Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

Norvir 100 mg powder for oral suspension · Abschnitt 4.5 · PDF-Seite 14

HOS-086214 · Präparat HOS-083284

Ceritinib Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. Caution should be exercised in administering ceritinib with ritonavir. Refer to the ceritinib SmPC for dosage adjustment recommendations. Monitor for ADRs related to ceritinib.

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): ceritinib (HOS-086215)

Wechselwirkungen · Norvir

Norvir 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 46

HOS-086421 · Präparat HOS-083284

Ceritinib Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. Caution should be exercised in administering ceritinib with ritonavir. Refer to the ceritinib SmPC for dosage adjustment recommendations. Monitor for ADRs related to ceritinib.

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): ceritinib (HOS-086215)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 14

HOS-108873 · Präparat HOS-093083

Due to BCRP (breast cancer resistance protein/ABCG2) and acute P-gp inhibition by lopinavir/ritonavir. Ceritinib Serum concentrations may be Caution should be exercised in increased due to CYP3A and administering ceritinib with P-gp inhibition by Kaletra. Refer to the ceritinib lopinavir/ritonavir. SmPC for dosage adjustment recommendations. Monitor for ADRs related to ceritinib. Most tyrosine kinase Most tyrosine kinase inhibitors Careful monitoring of the tolerance inhibitors such as dasatinib such as dasatinib and nilotinib, of these anticancer agents. and nilotinib, vincristine, also vincristine and vinblastine: vinblastine Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by lopinavir/ritonavir. Encorafenib Serum concentrations may be Co-administration of encorafenib increased due to CYP3A with Kaletra may increase inhibition by lopinavir/ritonavir. encorafenib exposure which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, patients should be carefully monitored for safety. Fostamatinib Increase in fostamatinib Co-administration of fostamatinib metabolite R406 exposure. with Kaletra may increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity, neutropenia, hypertension, or diarrhoea. Refer to the fostamatinib SmPC for dose reduction recommendations if such events occur.

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): ceritinib (HOS-086215) dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) encorafenib (HOS-086222) tyrosine (HOS-108875) nilotinib (HOS-086218) fostamatinib (HOS-086224)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 51

HOS-109008 · Präparat HOS-093083

Due to BCRP (breast cancer resistance protein/ABCG2) and acute P-gp inhibition by lopinavir/ritonavir. Ceritinib Serum concentrations may be Caution should be exercised in increased due to CYP3A and P-gp administering ceritinib with Kaletra. inhibition by lopinavir/ritonavir. Refer to the ceritinib SmPC for dosage adjustment recommendations. Monitor for ADRs related to ceritinib. Most tyrosine kinase Most tyrosine kinase inhibitors Careful monitoring of the tolerance inhibitors such as such as dasatinib and nilotinib, of these anticancer agents. dasatinib and nilotinib, also vincristine and vinblastine: vincristine, vinblastine Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by lopinavir/ritonavir. Encorafenib Serum concentrations may be Co-administration of encorafenib increased due to CYP3A with Kaletra may increase inhibition by lopinavir/ritonavir. encorafenib exposure which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, patients should be carefully monitored for safety. Fostamatinib Increase in fostamatinib Co-administration of fostamatinib metabolite R406 exposure. with Kaletra may increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity, neutropenia, hypertension, or diarrhoea. Refer to the fostamatinib SmPC for dose reduction recommendations if such events occur. Ibrutinib Serum concentrations may be Co-administration of ibrutinib and increased due to CYP3A Kaletra may increase ibrutinib inhibition by lopinavir/ritonavir. exposure which may increase the risk of toxicity including risk of tumor lysis syndrome. Co-administration of ibrutinib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, reduce the ibrutinib dose to 140 mg and monitor patient closely for toxicity.

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): ceritinib (HOS-086215) dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) encorafenib (HOS-086222) tyrosine (HOS-108875) nilotinib (HOS-086218) fostamatinib (HOS-086224) ibrutinib (HOS-086226)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 86

HOS-109082 · Präparat HOS-093083

Due to BCRP (breast cancer resistance protein/ABCG2) and acute P-gp inhibition by lopinavir/ritonavir. Ceritinib Serum concentrations may be Caution should be exercised in increased due to CYP3A and administering ceritinib with Kaletra. P-gp inhibition by Refer to the ceritinib SmPC for lopinavir/ritonavir. dosage adjustment recommendations. Monitor for ADRs related to ceritinib. Most tyrosine kinase Most tyrosine kinase inhibitors Careful monitoring of the tolerance inhibitors such as such as dasatinib and nilotinib, of these anticancer agents. dasatinib and nilotinib, also vincristine and vinblastine: vincristine, vinblastine Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by lopinavir/ritonavir. Encorafenib Serum concentrations may be Co-administration of encorafenib increased due to CYP3A with Kaletra may increase inhibition by lopinavir/ritonavir. encorafenib exposure which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, patients should be carefully monitored for safety.

