Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

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

HOS-086221 · Präparat HOS-083284

Encorafenib Serum concentrations may be increased when co-administered with ritonavir which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and ritonavir should be avoided. If the benefit is considered to outweigh the risk and ritonavir 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): encorafenib (HOS-086222)

Wechselwirkungen · Norvir

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

HOS-086423 · Präparat HOS-083284

Encorafenib Serum concentrations may be increased when co-administered with ritonavir which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and ritonavir should be avoided. If the benefit is considered to outweigh the risk and ritonavir 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): encorafenib (HOS-086222)

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)

Gegenanzeigen · Reyataz

REYATAZ 200 mg hard capsules REYATAZ 300 mg hard capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-112045 · Präparat HOS-093615

Co-administration with medicinal products that are strong inducers of CYP3A4 due to the potential for loss of therapeutic effect and development of possible resistance (e.g., rifampicin, St. John's wort, apalutamide, encorafenib, ivosidenib, carbamazepine, phenobarbital and phenytoin) (see section 4.5).

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) apalutamide (HOS-086212) encorafenib (HOS-086222) ivosidenib (HOS-112046) phenytoin (HOS-084531)

Gegenanzeigen · Reyataz

REYATAZ 50 mg oral powder · Abschnitt 4.3 · PDF-Seite 40

HOS-112153 · Präparat HOS-093615

Co-administration with medicinal products that are strong inducers of CYP3A4 due to the potential for loss of therapeutic effect and development of possible resistance (e.g., rifampicin, St. John's wort, apalutamide, encorafenib, ivosidenib, carbamazepine, phenobarbital and phenytoin) (see section 4.5).

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) apalutamide (HOS-086212) encorafenib (HOS-086222) ivosidenib (HOS-112046) phenytoin (HOS-084531)

Wechselwirkungen · Reyataz

REYATAZ 200 mg hard capsules REYATAZ 300 mg hard capsules · Abschnitt 4.5 · PDF-Seite 18–19

HOS-112101 · Präparat HOS-093615

18 Medicinal products by Interaction Recommendations concerning co- therapeutic area administration ANTINEOPLASTICS AND IMMUNOSUPRESSANTS Antineoplastics Apalutamide The mechanism of interaction is CYP3A4 Co-administration with REYATAZ induction by apalutamide and CYP3A4 (with or without ritonavir) is inhibition by atazanavir/ritonavir. contraindicated due to the potential for decreased atazanavir and ritonavir plasma concentration with subsequent loss of virologic response and possible resistance to the class of protease inhibitors (see section 4.3). In addition, serum concentrations of apalutamide may be increased when coadministered with atazanavir/ritonavir, resulting in the potential for serious adverse events including seizure. Encorafenib The mechanism of interaction is CYP3A4 Co-administration of encorafenib inhibition by atazanavir and/or ritonavir. with REYATAZ (with or without ritonavir) is contraindicated due to the potential for loss of virologic response, development of resistance, increase in encorafenib plasma concentration and subsequent risk of serious adverse events such as QT interval prolongation (see section 4.3). Ivosidenib The mechanism of interaction is CYP3A4 Co-administration of ivosidenib inhibition by atazanavir and/or ritonavir. with REYATAZ (with or without ritonavir) is contraindicated due to potential for loss of virologic response, development of resistance, increase in ivosidenib plasma concentration and subsequent risk of serious adverse events such as QT interval prolongation (see section 4.3). Irinotecan Atazanavir inhibits UGT and may interfere If REYATAZ is co-administered with the metabolism of irinotecan, with irinotecan, patients should be resulting in increased irinotecan toxicities. closely monitored for adverse events related to irinotecan. Immunosuppressants Cyclosporin Concentrations of these More frequent therapeutic Tacrolimus immunosuppressants may be increased concentration monitoring of these Sirolimus when co-administered with REYATAZ medicinal products is recommended due to CYP3A4 inhibition. until plasma levels have been stabilised. CARDIOVASCULAR AGENTS Antiarrhythmics Amiodarone, Concentrations of these antiarrhythmics Caution is warranted and Systemic lidocaine, may be increased when co-administered therapeutic concentration Quinidine with REYATAZ. The mechanism of monitoring is recommended when amiodarone or systemic available. The concomitant use of lidocaine/atazanavir interaction is CYP3A quinidine is contraindicated inhibition. Quinidine has a narrow (see section 4.3). therapeutic window and is contraindicated due to potential inhibition of CYP3A by REYATAZ.

