Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 21–22

HOS-108912 · Präparat HOS-093083

21 Inhaled, injectable or Fluticasone propionate, 50 g Greater effects may be expected intranasal fluticasone intranasal 4 times daily: when fluticasone propionate is propionate, budesonide, Plasma concentrations ↑ inhaled. Systemic corticosteroid triamcinolone Cortisol levels ↓ 86% effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide and triamcinolone. Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period. Phosphodiesterase(PDE5) inhibitors Avanafil Avanafil: The use of avanafil with Kaletra is (ritonavir 600 mg BID) AUC: ↑ 13-fold contraindicated (see section 4.3). Due to CYP3A inhibition by lopinavir/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): triamcinolone (HOS-086333) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) avanafil (HOS-086161) budesonide (HOS-086332) propionate (HOS-108915) beclomethasone (HOS-086334)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 57–58

HOS-109017 · Präparat HOS-093083

57 Inhaled, injectable or Fluticasone propionate, 50 g Greater effects may be expected intranasal fluticasone intranasal 4 times daily: when fluticasone propionate is propionate, budesonide, Plasma concentrations ↑ inhaled. Systemic corticosteroid triamcinolone Cortisol levels ↓ 86% effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide and triamcinolone. Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period. Phosphodiesterase(PDE5) inhibitors Avanafil Avanafil: The use of avanafil with Kaletra is (ritonavir 600 mg BID) AUC: ↑ 13-fold contraindicated (see section 4.3). Due to CYP3A inhibition by lopinavir/ritonavir. Tadalafil Tadalafil: For the treatment of pulmonary AUC: ↑ 2-fold arterial hypertension: Due to CYP3A4 inhibition by Co-administration of Kaletra with lopinavir/ritonavir. sildenafil is contraindicated (see Sildenafil Sildenafil: section 4.3). Co-administration of AUC: ↑ 11-fold Kaletra with tadalafil is not Due to CYP3A inhibition by recommended. lopinavir/ritonavir. For erectile dysfunction: Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Kaletra with increased monitoring for adverse events including hypotension, syncope, visual changes and prolonged erection (see section 4.4). When co-administered with Kaletra, sildenafil doses must not exceed 25 mg in 48 hours and tadalafil doses must not exceed 10 mg every 72 hours. Vardenafil Vardenafil: The use of vardenafil with Kaletra is AUC: ↑ 49-fold contraindicated (see section 4.3). Due to CYP3A inhibition by lopinavir/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): triamcinolone (HOS-086333) tadalafil (HOS-086316) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) avanafil (HOS-086161) budesonide (HOS-086332) propionate (HOS-108915) sildenafil (HOS-086162) beclomethasone (HOS-086334) vardenafil (HOS-086163)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 92–93

HOS-109093 · Präparat HOS-093083

92 Inhaled, injectable or Fluticasone propionate, 50 g Greater effects may be expected intranasal fluticasone intranasal 4 times daily: when fluticasone propionate is propionate, budesonide, Plasma concentrations ↑ inhaled. Systemic corticosteroid triamcinolone Cortisol levels ↓ 86% effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide and triamcinolone. Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period. Phosphodiesterase(PDE5) inhibitors Avanafil Avanafil: The use of avanafil with Kaletra is (ritonavir 600 mg BID) AUC: ↑ 13-fold contraindicated (see section 4.3). Due to CYP3A inhibition by lopinavir/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): triamcinolone (HOS-086333) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) avanafil (HOS-086161) budesonide (HOS-086332) propionate (HOS-108915) beclomethasone (HOS-086334)

Wechselwirkungen · Reyataz

REYATAZ 200 mg hard capsules REYATAZ 300 mg hard capsules · Abschnitt 4.5 · PDF-Seite 20–21

