Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

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

HOS-086216 · Präparat HOS-083284

Dasatinib, nilotinib, vincristine, Serum concentrations may be increased when co-administered with ritonavir vinblastine resulting in the potential for increased incidence of adverse events.

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): dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) nilotinib (HOS-086218)

Wechselwirkungen · Norvir

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

HOS-086422 · Präparat HOS-083284

Dasatinib, nilotinib, vincristine, Serum concentrations may be increased when co-administered with ritonavir resulting in vinblastine the potential for increased incidence of adverse reactions.

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): dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) nilotinib (HOS-086218)

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 · Prezista

PREZISTA 100 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 18–19

HOS-116385 · Präparat HOS-094447

18 ANTIMYCOBACTERIALS Rifampicin Not studied. Rifapentine and rifampicin The combination of rifapentine and Rifapentine are strong CYP3A inducers and have boosted PREZISTA is not been shown to cause profound decreases recommended. in concentrations of other protease inhibitors, which can result in virological The combination of rifampicin and failure and resistance development boosted PREZISTA is (CYP450 enzyme induction). During contraindicated (see section 4.3). attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with low dose ritonavir, a high frequency of liver reactions was seen with rifampicin. Rifabutin rifabutin AUC** ↑ 55% A dosage reduction of rifabutin by 150 mg once every other rifabutin Cmin** ↑ ND 75% of the usual dose of day rifabutin Cmax** ↔ 300 mg/day (i.e. rifabutin 150 mg darunavir AUC ↑ 53% once every other day) and darunavir Cmin ↑ 68% increased monitoring for rifabutin related adverse events is warranted darunavir Cmax ↑ 39% ** in patients receiving the sum of active moieties of rifabutin (parent combination with PREZISTA drug + 25-O-desacetyl metabolite) co-administered with ritonavir. In case of safety issues, a further The interaction trial showed a increase of the dosing interval for comparable daily systemic exposure for rifabutin and/or monitoring of rifabutin between treatment at 300 mg rifabutin levels should be once daily alone and 150 mg once every considered. other day in combination with Consideration should be given to PREZISTA/ritonavir (600/100 mg twice official guidance on the daily) with an about 10-fold increase in appropriate treatment of the daily exposure to the active tuberculosis in HIV infected metabolite 25-O-desacetylrifabutin. patients. Furthermore, AUC of the sum of active Based upon the safety profile of moieties of rifabutin (parent drug PREZISTA/ritonavir, the increase + 25-O-desacetyl metabolite) was in darunavir exposure in the increased 1.6-fold, while Cmax remained presence of rifabutin does not comparable. warrant a dose adjustment for Data on comparison with a 150 mg once PREZISTA/ritonavir. daily reference dose is lacking. Based on pharmacokinetic modeling, this dosage reduction of (Rifabutin is an inducer and substrate of 75% is also applicable if patients CYP3A.) An increase of systemic receive rifabutin at doses other exposure to darunavir was observed when than 300 mg/day. PREZISTA co-administered with 100 mg ritonavir was co-administered with Co-administration of PREZISTA rifabutin (150 mg once every other day). co-administered with cobicistat and rifabutin is not recommended. ANTINEOPLASTICS Dasatinib Not studied. Boosted PREZISTA is Concentrations of these medicinal Nilotinib expected to increase these antineoplastic products may be increased when Vinblastine plasma concentrations. co-administered with boosted Vincristine (CYP3A inhibition) PREZISTA resulting in the potential for increased adverse events usually associated with these agents. Caution should be exercised when combining one of these antineoplastic agents 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): dasatinib (HOS-086217) protease (HOS-085623) rifabutin (HOS-086262) vinblastine (HOS-086220) cobicistat (HOS-088111) vincristine (HOS-086219) rifapentine (HOS-116386) ritonavir (HOS-084521) nilotinib (HOS-086218)

