Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

Norvir 100 mg powder for oral suspension · Abschnitt 4.5 · PDF-Seite 11

HOS-086185 · Präparat HOS-083284

Medicinal product interactions – Ritonavir with antiretroviral agents other than protease inhibitors Co- Dose of Co- Dose of Medicinal Product AUC Cmin administered administered NORVIR (mg) Assessed Medicinal Medicinal Product Product (mg) Maraviroc 100 q12h 100 q12h Maraviroc ↑161% ↑28% Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure. For further information, refer to the SmPC for maraviroc. Raltegravir 400 single 100 q12h Raltegravir ↓ 16% ↓ 1% Co-adminsitration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

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) maraviroc (HOS-086186) raltegravir (HOS-086187)

Wechselwirkungen · Norvir

Norvir 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 44

HOS-086402 · Präparat HOS-083284

Co- Dose of Co- Dose of NORVIR Medicinal AUC Cmin administered administered (mg) Product Medicinal Medicinal Product Assessed Product (mg) Maraviroc 100 q12h 100 q12h Maraviroc ↑ 161% ↑ 28% Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure. For further information, refer to the SmPC for maraviroc. Raltegravir 400 single 100 q12h Raltegravir ↓ 16% ↓ 1% Co-adminsitration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

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): maraviroc (HOS-086186) raltegravir (HOS-086187)

Wechselwirkungen · Viramune

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

HOS-088108 · Präparat HOS-083615

Maraviroc Maraviroc AUC  1.01 (0.6-1.55) Maraviroc and Viramune can be 300 mg QD Maraviroc Cmin ND co-administered without dose Maraviroc Cmax  1.54 (0.94-2.52) adjustments. compared to historical controls

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): maraviroc (HOS-086186)

Wechselwirkungen · Viramune

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

HOS-088205 · Präparat HOS-083615

Maraviroc Maraviroc AUC  1.01 (0.6-1.55) Maraviroc and Viramune can be 300 mg QD Maraviroc Cmin ND co-administered without dose Maraviroc Cmax  1.54 (0.94-2.52) adjustments. compared to historical controls

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): maraviroc (HOS-086186)

Wechselwirkungen · Viramune

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

HOS-088298 · Präparat HOS-083615

Maraviroc Maraviroc AUC  1.01 (0.6-1.55) Maraviroc and Viramune can be 300 mg QD Maraviroc Cmin ND co-administered without dose Maraviroc Cmax  1.54 (0.94-2.52) adjustments. compared to historical controls

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): maraviroc (HOS-086186)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 12

HOS-108852 · Präparat HOS-093083

(inhibition of CYP3A enzymes) HIV CCR5 – antagonist Maraviroc Maraviroc: The dose of maraviroc should be AUC: ↑ 295% decreased to 150 mg twice daily Cmax: ↑ 97% during co-administration with Due to CYP3A inhibition by Kaletra 400/100 mg twice daily. lopinavir/ritonavir. Integrase inhibitor Raltegravir Raltegravir: No dose adjustment necessary AUC: ↔ Cmax: ↔ C12: ↓ 30% Lopinavir: ↔ Co-administration with other HIV protease inhibitors (PIs) According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended. Fosamprenavir/ ritonavir Fosamprenavir: Co-administration of increased (700/100 mg BID) Amprenavir concentrations are doses of fosamprenavir (1400 mg significantly reduced. BID) with Kaletra oral solution (Lopinavir/ritonavir (533/133 mg BID) to protease 400/100 mg BID) inhibitor-experienced patients resulted in a higher incidence of or gastrointestinal adverse events and elevations in triglycerides with the Fosamprenavir (1400 mg combination regimen without BID) increases in virological efficacy, when compared with standard (Lopinavir/ritonavir doses of fosamprenavir/ritonavir. 533/133 mg BID) Concomitant administration of these medicinal products is not recommended. Tipranavir/ritonavir Lopinavir: Concomitant administration of (500/100 mg BID) AUC: ↓ 55% these medicinal products is not Cmin: ↓ 70% recommended. Cmax: ↓ 47% Acid reducing agents Omeprazole (40 mg QD) Omeprazole: ↔ No dose adjustment necessary

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) maraviroc (HOS-086186) amprenavir (HOS-086183) raltegravir (HOS-086187) fosamprenavir (HOS-086182) tipranavir (HOS-086184) omeprazole (HOS-085912)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 48