HOS-112108 · Präparat HOS-093615

20 Medicinal products by Interaction Recommendations concerning co- therapeutic area administration Fluticasone propionate The fluticasone propionate plasma levels Co-administration of intranasal 50 μg 4 times daily increased significantly, whereas the REYATAZ/ritonavir and these for 7 days intrinsic cortisol levels decreased by glucocorticoids metabolised by (ritonavir 100 mg capsules twice approximately 86% (90% confidence CYP3A4 is not recommended daily) interval 82%-89%). Greater effects may be unless the potential benefit of expected when fluticasone propionate is treatment outweighs the risk of And inhaled. Systemic corticosteroid effects systemic corticosteroid effects including Cushing’s syndrome and adrenal (see section 4.4). Inhaled/Nasal Corticosteroids suppression have been reported in patients A dose reduction of the receiving ritonavir and inhaled or glucocorticoid should be considered intranasally administered fluticasone with close monitoring of local and propionate; this could also occur with systemic effects or a switch to a other corticosteroids metabolised via the glucocorticoid, which is not a P450 3A pathway, e.g., budesonide. The substrate for CYP3A4 (e.g., effects of high fluticasone systemic beclomethasone). Moreover, in case exposure on ritonavir plasma levels are yet of withdrawal of glucocorticoids, unknown. The mechanism of interaction is progressive dose reduction may CYP3A4 inhibition. have to be performed over a longer period. Concomitant use of REYATAZ (with or without ritonavir) and other Inhaled/Nasal Concomitant use of Inhaled/Nasal Corticosteroids is expected to produce the Corticosteroids and REYATAZ same effects. (with or without ritonavir) may increase plasma concentrations of Inhaled/Nasal corticosteroids. Use with caution. Consider alternatives to Inhaled/Nasal Corticosteroids, particularly for long-term use. ERECTILE DYSFUNCTION PDE5 Inhibitors Sildenafil, tadalafil, vardenafil Sildenafil, tadalafil, and vardenafil are Patients should be warned about metabolised by CYP3A4. Co- these possible side effects when administration with REYATAZ may result using PDE5 inhibitors for erectile in increased concentrations of the PDE5 dysfunction with REYATAZ (see inhibitor and an increase in PDE5- section 4.4). Also see PULMONARY associated adverse events, including ARTERIAL HYPERTENSION in hypotension, visual changes, and priapism. this table for further information The mechanism of this interaction is CYP3A4 inhibition. regarding co-administration of REYATAZ with sildenafil. GONADOTROPIN-RELEASING HORMONE (GnRH) RECEPTOR ANTAGONISTS Elagolix The mechanism of interaction is Concomitant use of elagolix anticipated increase in elagolix exposure in 200 mg twice daily with the presence of CYP3A4 inhibition by REYATAZ (with or without atazanavir and/or ritonavir. ritonavir) for more than 1 month is not recommended due to the potential risk of adverse events such as bone loss and hepatic transaminase elevations. Limit concomitant use of elagolix 150 mg once daily with REYATAZ (with or without ritonavir) to 6 months.

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): tadalafil (HOS-086316) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) elagolix (HOS-112109) budesonide (HOS-086332) propionate (HOS-108915) sildenafil (HOS-086162) ritonavir (HOS-084521) beclomethasone (HOS-086334) vardenafil (HOS-086163)

Wechselwirkungen · Reyataz

REYATAZ 200 mg hard capsules REYATAZ 300 mg hard capsules · Abschnitt 4.5 · PDF-Seite 24–25

HOS-112119 · Präparat HOS-093615

24 In case of withdrawal of ritonavir from the recommended atazanavir-boosted regimen (see section 4.4) The same recommendations for drug interactions would apply except:  that co-administration is not recommended with tenofovir, proton pump inhibitors, and buprenorphine and contraindicated with carbamazepine, phenytoin and phenobarbital.  that co-administration with famotidine is not recommended but if required, atazanavir without ritonavir should be administered either 2 hours after famotidine or 12 hours before. No single dose of famotidine should exceed 20 mg, and the total daily dose of famotidine should not exceed 40 mg.  the need to consider that:  co-administration of apixaban, dabigatran, or rivaroxaban and REYATAZ without ritonavir may affect apixaban, dabigatran, or rivaroxaban concentrations  co-administration of voriconazole and REYATAZ without ritonavir may affect atazanavir concentrations  co-administration of fluticasone and REYATAZ without ritonavir may increase fluticasone concentrations relative to fluticasone given alone  if an oral contraceptive is administered with REYATAZ without ritonavir, it is recommended that the oral contraceptive contain no more than 30 μg of ethinyloestradiol  no dose adjustment of lamotrigine is required