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): ceritinib (HOS-086215) dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) encorafenib (HOS-086222) tyrosine (HOS-108875) nilotinib (HOS-086218)

Wechselwirkungen · Vfend

VFEND 50 mg film-coated tablets VFEND 200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-109445 · Präparat HOS-093201

Erythromycin (1 g BID) Voriconazole Cmax and AUC ↔ [CYP3A4 inhibitor] The effect of voriconazole on either erythromycin or azithromycin is unknown. Rifabutin Concomitant use of voriconazole [potent CYP450 inducer] and rifabutin should be avoided Voriconazole Cmax  69% unless the benefit outweighs the 300 mg QD Voriconazole AUC  78% risk. The maintenance dose of Compared to voriconazole 200 mg voriconazole may be increased to 300 mg QD (coadministered BID, 5 mg/kg intravenously BID or with voriconazole 350 mg Voriconazole Cmax  4% from 200 mg to 350 mg orally BID)* Voriconazole AUC  32% BID (100 mg to 200 mg orally BID in patients less than 40 kg) (see section 4.2). Careful monitoring of full blood Rifabutin Cmax  195% counts and adverse reactions to 300 mg QD (coadministered Rifabutin AUC  331% rifabutin (e.g., uveitis) is with voriconazole 400 mg Compared to voriconazole 200 mg recommended when rifabutin is BID)* BID, coadministered with voriconazole. Voriconazole Cmax  104% Voriconazole AUC  87% Rifampicin (600 mg QD) Voriconazole Cmax  93% Contraindicated (see section [potent CYP450 inducer] Voriconazole AUC  96% 4.3) Anti-cancer agents Glasdegib Although not studied, voriconazole If concomitant use cannot be [CYP3A4 substrate] is likely to increase the plasma avoided, frequent ECG concentrations of glasdegib and monitoring is recommended (see increase risk of QTc prolongation. section 4.4). Tretinoin Although not studied, voriconazole Dose adjustment of tretinoin is [CYP3A4 substrate] may increase tretinoin recommended during treatment concentrations and increase risk of with voriconazole and after its adverse reactions (pseudotumor discontinuation. cerebri, hypercalcaemia). 11 Tyrosine kinase inhibitors Although not studied, voriconazole If concomitant use cannot be (including but not limited to: may increase plasma avoided, dose reduction of the axitinib, bosutinib, concentrations of tyrosine kinase tyrosine kinase inhibitor and cabozantinib, ceritinib, inhibitors metabolised by CYP3A4. close clinical monitoring is cobimetinib, dabrafenib, recommended (see section 4.4). dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) [CYP3A4 substrates] Venetoclax Although not studied, voriconazole Concomitant administration of [CYP3A substrate] is likely to significantly increase voriconazole is contraindicated the plasma concentrations of at initiation and during venetoclax. venetoclax dose titration phase (see section 4.3). Dose reduction of venetoclax is required as instructed in venetoclax prescribing information during steady daily dosing; close monitoring for signs of toxicity is recommended. Vinca Alkaloids (including but Although not studied, voriconazole Dose reduction of vinca alkaloids not limited to: vincristine and is likely to increase the plasma should be considered. vinblastine) concentrations of vinca alkaloids [CYP3A4 substrates] and lead to neurotoxicity. Anticoagulants Warfarin (30 mg single dose, Maximum increase in prothrombin Close monitoring of prothrombin coadministered with 300 mg time was approximately 2-fold. time or other suitable BID voriconazole) anticoagulation tests is [CYP2C9 substrate] recommended, and the dose of anticoagulants should be adjusted Other oral coumarins Although not studied, voriconazole accordingly. (including but not limited to: may increase the plasma phenprocoumon, concentrations of coumarins that acenocoumarol) may cause an increase in [CYP2C9 and CYP3A4 prothrombin time. substrates] Anticonvulsants Carbamazepine and Although not studied, Contraindicated (see section long-acting barbiturates carbamazepine and long-acting 4.3) (including but not limited to: barbiturates are likely to phenobarbital, mephobarbital) significantly decrease plasma [potent CYP450 inducers] voriconazole concentrations. Phenytoin Concomitant use of voriconazole [CYP2C9 substrate and potent and phenytoin should be avoided CYP450 inducer] unless the benefit outweighs the risk. Careful monitoring of 300 mg QD Voriconazole Cmax  49% phenytoin plasma levels is Voriconazole AUC  69% 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): axitinib (HOS-109448) ceritinib (HOS-086215) dasatinib (HOS-086217) cobimetinib (HOS-109451) phenobarbital (HOS-085617) carbamazepine (HOS-085618) rifabutin (HOS-086262) vinblastine (HOS-086220) glasdegib (HOS-109446) vincristine (HOS-086219) azithromycin (HOS-088112) phenprocoumon (HOS-091031) dabrafenib (HOS-109452) venetoclax (HOS-086143) tretinoin (HOS-109447) lead (HOS-085592) prothrombin (HOS-085093) sunitinib (HOS-109453) erythromycin (HOS-084514) ribociclib (HOS-109454) tyrosine (HOS-108875) acenocoumarol (HOS-109456) cabozantinib (HOS-109450) phenytoin (HOS-084531) warfarin (HOS-085950) bosutinib (HOS-109449) mephobarbital (HOS-109457) nilotinib (HOS-086218) ibrutinib (HOS-086226)

