Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

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

HOS-086206 · Präparat HOS-083284

Anticancer agents and kinase inhibitors Afatinib 20 mg, single dose 200 q12h/1h ↑ 48% ↑ 39% 40 mg, single dose before 40 mg, single dose 200 q12h/ co- ↑ 19% ↑ 4% administered 200 q12h/6h after ↑ 11% ↑ 5% Serum concentrations may be increased due to Breast Cancer Resistance Protein (BCRP) and acute P-gp inhibition by ritonavir. The extent of increase in AUC and Cmax depends on the timing of ritonavir administration. Caution should be exercised in administering afatinib with ritonavir (refer to the afatinib SmPC). Monitor for ADRs related to afatinib.

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): afatinib (HOS-086207)

Wechselwirkungen · Norvir

Norvir 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-086415 · Präparat HOS-083284

Anticancer agents and kinase inhibitors Afatinib 20 mg, single dose 200 ↑ 48% ↑ 39% 40 mg, single dose q12h/1h 40 mg, single dose before ↑ 19% ↑ 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): afatinib (HOS-086207)

Wechselwirkungen · Norvir

Norvir 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45–46

HOS-086416 · Präparat HOS-083284

45  Ritonavir effects on Non-antiretroviral Co-administered Medicinal Products Co-administered Medicinal Products Dose of Co-administered Medicinal Dose of Effect on Co- Effect on Co- Products (mg) NORVIR administered administered (mg) Medicinal Medicinal Products Products Cmax AUC 200 q12h/ co- ↑ 11% ↑ 5% administered 200 q12h/6h after Serum concentrations may be increased due to Breast Cancer Resistance Protein (BCRP) and acute P-gp inhibition by ritonavir. The extent of increase in AUC and Cmax depends on the timing of ritonavir administration. Caution should be exercised in administering afatinib with ritonavir (refer to the afatinib SmPC). Monitor for ADRs related to afatinib.

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): afatinib (HOS-086207)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 13–14

HOS-108871 · Präparat HOS-093083

13  In addition, co-administration of Serum concentrations of apalutamide and Kaletra may lead apalutamide may be increased to serious adverse events including due to CYP3A inhibition by seizure due to higher apalutamide lopinavir/ritonavir. levels. Concomitant use of Kaletra 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) dosage adjustment The extent of increase depends on recommendations. Monitor for the timing of ritonavir ADRs related to afatinib. administration.

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): apalutamide (HOS-086212) lead (HOS-085592) afatinib (HOS-086207)

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

HOS-109007 · Präparat HOS-093083

50  The extent of increase depends on dosage adjustment recommendations. the timing of ritonavir Monitor for ADRs related to afatinib. administration.

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): afatinib (HOS-086207)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 85–86

HOS-109081 · Präparat HOS-093083

85 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 Serum concentrations of to serious adverse events including apalutamide may be increased seizure due to higher apalutamide due 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) dosage adjustment The extent of increase depends on recommendations. Monitor for the timing of ritonavir ADRs related to afatinib. administration.

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): apalutamide (HOS-086212) lead (HOS-085592) afatinib (HOS-086207)

Gegenanzeigen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-214103 · Präparat HOS-155264

Hypersensitivity to afatinib 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 · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-214104 · Präparat HOS-155264

Interactions with drug transport systems

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

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-214105 · Präparat HOS-155264

Effects of P-gp and breast cancer resistance protein (BCRP) inhibitors on afatinib In vitro studies have demonstrated that afatinib is a substrate of P-gp and BCRP. When the strong P-gp and BCRP inhibitor ritonavir (200 mg twice a day for 3 days) was administered 1 hour before a single dose of 20 mg GIOTRIF, exposure to afatinib increased by 48% (area under the curve (AUC0-∞)) and 39% (maximum plasma concentration (Cmax)). In contrast, when ritonavir was administered simultaneously or 6 hours after 40 mg GIOTRIF, the relative bioavailability of afatinib was 119% (AUC0-∞) and 104% (Cmax) and 111% (AUC0-∞) and 105% (Cmax), respectively. Therefore, it is recommended to administer strong P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus,

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) quinidine (HOS-085593) itraconazole (HOS-084516) tacrolimus (HOS-085202) erythromycin (HOS-084514) ritonavir (HOS-084521) cyclosporine (HOS-084512) verapamil (HOS-090602)

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-214106 · Präparat HOS-155264

6 nelfinavir, saquinavir, and amiodarone) using staggered dosing, preferably 6 hours or 12 hours apart from GIOTRIF (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): nelfinavir (HOS-084520) saquinavir (HOS-084522) amiodarone (HOS-085596)

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-214107 · Präparat HOS-155264

Effects of P-gp inducers on afatinib Pre-treatment with rifampicin (600 mg once daily for 7 days), a potent inducer of P-gp, decreased the plasma exposure to afatinib by 34% (AUC0-∞) and 22% (Cmax) after administration of a single dose of 40 mg GIOTRIF. Strong P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital or St. John’s wort (Hypericum perforatum)) may decrease exposure to afatinib (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): phenobarbital (HOS-085617) carbamazepine (HOS-085618) phenytoin (HOS-084531)

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-214108 · Präparat HOS-155264

Effects of afatinib on P-gp substrates Based on in vitro data, afatinib is a moderate inhibitor of P-gp. However, based on clinical data it is considered unlikely that GIOTRIF treatment will result in changes of the plasma concentrations of other P-gp substrates.

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

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-214109 · Präparat HOS-155264

Interactions with BCRP In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. Afatinib may increase the bioavailability of orally administered BCRP substrates (including but not limited to rosuvastatin and sulfasalazine).

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): sulfasalazine (HOS-089673) rosuvastatin (HOS-086307)

Wechselwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-214110 · Präparat HOS-155264

Food effect on afatinib Co-administration of a high-fat meal with GIOTRIF resulted in a significant decrease of exposure to afatinib by about 50% in regard to Cmax and 39% in regard to AUC0-∞. This medicinal product should be administered without food (see sections 4.2 and 5.2).

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

Nebenwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-214111 · Präparat HOS-155264

Summary of the safety profile The types of adverse reactions (ADRs) were generally associated with the EGFR inhibitory mode of action of afatinib. The summary of all ADRs is shown in Table 2. The most frequent ADRs were diarrhoea and skin related adverse events (see section 4.4) as well as stomatitis and paronychia (see also Table 3, 4 and 5). Overall, dose reduction (see section 4.2) led to a lower frequency of common adverse reactions.

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

Nebenwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-214112 · Präparat HOS-155264

In patients treated with once daily GIOTRIF 40 mg, dose reductions due to ADRs occurred in 57% of the patients in the LUX-Lung 3 trial and in 25% of the patients in the LUX-Lung 8 trial. Discontinuation due to ADRs diarrhoea and rash/acne was 1.3% and 0% in LUX-Lung 3 and 3.8% and 2.0% in LUX-Lung 8, respectively.

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

Nebenwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-214113 · Präparat HOS-155264

ILD-like adverse reactions were reported in 0.7% of afatinib treated patients. Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis although in these cases there were potential alternative aetiologies (see section 4.4).

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

Nebenwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-214114 · Präparat HOS-155264

Tabulated list of adverse reactions Table 2 summarises the frequencies of ADRs from all NSCLC trials and from post-marketing experience with daily GIOTRIF doses of 40 mg or 50 mg as monotherapy. The following terms are used to rank the ADRs by frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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

Nebenwirkungen · Giotrif

GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8–9

HOS-214115 · Präparat HOS-155264

8 Table 2: Summary of ADRs per frequency category

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