Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.3 · PDF-Seite 7

HOS-135448 · Präparat HOS-097714

History of severe hypersensitivity to irinotecan 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.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): irinotecan (HOS-112102)

Gegenanzeigen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.3 · PDF-Seite 7

HOS-135449 · Präparat HOS-097714

Breast-feeding (see section 4.6).

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

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-135450 · Präparat HOS-097714

Information about drug interactions with ONIVYDE pegylated liposomal is referenced from the published scientific literature for nonliposomal irinotecan.

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): irinotecan (HOS-112102)

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-135451 · Präparat HOS-097714

Interaction affecting the use of ONIVYDE pegylated liposomal

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

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-135452 · Präparat HOS-097714

Strong CYP3A4 inducers Patients receiving concomitant non-liposomal irinotecan and CYP3A4 enzyme-inducing anticonvulsants phenytoin, phenobarbital or carbamazepine have substantially reduced exposure to irinotecan (AUC reduction by 12% with St John’s wort, 57%-79% with phenytoin, phenobarbital, or carbamazepine) and SN-38 (AUC reduction by 42% with St John’s wort, 36%-92% with phenytoin phenobarbital, or carbamazepine). Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

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) irinotecan (HOS-112102) phenytoin (HOS-084531)

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-135453 · Präparat HOS-097714

Strong CYP3A4 inhibitors and UGT1A1 inhibitors Patients receiving concomitant non-liposomal irinotecan and ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased SN-38 exposure by 109%. Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) may increase systemic exposure of ONIVYDE pegylated liposomal. Based on the drug interaction of non-liposomal irinotecan and ketoconazole, co-administration of ONIVYDE pegylated liposomal with other inhibitors of UGT1A1 (e.g. atazanavir, gemfibrozil, indinavir, regorafenib) may also increase systemic exposure of ONIVYDE pegylated liposomal.

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): indinavir (HOS-084518) nefazodone (HOS-084519) lopinavir (HOS-086269) atazanavir (HOS-086180) nelfinavir (HOS-084520) ketoconazole (HOS-084513) gemfibrozil (HOS-088403) grapefruit juice (HOS-088787) voriconazole (HOS-084524) telaprevir (HOS-090618) itraconazole (HOS-084516) saquinavir (HOS-084522) clarithromycin (HOS-084517) regorafenib (HOS-127084) ritonavir (HOS-084521) irinotecan (HOS-112102)

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-135458 · Präparat HOS-097714

Co-administration of ONIVYDE pegylated liposomal +5-FU/LV does not alter the pharmacokinetics of ONIVYDE pegylated liposomal based on the population pharmacokinetic analysis.

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

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 10–11

HOS-135459 · Präparat HOS-097714

Antineoplastic agents (including flucytosine as a prodrug for 5-fluorouracil) Adverse effects of irinotecan, such as myelosuppression, may be exacerbated by other 10 antineoplastic agents having a similar adverse-effect profile.

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): flucytosine (HOS-088525) fluorouracil (HOS-086023) irinotecan (HOS-112102)

Wechselwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.5 · PDF-Seite 11

HOS-135462 · Präparat HOS-097714

No interaction of ONIVYDE pegylated liposomal with other medicinal products is known.

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-135463 · Präparat HOS-097714

Summary of the safety profile

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-135464 · Präparat HOS-097714

ONIVYDE pegylated liposomal in combination with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX): The following adverse reactions, related to the administration of ONIVYDE pegylated liposomal, were reported in 370 patients treated in combination with oxaliplatin/5-FU/LV, who had not previously received chemotherapy for metastatic adenocarcinoma of the pancreas. The most common adverse reactions (incidence ≥20%) were diarrhoea, nausea, vomiting, decreased appetite, fatigue, asthenia, neutropenia, neutrophil count decreased and anaemia. The most common, severe adverse reactions (≥5% Grade 3 or 4) were diarrhoea, nausea, vomiting, decreased appetite, fatigue, asthenia, neutropenia, neutrophil count decreased, anaemia and hypokalaemia. The most common serious adverse reactions (≥2%) were diarrhoea, nausea, vomiting and dehydration.

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 11–12

HOS-135465 · Präparat HOS-097714

11 Adverse reactions seen with ONIVYDE pegylated liposomal which led to its permanent discontinuation occurred in 9.5 % of patients; the most frequent adverse reaction resulting in discontinuation was neutropenia. Dose reductions of ONIVYDE pegylated liposomal due to adverse events (regardless of causality assessment), occurred in 52.4% of patients; the most frequent adverse events requiring dose reduction (≥5%) were diarrhoea, nausea, neutropenia and neutrophil count decreased. ONIVYDE pegylated liposomal was withheld due to adverse events (regardless of causality assessment), in 1.9% of patients; the most frequent adverse events requiring interruption were hypersensitivity and infusion related reactions that occurred in 0.5% of patients.