Wechselwirkungen · Vfend

VFEND 200 mg powder for solution for infusion · Abschnitt 4.5 · PDF-Seite 42–43

HOS-109537 · Präparat HOS-093201

42 Rifabutin Concomitant use of voriconazole [potent CYP450 inducer] and rifabutin should be avoided Voriconazole Cmax  69% unless the benefit outweighs the 300 mg QD Voriconazole AUC  78% risk. The maintenance dose of Compared to voriconazole 200 mg voriconazole may be increased to 300 mg QD (coadministered BID, 5 mg/kg intravenously BID or with voriconazole 350 mg Voriconazole Cmax  4% from 200 mg to 350 mg orally BID)* Voriconazole AUC  32% BID (100 mg to 200 mg orally BID in patients less than 40 kg) (see section 4.2). Careful monitoring of full blood Rifabutin Cmax  195% counts and adverse reactions to 300 mg QD (coadministered Rifabutin AUC  331% rifabutin (e.g., uveitis) is with voriconazole 400 mg Compared to voriconazole 200 mg recommended when rifabutin is BID)* BID, coadministered with voriconazole. Voriconazole Cmax  104% Voriconazole AUC  87% Rifampicin (600 mg QD) Voriconazole Cmax  93% Contraindicated (see section [potent CYP450 inducer] Voriconazole AUC  96% 4.3) Anti-cancer agents Glasdegib Although not studied, voriconazole If concomitant use cannot be [CYP3A4 substrate] is likely to increase the plasma avoided, frequent ECG concentrations of glasdegib and monitoring is recommended (see increase risk of QTc prolongation. section 4.4). Tretinoin Although not studied, voriconazole Dose adjustment of tretinoin is [CYP3A4 substrate] may increase tretinoin recommended during treatment concentrations and increase risk of with voriconazole and after its adverse reactions (pseudotumor discontinuation. cerebri, hypercalcaemia). Tyrosine kinase inhibitors Although not studied, voriconazole If concomitant use cannot be (including but not limited to: may increase plasma avoided, dose reduction of the axitinib, bosutinib, concentrations of tyrosine kinase tyrosine kinase inhibitor and cabozantinib, ceritinib, inhibitors metabolised by CYP3A4. close clinical monitoring is cobimetinib, dabrafenib, recommended (see section 4.4). dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) [CYP3A4 substrates] Venetoclax Although not studied, voriconazole Concomitant administration of [CYP3A substrate] is likely to significantly increase voriconazole is contraindicated the plasma concentrations of at initiation and during venetoclax. venetoclax dose titration phase (see section 4.3). Dose reduction of venetoclax is required as instructed in venetoclax prescribing information during steady daily dosing; close monitoring for signs of toxicity is recommended. Vinca Alkaloids (including but Although not studied, voriconazole Dose reduction of vinca alkaloids not limited to: vincristine and is likely to increase the plasma should be considered. vinblastine) concentrations of vinca alkaloids [CYP3A4 substrates] and lead to neurotoxicity.

