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)

Gegenanzeigen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 8

HOS-116680 · Präparat HOS-094467

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 · Sprycel

SPRYCEL 10 mg/mL powder for oral suspension · Abschnitt 4.3 · PDF-Seite 43

HOS-116735 · Präparat HOS-094467

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 · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-116681 · Präparat HOS-094467

Active substances that may increase dasatinib plasma concentrations In vitro studies indicate that dasatinib is a CYP3A4 substrate. Concomitant use of dasatinib and medicinal products or substances which potently inhibit CYP3A4 (e.g. ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice) may increase exposure to dasatinib. Therefore, in patients receiving dasatinib, systemic administration of a potent CYP3A4 inhibitor is not recommended (see section 4.2).

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) grapefruit juice (HOS-088787) telithromycin (HOS-084523) itraconazole (HOS-084516) clarithromycin (HOS-084517) erythromycin (HOS-084514) ritonavir (HOS-084521)

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-116683 · Präparat HOS-094467

At clinically relevant concentrations, binding of dasatinib to plasma proteins is approximately 96% on the basis of in vitro experiments. No studies have been performed to evaluate dasatinib interaction with other protein-bound medicinal products. The potential for displacement and its clinical relevance are unknown.

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

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-116684 · Präparat HOS-094467

Active substances that may decrease dasatinib plasma concentrations When dasatinib was administered following 8 daily evening administrations of 600 mg rifampicin, a potent CYP3A4 inducer, the AUC of dasatinib was decreased by 82%. Other medicinal products that induce CYP3A4 activity (e.g. dexamethasone, phenytoin, carbamazepine, phenobarbital or herbal preparations containing Hypericum perforatum, also known as St. John´s Wort) may also increase metabolism and decrease dasatinib plasma concentrations. Therefore, concomitant use of potent CYP3A4 inducers with dasatinib is not recommended. In patients in whom rifampicin or other CYP3A4 inducers are indicated, alternative medicinal products with less enzyme induction potential should be used. Concomitant use of dexamethasone, a weak CYP3A4 inducer, with dasatinib is allowed; dasatinib AUC is predicted to decrease approximately 25% with concomitant use of dexamethasone, which is not likely to be clinically meaningful.

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) dexamethasone (HOS-084535) phenytoin (HOS-084531)

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-116685 · Präparat HOS-094467

Histamine-2 antagonists and proton pump inhibitors Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure. In a single-dose study in healthy subjects, the administration of famotidine 10 hours prior to a single dose of SPRYCEL reduced dasatinib exposure by 61%. In a study of 14 healthy subjects, administration of a single 100-mg 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): famotidine (HOS-112087) omeprazole (HOS-085912)

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-116687 · Präparat HOS-094467

11 of SPRYCEL 22 hours following a 4-day, 40-mg omeprazole dose at steady state reduced the AUC of dasatinib by 43% and the Cmax of dasatinib by 42%. The use of antacids should be considered in place of H2 antagonists or proton pump inhibitors in patients receiving SPRYCEL therapy (see section 4.4).

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): omeprazole (HOS-085912)

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-116688 · Präparat HOS-094467

Antacids Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. In healthy subjects, the concomitant use of aluminium hydroxide/magnesium hydroxide antacids with SPRYCEL reduced the AUC of a single dose of SPRYCEL by 55% and the Cmax by 58%. However, when antacids were administered 2 hours prior to a single dose of SPRYCEL, no relevant changes in dasatinib concentration or exposure were observed. Thus, antacids may be administered up to 2 hours prior to or 2 hours following SPRYCEL (see section 4.4).

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): magnesium hydroxide (HOS-088789)

Wechselwirkungen · Sprycel

SPRYCEL 20 mg film-coated tablets SPRYCEL 50 mg film-coated tablets SPRYCEL 70 mg film-coated tablets SPRYCEL 80 mg film-coated tablets SPRYCEL 100 mg film-coated tablets SPRYCEL 140 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-116690 · Präparat HOS-094467

Active substances that may have their plasma concentrations altered by dasatinib Concomitant use of dasatinib and a CYP3A4 substrate may increase exposure to the CYP3A4 substrate. In a study in healthy subjects, a single 100 mg dose of dasatinib increased AUC and Cmax exposure to simvastatin, a known CYP3A4 substrate, by 20 and 37% respectively. It cannot be excluded that the effect is larger after multiple doses of dasatinib. Therefore, CYP3A4 substrates known to have a narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids [ergotamine, dihydroergotamine]) should be administered with caution in patients receiving dasatinib (see section 4.4). In vitro data indicate a potential risk for interaction with CYP2C8 substrates, such as glitazones.

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): cisapride (HOS-085610) bepridil (HOS-085612) simvastatin (HOS-086158) quinidine (HOS-085593) ergot alkaloids (HOS-108807) pimozide (HOS-085600) astemizole (HOS-085608) ergotamine (HOS-086154) terfenadine (HOS-085607) dihydroergotamine (HOS-086152)