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) lamotrigine (HOS-086242) fluticasone (HOS-108914) phenobarbital (HOS-085617) carbamazepine (HOS-085618) famotidine (HOS-112087) dabigatran (HOS-112096) buprenorphine (HOS-086193) rivaroxaban (HOS-086236) voriconazole (HOS-084524) apixaban (HOS-112091) ritonavir (HOS-084521) phenytoin (HOS-084531)

Wechselwirkungen · Reyataz

REYATAZ 50 mg oral powder · Abschnitt 4.5 · PDF-Seite 56–57

HOS-112197 · Präparat HOS-093615

56 Medicinal products by Interaction Recommendations therapeutic area concerning co-administration Fluticasone propionate The fluticasone propionate plasma levels Co-administration of intranasal 50 μg 4 times daily increased significantly, whereas the REYATAZ/ritonavir and these for 7 days intrinsic cortisol levels decreased by glucocorticoids metabolised by (ritonavir 100 mg capsules approximately 86% (90% confidence CYP3A4 is not recommended twice daily) interval 82%-89%). Greater effects may be unless the potential benefit of expected when fluticasone propionate is treatment outweighs the risk of And inhaled. Systemic corticosteroid effects systemic corticosteroid effects including Cushing’s syndrome and adrenal (see section 4.4). Inhaled/Nasal Corticosteroids suppression have been reported in patients A dose reduction of the receiving ritonavir and inhaled or glucocorticoid should be intranasally administered fluticasone considered with close propionate; this could also occur with other monitoring of local and corticosteroids metabolised via the P450 systemic effects or a switch to 3A pathway, e.g., budesonide. The effects a glucocorticoid, which is not a of high fluticasone systemic exposure on substrate for CYP3A4 (e.g., ritonavir plasma levels are yet unknown. beclomethasone). Moreover, in The mechanism of interaction is CYP3A4 case of withdrawal of inhibition. glucocorticoids, progressive dose reduction may have to be Concomitant use of REYATAZ (with or performed over a longer without ritonavir) and other Inhaled/Nasal period. Corticosteroids is expected to produce the same effects. Concomitant use of Inhaled/Nasal Corticosteroids and REYATAZ (with or without ritonavir) may increase plasma concentrations of Inhaled/Nasal corticosteroids. Use with caution. Consider alternatives to Inhaled/Nasal Corticosteroids, particularly for long-term use. ERECTILE DYSFUNCTION PDE5 Inhibitors Sildenafil, tadalafil, Sildenafil, tadalafil, and vardenafil are Patients should be warned vardenafil metabolised by CYP3A4. Co- about these possible side administration with REYATAZ may result effects when using PDE5 in increased concentrations of the PDE5 inhibitors for erectile inhibitor and an increase in PDE5- dysfunction with REYATAZ associated adverse events, including (see section 4.4). Also see PULMONARY hypotension, visual changes, and priapism. ARTERIAL The mechanism of this interaction is CYP3A4 inhibition. HYPERTENSION in this table for further information regarding co-administration of REYATAZ with sildenafil. GONADOTROPIN-RELEASING HORMONE (GnRH) RECEPTOR ANTAGONISTS Elagolix The mechanism of interaction is anticipated Concomitant use of elagolix increase in elagolix exposure in the 200 mg twice daily with presence of CYP3A4 inhibition by REYATAZ (with or without atazanavir and/or ritonavir. ritonavir) for more than 1 month is not recommended due to the potential risk of adverse events such as bone loss and hepatic transaminase elevations. Limit concomitant use of elagolix 150 mg once daily with REYATAZ (with or without ritonavir) to 6 months.