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12

HOS-135466 · Präparat HOS-097714

ONIVYDE pegylated liposomal in combination with 5-fluorouracil and leucovorin: The following adverse reactions, related to the administration of ONIVYDE pegylated liposomal, were reported in 264 patients with metastatic adenocarcinoma of the pancreas treated after disease progression following gemcitabine-based therapy. The most common adverse reactions (incidence ≥ 20%) of ONIVYDE pegylated liposomal +5-FU/LV were: diarrhoea, nausea, vomiting, decreased appetite, neutropenia, fatigue, asthenia, anaemia, stomatitis and pyrexia. The most common serious adverse reactions (≥ 2%) of ONIVYDE pegylated liposomal therapy were diarrhoea, vomiting, febrile neutropenia, nausea, pyrexia, sepsis, dehydration, septic shock, pneumonia, acute renal failure, and thrombocytopenia. The rates of adverse reactions leading to permanent treatment discontinuation were 11% for the ONIVYDE pegylated liposomal +5-FU/LV arm. The most frequently reported adverse reactions leading to discontinuation were infection and diarrhoea for ONIVYDE pegylated liposomal +5-FU/LV arm.

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12

HOS-135467 · Präparat HOS-097714

Tabulated list of adverse reactions

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12

HOS-135468 · Präparat HOS-097714

The adverse reactions described in this section are derived from studies data and post-marketing experience of ONIVYDE pegylated liposomal. The adverse reactions that may occur during treatment with ONIVYDE pegylated liposomal are summarised below and are presented by system organ class and frequency category (Table 4). Within each system organ class and frequency category, adverse reactions are presented in order of decreasing seriousness. Frequencies categories used for adverse reactions are: 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)* and not known (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 · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12

HOS-135469 · Präparat HOS-097714

Table 4: Adverse reactions reported in patients treated with ONIVYDE pegylated liposomal

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12

HOS-135470 · Präparat HOS-097714

In combination with oxaliplatin/5- In combination with 5-FU/LV SOC FU/LV (in NAPOLI-3) (in NAPOLI-1 and in post-marketing Frequency* experience) Infections and Infestations Septic shock, Sepsis, Pneumonia, Sepsis, Urinary tract infection, Candida Common Febrile neutropenia, Gastroenteritis, infection, Nasopharyngitis Oral candidiasis Diverticulitis,Pneumonia, Anal abscess, Biliary sepsis Febrile infection, Gastroenteritis, Mucosal infection, Oral fungal infection, Clostridium difficile Uncommon infection, Conjunctivitis, Furuncle, Herpes simplex, Laryngitis, Periodontitis, Rash pustular, Sinusitis, Tooth infection, Vulvovaginal mycotic infection Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uncommon Peritumoural oedema Blood and lymphatic disorders Anaemia, Neutropenia, Neutropenia, Leukopenia, Anaemia, Very common Thrombocytopenia Thrombocytopenia

