Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 7

HOS-130502 · Präparat HOS-096931

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Breast-feeding during treatment and for 1 month after the last dose (see section 4.6).

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

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-130503 · Präparat HOS-096931

Pharmacodynamic interactions Clinical studies of olaparib in combination with other anticancer medicinal products, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. The recommended Lynparza monotherapy dose is not suitable for combination with myelosuppressive anticancer medicinal products.

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

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-130504 · Präparat HOS-096931

Combination of olaparib with vaccines or immunosuppressant agents has not been studied. Therefore, caution should be taken if these medicinal products are co-administered with Lynparza and patients should be closely monitored.

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

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-130505 · Präparat HOS-096931

Pharmacokinetic interactions Effect of other medicinal products on olaparib CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib.

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

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-130506 · Präparat HOS-096931

A clinical study to evaluate the impact of itraconazole, a known CYP3A inhibitor, has shown that co-administration with olaparib increased mean olaparib Cmax by 42% (90% CI: 33-52%) and mean AUC by 170% (90% CI: 144-197%). Therefore, known strong (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, boceprevir, telaprevir) or moderate (e.g. erythromycin, diltiazem, fluconazole, verapamil) inhibitors of this isozyme are not recommended with Lynparza (see section 4.4). If strong or moderate CYP3A inhibitors must be co-administered, the dose of Lynparza should be reduced. The recommended Lynparza dose reduction 9 is to 100 mg taken twice daily (equivalent to a total daily dose of 200 mg) with a strong CYP3A inhibitor or 150 mg taken twice daily (equivalent to a total daily dose of 300 mg) with a moderate CYP3A inhibitor (see sections 4.2 and 4.4). It is also not recommended to consume grapefruit juice while on Lynparza therapy as it is a CYP3A inhibitor.

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): diltiazem (HOS-086288) protease (HOS-085623) cobicistat (HOS-088111) grapefruit juice (HOS-088787) telaprevir (HOS-090618) telithromycin (HOS-084523) itraconazole (HOS-084516) fluconazole (HOS-087945) boceprevir (HOS-090617) clarithromycin (HOS-084517) erythromycin (HOS-084514) ritonavir (HOS-084521) verapamil (HOS-090602)

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130507 · Präparat HOS-096931

A clinical study to evaluate the impact of rifampicin, a known CYP3A inducer, has shown that co-administration with olaparib decreased olaparib mean Cmax by 71% (90% CI: 76-67%) and mean AUC by 87% (90% CI: 89-84%). Therefore, known strong inducers of this isozyme (e.g. phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarbital and St John’s Wort) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced. The magnitude of the effect of moderate to strong inducers (e.g. efavirenz, rifabutin) on olaparib exposure is not established, therefore the co-administration of Lynparza with these medicinal products is also not recommended (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) rifabutin (HOS-086262) rifapentine (HOS-116386) efavirenz (HOS-087947) nevirapine (HOS-088064) phenytoin (HOS-084531)

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130508 · Präparat HOS-096931

Effect of olaparib on other medicinal products Olaparib inhibits CYP3A4 in vitro and is predicted to be a mild CYP3A inhibitor in vivo. Therefore, caution should be exercised when sensitive CYP3A substrates or substrates with a narrow therapeutic margin (e.g. simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus and quetiapine) are combined with olaparib. Appropriate clinical monitoring is recommended for patients receiving CYP3A substrates with a narrow therapeutic margin concomitantly with olaparib.

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): quetiapine (HOS-086150) cisapride (HOS-085610) simvastatin (HOS-086158) ergot alkaloids (HOS-108807) tacrolimus (HOS-085202) pimozide (HOS-085600) sirolimus (HOS-085172) fentanyl (HOS-086196) cyclosporine (HOS-084512)

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130510 · Präparat HOS-096931

Induction of CYP1A2, 2B6 and 3A4 has been shown in vitro with CYP2B6 being most likely to be induced to a clinically relevant extent. The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded. Therefore, olaparib upon co-administration may reduce the exposure to substrates of these metabolic enzymes and transport protein. The efficacy of some hormonal contraceptives may be reduced if co-administered with olaparib (see sections 4.4 and 4.6).

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

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130511 · Präparat HOS-096931

In vitro, olaparib inhibits the efflux transporter P-gp (IC50=76 µM), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp (e.g. simvastatin, pravastatin, dabigatran, digoxin and colchicine). Appropriate clinical monitoring is recommended for patients receiving this type of medicinal product concomitantly.

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): simvastatin (HOS-086158) digoxin (HOS-086172) dabigatran (HOS-112096) colchicine (HOS-086147) pravastatin (HOS-086306)

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130512 · Präparat HOS-096931

In vitro, olaparib has been shown to be an inhibitor of BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1 and MATE2K. It cannot be excluded that olaparib may increase the exposure to substrates of BCRP (e.g. methotrexate, rosuvastatin), OATP1B1 (e.g. bosentan, glibenclamide, repaglinide, statins and valsartan), OCT1 (e.g. metformin), OCT2 (e.g. serum creatinine), OAT3 (e.g. furosemide and methotrexate), MATE1 (e.g. metformin) and MATE2K (e.g. metformin). In particular, caution should be exercised if olaparib is administered in combination with any statin.