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): tadalafil (HOS-086316) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) elagolix (HOS-112109) budesonide (HOS-086332) propionate (HOS-108915) sildenafil (HOS-086162) ritonavir (HOS-084521) beclomethasone (HOS-086334) vardenafil (HOS-086163)

Wechselwirkungen · Aptivus

Aptivus 250 mg soft capsules · Abschnitt 4.5 · PDF-Seite 22–23

HOS-114854 · Präparat HOS-094169

22  Bupropion 150 mg BID Bupropion Cmax ↓ 51% If the co-administration with Bupropion AUC ↓ 56% bupropion is judged unavoidable, this should be done under close Tipranavir ↔ clinical monitoring for bupropion efficacy, without exceeding the The reduction of bupropion recommended dosage, despite the plasma levels is likely due to observed induction. induction of CYP2B6 and UGT activity by RTV Loperamide 16 mg QD Loperamide Cmax ↓ 61% A pharmacodynamic interaction Loperamide AUC ↓ 51% study in healthy volunteers demonstrated that administration Mechanism unknown of loperamide and Aptivus, co- administered with low dose Tipranavir Cmax ↔ ritonavir, does not cause any Tipranavir AUC ↔ clinically relevant change in the Tipranavir Cmin ↓ 26% respiratory response to carbon dioxide. The clinical relevance of the reduced loperamide plasma concentration is unknown. Fluticasone propionate In a clinical study where ritonavir Concomitant administration of Interaction study 100 mg capsules bid were co- Aptivus, co-administered with performed only with administered with 50 µg low dose ritonavir, and these ritonavir intranasal fluticasone propionate glucocorticoids is not (4 times daily) for 7 days in recommended unless the healthy subjects, the fluticasone potential benefit of treatment propionate plasma levels outweighs the risk of systemic increased significantly, whereas corticosteroid effects (see the intrinsic cortisol levels section 4.4). A dose reduction of decreased by approximately 86% the glucocorticoid should be (90% confidence interval considered with close monitoring 82-89%). Greater effects may be of local and systemic effects or a expected when fluticasone switch to a glucocorticoid, which propionate is inhaled. Systemic is not a substrate for CYP3A4 corticosteroid effects including (e.g. beclomethasone). Moreover, Cushing’s syndrome and adrenal in case of withdrawal of suppression have been reported in glucocorticoids progressive dose patients receiving ritonavir and reduction may have to be inhaled or intranasally performed over a longer period. administered fluticasone The effects of high fluticasone propionate; this could also occur systemic exposure on ritonavir with other corticosteroids plasma levels are as yet metabolised via the P450 3A unknown. pathway e.g. budesonide. It is unknown whether the combination of tipranavir with ritonavir might cause a larger increase in fluticasone exposure.

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): bupropion (HOS-086329) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) loperamide (HOS-114855) budesonide (HOS-086332) propionate (HOS-108915) ritonavir (HOS-084521) beclomethasone (HOS-086334)

Wechselwirkungen · Prezista

PREZISTA 100 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 10

HOS-116313 · Präparat HOS-094447

Medicinal products that affect darunavir exposure (cobicistat as pharmacoenhancer) Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may therefore result in subtherapeutic plasma exposure to darunavir. Darunavir boosted with cobicistat is more sensitive to CYP3A induction than ritonavir-boosted darunavir: co-administration of darunavir/cobicistat with medicinal products that are strong inducers of CYP3A (e.g. St John’s Wort, rifampicin, carbamazepine, phenobarbital, and phenytoin) is contraindicated (see section 4.3). Co-administration of darunavir/cobicistat with weak to moderate CYP3A inducers (e.g. efavirenz, etravirine, nevirapine, fluticasone, and bosentan) is not recommended (see 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): fluticasone (HOS-108914) phenobarbital (HOS-085617) carbamazepine (HOS-085618) cobicistat (HOS-088111) etravirine (HOS-088088) efavirenz (HOS-087947) nevirapine (HOS-088064) bosentan (HOS-086291) phenytoin (HOS-084531)