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

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): protease (HOS-085623) lidocaine (HOS-108866) apalutamide (HOS-086212) quinidine (HOS-085593) encorafenib (HOS-086222) tacrolimus (HOS-085202) ivosidenib (HOS-112046) sirolimus (HOS-085172) ritonavir (HOS-084521) amiodarone (HOS-085596) irinotecan (HOS-112102)

Wechselwirkungen · Reyataz

REYATAZ 50 mg oral powder · Abschnitt 4.5 · PDF-Seite 54

HOS-112191 · Präparat HOS-093615

Close monitoring of patient's virologic response should be exercised. Lamotrigine Co-administration of lamotrigine and Lamotrigine should be used REYATAZ/ritonavir may decrease with caution in combination lamotrigine plasma concentrations due to with REYATAZ/ritonavir. UGT1A4 induction. If necessary, monitor lamotrigine concentrations and adjust the dose accordingly. ANTINEOPLASTICS AND IMMUNOSUPRESSANTS Antineoplastics Apalutamide The mechanism of interaction is CYP3A4 Co-administration with induction by apalutamide and CYP3A4 REYATAZ (with or without inhibition by atazanavir/ritonavir. ritonavir) is contraindicated due to the potential for decreased atazanavir and ritonavir plasma concentration with subsequent loss of virologic response and possible resistance to the class of protease inhibitors (see section 4.3). In addition, serum concentrations of apalutamide may be increased when coadministered with atazanavir/ritonavir, resulting in the potential for serious adverse events including seizure. Encorafenib The mechanism of interaction is CYP3A4 Co-administration of inhibition by atazanavir and/or ritonavir. encorafenib with REYATAZ (with or without ritonavir) is contraindicated due to potential for loss of virologic response, development of resistance, increase in encorafenib plasma concentration and subsequent risk of serious adverse events such as QT interval prolongation (see section 4.3).

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): lamotrigine (HOS-086242) protease (HOS-085623) apalutamide (HOS-086212) encorafenib (HOS-086222) ritonavir (HOS-084521)

Wechselwirkungen · Mektovi

Mektovi 15 mg film-coated tablets Mektovi 45 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-140006 · Präparat HOS-098436

While encorafenib is a relatively potent reversible inhibitor of UGT1A1, no differences in binimetinib exposure have been observed clinically when binimetinib is co-administered with encorafenib (see section 5.2).

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): encorafenib (HOS-086222)

Gegenanzeigen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.3 · PDF-Seite 8

HOS-140057 · Präparat HOS-098444

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 · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140058 · Präparat HOS-098444

Effects of other medicinal products on encorafenib

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

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140059 · Präparat HOS-098444

Encorafenib is primarily metabolised by CYP3A4.

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

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140060 · Präparat HOS-098444

