Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-125461 · Präparat HOS-096073

An in vitro study indicates that drug-drug interactions are unlikely to occur at therapeutic doses as a result of induction by bosutinib on the metabolism of medicinal products that are substrates for CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosutinib (HOS-109449)

Wechselwirkungen · Bosulif

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HOS-125462 · Präparat HOS-096073

In vitro studies indicate that clinical drug-drug interactions are unlikely to occur at therapeutic doses as a result of inhibition by bosutinib on the metabolism of medicinal products that are substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosutinib (HOS-109449)

Wechselwirkungen · Bosulif

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HOS-125463 · Präparat HOS-096073

In vitro studies indicate that bosutinib has a low potential to inhibit breast cancer resistance protein (BCRP, systemically), organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2 at clinically relevant concentrations, but may have the potential to inhibit BCRP in the gastrointestinal tract and OCT1.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosutinib (HOS-109449)

Wechselwirkungen · Bosulif

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HOS-125464 · Präparat HOS-096073

Anti-arrhythmic medicinal products and other substances that may prolong QT Bosutinib should be used with caution in patients who have or may develop prolongation of QT, including those patients taking anti-arrhythmic medicinal products such as amiodarone, disopyramide, procainamide, quinidine and sotalol or other medicinal products that may lead to QT prolongation such as chloroquine, halofantrine, clarithromycin, domperidone, haloperidol, methadone, and moxifloxacin (see section 4.4).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sotalol (HOS-085597) methadone (HOS-086198) halofantrine (HOS-085606) quinidine (HOS-085593) domperidone (HOS-114656) lead (HOS-085592) disopyramide (HOS-085595) procainamide (HOS-086617) clarithromycin (HOS-084517) moxifloxacin (HOS-085604) haloperidol (HOS-085602) amiodarone (HOS-085596) bosutinib (HOS-109449) chloroquine (HOS-109138)

Nebenwirkungen · Bosulif

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HOS-125465 · Präparat HOS-096073

Summary of safety profile

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Nebenwirkungen · Bosulif

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HOS-125466 · Präparat HOS-096073

A total of 1 372 leukaemia adult patients received at least 1 dose of single-agent bosutinib. The median duration of therapy was 26.30 months (range: 0.03 to 170.49 months). These patients were either newly-diagnosed, with CP CML or were resistant or intolerant to prior therapy with chronic, accelerated, or blast phase CML or Ph+ acute lymphoblastic leukaemia (ALL). The safety analyses included data from a completed extension study.

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

Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-125467 · Präparat HOS-096073

At least 1 adverse reaction of any toxicity grade was reported for 1,349 (98.3%) patients. The most frequent adverse reactions reported for  20% of patients were diarrhoea (80.4%), nausea (41.5%), abdominal pain (35.6%), thrombocytopenia (34.4%), vomiting (33.7%), rash (32.8%), ALT increased (28.0%), anaemia (27.2%), pyrexia (23.4%), AST increased (22.5%), fatigue (32.0%), and headache (20.3%). At least 1 Grade 3 or Grade 4 adverse reaction was reported for 943 (68.7%) patients. The Grade 3 or Grade 4 adverse reactions reported for  5% of patients were thrombocytopenia (19.7%), ALT increased (14.6%), neutropenia (10.6%), diarrhoea (10.6%), anaemia (10.3%), lipase increased (10.1%), AST increased (6.7%), and rash (5.0%).

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

Nebenwirkungen · Bosulif

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HOS-125468 · Präparat HOS-096073

12 Tabulated list of adverse reactions

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Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 13

HOS-125469 · Präparat HOS-096073

These adverse reactions are presented by system organ class and frequency. Frequency categories 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 < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions 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 · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 13

HOS-125470 · Präparat HOS-096073

Table 4 – Adverse reactions for bosutinib

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Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 13

