Wirkstoffe & Arzneimittelsicherheit

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.

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 9

HOS-214116 · Präparat HOS-155264

Body System Very Common Uncommon Rare common Infections and Paronychia1 Cystitis infestations Metabolism and nutrition Decreased Dehydration disorders appetite Hypokalaemia Nervous system disorders Dysgeusia Eye disorders Conjunctivitis Keratitis Dry eye Aberrant eyelash growth Respiratory, thoracic and Epistaxis Rhinorrhoea Interstitial lung mediastinal disorders disease Gastrointestinal disorders Diarrhoea Dyspepsia Pancreatitis Stomatitis2 Cheilitis Gastrointestinal Nausea perforation Vomiting Hepatobiliary disorders Alanine aminotransferase increased

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 9

HOS-214117 · Präparat HOS-155264

Aspartate aminotransferase increased Skin and subcutaneous Rash3 Palmar-plantar Stevens-Johnson tissue disorders Dermatitis erythrodysaesthesia syndrome7 acneiform4 syndrome Toxic epidermal Pruritus5 Nail disorders8 necrolysis7 Dry skin6 Musculoskeletal and Muscle spasms connective tissue disorders Renal and urinary Renal impairment/ disorders Renal failure General disorders and Pyrexia administration site conditions Investigations Weight decreased 1 Includes Paronychia, Nail infection, Nail bed infection 2 Includes Stomatitis, Aphthous stomatitis, Mucosal inflammation, Mouth ulceration, Oral mucosa erosion, Mucosal erosion, Mucosal ulceration 3 Includes group of rash preferred terms 4 Includes Acne, Acne pustular, Dermatitis acneiform 5 Includes Pruritus, Pruritus generalised 6 Includes Dry skin, Skin chapped 7 Based on post-marketing experience 8 Includes Nail disorder, Onycholysis, Nail toxicity, Onychoclasis, Ingrowing nail, Nail pitting, Onychomadesis, Nail discoloration, Nail dystrophy, Nail ridging, and Onychogryphosis

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 9

HOS-214118 · Präparat HOS-155264

Description of selected adverse reactions Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 3 and LUX-Lung 7 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Tables 3 and 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 9–10

HOS-214119 · Präparat HOS-155264

9 Table 3: Very common ADRs in trial LUX-Lung 3

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 10

HOS-214120 · Präparat HOS-155264

GIOTRIF Pemetrexed/ (40 mg/day) Cisplatin N = 229 N = 111 NCI-CTC Grade Any 3 4 Any 3 4 Grade Grade MedDRA Preferred Term % % % % % % Infections and infestations Paronychia1 57.6 11.4 0 0 0 0 Metabolism and nutrition disorders Decreased appetite 20.5 3.1 0 53.2 2.7 0 Respiratory, thoracic and mediastinal disorders Epistaxis 13.1 0 0 0.9 0.9 0 Gastrointestinal disorders Diarrhoea 95.2 14.4 0 15.3 0 0 Stomatitis2 69.9 8.3 0.4 13.5 0.9 0 Cheilitis 12.2 0 0 0.9 0 0 Skin and subcutaneous tissue disorders Rash3 70.3 14 0 6.3 0 0 Dermatitis acneiform4 34.9 2.6 0 0 0 0 Dry skin5 29.7 0.4 0 1.8 0 0 Pruritus6 19.2 0.4 0 0.9 0 0 Investigations Weight decreased 10.5 0 0 9.0 0 0 1 Includes Paronychia, Nail infection, Nail bed infection 2 Includes Stomatitis, Aphthous stomatitis, Mucosal inflammation, Mouth ulceration, Oral mucosa erosion, Mucosal erosion, Mucosal ulceration 3 Includes group of rash preferred terms 4 Includes Acne, Acne pustular, Dermatitis acneiform 5 Includes Dry skin, Skin chapped 6 Includes Pruritus, Pruritus generalised

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 10–11

HOS-214121 · Präparat HOS-155264

10 Table 4: Very common ADRs in trial LUX-Lung 7

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 11

HOS-214122 · Präparat HOS-155264

GIOTRIF Gefitinib (40 mg/day) N = 160 N = 159 NCI-CTC Grade Any 3 4 Any 3 4 Grade Grade MedDRA Preferred Term % % % % % % Infections and infestations Paronychia1 57.5 1.9 0 17.0 0.6 0 2 Cystitis 11.3 1.3 0 7.5 1.3 0.6 Metabolism and nutrition disorders Decreased appetite 27.5 1.3 0 24.5 1.9 0 Hypokalaemia3 10.6 2.5 1.3 5.7 1.3 0 Respiratory, thoracic and mediastinal disorders Rhinorrhoea4 19.4 0 0 7.5 0 0 Epistaxis 18.1 0 0 8.8 0 0 Gastrointestinal disorders Diarrhoea 90.6 13.8 0.6 64.2 3.1 0 Stomatitis5 64.4 4.4 0 27.0 0 0 Nausea 25.6 1.3 0 27.7 1.3 0 Vomiting 19.4 0.6 0 13.8 2.5 0 Dyspepsia 10.0 0 0 8.2 0 0 Hepatobiliary disorders Alanine aminotransferase increased 11.3 0 0 27.7 8.8 0.6 Skin and subcutaneous tissue disorders Rash6 80.0 7.5 0 67.9 3.1 0 Dry skin 32.5 0 0 39.6 0 0 7 Pruritus 25.6 0 0 25.2 0 0 Dermatitis acneiform8 23.8 1.9 0 32.1 0.6 0 General disorders and administration site conditions Pyrexia 13.8 0 0 6.3 0 0 Investigations Weight decreased 10.0 0.6 0 5.7 0.6 0 1 Includes Paronychia, Nail infection, Nail bed infection 2 Includes Cystitis, Urinary tract infection 3 Includes Hypokalaemia, Blood potassium decreased 4 Includes Rhinorrhoea, Nasal inflammation 5 Includes Stomatitis, Aphthous stomatitis, Mucosal inflammation, Mouth ulceration, Mucosal erosion 6 Includes group of rash preferred terms 7 Includes Pruritus, Pruritus generalised 8 Includes Dermatitis acneiform, Acne

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