HOS-109004 · Präparat HOS-093083

(inhibition of CYP3A enzymes) HIV CCR5 – antagonist Maraviroc Maraviroc: The dose of maraviroc should be AUC: ↑ 295% decreased to 150 mg twice daily Cmax: ↑ 97% during co-administration with Kaletra Due to CYP3A inhibition by 400/100 mg twice daily. lopinavir/ritonavir. Integrase inhibitor Raltegravir Raltegravir: No dose adjustment necessary AUC: ↔ Cmax: ↔ C12: ↓ 30% Lopinavir: ↔ Co-administration with other HIV protease inhibitors (PIs) According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended. Fosamprenavir/ Fosamprenavir: Co-administration of increased doses ritonavir (700/100 mg Amprenavir concentrations are of fosamprenavir (1400 mg BID) BID) significantly reduced. with Kaletra oral solution (533/133 mg BID) to protease inhibitor-experienced patients

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) maraviroc (HOS-086186) amprenavir (HOS-086183) raltegravir (HOS-086187) fosamprenavir (HOS-086182)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 83–84

HOS-109078 · Präparat HOS-093083

83 Maraviroc Maraviroc: The dose of maraviroc should be AUC: ↑ 295% decreased to 150 mg twice daily Cmax: ↑ 97% during co-administration with Due to CYP3A inhibition by Kaletra 400/100 mg twice daily. lopinavir/ritonavir. Integrase inhibitor Raltegravir Raltegravir: No dose adjustment necessary AUC: ↔ Cmax: ↔ C12: ↓ 30% Lopinavir: ↔ Co-administration with other HIV protease inhibitors (PIs) According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended. Fosamprenavir/ Fosamprenavir: Co-administration of increased ritonavir (700/100 mg Amprenavir concentrations are doses of fosamprenavir (1400 mg BID) significantly reduced. BID) with Kaletra oral solution (533/133 mg BID) to protease (Lopinavir/ritonavir inhibitor-experienced patients 400/100 mg BID) resulted in a higher incidence of gastrointestinal adverse events and or elevations in triglycerides with the combination regimen without Fosamprenavir increases in virological efficacy, (1400 mg BID) when compared with standard doses of fosamprenavir/ritonavir. (Lopinavir/ritonavir Concomitant administration of these 533/133 mg BID) medicinal products is not recommended. Kaletra must not be administered once daily in combination with amprenavir. Tipranavir/ritonavir Lopinavir: Concomitant administration of these (500/100 mg BID) AUC: ↓ 55% medicinal products is not Cmin: ↓ 70% recommended. Cmax: ↓ 47% Acid reducing agents Omeprazole (40 mg Omeprazole: ↔ No dose adjustment necessary QD) Lopinavir: ↔ Ranitidine (150 mg Ranitidine: ↔ No dose adjustment necessary single dose) Alpha1 adrenoreceptor antagonist Alfuzosin Alfuzosin: Concomitant administration of Due to CYP3A inhibition by Kaletra and alfuzosin is contra- lopinavir/ritonavir, concentrations indicated (see section 4.3) as of alfuzosin are expected to alfuzosin-related toxicity, including increase. hypotension, may be increased.

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) protease (HOS-085623) maraviroc (HOS-086186) amprenavir (HOS-086183) ranitidine (HOS-085660) raltegravir (HOS-086187) fosamprenavir (HOS-086182) tipranavir (HOS-086184) omeprazole (HOS-085912)

Wechselwirkungen · Prezista

PREZISTA 100 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 14–15

HOS-116357 · Präparat HOS-094447

14 HIV Protease inhibitors (PIs) - with co-administration of low dose ritonavir† Lopinavir/ritonavir lopinavir AUC ↑ 9% Due to a decrease in the exposure 400/100 mg twice daily lopinavir Cmin ↑ 23% (AUC) of darunavir by 40%, lopinavir Cmax ↓ 2% appropriate doses of the darunavir AUC ↓ 38% ‡ combination have not been darunavir Cmin ↓ 51% ‡ established. Hence, concomitant ‡ use of boosted PREZISTA and the darunavir Cmax ↓ 21% Lopinavir/ritonavir combination product lopinavir AUC ↔ 533/133.3 mg twice daily lopinavir/ritonavir is lopinavir Cmin ↑ 13% contraindicated (see section 4.3). lopinavir Cmax ↑ 11% 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 dailymaraviroc Cmin ND 150 mg twice daily when maraviroc Cmax ↑ 129% co-administered with boosted darunavir, ritonavir concentrations were PREZISTA. consistent with historical data α1-ADRENORECEPTOR ANTAGONIST Alfuzosin Based on theoretical considerations Co-administration of boosted PREZISTA is expected to increase PREZISTA and alfuzosin is alfuzosin plasma concentrations. contraindicated (see section 4.3). (CYP3A inhibition) ANAESTHETIC Alfentanil Not studied. The metabolism of alfentanil The concomitant use with boosted is mediated via CYP3A, and may as such PREZISTA may require to lower be inhibited by boosted PREZISTA. the dose of alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression. ANTIANGINA/ANTIARRHYTHMIC Disopyramide Not studied. Boosted PREZISTA is Caution is warranted and Flecainide expected to increase these antiarrhythmic therapeutic concentration Lidocaine (systemic) plasma concentrations. monitoring, if available, is Mexiletine (CYP3A and/or CYP2D6 inhibition) recommended for these Propafenone antiarrhythmics when co-administered with boosted PREZISTA.