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): axitinib (HOS-109448) ceritinib (HOS-086215) dasatinib (HOS-086217) cobimetinib (HOS-109451) rifabutin (HOS-086262) vinblastine (HOS-086220) glasdegib (HOS-109446) vincristine (HOS-086219) dabrafenib (HOS-109452) venetoclax (HOS-086143) tretinoin (HOS-109447) lead (HOS-085592) sunitinib (HOS-109453) ribociclib (HOS-109454) tyrosine (HOS-108875) cabozantinib (HOS-109450) bosutinib (HOS-109449) nilotinib (HOS-086218) ibrutinib (HOS-086226)

Wechselwirkungen · Vfend

VFEND 40 mg/ml powder for oral suspension · Abschnitt 4.5 · PDF-Seite 75–76

HOS-109603 · Präparat HOS-093201

75 Tyrosine kinase inhibitors Although not studied, voriconazole If concomitant use cannot be (including but not limited to: may increase plasma avoided, dose reduction of the axitinib, bosutinib, concentrations of tyrosine kinase tyrosine kinase inhibitor and cabozantinib, ceritinib, inhibitors metabolised by CYP3A4. close clinical monitoring is cobimetinib, dabrafenib, recommended (see section 4.4). dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) [CYP3A4 substrates] Venetoclax Although not studied, voriconazole Concomitant administration of [CYP3A substrate] is likely to significantly increase voriconazole is contraindicated the plasma concentrations of at initiation and during venetoclax. venetoclax dose titration phase (see section 4.3). Dose reduction of venetoclax is required as instructed in venetoclax prescribing information during steady daily dosing; close monitoring for signs of toxicity is recommended. Vinca Alkaloids (including but Although not studied, voriconazole Dose reduction of vinca alkaloids not limited to: vincristine and is likely to increase the plasma should be considered. vinblastine) concentrations of vinca alkaloids [CYP3A4 substrates] and lead to neurotoxicity. Anticoagulants Warfarin (30 mg single dose, Maximum increase in prothrombin Close monitoring of prothrombin coadministered with 300 mg time was approximately 2-fold. time or other suitable BID voriconazole) anticoagulation tests is [CYP2C9 substrate] recommended, and the dose of anticoagulants should be adjusted Other oral coumarins Although not studied, voriconazole accordingly. (including but not limited to: may increase the plasma phenprocoumon, concentrations of coumarins that acenocoumarol) may cause an increase in [CYP2C9 and CYP3A4 prothrombin time. substrates] Anticonvulsants Carbamazepine and Although not studied, Contraindicated (see section long-acting barbiturates carbamazepine and long-acting 4.3) (including but not limited to: barbiturates are likely to phenobarbital, mephobarbital) significantly decrease plasma [potent CYP450 inducers] voriconazole concentrations. Phenytoin Concomitant use of voriconazole [CYP2C9 substrate and potent and phenytoin should be avoided CYP450 inducer] unless the benefit outweighs the risk. Careful monitoring of 300 mg QD Voriconazole Cmax  49% phenytoin plasma levels is Voriconazole AUC  69% 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): axitinib (HOS-109448) ceritinib (HOS-086215) dasatinib (HOS-086217) cobimetinib (HOS-109451) phenobarbital (HOS-085617) carbamazepine (HOS-085618) vinblastine (HOS-086220) vincristine (HOS-086219) phenprocoumon (HOS-091031) dabrafenib (HOS-109452) venetoclax (HOS-086143) lead (HOS-085592) prothrombin (HOS-085093) sunitinib (HOS-109453) ribociclib (HOS-109454) tyrosine (HOS-108875) acenocoumarol (HOS-109456) cabozantinib (HOS-109450) phenytoin (HOS-084531) warfarin (HOS-085950) bosutinib (HOS-109449) mephobarbital (HOS-109457) nilotinib (HOS-086218) ibrutinib (HOS-086226)

Wechselwirkungen · Advagraf

Advagraf 0.5 mg prolonged-release hard capsules Advagraf 1 mg prolonged-release hard capsules Advagraf 3 mg prolonged-release hard capsules Advagraf 5 mg prolonged-release hard capsules · Abschnitt 4.5 · PDF-Seite 10–11

