Wirkstoffe & Arzneimittelsicherheit

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)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-146765 · Präparat HOS-099564

Caution is advised when administering with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index. Dose reduction of medicinal products with a narrow therapeutic index that are metabolised by CYP2D6 should be considered. Examples of medicinal products metabolised by CYP2D6 include metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, oxycodone and 6 tramadol (the latter three medicinal products requiring CYP2D6 to form their active analgesic 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): propafenone (HOS-084530) codeine (HOS-090544) desipramine (HOS-086249) flecainide (HOS-086203) oxycodone (HOS-109487) risperidone (HOS-086280) venlafaxine (HOS-086573) haloperidol (HOS-085602) propranolol (HOS-084529) metoprolol (HOS-090094) tramadol (HOS-112871)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-146775 · Präparat HOS-099564

In a CYP2C8 drug-drug interaction study in healthy subjects, the AUC of pioglitazone was increased by 46% and the AUCs for M-III and M-IV, the active metabolites of pioglitazone, each decreased by 10% when pioglitazone was given together with a single dose of 1000 mg abiraterone acetate. Patients should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly. Examples of medicinal products metabolised by CYP2C8 include pioglitazone and repaglinide (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): pioglitazone (HOS-089663) repaglinide (HOS-086935)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-146778 · Präparat HOS-099564

In vitro, the major metabolites abiraterone sulphate and N-oxide abiraterone sulphate were shown to inhibit the hepatic uptake transporter OATP1B1 and as a consequence it may increase the concentrations of medicinal products eliminated by OATP1B1. There are no clinical data available to confirm transporter based interaction.

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 7

HOS-146779 · Präparat HOS-099564

Use with products known to prolong QT interval Since androgen deprivation treatment may prolong the QT interval, caution is advised when administering Abiraterone Mylan with medicinal products known to prolong the QT interval or medicinal products able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc.

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): sotalol (HOS-085597) methadone (HOS-086198) dofetilide (HOS-085598) ibutilide (HOS-085599) quinidine (HOS-085593) disopyramide (HOS-085595) moxifloxacin (HOS-085604) amiodarone (HOS-085596)

Wechselwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-146780 · Präparat HOS-099564

Use with spironolactone Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use with Abiraterone Mylan is not recommended (see section 5.1).

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): spironolactone (HOS-112481)

Nebenwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 7

HOS-146782 · Präparat HOS-099564

Summary of the safety profile In an analysis of adverse reactions of composite Phase 3 studies with abiraterone acetate, adverse

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

Nebenwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 7–8

HOS-146783 · Präparat HOS-099564

7 reactions that were observed in ≥ 10 % of patients were peripheral oedema, hypokalaemia, hypertension, urinary tract infection, and alanine aminotransferase increased and/or aspartate aminotransferase increased. Other important adverse reactions include, cardiac disorders, hepatotoxicity, fractures, and allergic alveolitis.

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

Nebenwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-146784 · Präparat HOS-099564

Abiraterone 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% vs. 1%, CTCAE (version 4.0) Grades 3 and 4 hypertension were observed in 7% vs. 5%, and fluid retention (peripheral oedema) Grades 3 and 4 were observed in 1% vs. 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 · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-146785 · Präparat HOS-099564

Tabulated list of adverse reactions In studies of patients with metastatic advanced prostate cancer who were using a LHRH analogue, or were previously treated with orchiectomy, abiraterone was administered at a dose of 1000 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 · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-146786 · Präparat HOS-099564

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 · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-146787 · Präparat HOS-099564

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 · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-146788 · Präparat HOS-099564

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 increasedb 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

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

Nebenwirkungen · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8–9

HOS-146789 · Präparat HOS-099564

8  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 · Abiraterone Mylan

Abiraterone Mylan 500 mg film-coated tablets Abiraterone Mylan 1000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-146790 · Präparat HOS-099564

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.