Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

Norvir 100 mg powder for oral suspension · Abschnitt 4.5 · PDF-Seite 13

HOS-086208 · Präparat HOS-083284

Abemaciclib Serum concentrations may be increased due to CYP3A4 inhibition by 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): abemaciclib (HOS-086209)

Wechselwirkungen · Norvir

Norvir 100 mg powder for oral suspension · Abschnitt 4.5 · PDF-Seite 13

HOS-086210 · Präparat HOS-083284

Co-administration of abemaciclib and ritonavir should be avoided. If this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib.

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): abemaciclib (HOS-086209)

Wechselwirkungen · Norvir

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

HOS-086417 · Präparat HOS-083284

Abemaciclib Serum concentrations may be increased due to CYP3A4 inhibition by 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): abemaciclib (HOS-086209)

Wechselwirkungen · Norvir

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

HOS-086418 · Präparat HOS-083284

Co-administration of abemaciclib and ritonavir should be avoided. If this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib.

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): abemaciclib (HOS-086209)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 12–13

HOS-108863 · Präparat HOS-093083

12  CYP3A4 inhibition by concomitantly administered with lopinavir/ritonavir. Kaletra. Antianginal Ranolazine Due to CYP3A inhibition by The concomitant administration of lopinavir/ritonavir, concentrations Kaletra and ranolazine is of ranolazine are expected to contraindicated (see section 4.3). increase. Antiarrhythmics Amiodarone, Dronedarone Amiodarone, Dronedarone: Concomitant administration of Concentrations may be increased Kaletra and amiodarone or due to CYP3A4 inhibition by dronedarone is contraindicated (see lopinavir/ritonavir. section 4.3) as the risk of arrhythmias or other serious adverse reactions may be increased. Digoxin Digoxin: Caution is warranted and Plasma concentrations may be therapeutic drug monitoring of increased due to P-glycoprotein digoxin concentrations, if inhibition by lopinavir/ritonavir. available, is recommended in case The increased digoxin level may of co-administration of Kaletra and lessen over time as P-gp digoxin. Particular caution should induction develops. be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on P-gp is expected to significantly increase digoxin levels. Initiation of digoxin in patients already taking Kaletra is likely to result in lower than expected increases of digoxin concentrations. Bepridil, Systemic Bepridil, Systemic Lidocaine, Caution is warranted and Lidocaine, and Quinidine Quinidine: therapeutic drug concentration Concentrations may be increased monitoring is recommended when when co-administered with available. lopinavir/ritonavir. Antibiotics Clarithromycin Clarithromycin: For patients with renal impairment Moderate increases in (CrCL < 30 ml/min) dose reduction clarithromycin AUC are expected of clarithromycin should be due to CYP3A inhibition by considered (see section 4.4). lopinavir/ritonavir. Caution should be exercised in administering clarithromycin with Kaletra to patients with impaired hepatic or renal function. Anticancer agents and kinase inhibitors Abemaciclib Serum concentrations may be Co-administration of abemaciclib increased due to CYP3A and Kaletra should be avoided. If inhibition by ritonavir. this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib. Apalutamide Apalutamide is a moderate to Decreased exposure of Kaletra may strong CYP3A4 inducer and this result in potential loss of may lead to a decreased exposure virological response. of lopinavir/ritonavir.

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

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): dronedarone (HOS-086144) abemaciclib (HOS-086209) lidocaine (HOS-108866) apalutamide (HOS-086212) bepridil (HOS-085612) quinidine (HOS-085593) digoxin (HOS-086172) lead (HOS-085592) clarithromycin (HOS-084517) amiodarone (HOS-085596) ranolazine (HOS-086141)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 49–50