HOS-116802 · Präparat HOS-094481

10 Drug/Substance Class or Drug interaction effect Recommendations concerning Name co-administration Strong CYP3A4 inhibitors: May increase tacrolimus whole It is recommended that antifungal agents (e.g., blood trough concentrations and concomitant use should be ketoconazole, itraconazole, increase the risk of serious adverse avoided. If co-administration posaconazole, voriconazole), reactions (e.g., nephrotoxicity, of a strong CYP3A4 inhibitor the macrolide antibiotics neurotoxicity, QT prolongation) is unavoidable, consider (e.g., telithromycin, which requires close monitoring omitting the dose of tacrolimus troleandomycin, [see section 4.4]. the day the strong CYP3A4 clarithromycin, josamycin), Rapid and sharp increases in inhibitor is initiated. Reinitiate HIV protease inhibitors tacrolimus levels may occur, as tacrolimus the next day at a (e.g., ritonavir, nelfinavir, early as within 1-3 days after co- reduced dose based on saquinavir), HCV protease administration, despite immediate tacrolimus blood inhibitors (e.g., telaprevir, reduction of tacrolimus dose. concentrations. Changes in boceprevir, and the Overall tacrolimus exposure may both tacrolimus dose and/or combination of ombitasvir increase > 5 fold. When ritonavir dosing frequency should be and paritaprevir with combinations are co-administered, individualized and adjusted as ritonavir, when used with tacrolimus exposure may increase needed based on tacrolimus and without dasabuvir), > 50 fold. Nearly all patients may trough concentrations, which nefazodone, the require a reduction in tacrolimus should be assessed at initiation, pharmacokinetic enhancer dose and temporary interruption of monitored frequently cobicistat, and the kinase tacrolimus may also be necessary. throughout (starting within the inhibitors idelalisib, The effect on tacrolimus blood first few days) and re- ceritinib. concentrations may remain for evaluated on and after Strong interactions have also several days after co-administration completion of the CYP3A4 been observed with the is completed. inhibitor. Upon completion, macrolide antibiotic appropriate dose and dosing erythromycin frequency of tacrolimus should be guided by tacrolimus blood concentrations. Monitor renal function, ECG for QT prolongation, and other side effects closely. Moderate or weak CYP3A4 May increase tacrolimus whole Monitor tacrolimus whole inhibitors: blood trough concentrations and blood trough concentrations antifungal agents (e.g., increase the risk of serious adverse frequently, starting within the fluconazole, isavuconazole, reactions (e.g., neurotoxicity, QT first few days of co- clotrimazole, miconazole), prolongation) [see section 4.4]. A administration. Reduce the macrolide antibiotics rapid increase in tacrolimus level tacrolimus dose if needed [see (e.g., azithromycin), calcium may occur. section 4.2]. Monitor renal channel blockers (e.g., function, ECG for QT nifedipine, nicardipine, prolongation, and other side diltiazem, verapamil), effects closely. amiodarone, danazol, ethinylestradiol, lansoprazole, omeprazole, the HCV antivirals elbasvir/grazoprevir and glecaprevir/pibrentasvir, the CMV antiviral letermovir, and the tyrosine kinase inhibitors nilotinib, crizotinib and imatinib and (Chinese) herbal remedies containing extracts of Schisandra sphenanthera

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): lansoprazole (HOS-085166) letermovir (HOS-090621) ceritinib (HOS-086215) josamycin (HOS-113844) diltiazem (HOS-086288) nefazodone (HOS-084519) elbasvir (HOS-108814) isavuconazole (HOS-085186) nifedipine (HOS-086289) nelfinavir (HOS-084520) nicardipine (HOS-090619) protease (HOS-085623) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) crizotinib (HOS-116818) cobicistat (HOS-088111) glecaprevir (HOS-086297) azithromycin (HOS-088112) clotrimazole (HOS-090574) calcium (HOS-085615) imatinib (HOS-110212) dasabuvir (HOS-110302) voriconazole (HOS-084524) telaprevir (HOS-090618) telithromycin (HOS-084523) grazoprevir (HOS-108815) itraconazole (HOS-084516) saquinavir (HOS-084522) danazol (HOS-085473) fluconazole (HOS-087945) ombitasvir (HOS-110300) boceprevir (HOS-090617) clarithromycin (HOS-084517) erythromycin (HOS-084514) troleandomycin (HOS-090575) ritonavir (HOS-084521) amiodarone (HOS-085596) paritaprevir (HOS-110301) tyrosine (HOS-108875) posaconazole (HOS-085622) nilotinib (HOS-086218) miconazole (HOS-115630) idelalisib (HOS-116811) omeprazole (HOS-085912) verapamil (HOS-090602)

