Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 30

HOS-125321 · Präparat HOS-096037

ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action. In Phase 3 studies, anticipated mineralocorticoid adverse reactions were seen more commonly in patients treated with abiraterone acetate than in patients treated with placebo: hypokalaemia 18% vs. 8%, hypertension 22% vs. 16% and fluid retention (peripheral oedema) 23% vs. 17%, respectively. In patients treated with abiraterone acetate versus patients treated with placebo: CTCAE (version 4.0) Grades 3 and 4 hypokalaemia were observed in 6% versus 1%, CTCAE (version 4.0) Grades 3 and 4 hypertension were observed in 7% versus 5%, and fluid retention (peripheral oedema) Grades 3 and 4 were observed in 1% versus 1% of patients, respectively. Mineralocorticoid reactions generally were able to be successfully managed medically. Concomitant use of a corticosteroid reduces the incidence and severity of these adverse reactions (see section 4.4).

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 30–31

HOS-125322 · Präparat HOS-096037

30 Tabulated list of adverse reactions In studies of patients with metastatic advanced prostate cancer who were using an LHRH analogue, or were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1 000 mg daily in combination with low dose prednisone or prednisolone (either 5 or 10 mg daily depending on the indication).

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 31

HOS-125323 · Präparat HOS-096037

Adverse reactions observed during clinical studies and post-marketing experience are listed below by frequency category. Frequency categories are defined as follows: 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) and not known (frequency cannot be estimated from the available data).

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 31

HOS-125324 · Präparat HOS-096037

Within each frequency grouping, undesirable effects 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 · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 31

HOS-125325 · Präparat HOS-096037

Table 1: Adverse reactions identified in clinical studies and post-marketing System Organ Class Adverse reaction and frequency Infections and infestations very common: urinary tract infection common: sepsis Immune system disorders not known: anaphylactic reactions Endocrine disorders uncommon: adrenal insufficiency Metabolism and nutrition disorders very common: hypokalaemia common: hypertriglyceridaemia Cardiac disorders common: cardiac failure*, angina pectoris, atrial fibrillation, tachycardia uncommon: other arrhythmias not known: myocardial infarction, QT prolongation (see sections 4.4 and 4.5) Vascular disorders very common: hypertension Respiratory, thoracic and mediastinal rare: allergic alveolitisa disorders Gastrointestinal disorders very common: diarrhoea common: dyspepsia Hepatobiliary disorders very common: alanine aminotransferase increased and/or aspartate aminotransferase increased b rare: hepatitis fulminant, acute hepatic failure Skin and subcutaneous tissue disorders common: rash Musculoskeletal and connective tissue uncommon: myopathy, rhabdomyolysis disorders Renal and urinary disorders common: haematuria General disorders and administration site very common: oedema peripheral conditions Injury, poisoning and procedural common: fractures** complications * Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased ** Fractures includes osteoporosis and all fractures with the exception of pathological fractures a Spontaneous reports from post-marketing experience b Alanine aminotransferase increased and/or aspartate aminotransferase increased includes ALT increased, AST increased, and hepatic function abnormal.

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 31

HOS-125326 · Präparat HOS-096037

The following CTCAE (version 4.0) Grade 3 adverse reactions occurred in patients treated with abiraterone acetate: hypokalaemia 5%; urinary tract infection 2%; alanine aminotransferase increased and/or aspartate aminotransferase increased 4%; hypertension 6%; fractures 2%; peripheral oedema, cardiac failure, and atrial fibrillation 1% each. CTCAE (version 4.0) Grade 3 hypertriglyceridaemia and angina pectoris occurred in < 1% of patients. CTCAE (version 4.0) Grade 4 urinary tract infection, alanine aminotransferase increased and/or aspartate aminotransferase increased, hypokalaemia, cardiac failure, atrial fibrillation, and fractures occurred in < 1% of patients.