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): furosemide (HOS-089060) rosuvastatin (HOS-086307) creatinine (HOS-086273) valsartan (HOS-088810) bosentan (HOS-086291) repaglinide (HOS-086935) metformin (HOS-091032) methotrexate (HOS-087522)

Wechselwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-130513 · Präparat HOS-096931

Combination with anastrozole, letrozole and tamoxifen A clinical study has been performed to assess the combination of olaparib with anastrozole, letrozole or tamoxifen. No clinically relevant interactions were observed.

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): anastrozole (HOS-090912) tamoxifen (HOS-088380) letrozole (HOS-130515)

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130516 · Präparat HOS-096931

Summary of the safety profile Lynparza has been associated with adverse reactions generally of mild or moderate severity (CTCAE grade 1 or 2) and generally not requiring treatment discontinuation. The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy (≥10%) were nausea, fatigue/asthenia, anaemia, vomiting, diarrhoea, decreased appetite, headache, neutropenia, dysgeusia, cough, leukopenia, dizziness, dyspnoea and dyspepsia.

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-130517 · Präparat HOS-096931

The Grade ≥3 adverse reactions occurring in > 2% of patients were anaemia (14%), neutropenia (5%), fatigue/asthenia (4%), leukopenia (2%) and thrombocytopenia (2%).

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-130518 · Präparat HOS-096931

11 Adverse reactions that most commonly led to dose interruptions and/ or reductions in monotherapy were anaemia (16%), nausea (7%), fatigue/asthenia (6%), neutropenia (6%) and vomiting (6%). Adverse reactions that most commonly led to permanent discontinuation were anaemia (1.7%), nausea (0.9%), fatigue/asthenia (0.8%), thrombocytopenia (0.7%), neutropenia (0.6%) and vomiting (0.5%).

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130519 · Präparat HOS-096931

When Lynparza is used in combination with bevacizumab for ovarian cancer, in combination with abiraterone and prednisone or prednisolone for prostate cancer, or in combination with durvalumab following treatment with durvalumab in combination with platinum-based chemotherapy for endometrial cancer, the safety profile is generally consistent with that of the individual therapies.

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130520 · Präparat HOS-096931

When used in combination with bevacizumab, adverse events led to dose interruption and/ or reduction of olaparib in 57% of patients and led to permanent discontinuation of treatment with olaparib and placebo in 21% and 6% of patients, respectively. The adverse reactions that most commonly led to dose interruption and/or reduction of olaparib were anaemia (21.7%), nausea (9.5%), fatigue/asthenia (5.4%), vomiting (3.7%), neutropenia (3.6%), thrombocytopenia (3.0%) and diarrhoea (2.6%). The adverse reactions that most commonly led to permanent discontinuation were anaemia (3.7%), nausea (3.6%) and fatigue/asthenia (1.5%).

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130521 · Präparat HOS-096931

When used in combination with abiraterone, adverse events led to dose interruption and/or reduction of olaparib in 50.7% of patients and led to permanent discontinuation of treatment with olaparib and placebo in 19.0% and 8.8% of patients, respectively. The adverse reactions that most commonly led to dose interruption and/or reduction of olaparib were anaemia (17.1%), fatigue/asthenia (5.5%), nausea (4.1%), neutropenia (3.4%), vomiting (2.3%), diarrhoea (2.1%) and venous thrombotic events (2.1%). The adverse reactions that most commonly led to permanent discontinuation were anaemia (4.5%) and fatigue/asthenia (1.3%).

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130522 · Präparat HOS-096931

When used in combination with durvalumab following treatment with durvalumab in combination with platinum-based chemotherapy, adverse events led to dose interruption and/or reduction of olaparib in 59.9% of patients and led to permanent discontinuation of treatment with olaparib in 10.9% of patients. The adverse reactions that most commonly led to dose interruption and/or reduction of olaparib were anaemia (20.8%), nausea (8.3%), neutropenia (7.3%), fatigue/asthenia (5.7%), thrombocytopenia (4.2%), vomiting (4.2%), blood creatinine increased (3.1%), leukopenia (3.1%), and decreased appetitive (2.6%), diarrhoea (2.1%). The adverse reactions that most commonly led to permanent discontinuation of olaparib were anaemia (3.6%) and neutropenia (1%).

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130523 · Präparat HOS-096931

Tabulated list of adverse reactions The safety profile is based on pooled data from 4499 patients with solid tumours treated with Lynparza monotherapy in clinical trials at the recommended dose.

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

Nebenwirkungen · Lynparza

Lynparza 100 mg film-coated tablets Lynparza 150 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-130524 · Präparat HOS-096931

The following adverse reactions have been identified in clinical trials with patients receiving Lynparza monotherapy where patient exposure is known. Adverse drug reactions are listed by MedDRA System Organ Class (SOC) and then by MedDRA preferred term in Table 1. Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurrence of adverse reactions are defined as: very common (≥1/10); common (1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from available data).

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