Wechselwirkungen · Prezista

PREZISTA 100 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 19–20

HOS-116394 · Präparat HOS-094447

19 ANTIPSYCHOTICS/NEUROLEPTICS Quetiapine Not studied. Boosted PREZISTA is Concomitant administration of expected to increase these antipsychotic boosted PREZISTA and quetiapine plasma concentrations. is contraindicated as it may (CYP3A inhibition) increase quetiapine-related toxicity. Increased concentrations of quetiapine may lead to coma (see section 4.3). Perphenazine Not studied. Boosted PREZISTA is A dose decrease may be needed for Risperidone expected to increase these antipsychotic these drugs when co-administered Thioridazine plasma concentrations. with boosted PREZISTA. (CYP3A, CYP2D6 and/or P-gp Lurasidone inhibition) Concomitant administration of Pimozide boosted PREZISTA and Sertindole lurasidone, pimozide or sertindole is contraindicated (see section 4.3). β-BLOCKERS Carvedilol Not studied. Boosted PREZISTA is Clinical monitoring is Metoprolol expected to increase these β-blocker recommended when Timolol plasma concentrations. co-administering boosted (CYP2D6 inhibition) PREZISTA with β-blockers. A lower dose of the β-blocker should be considered. CALCIUM CHANNEL BLOCKERS Amlodipine Not studied. Boosted PREZISTA can be Clinical monitoring of therapeutic Diltiazem expected to increase the plasma and adverse effects is Felodipine concentrations of calcium channel recommended when these Nicardipine blockers. medicines are concomitantly Nifedipine (CYP3A and/or CYP2D6 inhibition) administered with boosted Verapamil PREZISTA. CORTICOSTEROIDS Corticosteroids primarily Fluticasone: in a clinical study where Concomitant use of boosted metabolised by CYP3A ritonavir 100 mg capsules twice daily PREZISTA and corticosteroids (all (including were co-administered with 50 g routes of administration) that are betamethasone, intranasal fluticasone propionate (4 times metabolised by CYP3A may budesonide, fluticasone, daily) for 7 days in healthy subjects, increase the risk of development of mometasone, prednisone, fluticasone propionate plasma systemic corticosteroid effects, triamcinolone) concentrations increased significantly, including Cushing’s syndrome and whereas the intrinsic cortisol levels adrenal suppression. decreased by approximately 86% (90% CI 82-89%). Greater effects may be Co-administration with CYP3A- expected when fluticasone is inhaled. metabolised corticosteroids is not Systemic corticosteroid effects including recommended unless the potential Cushing’s syndrome and adrenal benefit to the patient outweighs the suppression have been reported in risk, in which case patients should patients receiving ritonavir and inhaled or be monitored for systemic intranasally administered fluticasone. The corticosteroid effects. effects of high fluticasone systemic exposure on ritonavir plasma levels are Alternative corticosteroids which unknown. are less dependent on CYP3A metabolism e.g. beclomethasone Other corticosteroids: interaction not should be considered, particularly studied. Plasma concentrations of these for long term use. medicinal products may be increased when co-administered with boosted PREZISTA, resulting in reduced serum cortisol concentrations. Dexamethasone Not studied. Dexamethasone may Systemic dexamethasone should (systemic) decrease plasma concentrations of be used with caution when darunavir. combined with boosted (CYP3A induction) 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): sertindole (HOS-085601) quetiapine (HOS-086150) diltiazem (HOS-086288) triamcinolone (HOS-086333) nifedipine (HOS-086289) fluticasone (HOS-108914) nicardipine (HOS-090619) felodipine (HOS-108908) fluticasone propionate (HOS-086331) carvedilol (HOS-115322) risperidone (HOS-086280) amlodipine (HOS-086287) thioridazine (HOS-086281) perphenazine (HOS-116395) calcium (HOS-085615) betamethasone (HOS-090066) dexamethasone (HOS-084535) lead (HOS-085592) budesonide (HOS-086332) pimozide (HOS-085600) mometasone (HOS-114048) ritonavir (HOS-084521) beclomethasone (HOS-086334) lurasidone (HOS-086148) prednisone (HOS-084526) metoprolol (HOS-090094) timolol (HOS-090571) verapamil (HOS-090602)