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 31–32

HOS-125327 · Präparat HOS-096037

31 A higher incidence of hypertension and hypokalaemia was observed in the hormone sensitive population (study 3011). Hypertension was reported in 36.7% of patients in the hormone sensitive population (study 3011) compared to 11.8% and 20.2% in studies 301 and 302, respectively. Hypokalaemia was observed in 20.4% of patients in the hormone sensitive population (study 3011) compared to 19.2% and 14.9% in 301 and 302, respectively).

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 32

HOS-125328 · Präparat HOS-096037

The incidence and severity of adverse events was higher in the subgroup of patients with baseline ECOG2 performance status grade and also in elderly patients (≥75 years).

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 32

HOS-125329 · Präparat HOS-096037

Description of selected adverse reactions Cardiovascular reactions The three Phase 3 studies excluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA Class III or IV heart failure (study 301) or Class II to IV heart failure (studies 3011 and 302) or cardiac ejection fraction measurement of < 50%. All patients enrolled (both active and placebo-treated patients) were concomitantly treated with androgen deprivation therapy, predominantly with the use of LHRH analogues, which has been associated with diabetes, myocardial infarction, cerebrovascular accident and sudden cardiac death. The incidence of cardiovascular adverse reactions in the Phase 3 studies in patients taking abiraterone acetate versus patients taking placebo were as follows: atrial fibrillation 2.6% vs. 2.0%, tachycardia 1.9% vs. 1.0%, angina pectoris 1.7% vs. 0.8%, cardiac failure 0.7% vs. 0.2%, and arrhythmia 0.7% vs. 0.5%.

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 32

HOS-125330 · Präparat HOS-096037

Hepatotoxicity Hepatotoxicity with elevated ALT, AST and total bilirubin has been reported in patients treated with abiraterone acetate. Across Phase 3 clinical studies, hepatotoxicity grades 3 and 4 (e.g., ALT or AST increases of > 5 x ULN or bilirubin increases > 1.5 x ULN) were reported in approximately 6% of patients who received abiraterone acetate, typically during the first 3 months after starting treatment. In Study 3011, grade 3 or 4 hepatotoxicity was observed in 8.4% of patients treated with ZYTIGA. Ten patients who received ZYTIGA were discontinued because of hepatotoxicity; two had Grade 2 hepatotoxicity, six had Grade 3 hepatotoxicity, and two had Grade 4 hepatotoxicity. No patient died of hepatotoxicity in Study 3011. In the Phase 3 clinical studies, patients whose baseline ALT or AST were elevated were more likely to experience liver function test elevations than those beginning with normal values. When elevations of either ALT or AST > 5 x ULN, or elevations in bilirubin > 3 x ULN were observed, abiraterone acetate was withheld or discontinued. In two instances marked increases in liver function tests occurred (see section 4.4). These two patients with normal baseline hepatic function, experienced ALT or AST elevations 15 to 40 x ULN and bilirubin elevations 2 to 6 x ULN. Upon discontinuation of treatment, both patients had normalisation of their liver function tests and one patient was re-treated without recurrence of the elevations. In study 302, Grade 3 or 4 ALT or AST elevations were observed in 35 (6.5%) patients treated with abiraterone acetate. Aminotransferase elevations resolved in all but 3 patients (2 with new multiple liver metastases and 1 with AST elevation approximately 3 weeks after the last dose of abiraterone acetate). In Phase 3 clinical studies, treatment discontinuations due to ALT and AST increases or abnormal hepatic function were reported in 1.1% of patients treated with abiraterone acetate and 0.6% of patients treated with placebo; no deaths were reported due to hepatotoxicity events.