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) lopinavir (HOS-086269) propafenone (HOS-084530) protease (HOS-085623) flecainide (HOS-086203) lidocaine (HOS-108866) mexiletine (HOS-086341) disopyramide (HOS-085595) maraviroc (HOS-086186) ritonavir (HOS-084521)

Wechselwirkungen · Prezista

PREZISTA 75 mg film-coated tablets PREZISTA 150 mg film-coated tablets PREZISTA 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 56

HOS-116515 · Präparat HOS-094447

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 lopinavir AUC ↑ 9% Due to a decrease in the exposure 400/100 mg twice daily lopinavir Cmin ↑ 23% (AUC) of darunavir by 40%, lopinavir Cmax ↓ 2% appropriate doses of the darunavir AUC ↓ 38%‡ combination have not been darunavir Cmin ↓ 51% ‡ established. Hence, concomitant ‡ use of PREZISTA co-administered darunavir Cmax ↓ 21% with low dose ritonavir and the lopinavir AUC ↔ Lopinavir/ritonavir 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 dailymaraviroc Cmin ND 150 mg twice daily when maraviroc Cmax ↑ 129% co-administered with PREZISTA darunavir, ritonavir concentrations were with low dose ritonavir. consistent with historical data α1-ADRENORECEPTOR ANTAGONIST Alfuzosin Based on theoretical considerations Co-administration of PREZISTA PREZISTA is expected to increase with low dose ritonavir and alfuzosin plasma concentrations. alfuzosin is contraindicated (see (CYP3A inhibition) section 4.3). ANAESTHETIC Alfentanil Not studied. The metabolism of alfentanil The concomitant use with is mediated via CYP3A, and may as such PREZISTA and low dose ritonavir be inhibited by PREZISTA may require to lower the dose of co-administered with low dose ritonavir. alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression.

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

Wechselwirkungen · Prezista

PREZISTA 400 mg film-coated tablets PREZISTA 800 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 95–96

HOS-116606 · Präparat HOS-094447

95  Saquinavir # It is not recommended to combine darunavir AUC ↓ 26% 1,000 mg twice daily # darunavir Cmin ↓ 42% PREZISTA co-administered with # darunavir Cmax ↓ 17% low dose ritonavir with saquinavir. saquinavir AUC ↓ 6% saquinavir Cmin ↓ 18% PREZISTA co-administered with cobicistat should not be used in saquinavir Cmax ↓ 6% combination with another antiretroviral agent that requires Saquinavir: comparison of pharmacoenhancement by means saquinavir/ritonavir 1,000/100 mg twice of co-administration with an daily vs. saquinavir/darunavir/ritonavir inhibitor of CYP3A4 (see section 1,000/400/100 mg twice daily 4.5). 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 lopinavir AUC ↑ 9% Due to a decrease in the exposure 400/100 mg twice daily lopinavir Cmin ↑ 23% (AUC) of darunavir by 40%, lopinavir Cmax ↓ 2% appropriate doses of the darunavir AUC ↓ 38%‡ combination have not been darunavir Cmin ↓ 51% ‡ established. Hence, concomitant ‡ use of boosted PREZISTA and the darunavir Cmax ↓ 21% Lopinavir/ritonavir combination product lopinavir AUC ↔ 533/133.3 mg twice daily lopinavir/ritonavir is lopinavir Cmin ↑ 13% contraindicated (see section 4.3). lopinavir Cmax ↑ 11% 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 dailymaraviroc Cmin ND 150 mg twice daily when maraviroc Cmax ↑ 129% co-administered with boosted darunavir, ritonavir concentrations were PREZISTA. consistent with historical data α1-ADRENORECEPTOR ANTAGONIST Alfuzosin Based on theoretical considerations Co-administration of boosted PREZISTA is expected to increase PREZISTA and alfuzosin is alfuzosin plasma concentrations. contraindicated (see section 4.3). (CYP3A inhibition) ANAESTHETIC Alfentanil Not studied. The metabolism of alfentanil The concomitant use with boosted is mediated via CYP3A, and may as such PREZISTA may require to lower be inhibited by boosted PREZISTA. the dose of alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression.