CYP3A4 inhibitors Co-administration of moderate (diltiazem) and strong (posaconazole) CYP3A4 inhibitors with single doses of encorafenib in healthy volunteers resulted in a 2 and 3-fold increase in the area under the concentration-time curve (AUC), respectively and in 44.6% and 68.3% increase in maximum encorafenib concentration (Cmax) respectively. Model based predictions indicate that the effect of posaconazole after repeated administrations could be similar for AUC (3-fold increase) and slightly greater for Cmax (2.7-fold increase). Model-based predictions for ketoconazole suggest an increase of approx. 5-fold for encorafenib AUC and 3 to 4- fold for encorafenib Cmax after administration of encorafenib 450 and 300 mg QD, respectively. Therefore, concomitant administration of encorafenib with strong CYP3A4 inhibitors should be avoided (due to increased encorafenib exposure and potential increase in toxicity, see section 5.2). Examples of strong CYP3A4 inhibitors include, but are not limited to, ritonavir, itraconazole, clarithromycin, telithromycin, posaconazole and grapefruit juice. If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety. Moderate CYP3A4 inhibitors should be co-administered with caution. Examples of moderate CYP3A4 inhibitors include, but are not limited to, amiodarone, erythromycin, fluconazole, diltiazem, amprenavir and imatinib. When encorafenib is co-administered with a moderate CYP3A inhibitor, 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): diltiazem (HOS-086288) ketoconazole (HOS-084513) grapefruit juice (HOS-088787) imatinib (HOS-110212) telithromycin (HOS-084523) itraconazole (HOS-084516) fluconazole (HOS-087945) clarithromycin (HOS-084517) erythromycin (HOS-084514) amprenavir (HOS-086183) ritonavir (HOS-084521) amiodarone (HOS-085596) posaconazole (HOS-085622)

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140061 · Präparat HOS-098444

CYP3A4 inducers Co-administration of encorafenib with a strong CYP3A4 inducer was not assessed in a clinical study; however, a reduction in encorafenib exposure is likely and may result in compromised efficacy of encorafenib. Examples of strong CYP3A4 inducers include, but are not limited to carbamazepine, rifampicin, phenytoin and St. John’s Wort. Alternative agents with no to moderate CYP3A induction potential 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): carbamazepine (HOS-085618) phenytoin (HOS-084531)

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140062 · Präparat HOS-098444

Effects of encorafenib on other medicinal products

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

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140063 · Präparat HOS-098444

CYP substrates Encorafenib is a strong inducer of CYP3A4. Concomitant use with agents that are substrates of CYP3A4 (e.g., hormonal contraceptives) may result in loss of efficacy of these agents. If the coadministration of narrow therapeutic index CYP3A4 substrates cannot be avoided, adjust the dose of these substrates in accordance with their approved SmPC. Encorafenib is an inhibitor of UGT1A1. Concomitant agents that are substrates of UGT1A1 (e.g. raltegravir, atorvastatin, dolutegravir) may have increased exposure and should be therefore administered with caution.

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): atorvastatin (HOS-086304) dolutegravir (HOS-089992) raltegravir (HOS-086187)

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140064 · Präparat HOS-098444

Effect of encorafenib on binimetinib While encorafenib is a relatively potent reversible inhibitor of UGT1A1, no differences in binimetinib exposure have been observed clinically when binimetinib was co-administered with encorafenib.

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): binimetinib (HOS-140001)

Wechselwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-140065 · Präparat HOS-098444

Transporter substrates In vivo, encorafenib is an inhibitor of OATP1B1, OATP1B3 and/or BCRP. Coadministration of encorafenib with OATP1B1, OATP1B3 or BCRP substrates (such as rosuvastatin, atorvastatin, methotrexate) can result in increased concentrations (see section 5.2). In vitro, encorafenib potentially inhibits a number of other transporters. Agents that are substrates of renal transporters OAT1, OAT3, OCT2 (such as furosemide, penicillin) or agents that are substrates of the hepatic transporters OCT1 (such as, bosentan) or substrates of P-gp (e.g. posaconazole) may also have increased exposure. Therefore, these agents, substrates of transporters should be co-administered with caution.

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): furosemide (HOS-089060) atorvastatin (HOS-086304) rosuvastatin (HOS-086307) bosentan (HOS-086291) posaconazole (HOS-085622) methotrexate (HOS-087522)

Nebenwirkungen · Braftovi

Braftovi 50 mg hard capsules Braftovi 75 mg hard capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-140066 · Präparat HOS-098444

Summary of safety profile

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