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 32

HOS-125331 · Präparat HOS-096037

In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with baseline hepatitis or significant abnormalities of liver function tests. In the 3011 trial, patients with baseline ALT and AST > 2.5 X ULN, bilirubin > 1.5 X ULN or those with active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction were excluded. In the 301 trial, patients with baseline ALT and AST ≥ 2.5 x ULN in the absence of liver metastases and > 5 x ULN in the presence of liver metastases were excluded. In the 302 trial, patients with liver metastases were not eligible and patients with baseline ALT and AST ≥ 2.5 x ULN were excluded. Abnormal liver function tests developing in patients participating in clinical trials were vigorously managed by requiring treatment interruption and permitting re-treatment only after return of liver function tests to the patient’s baseline (see section 4.2). Patients with elevations of ALT or AST > 20 x ULN were not re-treated. The safety of re-treatment in such patients is unknown. The mechanism for hepatotoxicity is not understood.

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

Nebenwirkungen · Zytiga

ZYTIGA 500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 32–33

HOS-125332 · Präparat HOS-096037

32 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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

Wechselwirkungen · Orgovyx

Orgovyx 120 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-146567 · Präparat HOS-099534

Non nucleoside reverse transcriptase inhibitors efavirenz. Combination with other medicines for advanced hormone-sensitive prostate cancer Abiraterone Therapeutic Expected: ↔ Expected: ↔ Abiraterone and dose for docetaxel are not Orgovyx known 8 (not an inhibitors/inducers of inhibitor/inducer of enzymes and CYP3A4 and/or P-gp) transporters contributing to the Docetaxel Therapeutic Expected: ↔ Expected: ↔ metabolism and dose for Orgovyx transport of relugolix. (not an inhibitor/inducer of CYP3A4 and/or P-gp) No clinically meaningful interaction is expected and no dose adjustment of Orgovyx is required.

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): docetaxel (HOS-084505) efavirenz (HOS-087947) abiraterone (HOS-125270)

Wechselwirkungen · Orgovyx

Orgovyx 120 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13–14

HOS-146596 · Präparat HOS-099534

13  Therapeutic dose for Abiraterone Expected: Expected: No clinically Orgovyx ↔ ↔ meaningful changes (CYP3A4 in exposure are substrate) expected and no dose adjustments are necessary for Therapeutic dose for Docetaxel Expected: Expected: abiraterone, Orgovyx ↔ ↔ (CYP3A enzalutamide, substrate) apalutamide, darolutamide or docetaxel when co- administered with relugolix. Therapeutic dose for Darolutamide Expected: Expected: Orgovyx ↔ ↔ (CYP3A, P- gp and BCRP substrate)

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) docetaxel (HOS-084505) abiraterone (HOS-125270) darolutamide (HOS-142070) enzalutamide (HOS-116829)

Gegenanzeigen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-146755 · Präparat HOS-099564

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Women who are or may potentially be pregnant (see section 4.6). • Severe hepatic impairment [Child-Pugh Class C (see sections 4.2, 4.4 and 5.2)]. • Abiraterone Mylan with prednisone or prednisolone is contraindicated in combination with Ra-223.

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): prednisolone (HOS-086337) prednisone (HOS-084526)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-146758 · Präparat HOS-099564

Effect of food on abiraterone Administration with food significantly increases the absorption of abiraterone. The efficacy and safety when given with food have not been established therefore this medicinal product must not be taken with 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.

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-146759 · Präparat HOS-099564

Interactions with other medicinal products Potential for other medicinal products to affect abiraterone exposures In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer rifampicin, 600 mg daily for 6 days followed by a single dose of abiraterone acetate 1000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55%.

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

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-146760 · Präparat HOS-099564

Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John's wort [Hypericum perforatum]) during treatment are to be avoided, unless there is no therapeutic alternative.

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) rifabutin (HOS-086262) rifapentine (HOS-116386) phenytoin (HOS-084531)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-146762 · Präparat HOS-099564

In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

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)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-146763 · Präparat HOS-099564

Potential to affect exposures to other medicinal products Abiraterone is an inhibitor of the hepatic drug-metabolising enzymes CYP2D6 and CYP2C8. In a study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was increased approximately 2.9 fold. The AUC24 for dextrorphan, the active metabolite of dextromethorphan, increased approximately 33%.

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): dextromethorphan (HOS-109265) prednisone (HOS-084526)