HOS-125471 · Präparat HOS-096073

Infections and infestations Very common Nasopharyngitis Respiratory tract infectiona Common Influenzab Pneumoniac Bronchitis Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uncommon Tumour lysis syndrome** Blood and lymphatic system disorders Very common Thrombocytopeniad Anaemiae Neutropeniaf Common Leukopeniag Uncommon Febrile neutropenia Granulocytopenia Immune system disorders Common Drug hypersensitivity Uncommon Anaphylactic shock Metabolism and nutrition disorders Very common Decreased appetite Common Hypophosphataemiah Dehydration Hyperkalaemiai Nervous system disorders Very common Headache Dizziness Common Dysgeusia Ear and labyrinth disorders Common Tinnitus Cardiac disorders Common Pericardial effusion, Cardiac failurej, Cardiac ischaemick Uncommon Pericarditis Vascular disorders Common Hypertensionl Respiratory, thoracic and mediastinal disorders Very common Cough Dyspnoea Pleural effusion Common Pulmonary hypertensionm Uncommon Respiratory failure Acute pulmonary oedeman Not known Interstitial lung disease

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

Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 13–14

HOS-125472 · Präparat HOS-096073

13 Gastrointestinal disorders Very common Diarrhoea Nausea Abdominal paino Vomiting Common Gastritis Gastrointestinal haemorrhagep Pancreatitis acuteq Hepatobiliary disorders Common Hepatic function abnormalr Hepatotoxicitys Uncommon Liver injuryt Skin and subcutaneous tissue disorders Very common Rashu Common Pruritus Acne Urticaria Photosensitivity reactionv Uncommon Drug eruption Exfoliative rash Erythema multiforme Cutaneous vasculitis** Not known Stevens-Johnson Syndrome**, Toxic epidermal necrolysis** Musculoskeletal and connective tissue disorders Very common Arthralgia, Back pain Common Myalgia Renal and urinary disorders Common Acute kidney injury Renal failure Renal impairment General disorders and administration site conditions Very common Fatiguew Pyrexia Oedemax Common Chest painy Pain Investigations Very common Alanine aminotransferase increasedz Aspartate aminotransferase increased Lipase increasedaa Blood creatinine increased Common Amylase increasedbb Blood creatine phosphokinase increased Blood bilirubin increasedcc Gamma-glutamyltransferase increased Electrocardiogram QT prolongeddd a Respiratory tract infection includes Lower respiratory tract infection, Respiratory tract infection, Respiratory tract infection viral, Upper respiratory tract infection, Viral upper respiratory tract infection b Influenza includes H1N1 influenza, Influenza c Pneumonia includes Atypical pneumonia, Pneumonia, Pneumonia bacterial, Pneumonia fungal, Pneumonia necrotising, Pneumonia streptococcal d Thrombocytopenia includes Platelet count decreased, Thrombocytopenia e Anaemia includes Anaemia, Haemoglobin decreased, Red blood cell count decreased f Neutropenia includes Neutropenia, Neutrophil count decreased g Leukopenia includes Leukopenia, White blood cell count decreased

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Nebenwirkungen · Bosulif

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HOS-125473 · Präparat HOS-096073

14  h Hypophosphataemia includes Blood phosphorus decreased, Hypophosphataemia i Hyperkalaemia includes Blood potassium increased, Hyperkalaemia j Cardiac failure includes Cardiac failure, Cardiac failure acute, Cardiac failure chronic, Cardiac failure congestive, Cardiogenic shock, Cardiorenal syndrome, Ejection fraction decreased, Left ventricular failure k Cardiac ischaemic includes Acute coronary syndrome, Acute myocardial infarction, Angina pectoris, Angina unstable, Arteriosclerosis coronary artery, Coronary artery disease, Coronary artery occlusion, Coronary artery stenosis, Myocardial infarction, Myocardial ischaemia, Troponin increased l Hypertension includes the Blood pressure increased, Blood pressure systolic increased, Essential hypertension, Hypertension, Hypertensive crisis m Pulmonary hypertension includes Pulmonary arterial hypertension, Pulmonary arterial pressure increased, Pulmonary hypertension n Acute pulmonary oedema includes Acute pulmonary oedema, Pulmonary oedema o Abdominal pain includes Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness, Gastrointestinal pain p Gastrointestinal haemorrhage includes Anal haemorrhage, Gastric haemorrhage, Gastrointestinal haemorrhage, Intestinal haemorrhage, Lower gastrointestinal haemorrhage, Rectal haemorrhage, Upper gastrointestinal haemorrhage q Pancreatitis acute includes Pancreatitis, Pancreatitis acute r Hepatic function abnormal includes Hepatic enzyme increased, Hepatic function abnormal, Liver function test abnormal, Liver function test increased, Transaminases increased s Hepatotoxicity includes Hepatitis, Hepatitis toxic, Hepatotoxicity, Liver disorder t Liver injury includes Drug-induced liver injury, Hepatocellular injury, Liver injury u Rash includes Rash, Rash macular, Rash maculo-papular, Rash papular, Rash pruritic v Photosensitivity reaction includes Photosensitivity reaction, Polymorphic light eruption w Fatigue includes Asthenia, Fatigue, Malaise x Oedema includes Eyelid oedema, Face oedema, Generalised oedema, Localised oedema, Oedema, Oedema peripheral, Periorbital oedema, Periorbital swelling, Peripheral swelling, Swelling, Swelling of eyelid y Chest pain includes Chest discomfort, Chest pain z Alanine aminotransferase increased includes Alanine aminotransferase abnormal, Alanine aminotransferase increased aa Lipase increased includes Hyperlipasaemia, Lipase increased bb Amylase increased includes Amylase increased, Hyperamylasaemia cc Blood bilirubin increased includes Bilirubin conjugated increased, Blood bilirubin increased, Blood bilirubin unconjugated increased, Hyperbilirubinaemia dd Electrocardiogram QT prolonged includes Electrocardiogram QT prolonged, Long QT syndrome