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 12–14

HOS-135471 · Präparat HOS-097714

12  Febrile neutropenia, Leukopenia, Lymphopenia Common Lymphopenia Uncommon Pancytopenia, Haemolytic anaemia Immune system disorders Uncommon Hypersensitivity Hypersensitivity Anaphylactic/Anaphylactoid reaction, Not known Angioedema Metabolism and nutrition disorders Hypokalaemia, Hypomagnesaemia, Very common Hypokalaemia, Decreased appetite, Dehydration, Decreased appetite Dehydration, Hyponatraemia, Hypoglycaemia, Hyponatraemia, Hypophosphataemia, Hypophosphataemia Common Hypomagnesaemia, Hypoalbuminaemia, Hypocalcaemia Electrolyte imbalance, Hypercalcaemia, Cell death, Hypochloraemia, Gout, Uncommon Hyperglycaemia, Hyperkalaemia, Iron deficiency, Malnutrition Psychiatric disorders Common Insomnia Insomnia, Confusional state, Uncommon Depression, Neurosis, Nervous system disorders Neuropathy peripheral, Dysgeusia, Dizziness Very common Paraesthesia Tremor, Neurotoxicity, Dysaesthesia, Cholinergic syndrome, Dysgeusia Common Cholinergic syndrome, Headache, Dizziness Seizure, Cerebral haemorrhage, Cerebral ischaemia, Ischaemic stroke, Anosmia, Ageusia, Balance disorder, Uncommon Hypersomnia, Hypoaesthesia, Intellectual disability, Lethargy, Memory impairment, Presyncope, Syncope, Transient ischaemic attack Eye disorders Common Vision blurred Uncommon Eye irritation, Visual acuity reduced Ear and labyrinth disorders Uncommon Vertigo Cardiac disorders Common Tachycardia Hypotension Angina pectoris, Acute myocardial Uncommon infarction, Palpitations Vascular disorders Pulmonary embolism, Thomboembolic Common Hypotension, Thromboembolic events events Hypertension, Peripheral coldness, Uncommon Haematoma, Phlebitis Respiratory, thoracic and mediastinal disorders Pulmonary embolism, Hiccups, Dyspnoea, Dysphonia Common Dyspnoea, Epistaxis Oropharyngeal pain, Cough, Hyperoxia, Hypoxia, Interstitial lung disease Uncommon Nasal inflammation, Atelectasis, (including pneumonitis) Dysphonia, Pneumonitis Gastro-intestinal disorders Diarrhoea, Nausea, Vomiting, Diarrhoea, Vomiting, Nausea, Very common Abdominal pain/discomfort, Stomatitis Abdominal pain, Stomatitis Colitis, Enterocolitis, Constipation, Dry Colitis, Haemorrhoids Common mouth, Flatulence, Abdominal 13  distension, Dyspepsia, Gastrooesophageal reflux disease, Haemorrhoids, Dysphagia, Gastrointestinal toxicity, Duodenal Oesophagitis, Proctitis obstruction, Anal incontinence, Aphthous ulcer, Oral dysaesthesia, Oral pain, Tongue disorder, Anal fissure, Angular cheilitis, Dyschezia, Paraesthesia oral, Dental caries, Uncommon Eructation, Gastric disorder, Gastritis, Gingival disorder, Gingival pain, Haematochezia, Hyperaesthesia teeth, Ileus paralytic, Lip swelling, Mouth ulceration, Oesophageal spasm, Periodontal disease, Rectal haemorrhage Hepatobiliary disorders Common Hyperbilirubinaemia Hypoalbuminaemia Cholangitis, Hepatitis toxic, Uncommon Cholestasis, Hepatic cytolysis, Skin and subcutaneous tissue disorders Very common Alopecia Alopecia Dry skin, Palmar-plantar Pruritus Common erythrodysaesthesia syndrome, Rash, Skin hyperpigmentation Pruritus, Hyperhidrosis, Dermatitis Urticaria, Rash, Nail discolouration bullous, Dermatitis exfoliative generalised, Erythema, Nail toxicity, Uncommon Papule, Petechiae, Psoriasis, Sensitive skin, Skin exfoliation, Skin lesion, Telangiectasia, Urticaria Not known Erythema Musculoskeletal and connective tissue disorders Muscular weakness, Myalgia, Muscle Common spasms Arthralgia, Back pain, Bone pain, Pain Uncommon in extremity, Polyarthritis Renal and urinary disorders Common Acute kidney injury Acute renal failure Renal impairment, Renal failure, Uncommon Dysuria, Proteinuria Reproductive system and breast disorders Uncommon Vulvovaginal dryness General disorders and administration site conditions Pyrexia, Peripheral oedema, Mucosal Very common Asthenia, Mucosal inflammation inflammation, Asthenia Common Pyrexia, Oedema, Chills Infusion related reaction, Oedema Malaise, General physical health deterioration, Inflammation, Multiple organ dysfunction syndrome, Influenza Uncommon like illness, Non-cardiac chest pain, Axillary pain, Chest pain, Hypothermia, Pain, Swelling face, Temperature intolerance, Xerosis Investigations Very common Weight decreased Weight decreased Transaminases (ALT and AST) Increased bilirubin, Transaminases increased, Blood alkaline phosphatase (ALT and AST) increased, International Common increased, Gamma-glutamyltransferase normalised ratio increased increased, Blood creatinine increased

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 14–15

HOS-135472 · Präparat HOS-097714

14  International normalised ratio increased, Protein total decreased, Creatinine renal Uncommon clearance decreased, Electrocardiogram QT prolonged, Monocyte count increased, Troponin I increased Injury, poisoning and procedural complications Common Infusion related reaction * Rare occurrence cannot be estimated from NAPOLI-1 study due to the small sample size.

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

Nebenwirkungen · Onivyde pegylated liposomal (previously Onivyde)

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion · Abschnitt 4.8 · PDF-Seite 15

HOS-135473 · Präparat HOS-097714

Description of selected adverse reactions

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