Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 6

HOS-150300 · Präparat HOS-100288

Hypersensitivity to the active substances 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.

Gegenanzeigen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 6

HOS-150301 · Präparat HOS-100288

Women who are or may become pregnant (see section 4.6).

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

Gegenanzeigen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 6

HOS-150302 · Präparat HOS-100288

Severe hepatic impairment [Child-Pugh Class C (see sections 4.2, 4.4 and 5.2)].

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

Gegenanzeigen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 6

HOS-150303 · Präparat HOS-100288

Akeega plus prednisone or prednisolone is contraindicated in combination with Ra-223 treatment.

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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-150304 · Präparat HOS-100288

Pharmacokinetic interactions No clinical study evaluating drug interactions has been performed using Akeega. Interactions that have been identified in studies with individual components of Akeega (niraparib or abiraterone acetate) determine the interactions that may occur with Akeega.

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): niraparib (HOS-136825)

Wechselwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-150305 · Präparat HOS-100288

Effects of other medicinal products on niraparib or abiraterone acetate CYP3A4 inducers and inhibitors Abiraterone is a CYP3A4 substrate. In a clinical study in healthy subjects pretreated with the strong CYP3A4 inducer rifampicin, 600 mg daily for six days, followed by a single dose of abiraterone acetate 1 000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55%. Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St. John’s

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): niraparib (HOS-136825) acetate (HOS-088133) phenobarbital (HOS-085617) carbamazepine (HOS-085618) rifabutin (HOS-086262) rifapentine (HOS-116386) phenytoin (HOS-084531)

Wechselwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-150307 · Präparat HOS-100288

9 wort [Hypericum perforatum]) during treatment with Akeega should be avoided unless there is no therapeutic alternative (see section 4.4).

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

Wechselwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150308 · Präparat HOS-100288

In a separate clinical study in 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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150309 · Präparat HOS-100288

Effects of niraparib or abiraterone acetate on other medicinal products CYP2D6 substrates Abiraterone is an inhibitor of CYP2D6. In a clinical study to determine the effects of abiraterone acetate plus prednisone (AAP) 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%. 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 tramadol.

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): niraparib (HOS-136825) propafenone (HOS-084530) codeine (HOS-090544) acetate (HOS-088133) desipramine (HOS-086249) flecainide (HOS-086203) oxycodone (HOS-109487) risperidone (HOS-086280) venlafaxine (HOS-086573) haloperidol (HOS-085602) propranolol (HOS-084529) dextromethorphan (HOS-109265) prednisone (HOS-084526) metoprolol (HOS-090094) tramadol (HOS-112871)

Wechselwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150310 · Präparat HOS-100288

CYP2C8 substrates Abiraterone is an inhibitor of CYP2C8. In a clinical study in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, 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 1 000 mg abiraterone acetate. Patients should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with Akeega because of the abiraterone acetate component. 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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150311 · Präparat HOS-100288

Pharmacodynamic interactions Akeega with vaccines or immunosuppressant agents has not been studied. The data on niraparib, in combination with cytotoxic medicinal products, are limited. Caution should be taken if Akeega is used in combination with live or live-attenuated vaccines, immunosuppressant agents or with other cytotoxic medicinal products.

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): niraparib (HOS-136825)

Wechselwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150312 · Präparat HOS-100288

Use with products known to prolong QT interval Since androgen deprivation treatment may prolong the QT interval, caution is advised when administering Akeega 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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-150313 · Präparat HOS-100288

Use with spironolactone Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use with Akeega 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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-150314 · Präparat HOS-100288

Summary of the safety profile The overall safety profile of Akeega is based on pooled data from two clinical Phase 3 trials with 559 patients (AMPLITUDE [n=347] and MAGNITUDE cohort 1 [n=212]). The most common adverse reactions of all grades occurring in >10% in the niraparib plus AAP arm were anaemia (51.9%), hypertension (40.1%), fatigue (39.7%), musculoskeletal pain (35.8%), constipation (34.7%), nausea (28.6%), hypokalaemia (22.0%), thrombocytopenia (20.9%), neutropenia (19.7%), oedema (18.1%), respiratory tract infections (17.7%), dyspnoea (16.6%), vomiting (15.7%), decreased appetite (15.0%), leukopenia (14.5%), hot flush (14.1%), dizziness (14.0%), weight decreased (14.0%), abdominal pain (13.4%), hyperglycaemia (13.4%), insomnia (13.1%), diarrhoea (12.3%), lymphopenia (12.2%), headache (12.0%), blood creatinine increased (11.8%), urinary tract infection (11.8%), and cough (10.4%). The most frequently observed Grade 3-4 adverse reactions were anaemia (29.7%), hypertension (22.7%), hypokalaemia (9.3%), neutropenia (8.4%), thrombocytopenia (7.5%), and lymphopenia (5.2%).