HOS-109006 · Präparat HOS-093083

49 Antiarrhythmics Amiodarone, Amiodarone, Dronedarone: Concomitant administration of Dronedarone Concentrations may be increased Kaletra and amiodarone or due to CYP3A4 inhibition by dronedarone is contraindicated (see lopinavir/ritonavir. section 4.3) as the risk of arrhythmias or other serious adverse reactions may be increased. Digoxin Digoxin: Caution is warranted and therapeutic Plasma concentrations may be drug monitoring of digoxin increased due to P-glycoprotein concentrations, if available, is inhibition by lopinavir/ritonavir. recommended in case of The increased digoxin level may co-administration of Kaletra and lessen over time as P-gp digoxin. Particular caution should be induction develops. used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on P-gp is expected to significantly increase digoxin levels. Initiation of digoxin in patients already taking Kaletra is likely to result in lower than expected increases of digoxin concentrations. Bepridil, Systemic Bepridil, Systemic Lidocaine, Caution is warranted and therapeutic Lidocaine, and Quinidine: drug concentration monitoring is Quinidine Concentrations may be increased recommended when available. when co-administered with lopinavir/ritonavir. Antibiotics Clarithromycin Clarithromycin: For patients with renal impairment Moderate increases in (CrCL < 30 ml/min) dose reduction clarithromycin AUC are expected of clarithromycin should be due to CYP3A inhibition by considered (see section 4.4). Caution lopinavir/ritonavir. should be exercised in administering clarithromycin with Kaletra to patients with impaired hepatic or renal function. Anticancer agents and kinase inhibitors Abemaciclib Serum concentrations may be Co-administration of abemaciclib increased due to CYP3A and Kaletra should be avoided. If inhibition by ritonavir. this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib. Apalutamide Apalutamide is a moderate to Decreased exposure of Kaletra may strong CYP3A4 inducer and this result in potential loss of virological may lead to a decreased exposure response. of lopinavir/ritonavir. In addition, co-administration of apalutamide and Kaletra may lead to Serum concentrations of serious adverse events including apalutamide may be increased due seizure due to higher apalutamide to CYP3A inhibition by levels. Concomitant use of Kaletra lopinavir/ritonavir. with apalutamide is not recommended. Afatinib Afatinib: Caution should be exercised in AUC: ↑ administering afatinib with Kaletra. (Ritonavir 200 mg twice Cmax: ↑ Refer to the afatinib SmPC for daily)

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): dronedarone (HOS-086144) abemaciclib (HOS-086209) lidocaine (HOS-108866) apalutamide (HOS-086212) bepridil (HOS-085612) quinidine (HOS-085593) digoxin (HOS-086172) lead (HOS-085592) afatinib (HOS-086207) clarithromycin (HOS-084517) amiodarone (HOS-085596)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 84–85

HOS-109080 · Präparat HOS-093083

84 Fentanyl Fentanyl: Careful monitoring of adverse Increased risk of side-effects effects (notably respiratory (respiratory depression, sedation) depression but also sedation) is due to higher plasma recommended when fentanyl is concentrations because of concomitantly administered with CYP3A4 inhibition by Kaletra. lopinavir/ritonavir. Antianginal Ranolazine Due to CYP3A inhibition by The concomitant administration of lopinavir/ritonavir, concentrations Kaletra and ranolazine is of ranolazine are expected to contraindicated (see section 4.3). increase. Antiarrhythmics Amiodarone, Amiodarone, Dronedarone: Concomitant administration of Dronedarone Concentrations may be increased Kaletra and amiodarone or due to CYP3A4 inhibition by dronedarone is contraindicated (see lopinavir/ritonavir. section 4.3) as the risk of arrhythmias or other serious adverse reactions may be increased. Digoxin Digoxin: Caution is warranted and Plasma concentrations may be therapeutic drug monitoring of increased due to P-glycoprotein digoxin concentrations, if available, inhibition by lopinavir/ritonavir. is recommended in case of The increased digoxin level may co-administration of Kaletra and lessen over time as P-gp digoxin. Particular caution should induction develops. be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on P-gp is expected to significantly increase digoxin levels. Initiation of digoxin in patients already taking Kaletra is likely to result in lower than expected increases of digoxin concentrations. Bepridil, Systemic Bepridil, Systemic Lidocaine, Caution is warranted and Lidocaine, and Quinidine: therapeutic drug concentration Quinidine Concentrations may be increased monitoring is recommended when when co-administered with available. lopinavir/ritonavir. Antibiotics Clarithromycin Clarithromycin: For patients with renal impairment Moderate increases in (CrCL < 30 ml/min) dose reduction clarithromycin AUC are expected of clarithromycin should be due to CYP3A inhibition by considered (see section 4.4). lopinavir/ritonavir. Caution should be exercised in administering clarithromycin with Kaletra to patients with impaired hepatic or renal function. Anticancer agents and kinase inhibitors Abemaciclib Serum concentrations may be Co-administration of abemaciclib increased due to CYP3A and Kaletra should be avoided. If inhibition by ritonavir. this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib.