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 60–61

HOS-116525 · Präparat HOS-094447

60  Rifabutin rifabutin AUC** ↑ 55% A dosage reduction of rifabutin by 150 mg once every other rifabutin Cmin** ↑ ND 75% of the usual dose of day rifabutin Cmax** ↔ 300 mg/day (i.e. rifabutin 150 mg darunavir AUC ↑ 53% once every other day) and darunavir Cmin ↑ 68% increased monitoring for rifabutin related adverse events is warranted darunavir Cmax ↑ 39% ** in patients receiving the sum of active moieties of rifabutin (parent combination with PREZISTA drug + 25-O-desacetyl metabolite) co-administered with ritonavir. In case of safety issues, a further The interaction trial showed a increase of the dosing interval for comparable daily systemic exposure for rifabutin and/or monitoring of rifabutin between treatment at 300 mg rifabutin levels should be once daily alone and 150 mg once every considered. other day in combination with Consideration should be given to PREZISTA/ritonavir (600/100 mg twice official guidance on the daily) with an about 10-fold increase in appropriate treatment of the daily exposure to the active tuberculosis in HIV infected metabolite 25-O-desacetylrifabutin. patients. Furthermore, AUC of the sum of active Based upon the safety profile of moieties of rifabutin (parent drug PREZISTA/ritonavir, the increase + 25-O-desacetyl metabolite) was in darunavir exposure in the increased 1.6-fold, while Cmax remained presence of rifabutin does not comparable. warrant a dose adjustment for Data on comparison with a 150 mg once PREZISTA/ritonavir. daily reference dose is lacking. Based on pharmacokinetic modeling, this dosage reduction of (Rifabutin is an inducer and substrate of 75% is also applicable if patients CYP3A.) An increase of systemic receive rifabutin at doses other exposure to darunavir was observed when than 300 mg/day. PREZISTA co-administered with 100 mg ritonavir was co-administered with rifabutin (150 mg once every other day). ANTINEOPLASTICS Dasatinib Not studied. PREZISTA is expected to Concentrations of these medicinal Nilotinib increase these antineoplastic plasma products may be increased when Vinblastine concentrations. co-administered with PREZISTA Vincristine (CYP3A inhibition) with low dose ritonavir resulting in the potential for increased adverse events usually associated with these agents. Caution should be exercised when combining one of these antineoplastic agents with PREZISTA 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): dasatinib (HOS-086217) rifabutin (HOS-086262) vinblastine (HOS-086220) vincristine (HOS-086219) ritonavir (HOS-084521) nilotinib (HOS-086218)

Wechselwirkungen · Prezista

PREZISTA 400 mg film-coated tablets PREZISTA 800 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 100–101