Wechselwirkungen · Modigraf

Modigraf 0.2 mg granules for oral suspension Modigraf 1 mg granules for oral suspension · Abschnitt 4.5 · PDF-Seite 10–11

HOS-209742 · Präparat HOS-154375

10 Medicinal products which have effects on tacrolimus Drug/Substance Class or Drug interaction effect Recommendations concerning co- Name administration Grapefruit or grapefruit juice May increase tacrolimus Avoid grapefruit or grapefruit whole blood trough juice. concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see section 4.4]. Ciclosporin May increase tacrolimus The simultaneous use of whole blood trough ciclosporin and tacrolimus should concentrations. In addition, be avoided [see section 4.4]. synergistic/additive nephrotoxic effects can occur. Products known to have May enhance nephrotoxic or Concurrent use of tacrolimus with nephrotoxic or neurotoxic neurotoxic effects of drugs known to have nephrotoxic effects: tacrolimus. effects should be avoided. When aminoglycosides, gyrase co-administration cannot be inhibitors, vancomycin, avoided, monitor renal function sulfamethoxazole + and other side effects and adjust trimethoprim, NSAIDs, tacrolimus dose if needed. ganciclovir, acyclovir, amphotericin B, ibuprofen cidofovir, foscarnet Strong CYP3A4 inhibitors: May increase tacrolimus It is recommended that antifungal agents (e.g., whole blood trough concomitant use should be ketoconazole, itraconazole, concentrations and increase avoided. If co-administration of a posaconazole, voriconazole), the risk of serious adverse strong CYP3A4 inhibitor is the macrolide antibiotics reactions (e.g., unavoidable, consider omitting (e.g., telithromycin, nephrotoxicity, the dose of tacrolimus the day the troleandomycin, neurotoxicity, QT strong CYP3A4 inhibitor is clarithromycin, josamycin), prolongation) which requires initiated. Reinitiate tacrolimus the HIV protease inhibitors (e.g., close monitoring [see next day at a reduced dose based ritonavir, nelfinavir, section 4.4]. on tacrolimus blood saquinavir), HCV protease Rapid and sharp increases in concentrations. Changes in both inhibitors (e.g., telaprevir, tacrolimus levels may occur, tacrolimus dose and/or dosing boceprevir, and the as early as within 1-3 days frequency should be combination of ombitasvir after co-administration, individualized and adjusted as and paritaprevir with despite immediate reduction needed based on tacrolimus ritonavir, when used with and of tacrolimus dose. Overall trough concentrations, which without dasabuvir), tacrolimus exposure may should be assessed at initiation, nefazodone, the increase > 5 fold. When monitored frequently throughout pharmacokinetic enhancer ritonavir combinations are (starting within the first few days) cobicistat and the kinase co-administered, tacrolimus and re-evaluated on and after inhibitors idelalisib, ceritinib. exposure may increase > 50 completion of the CYP3A4 Strong interactions have also fold. inhibitor. Upon completion, been observed with the Nearly all patients may appropriate dose and dosing macrolide antibiotic require a reduction in frequency of tacrolimus should be erythromycin tacrolimus dose and guided by tacrolimus blood temporary interruption of concentrations. Monitor renal tacrolimus may also be function, ECG for QT necessary. prolongation, and other side effects closely.