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) lopinavir (HOS-086269) protease (HOS-085623) cobicistat (HOS-088111) saquinavir (HOS-084522) maraviroc (HOS-086186) ritonavir (HOS-084521)

Gegenanzeigen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-118451 · Präparat HOS-094825

Hypersensitivity to the active substance or to peanut or soya 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 · Celsentri

CELSENTRI 20 mg/mL oral solution · Abschnitt 4.3 · PDF-Seite 31

HOS-118496 · Präparat HOS-094825

Hypersensitivity to the active substance 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.

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-118452 · Präparat HOS-094825

Maraviroc is metabolised by cytochrome P450 CYP3A4 and CYP3A5. Co-administration of maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects. Co-administration of maraviroc with medicinal products that inhibit CYP3A4 may increase maraviroc plasma concentrations. Dose adjustment of maraviroc is recommended when maraviroc is co-administered with potent CYP3A4 inhibitors and/or inducers. Further details for concomitantly administered medicinal products are provided below (see Table 2).

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

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-118453 · Präparat HOS-094825

Maraviroc is a substrate for the transporters P-glycoprotein and OATP1B1, but the effect of these transporters on the exposure to maraviroc is not known.

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

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-118454 · Präparat HOS-094825

Based on the in vitro and clinical data, the potential for maraviroc to affect the pharmacokinetics of co-administered medicinal products is low. In vitro studies have shown that maraviroc does not inhibit OATP1B1, MRP2 or any of the major P450 enzymes at clinically relevant concentrations (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4). Maraviroc had no clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives ethinylestradiol and levonorgestrel, or urinary 6β-hydroxycortisol/cortisol ratio, suggesting no inhibition or induction of CYP3A4 in vivo. At higher exposure of maraviroc a potential inhibition of CYP2D6 cannot be excluded.

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): levonorgestrel (HOS-089677) midazolam (HOS-086167)

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-118455 · Präparat HOS-094825

Renal clearance accounts for approximately 23% of total clearance of maraviroc when maraviroc is administered without CYP3A4 inhibitors. In vitro studies have shown that maraviroc does not inhibit any of the major renal uptake transporters at clinically relevant concentrations (OAT1, OAT3, OCT2, OCTN1, and OCTN2). Additionally, co-administration of maraviroc with tenofovir (substrate for renal elimination) and cotrimoxazole (contains trimethoprim, a renal cation transport inhibitor), showed no effect on the pharmacokinetics of maraviroc. In addition, co-administration of maraviroc with lamivudine/zidovudine showed no effect of maraviroc on lamivudine (primarily renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics. Maraviroc inhibits P-glycoprotein in vitro (IC50 is 183 μM). However, maraviroc does not significantly affect the pharmacokinetics of digoxin in vivo. It may not be excluded that maraviroc can increase the exposure to the P-glycoprotein substrate dabigatran etexilate.

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) trimethoprim (HOS-085184) digoxin (HOS-086172) lamivudine (HOS-085829) zidovudine (HOS-085837) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Celsentri

CELSENTRI 150 mg film-coated tablets CELSENTRI 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7–8

HOS-118456 · Präparat HOS-094825

7 Table 2: Interactions and adulta dose recommendations with other medicinal products

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

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

HOS-118459 · Präparat HOS-094825

Thus, CELSENTRI dose should be modified in line with the recommendation for co-administration with respective PI/ritonavir combination (see ‘Protease Inhibitors’). Raltegravir 400 mg BID Maraviroc AUC12: ↓ 0.86 No clinically significant (maraviroc 300 mg BID) Maraviroc Cmax: ↓ 0.79 interaction seen. CELSENTRI 300 mg Raltegravir AUC12: ↓ 0.63 twice daily and raltegravir Raltegravir Cmax: ↓ 0.67 can be co-administered Raltegravir C12: ↓ 0.72 without dose adjustment.

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) raltegravir (HOS-086187) ritonavir (HOS-084521)