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Nebenwirkungen · Bosulif

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HOS-125474 · Präparat HOS-096073

**Adverse reaction identified post marketing in adults.

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Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 15

HOS-125475 · Präparat HOS-096073

Paediatric populations

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Nebenwirkungen · Bosulif

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HOS-125476 · Präparat HOS-096073

A total of 55 paediatric patients ≥ 1 year of age received at least 1 dose of bosutinib in the Phase I/II, multicentre, international, single-arm, open-label BCHILD study. The median duration of treatment was 13.5 months (range: 0.2 to 60.9 months). These patients were either newly-diagnosed CP Ph+ CML or resistant or intolerant Ph+ CML-CP and CML-AP.

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

Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 15

HOS-125477 · Präparat HOS-096073

At least 1 adverse reaction of any toxicity grade was reported for 54 (98.2%) paediatric patients. The most frequent adverse reactions reported were diarrhoea (82%), abdominal pain (65%), vomiting (56%), nausea (51%), rash (36%), fatigue (35%), thrombocytopenia (35%), headache (33%), pyrexia (33%), ALT increased (29%), and decreased appetite (24%). The most frequent Grade 3 or Grade 4 adverse reactions reported were thrombocytopenia (18%), ALT increased (15%) and diarrhoea (13%).

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

Nebenwirkungen · Bosulif

Bosulif 100 mg film-coated tablets Bosulif 400 mg film-coated tablets Bosulif 500 mg film-coated tablets Bosulif 50 mg hard capsules Bosulif 100 mg hard capsules · Abschnitt 4.8 · PDF-Seite 15

HOS-125478 · Präparat HOS-096073

Blood and lymphatic system disorders

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Nebenwirkungen · Bosulif

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HOS-125479 · Präparat HOS-096073

15 Blood and lymphatic events in 55 paediatric patients in the BCHILD study include thrombocytopenia in 19 (34.5%) patients, anaemia in 10 patients (18.2%), and neutropenia in 7 patients (12.7%). One patient discontinued treatment due to Grade 4 neutropenia. Among patients with blood and lymphatic events, 37.5% were managed with treatment interruption and 16.7% required dose reduction. Among patients with dose interruptions, none had a positive rechallenge when bosutinib was restarted. The median time to first event was 13 days (range: 1 to 757 days) and the median cumulative duration of grade 3/4 events was 16.0 (range: 4 to 47) days.

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Nebenwirkungen · Bosulif

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HOS-125480 · Präparat HOS-096073

Hepatobiliary disorders Of the 55 participants, the incidence based on laboratory data of ALT and AST increased was 67.3% and 63.6%, respectively and 43 (78.2% participants experienced an increase in either ALT or AST). Most cases of transaminase elevation occurred early in treatment; of participants who experienced transaminase elevations of any grade, 83.7% experienced their first event within 3 months. The median time to onset of ALT and AST increased was 22.0 days (range: 9 to 847 days) and 18.5 days (range: 9 to 169 days), respectively. The median duration of Grade 3/4 events was 18.0 days (range: 2 to 132 days) and 12 days (range: 5 to 19 days) for ALT and AST increased, respectively.

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