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): dronedarone (HOS-086144) abemaciclib (HOS-086209) lidocaine (HOS-108866) bepridil (HOS-085612) quinidine (HOS-085593) digoxin (HOS-086172) clarithromycin (HOS-084517) fentanyl (HOS-086196) amiodarone (HOS-085596) ranolazine (HOS-086141)

Gegenanzeigen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 7

HOS-137572 · Präparat HOS-098067

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 · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137573 · Präparat HOS-098067

Effects of other medicinal products on the pharmacokinetics of abemaciclib

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

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137574 · Präparat HOS-098067

Abemaciclib is primarily metabolised by CYP3A4.

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

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137575 · Präparat HOS-098067

CYP3A4 inhibitors Co-administration of abemaciclib with CYP3A4 inhibitors can increase plasma concentrations of abemaciclib. In patients with advanced and/or metastatic cancer, co-administration of the CYP3A4 inhibitor clarithromycin resulted in a 3.4-fold increase in the plasma exposure of abemaciclib and a 2.5-fold increase in the combined unbound potency adjusted plasma exposure of abemaciclib and its active metabolites.

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): clarithromycin (HOS-084517)

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137576 · Präparat HOS-098067

Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 inhibitors need to be co-administered, the dose of abemaciclib should be reduced (see section 4.2), followed by careful monitoring of toxicity. Examples of strong CYP3A4 inhibitors include, but not limited to: clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or voriconazole. Avoid grapefruit or grapefruit juice.

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): lopinavir (HOS-086269) ketoconazole (HOS-084513) grapefruit juice (HOS-088787) voriconazole (HOS-084524) itraconazole (HOS-084516) clarithromycin (HOS-084517) ritonavir (HOS-084521) posaconazole (HOS-085622)

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137577 · Präparat HOS-098067

No dose adjustment is necessary for patients treated with moderate or weak CYP3A4 inhibitors. There should, however, be close monitoring for signs of toxicity.

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

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137578 · Präparat HOS-098067

CYP3A4 inducers Co-administration of abemaciclib with the strong CYP3A4 inducer rifampicin decreased the plasma concentration of abemaciclib by 95 % and unbound potency adjusted plasma concentration of abemaciclib plus its active metabolites by 77 % based on AUC0-∞. Concomitant use of strong CYP3A4 inducers (including, but not limited to: carbamazepine, phenytoin, rifampicin and St. John’s wort) should be avoided due to the risk of decreased efficacy of abemaciclib.

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 · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-137579 · Präparat HOS-098067

8 Effects of abemaciclib on the pharmacokinetics of other medicinal products

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

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-137580 · Präparat HOS-098067

Medicinal products that are substrates of transporters Abemaciclib and its major active metabolites inhibit the renal transporters organic cation transporter 2 (OCT2), multidrug and extrusion toxin protein (MATE1), and MATE2-K. In vivo interactions of abemaciclib with clinically relevant substrates of these transporters, such as dofetilide or creatinine, may occur (see section 4.8). In a clinical drug interaction study with metformin (substrate of OCT2, MATE1 and 2) co-administered with 400 mg abemaciclib, a small but not clinically relevant increase (37 %) in metformin plasma exposure was observed. This was found to be due to reduced renal secretion with unaffected glomerular filtration.

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): dofetilide (HOS-085598) creatinine (HOS-086273) metformin (HOS-091032)

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-137582 · Präparat HOS-098067

In healthy subjects, co-administration of abemaciclib and the P-glycoprotein (P-gp) substrate loperamide resulted in an increase in loperamide plasma exposure of 9 % based on AUC0-∞ and 35 % based on Cmax. This was not considered to be clinically relevant. However, based on the in vitro inhibition of P-gp and breast cancer resistance protein (BCRP) observed with abemaciclib, in vivo interactions of abemaciclib with narrow therapeutic index substrates of these transporters, such as digoxin or dabigatran etexilate, may 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): digoxin (HOS-086172) loperamide (HOS-114855) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-137584 · Präparat HOS-098067

In a clinical study in patients with breast cancer, there was no clinically-relevant pharmacokinetic drug interaction between abemaciclib and anastrozole, fulvestrant, exemestane, letrozole or tamoxifen.

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): anastrozole (HOS-090912) tamoxifen (HOS-088380) fulvestrant (HOS-112832) exemestane (HOS-137585) letrozole (HOS-130515)

Wechselwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-137586 · Präparat HOS-098067

It is currently unknown whether abemaciclib may reduce the effectiveness of systemically acting hormonal contraceptives.

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

Nebenwirkungen · Verzenios

Verzenios 50 mg film-coated tablets Verzenios 100 mg film-coated tablets Verzenios 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-137587 · Präparat HOS-098067

Summary of the safety profile

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