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

Nebenwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-150315 · Präparat HOS-100288

Tabulated list of adverse reactions Adverse reactions observed during clinical studies 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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-150316 · Präparat HOS-100288

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 · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-150317 · Präparat HOS-100288

Table 3: Adverse reactions identified in clinical studies System Organ Class Frequency Adverse reaction Infections and infestations very common respiratory tract infections1, urinary tract infection2 common pneumonia, gastrointestinal infection3, sepsis4 uncommon skin infection5, conjunctivitis Neoplasms benign, malignant uncommon myelodysplastic syndrome/acute myeloid and unspecified (including leukaemia cysts and polyps) Blood and lymphatic system very common anaemia, thrombocytopenia, neutropenia, disorders leukopenia, lymphopenia not known pancytopenia6 Immune system disorders uncommon hypersensitivity7

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

Nebenwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-150318 · Präparat HOS-100288

11 Endocrine disorders not known adrenal insufficiency8 Metabolism and nutrition very common decreased appetite, hypokalaemia, disorders hyperglycaemia common lipid metabolism disorders9 Psychiatric disorders very common insomnia common depression, anxiety, confusional state Nervous system disorders very common dizziness, headache common lethargy, cognitive disorder, dysgeusia10 not known posterior reversible encephalopathy syndrome (PRES)6 Cardiac disorders common cardiac failure11, arrhythmia12, angina pectoris13, tachycardia14, palpitations uncommon myocardial infarction15 Vascular disorders very common hypertension16, hot flush not known hypertensive crisis6 Respiratory, thoracic and very common dyspnoea17, cough mediastinal disorders common pulmonary embolism, epistaxis uncommon pneumonitis not known allergic alveolitis8 Gastrointestinal disorders very common constipation, nausea, vomiting, abdominal pain18, diarrhoea common gastritis, abdominal distention, dyspepsia, stomatitis, dry mouth

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

Nebenwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-150319 · Präparat HOS-100288

Hepatobiliary disorders common hyperbilirubinaemia uncommon hepatic failure, hepatitis19 Skin and subcutaneous tissue common rash20, pruritus, photosensitivity reaction disorders Musculoskeletal and very common musculoskeletal pain21 connective tissue disorders not known rhabdomyolysis8, myopathy8 Renal and urinary disorders common haematuria, acute kidney injury uncommon urethral haemorrhage General disorders and very common fatigue22, oedema23 administration site conditions common non-cardiac chest pain uncommon chest pain, mucosal inflammation Investigations very common weight decreased, blood creatinine increased common blood alkaline phosphatase increased, AST increased, ALT increased uncommon electrocardiogram QT prolongation, gamma-glutamyl transferase increased Injury, poisoning and common fractures24 procedural complications 1 Includes upper respiratory tract infection, lower respiratory tract infection, laryngitis, rhinitis, bronchitis, nasopharyngitis, respiratory tract infection viral, laryngopharyngitis, viral upper respiratory tract infection 2 Includes cystitis 3 Includes gastroenteritis, gastroeneteritis viral, fungal oesophagitis, oesophageal candidiasis, oropharyngeal candidiasis 4 Includes urosepsis 5 Includes streptococcal infection 6 Not observed with Akeega. Reported with niraparib monotherapy 7 Hypersensitivity without anaphylaxis was observed in AMPLITUDE. Anaphylactic reactions were not reported in Akeega clinical studies, but were reported post-marketing with niraparib monotherapy 8 Not observed with Akeega. Reported in post-marketing experience with abiraterone monotherapy 9 Includes hypercholesterolaemia, hypertriglyceridaemia, dyslipidaemia 10 Includes taste disorder 11 Includes cardiac failure acute, cardiac failure congestive, cor pulmonale, left ventricular dysfunction 12 Includes atrial fibrillation, extrasystoles, supraventricular extrasystoles, ventricular extrasystoles, sinus arrhythmia 13 Includes coronary artery disease, acute coronary syndrome 14 Includes sinus tachycardia, atrial tachycardia 15 Includes myocardial ischaemia

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

Nebenwirkungen · Akeega

Akeega 50 mg/500 mg film-coated tablets Akeega 100 mg/500 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12–13

HOS-150320 · Präparat HOS-100288

12  16 Includes systolic hypertension 17 Includes dyspnoea exertional 18 Includes abdominal pain upper, abdominal pain lower 19 Includes hepatic function abnormal, hepatitis acute, fulminant hepatitis, hepatic cytolysis, hepatotoxicity 20 Includes erythema, dermatitis, rash maculo-papular, rash pruritic 21 Includes arthralgia, back pain, myalgia, musculoskeletal discomfort 22 Includes asthenia 23 Includes oedema peripheral, swelling, face oedema, peripheral swelling, swelling face 24 Includes osteoporosis, rib fracture, femoral neck fracture, femur fracture, ankle fracture, humerus fracture, fibula fracture, lower limb fracture, sternal fracture, stress fracture, upper limb fracture, acetabulum fracture, radius fracture, thoracic vertebral fracture, tibia fracture

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