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): foscarnet (HOS-110484) sulfamethoxazole (HOS-084533) ceritinib (HOS-086215) josamycin (HOS-113844) nefazodone (HOS-084519) nelfinavir (HOS-084520) ibuprofen (HOS-087884) protease (HOS-085623) amphotericin B (HOS-109312) trimethoprim (HOS-085184) ketoconazole (HOS-084513) cobicistat (HOS-088111) cidofovir (HOS-110482) grapefruit juice (HOS-088787) dasabuvir (HOS-110302) voriconazole (HOS-084524) telaprevir (HOS-090618) telithromycin (HOS-084523) itraconazole (HOS-084516) saquinavir (HOS-084522) ombitasvir (HOS-110300) boceprevir (HOS-090617) clarithromycin (HOS-084517) vancomycin (HOS-110486) erythromycin (HOS-084514) troleandomycin (HOS-090575) ritonavir (HOS-084521) ganciclovir (HOS-085194) paritaprevir (HOS-110301) acyclovir (HOS-088527) posaconazole (HOS-085622) idelalisib (HOS-116811)

Wechselwirkungen · Voriconazole Hikma (previously Voriconazole Hospira)

Voriconazole Hikma 200 mg powder for solution for infusion · Abschnitt 4.5 · PDF-Seite 11–12

HOS-130932 · Präparat HOS-096981

11 Rifabutin Concomitant use of voriconazole [potent CYP450 inducer] and rifabutin should be avoided Voriconazole Cmax ↓ 69% unless the benefit outweighs the 300 mg QD Voriconazole AUCτ ↓ 78% risk. The maintenance dose of Compared to voriconazole 200 mg voriconazole may be increased to 300 mg QD (coadministered BID, 5 mg/kg intravenously BID or with voriconazole 350 mg Voriconazole Cmax ↓ 4% from 200 mg to 350 mg orally BID)* Voriconazole AUCτ ↓ 32% BID (100 mg to 200 mg orally BID in patients less than 40 kg) (see section 4.2). Careful monitoring of full blood Rifabutin Cmax ↑ 195% counts and adverse reactions to 300 mg QD (coadministered Rifabutin AUCτ ↑ 331% rifabutin (e.g., uveitis) is with voriconazole 400 mg Compared to voriconazole 200 mg recommended when rifabutin is BID)* BID, coadministered with Voriconazole Cmax ↑ 104% voriconazole. Voriconazole AUCτ ↑ 87% Rifampicin (600 mg QD) Voriconazole Cmax ↓ 93% Contraindicated (see section [potent CYP450 inducer] Voriconazole AUCτ ↓ 96% 4.3) Anti-cancer agents Glasdegib Although not studied, voriconazole If concomitant use cannot be [CYP3A4 substrate] is likely to increase the plasma avoided, frequent ECG concentrations of glasdegib and monitoring is recommended (see increase risk of QTc prolongation. section 4.4). Tretinoin Although not studied, voriconazole Dose adjustment of tretinoin is [CYP3A4 substrate] may increase tretinoin recommended during treatment concentrations and increase risk of with voriconazole and after its adverse reactions (pseudotumor discontinuation. cerebri, hypercalcaemia). Tyrosine kinase inhibitors Although not studied, voriconazole If concomitant use cannot be (including but not limited to: may increase plasma avoided, dose reduction of the axitinib, bosutinib, concentrations of tyrosine kinase tyrosine kinase inhibitor and cabozantinib, ceritinib, inhibitors metabolised by CYP3A4. close clinical monitoring is cobimetinib, dabrafenib, recommended (see section 4.4). dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) [CYP3A4 substrates] Venetoclax Although not studied, voriconazole Concomitant administration of [CYP3A substrate] voriconazole is contraindicated is likely to significantly increase the plasma concentrations of at initiation and during venetoclax. venetoclax dose titration phase (see section 4.3). Dose reduction of venetoclax is required as instructed in venetoclax prescribing information during steady daily dosing; close monitoring for signs of toxicity is recommended. Vinca Alkaloids (including but Although not studied, voriconazole Dose reduction of vinca alkaloids not limited to: vincristine and is likely to increase the plasma should be considered. vinblastine) concentrations of vinca alkaloids [CYP3A4 substrates] and lead to neurotoxicity. Anticoagulants

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): axitinib (HOS-109448) ceritinib (HOS-086215) dasatinib (HOS-086217) cobimetinib (HOS-109451) rifabutin (HOS-086262) vinblastine (HOS-086220) glasdegib (HOS-109446) vincristine (HOS-086219) dabrafenib (HOS-109452) venetoclax (HOS-086143) tretinoin (HOS-109447) lead (HOS-085592) sunitinib (HOS-109453) ribociclib (HOS-109454) tyrosine (HOS-108875) cabozantinib (HOS-109450) bosutinib (HOS-109449) nilotinib (HOS-086218) ibrutinib (HOS-086226)

Gegenanzeigen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.3 · PDF-Seite 5

HOS-131685 · Präparat HOS-097124

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.

