with caution with Cobicistat frequent renal monitoring, if other alternatives are ↔ Cmax 1.25 (1.18, 1.32) not available (see section 4.4). ↑ AUC 1.59 (1.49, 1.70) ↑ Cmin 4.25 (3.47, 5.22)

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) cobicistat (HOS-088111) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 55

HOS-132363 · Präparat HOS-097208

GS-331007 ↔ Cmax 1.09 (0.99, 1.19) ↔ AUC 1.02 (0.97, 1.08) Elvitegravir/ cobicistat/ Interaction not studied. When given with elvitegravir/ cobicistat/ emtricitabine/ tenofovir Expected: emtricitabine/ tenofovir disoproxil fumarate, disoproxil fumarate ↔ Emtricitabine Harvoni is expected to increase the concentration of (150 mg/ 150 mg/ 200 mg/ ↑ Tenofovir tenofovir. 300 mg once daily)/ ledipasvir (90 mg once Observed: The safety of tenofovir disoproxil fumarate in the daily)c/ sofosbuvir (400 mg Elvitegravir setting of Harvoni and a pharmacokinetic enhancer once daily)c ↔ Cmax 0.88 (0.82, 0.95) (e.g. ritonavir or cobicistat) has not been ↔ AUC 1.02 (0.95, 1.09) established. ↑ Cmin 1.36 (1.23, 1.49) The combination should be used with caution with Cobicistat frequent renal monitoring, if other alternatives are ↔ Cmax 1.25 (1.18, 1.32) not available (see section 4.4). ↑ AUC 1.59 (1.49, 1.70) ↑ Cmin 4.25 (3.47, 5.22)

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) cobicistat (HOS-088111) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Gegenanzeigen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-133891 · Präparat HOS-097520

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

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

Gegenanzeigen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-133892 · Präparat HOS-097520

Co-administration with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious or life-threatening adverse reactions. Therefore, Genvoya should not be co-administered with medicinal products that include, but are not limited to, the following (see sections 4.4 and 4.5): • alpha 1-adrenoreceptor antagonists: alfuzosin • antiarrhythmics: amiodarone, quinidine • ergot derivatives: dihydroergotamine, ergometrine, ergotamine • gastrointestinal motility agents: cisapride • HMG Co-A reductase inhibitors: lovastatin, simvastatin • lipid-modifying agent: lomitapide • neuroleptics/antipsychotics: pimozide, lurasidone • PDE-5 inhibitors: sildenafil for the treatment of pulmonary arterial hypertension • sedatives/hypnotics: orally administered midazolam, triazolam

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): alfuzosin (HOS-086139) cisapride (HOS-085610) lovastatin (HOS-086157) lomitapide (HOS-086160) simvastatin (HOS-086158) quinidine (HOS-085593) pimozide (HOS-085600) sildenafil (HOS-086162) ergotamine (HOS-086154) amiodarone (HOS-085596) lurasidone (HOS-086148) triazolam (HOS-086168) dihydroergotamine (HOS-086152) midazolam (HOS-086167)

Gegenanzeigen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-133905 · Präparat HOS-097520

Co-administration with medicinal products that are strong inducers of CYP3A due to the potential for loss of virologic response and possible resistance to Genvoya. Therefore, Genvoya should not be co-administered with medicinal products that include, but are not limited to, the following (see sections 4.4 and 4.5): • anticonvulsants: carbamazepine, phenobarbital, phenytoin • antimycobacterials: rifampicin • herbal products: St. John’s wort (Hypericum perforatum)

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) phenytoin (HOS-084531)

Gegenanzeigen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-133906 · Präparat HOS-097520

Co-administration with dabigatran etexilate, a P-glycoprotein (P-gp) substrate (see section 4.5).

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): dabigatran etexilate (HOS-086233)

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133908 · Präparat HOS-097520

Genvoya should not be co-administered with other antiretroviral medicinal products. Therefore, information regarding drug-drug interactions with other antiretroviral products (including protease inhibitors [PIs] and non-nucleoside reverse transcriptase inhibitors [NNRTIs]) is not provided (see section 4.4). Interaction studies have only been performed in adults.

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)

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133909 · Präparat HOS-097520

Genvoya should not be administered concomitantly with medicinal products containing tenofovir alafenamide, tenofovir disoproxil, lamivudine or adefovir dipivoxil used for the treatment of HBV infection.

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) adefovir dipivoxil (HOS-110478) tenofovir disoproxil (HOS-108843) lamivudine (HOS-085829)

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133914 · Präparat HOS-097520

Elvitegravir

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

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133915 · Präparat HOS-097520

Elvitegravir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A may affect the exposure of elvitegravir. Co-administration of Genvoya with medicinal products that induce CYP3A may result in decreased plasma concentrations of elvitegravir and reduced therapeutic effect of Genvoya (see “Concomitant use contraindicated” and section 4.3). Elvitegravir may have the potential to induce CYP2C9 and/or inducible uridine diphosphate glucuronosyltransferase (UGT) enzymes; as such it may decrease the plasma concentration of substrates of these enzymes.

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): uridine (HOS-085192)

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133917 · Präparat HOS-097520

Cobicistat

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

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133918 · Präparat HOS-097520

Cobicistat is a strong mechanism-based inhibitor of CYP3A and is also a CYP3A substrate. Cobicistat is also a weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6. Medicinal products that inhibit CYP3A may decrease the clearance of cobicistat, resulting in increased plasma concentrations of cobicistat. Medicinal products that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s).

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

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133919 · Präparat HOS-097520

Medicinal products that are highly dependent on CYP3A metabolism and have high first pass metabolism are the most susceptible to large increases in exposure when co-administered with cobicistat (see “Concomitant use contraindicated” and section 4.3).

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

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133920 · Präparat HOS-097520

Cobicistat is an inhibitor of the following transporters: P-gp, breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration with medicinal products that are substrates of P-gp, BCRP, OATP1B1 and OATP1B3 may result in increased plasma concentrations of these products.

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

Wechselwirkungen · Genvoya

Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets Genvoya 90 mg/90 mg/120 mg/6 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-133921 · Präparat HOS-097520

Emtricitabine

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