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 61–62

HOS-116527 · Präparat HOS-094447

61  Perphenazine Not studied. PREZISTA is expected to A dose decrease may be needed for Risperidone increase these antipsychotic plasma these drugs when co-administered Thioridazine concentrations. with PREZISTA co-administered (CYP3A, CYP2D6 and/or P-gp with low dose ritonavir. inhibition) Lurasidone Concomitant administration of Pimozide PREZISTA with low dose Sertindole ritonavir and lurasidone, pimozide or sertindole is contraindicated (see section 4.3). β-BLOCKERS Carvedilol Not studied. PREZISTA is expected to Clinical monitoring is Metoprolol increase these β-blocker plasma recommended when Timolol concentrations. co-administering PREZISTA with (CYP2D6 inhibition) β-blockers. A lower dose of the β-blocker should be considered. CALCIUM CHANNEL BLOCKERS Amlodipine Not studied. PREZISTA co-administered Clinical monitoring of therapeutic Diltiazem with low dose ritonavir can be expected and adverse effects is Felodipine to increase the plasma concentrations of recommended when these Nicardipine calcium channel blockers. medicines are concomitantly Nifedipine (CYP3A and/or CYP2D6 inhibition) administered with PREZISTA with Verapamil low dose ritonavir. CORTICOSTEROIDS Corticosteroids primarily Fluticasone: in a clinical study where Concomitant use of PREZISTA metabolised by CYP3A ritonavir 100 mg capsules twice daily with low dose ritonavir and (including were co-administered with 50 g corticosteroids (all routes of betamethasone, intranasal fluticasone propionate (4 times administration) that are budesonide, fluticasone, daily) for 7 days in healthy subjects, metabolised by CYP3A may mometasone, prednisone, fluticasone propionate plasma increase the risk of development of triamcinolone) concentrations increased significantly, systemic corticosteroid effects, whereas the intrinsic cortisol levels including Cushing’s syndrome and decreased by approximately 86% (90% adrenal suppression. CI 82-89%). Greater effects may be expected when fluticasone is inhaled. Co-administration with CYP3A- Systemic corticosteroid effects including metabolised corticosteroids is not Cushing’s syndrome and adrenal recommended unless the potential suppression have been reported in benefit to the patient outweighs the patients receiving ritonavir and inhaled or risk, in which case patients should intranasally administered fluticasone. The be monitored for systemic effects of high fluticasone systemic corticosteroid effects. exposure on ritonavir plasma levels are unknown. Alternative corticosteroids which are less dependent on CYP3A Other corticosteroids: interaction not metabolism e.g. beclomethasone studied. Plasma concentrations of these should be considered, particularly medicinal products may be increased for long term use. when co-administered with PREZISTA with low dose ritonavir, resulting in reduced serum cortisol concentrations. Dexamethasone Not studied. Dexamethasone may Systemic dexamethasone should (systemic) decrease plasma concentrations of be used with caution when darunavir. combined with PREZISTA (CYP3A induction) 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): sertindole (HOS-085601) diltiazem (HOS-086288) triamcinolone (HOS-086333) nifedipine (HOS-086289) fluticasone (HOS-108914) nicardipine (HOS-090619) felodipine (HOS-108908) fluticasone propionate (HOS-086331) carvedilol (HOS-115322) risperidone (HOS-086280) amlodipine (HOS-086287) thioridazine (HOS-086281) perphenazine (HOS-116395) calcium (HOS-085615) betamethasone (HOS-090066) dexamethasone (HOS-084535) budesonide (HOS-086332) pimozide (HOS-085600) mometasone (HOS-114048) ritonavir (HOS-084521) beclomethasone (HOS-086334) lurasidone (HOS-086148) prednisone (HOS-084526) metoprolol (HOS-090094) timolol (HOS-090571) verapamil (HOS-090602)