Gegenanzeigen · Zykadia

Zykadia 150 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 31

HOS-131739 · Präparat HOS-097124

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 · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 7

HOS-131686 · Präparat HOS-097124

Agents that may increase ceritinib plasma concentrations

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

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 7

HOS-131687 · Präparat HOS-097124

Strong CYP3A inhibitors In healthy subjects, co-administration of a single 450 mg fasted ceritinib dose with ketoconazole (200 mg twice daily for 14 days), a strong CYP3A/P-gp inhibitor, resulted in 2.9-fold and 1.2-fold increase in ceritinib AUCinf and Cmax, respectively, compared to when ceritinib was given alone. The steady-state AUC of ceritinib at reduced doses after co-administration with ketoconazole 200 mg twice daily for 14 days was predicted by simulations to be similar to the steady-state AUC of ceritinib alone. Concomitant use of strong CYP3A inhibitors should be avoided during treatment with ceritinib. If it is not possible to avoid concomitant use with strong CYP3A inhibitors (including, but not limited to, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole and

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): ketoconazole (HOS-084513) voriconazole (HOS-084524) telithromycin (HOS-084523) itraconazole (HOS-084516) saquinavir (HOS-084522) ritonavir (HOS-084521) posaconazole (HOS-085622)

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 7–8

HOS-131688 · Präparat HOS-097124

7 nefazodone), the dose of ceritinib should be reduced by approximately one third, rounded to the nearest multiple of the 150 mg dose strength. After discontinuation of a strong CYP3A inhibitor, ceritinib should be resumed at the dose that was taken prior to initiating the strong CYP3A inhibitor.

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): nefazodone (HOS-084519)

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 8

HOS-131689 · Präparat HOS-097124

P-gp inhibitors Based on in vitro data, ceritinib is a substrate of the efflux transporter P-glycoprotein (P-gp). If ceritinib is administered with medicinal products that inhibit P-gp, an increase in ceritinib concentration is likely. Caution should be exercised with concomitant use of P-gp inhibitors and ADRs carefully monitored.

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

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 8

HOS-131690 · Präparat HOS-097124

Agents that may decrease ceritinib plasma concentrations

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

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 8

HOS-131691 · Präparat HOS-097124

Strong CYP3A and P-gp inducers In healthy subjects, co-administration of a single 750 mg fasted ceritinib dose with rifampicin (600 mg daily for 14 days), a strong CYP3A/P-gp inducer, resulted in 70% and 44% decreases in ceritinib AUCinf and Cmax, respectively, compared to when ceritinib was given alone. Co-administration of ceritinib with strong CYP3A/P-gp inducers decreases ceritinib plasma concentrations. Concomitant use of strong CYP3A inducers should be avoided; this includes, but is not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John’s Wort (Hypericum perforatum). Caution should be exercised with concomitant use of P-gp inducers.

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) rifabutin (HOS-086262) phenytoin (HOS-084531)

Wechselwirkungen · Zykadia

Zykadia 150 mg hard capsules · Abschnitt 4.5 · PDF-Seite 8

HOS-131692 · Präparat HOS-097124

Agents that affect gastric pH Ceritinib demonstrates pH-dependent solubility and becomes poorly soluble as pH increases in vitro. Acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) can alter the solubility of ceritinib and reduce its bioavailability. Co-administration of a single 750 mg fasted ceritinib dose with a proton pump inhibitor (esomeprazole) 40 mg daily for 6 days in healthy, fasting subjects decreased ceritinib AUC by 76% and Cmax by 79%. The drug-drug interaction study was designed to observe the impact of proton pump inhibitor in the worst scenario, but in clinical use the impact of proton pump inhibitor on ceritinib exposure appears to be less pronounced. A dedicated study to evaluate the effect of gastric acid-reducing agents on the bioavailability of ceritinib under steady state has not been conducted. Caution is advised with concomitant use of proton pump inhibitors, as exposure of ceritinib may be reduced. There is no data with concomitant use of H2 blockers or antacids. However, the risk for a clinically relevant decrease in bioavailability of ceritinib is possibly lower with concomitant use of H2 blockers if they are administered 10 hours before or 2 hours after the ceritinib dose, and with antacids if they are administered 2 hours before or 2 hours after the ceritinib dose.

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

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): esomeprazole (HOS-087944)