HOS-116615 · Präparat HOS-094447

100 ANTIMYCOBACTERIALS Rifampicin Not studied. Rifapentine and rifampicin The combination of rifapentine and Rifapentine are strong CYP3A inducers and have boosted PREZISTA is not been shown to cause profound decreases recommended. in concentrations of other protease inhibitors, which can result in virological The combination of rifampicin and failure and resistance development boosted PREZISTA is (CYP450 enzyme induction). During contraindicated (see section 4.3). attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with low dose ritonavir, a high frequency of liver reactions was seen with rifampicin. Rifabutin rifabutin AUC** ↑ 55% A dosage reduction of rifabutin by 150 mg once every other rifabutin Cmin** ↑ ND 75% of the usual dose of day rifabutin Cmax** ↔ 300 mg/day (i.e. rifabutin 150 mg darunavir AUC ↑ 53% once every other day) and darunavir Cmin ↑ 68% increased monitoring for rifabutin related adverse events is warranted darunavir Cmax ↑ 39% ** in patients receiving the sum of active moieties of rifabutin (parent combination with PREZISTA drug + 25-O-desacetyl metabolite) co-administered with ritonavir. In case of safety issues, a further The interaction trial showed a increase of the dosing interval for comparable daily systemic exposure for rifabutin and/or monitoring of rifabutin between treatment at 300 mg rifabutin levels should be once daily alone and 150 mg once every considered. other day in combination with Consideration should be given to PREZISTA/ritonavir (600/100 mg twice official guidance on the daily) with an about 10-fold increase in appropriate treatment of the daily exposure to the active tuberculosis in HIV infected metabolite 25-O-desacetylrifabutin. patients. Furthermore, AUC of the sum of active Based upon the safety profile of moieties of rifabutin (parent drug PREZISTA/ritonavir, the increase + 25-O-desacetyl metabolite) was in darunavir exposure in the increased 1.6-fold, while Cmax remained presence of rifabutin does not comparable. warrant a dose adjustment for Data on comparison with a 150 mg once PREZISTA/ritonavir. daily reference dose is lacking. Based on pharmacokinetic modeling, this dosage reduction of (Rifabutin is an inducer and substrate of 75% is also applicable if patients CYP3A.) An increase of systemic receive rifabutin at doses other exposure to darunavir was observed when than 300 mg/day. PREZISTA co-administered with 100 mg ritonavir was co-administered with Co-administration of PREZISTA rifabutin (150 mg once every other day). co-administered with cobicistat and rifabutin is not recommended. ANTINEOPLASTICS Dasatinib Not studied. Boosted PREZISTA is Concentrations of these medicinal Nilotinib expected to increase these antineoplastic products may be increased when Vinblastine plasma concentrations. co-administered with boosted Vincristine (CYP3A inhibition) PREZISTA resulting in the potential for increased adverse events usually associated with these agents. Caution should be exercised when combining one of these antineoplastic agents 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): dasatinib (HOS-086217) protease (HOS-085623) rifabutin (HOS-086262) vinblastine (HOS-086220) cobicistat (HOS-088111) vincristine (HOS-086219) rifapentine (HOS-116386) ritonavir (HOS-084521) nilotinib (HOS-086218)

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)

Gegenanzeigen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.3 · PDF-Seite 6

HOS-118196 · Präparat HOS-094783

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 · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 10

HOS-118197 · Präparat HOS-094783

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated. It may be given with hydroxyurea or anagrelide if clinically indicated.

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): hydroxyurea (HOS-115724) anagrelide (HOS-111551)

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 10

HOS-118199 · Präparat HOS-094783

Nilotinib is mainly metabolised in the liver with CYP3A4 expected to be the main contributor to the oxidative metabolism. Nilotinib is also a substrate for the multi-drug efflux pump, P-glycoprotein (P-gp). Therefore, absorption and subsequent elimination of systemically absorbed nilotinib may be influenced by substances that affect CYP3A4 and/or P-gp.

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

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 10

HOS-118200 · Präparat HOS-094783

Substances that may increase nilotinib serum concentrations

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

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 10

HOS-118201 · Präparat HOS-094783

Concomitant administration of nilotinib with imatinib (a substrate and moderator of P-gp and CYP3A4), had a slight inhibitory effect on CYP3A4 and/or P-gp. The AUC of imatinib was increased by 18% to 39%, and the AUC of nilotinib was increased by 18% to 40%. These changes are unlikely to be clinically important.

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): imatinib (HOS-110212)

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 10–11

HOS-118202 · Präparat HOS-094783

10 The exposure to nilotinib in healthy subjects was increased 3-fold when co-administered with the strong CYP3A4 inhibitor ketoconazole. Concomitant treatment with strong CYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin, should therefore be avoided (see section 4.4). Increased exposure to nilotinib might also be expected with moderate CYP3A4 inhibitors. Alternative concomitant medicinal products with no or minimal CYP3A4 inhibition should be considered.

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) clarithromycin (HOS-084517) ritonavir (HOS-084521)

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118203 · Präparat HOS-094783

Substances that may decrease nilotinib serum concentrations

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

Wechselwirkungen · Tasigna

Tasigna 50 mg hard capsules Tasigna 150 mg hard capsules Tasigna 200 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118204 · Präparat HOS-094783

Rifampicin, a potent CYP3A4 inducer, decreases nilotinib Cmax by 64% and reduces nilotinib AUC by 80%. Rifampicin and nilotinib should not be used concomitantly.

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