Wechselwirkungen · Prezista

PREZISTA 400 mg film-coated tablets PREZISTA 800 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 91

HOS-116585 · Präparat HOS-094447

Medicinal products that affect darunavir exposure (cobicistat as pharmacoenhancer) Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may therefore result in subtherapeutic plasma exposure to darunavir. Darunavir boosted with cobicistat is more sensitive to CYP3A induction than ritonavir-boosted darunavir: co-administration of darunavir/cobicistat with medicinal products that are strong inducers of CYP3A (e.g. St John’s Wort, rifampicin, carbamazepine, phenobarbital, and phenytoin) is contraindicated (see section 4.3). Co-administration of darunavir/cobicistat with weak to moderate CYP3A inducers (e.g. efavirenz, etravirine, nevirapine, fluticasone, and bosentan) is not recommended (see 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): fluticasone (HOS-108914) phenobarbital (HOS-085617) carbamazepine (HOS-085618) cobicistat (HOS-088111) etravirine (HOS-088088) efavirenz (HOS-087947) nevirapine (HOS-088064) bosentan (HOS-086291) phenytoin (HOS-084531)

Wechselwirkungen · Prezista

PREZISTA 400 mg film-coated tablets PREZISTA 800 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 101–102

HOS-116617 · Präparat HOS-094447

101 ANTIPSYCHOTICS/NEUROLEPTICS Quetiapine Not studied. Boosted PREZISTA is Concomitant administration of expected to increase these antipsychotic boosted PREZISTA and quetiapine plasma concentrations. is contraindicated as it may (CYP3A inhibition) increase quetiapine-related toxicity. Increased concentrations of quetiapine may lead to coma (see section 4.3). Perphenazine Not studied. Boosted PREZISTA is A dose decrease may be needed for Risperidone expected to increase these antipsychotic these drugs when co-administered Thioridazine plasma concentrations. with boosted PREZISTA. (CYP3A, CYP2D6 and/or P-gp Lurasidone inhibition) Concomitant administration of Pimozide boosted PREZISTA and Sertindole lurasidone, pimozide or sertindole is contraindicated (see section 4.3). β-BLOCKERS Carvedilol Not studied. Boosted PREZISTA is Clinical monitoring is Metoprolol expected to increase these β-blocker recommended when Timolol plasma concentrations. co-administering boosted (CYP2D6 inhibition) PREZISTA with β-blockers. A lower dose of the β-blocker should be considered. CALCIUM CHANNEL BLOCKERS Amlodipine Not studied. Boosted PREZISTA can be Clinical monitoring of therapeutic Diltiazem expected to increase the plasma and adverse effects is Felodipine concentrations of calcium channel recommended when these Nicardipine blockers. medicines are concomitantly Nifedipine (CYP3A and/or CYP2D6 inhibition) administered with boosted Verapamil PREZISTA. CORTICOSTEROIDS Corticosteroids primarily Fluticasone: in a clinical study where Concomitant use of boosted metabolised by CYP3A ritonavir 100 mg capsules twice daily PREZISTA and corticosteroids (all (including were co-administered with 50 g routes of administration) that are betamethasone, intranasal fluticasone propionate (4 times metabolised by CYP3A may budesonide, fluticasone, daily) for 7 days in healthy subjects, increase the risk of development of mometasone, prednisone, fluticasone propionate plasma systemic corticosteroid effects, triamcinolone) concentrations increased significantly, including Cushing’s syndrome and whereas the intrinsic cortisol levels adrenal suppression. decreased by approximately 86% (90% CI 82-89%). Greater effects may be Co-administration with CYP3A- expected when fluticasone is inhaled. metabolised corticosteroids is not Systemic corticosteroid effects including recommended unless the potential Cushing’s syndrome and adrenal benefit to the patient outweighs the suppression have been reported in risk, in which case patients should patients receiving ritonavir and inhaled or be monitored for systemic intranasally administered fluticasone. The corticosteroid effects. effects of high fluticasone systemic exposure on ritonavir plasma levels are Alternative corticosteroids which unknown. are less dependent on CYP3A metabolism e.g. beclomethasone Other corticosteroids: interaction not should be considered, particularly studied. Plasma concentrations of these for long term use. medicinal products may be increased when co-administered with boosted PREZISTA, resulting in reduced serum cortisol concentrations. Dexamethasone Not studied. Dexamethasone may Systemic dexamethasone should (systemic) decrease plasma concentrations of be used with caution when darunavir. combined with boosted (CYP3A induction) 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): sertindole (HOS-085601) quetiapine (HOS-086150) diltiazem (HOS-086288) triamcinolone (HOS-086333) nifedipine (HOS-086289) fluticasone (HOS-108914) nicardipine (HOS-090619) felodipine (HOS-108908) fluticasone propionate (HOS-086331) carvedilol (HOS-115322) risperidone (HOS-086280) amlodipine (HOS-086287) thioridazine (HOS-086281) perphenazine (HOS-116395) calcium (HOS-085615) betamethasone (HOS-090066) dexamethasone (HOS-084535) lead (HOS-085592) budesonide (HOS-086332) pimozide (HOS-085600) mometasone (HOS-114048) ritonavir (HOS-084521) beclomethasone (HOS-086334) lurasidone (HOS-086148) prednisone (HOS-084526) metoprolol (HOS-090094) timolol (HOS-090571) verapamil (HOS-090602)

Gegenanzeigen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.3 · PDF-Seite 3

HOS-117576 · Präparat HOS-094649

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 · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.5 · PDF-Seite 4

HOS-117577 · Präparat HOS-094649

Interaction with CYP3A inhibitors

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

Wechselwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.5 · PDF-Seite 4

HOS-117578 · Präparat HOS-094649

Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by the cytochrome P450 3A4.

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

Wechselwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.5 · PDF-Seite 4

HOS-117579 · Präparat HOS-094649

Based on data with another glucocorticoid (fluticasone propionate), that is metabolised by CYP3A4, coadministration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

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): fluticasone propionate (HOS-086331) ritonavir (HOS-084521)

Wechselwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.5 · PDF-Seite 4

HOS-117580 · Präparat HOS-094649

Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat-containing products as an increase in the risk of systemic side effects is expected. Co- administration should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects, in which case patients should be monitored for systemic corticosteroid side effects. In a drug interaction study of intranasal fluticasone furoate with the potent CYP3A4 inhibitor ketoconazole there were more subjects with measurable fluticasone furoate concentrations in the ketoconazole group (6 of the 20 subjects) compared to placebo (1 out of 20 subjects). This small increase in exposure did not result in a statistically significant difference in 24 hour serum cortisol levels between the two groups.

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): placebo (HOS-088378) ketoconazole (HOS-084513)

Wechselwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.5 · PDF-Seite 4–5

HOS-117581 · Präparat HOS-094649

4 The enzyme induction and inhibition data suggest that there is no theoretical basis for anticipating metabolic interactions between fluticasone furoate and the cytochrome P450 mediated metabolism of other compounds at clinically relevant intranasal doses. Therefore, no clinical studies have been conducted to investigate interactions of fluticasone furoate on other drugs.

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Nebenwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.8 · PDF-Seite 5

HOS-117582 · Präparat HOS-094649

Summary of the safety profile

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Nebenwirkungen · Avamys

AVAMYS 27.5 micrograms/spray, nasal spray suspension · Abschnitt 4.8 · PDF-Seite 5

HOS-117583 · Präparat HOS-094649

The most commonly reported adverse reactions during treatment with fluticasone furoate are epistaxis, nasal ulceration and headache. The most serious undesirable effects are rare reports of hypersensitivity reactions, including anaphylaxis (less than 1 case per 1000 patients).

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