Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115579 · Präparat HOS-094307

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4). The concomitant administration of deferasirox with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

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

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115580 · Präparat HOS-094307

Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (AUC), but the mechanism of the interaction remains unclear. If possible, evaluation of the pharmacokinetics (AUC, clearance) of a busulfan test dose should be performed to allow dose adjustment.

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): busulfan (HOS-115553)

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115554 · Präparat HOS-094307

Summary of the safety profile The most frequent reactions reported during chronic treatment in clinical studies conducted with deferasirox dispersible tablets in adult and paediatric patients include gastrointestinal disturbances (mainly nausea, vomiting, diarrhoea or abdominal pain) and skin rash. Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years and in the elderly. These reactions are dose- dependent, mostly mild to moderate, generally transient and mostly resolve even if treatment is continued.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115555 · Präparat HOS-094307

During clinical studies dose-dependent increases in serum creatinine occurred in about 36% of patients, though most remained within the normal range. Decreases in mean creatinine clearance have been observed in both paediatric and adult patients with beta-thalassemia and iron overload during the first year of treatment, but there is evidence that this does not decrease further in subsequent years of treatment. Elevations of liver transaminases have been reported. Safety monitoring schedules for renal and liver parameters are recommended. Auditory (decreased hearing) and ocular (lens opacities) disturbances are uncommon, and yearly examinations are also recommended (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115556 · Präparat HOS-094307

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of EXJADE (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115557 · Präparat HOS-094307

Tabulated list of adverse reactions Adverse reactions are ranked below using the following convention: 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 · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13–14

HOS-115558 · Präparat HOS-094307

13 Table 6

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-115559 · Präparat HOS-094307

Blood and lymphatic system disorders Not known: Pancytopenia1, thrombocytopenia1, anaemia aggravated1, neutropenia1 Immune system disorders Not known: Hypersensitivity reactions (including anaphylactic reactions and angioedema)1 Metabolism and nutrition disorders Not known: Metabolic acidosis1 Psychiatric disorders Uncommon: Anxiety, sleep disorder Nervous system disorders Common: Headache Uncommon: Dizziness Eye disorders Uncommon: Cataract, maculopathy Rare: Optic neuritis Ear and labyrinth disorders Uncommon: Deafness Respiratory, thoracic and mediastinal disorders Uncommon: Laryngeal pain Gastrointestinal disorders Common: Diarrhoea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia Uncommon: Gastrointestinal haemorrhage, gastric ulcer (including multiple ulcers), duodenal ulcer, gastritis Rare: Oesophagitis Not known: Gastrointestinal perforation1, acute pancreatitis1 Hepatobiliary disorders Common: Transaminases increased Uncommon: Hepatitis, cholelithiasis Not known: Hepatic failure1, 2 Skin and subcutaneous tissue disorders Common: Rash, pruritus Uncommon: Pigmentation disorder Rare: Drug reaction with eosinophilia and systemic symptoms (DRESS) Not known: Stevens-Johnson syndrome1, hypersensitivity vasculitis1, urticaria1, erythema multiforme1, alopecia1, toxic epidermal necrolysis (TEN)1 Renal and urinary disorders Very common: Blood creatinine increased Common: Proteinuria Uncommon: Renal tubular disorder2 (acquired Fanconi syndrome), glycosuria Not known: Acute renal failure1, 2, tubulointerstitial nephritis1, nephrolithiasis1, renal tubular necrosis1 General disorders and administration site conditions Uncommon: Pyrexia, oedema, fatigue 1 Adverse reactions reported during post-marketing experience. These are derived from spontaneous reports for which it is not always possible to reliably establish frequency or a causal relationship to exposure to the medicinal product. 2 Severe forms associated with changes in consciousness in the context of hyperammonaemic encephalopathy have been reported.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14–15

HOS-115560 · Präparat HOS-094307

14 Description of selected adverse reactions Gallstones and related biliary disorders were reported in about 2% of patients. Elevations of liver transaminases were reported as an adverse reaction in 2% of patients. Elevations of transaminases greater than 10 times the upper limit of the normal range, suggestive of hepatitis, were uncommon (0.3%). During post-marketing experience, hepatic failure, sometimes fatal, has been reported with deferasirox (see section 4.4). There have been post-marketing reports of metabolic acidosis. The majority of these patients had renal impairment, renal tubulopathy (Fanconi syndrome) or diarrhoea, or conditions where acid-base imbalance is a known complication (see section 4.4). Cases of serious acute pancreatitis were observed without documented underlying biliary conditions. As with other iron chelator treatment, high-frequency hearing loss and lenticular opacities (early cataracts) have been uncommonly observed in patients treated with deferasirox (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115561 · Präparat HOS-094307

Creatinine clearance in transfusional iron overload In a retrospective meta-analysis of 2 102 adult and paediatric beta-thalassaemia patients with transfusional iron overload treated with deferasirox dispersible tablets in two randomised and four open label studies of up to five years’ duration, a mean creatinine clearance decrease of 13.2% in adult patients (95% CI: -14.4% to -12.1%; n=935) and 9.9% (95% CI: -11.1% to -8.6%; n=1 142) in paediatric patients was observed during the first year of treatment. In 250 patients who were followed for up to five years, no further decrease in mean creatinine clearance levels was observed.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115562 · Präparat HOS-094307

Clinical study in patients with non-transfusion-dependent thalassaemia syndromes In a 1-year study in patients with non-transfusion-dependent thalassaemia syndromes and iron overload (dispersible tablets at a dose of 10 mg/kg/day), diarrhoea (9.1%), rash (9.1%), and nausea (7.3%) were the most frequent study drug-related adverse events. Abnormal serum creatinine and creatinine clearance values were reported in 5.5% and 1.8% of patients, respectively. Elevations of liver transaminases greater than 2 times the baseline and 5 times the upper limit of normal were reported in 1.8% of patients.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115563 · Präparat HOS-094307

Paediatric population In three clinical studies, growth and sexual development of paediatric patients treated with deferasirox for up to 5 years were not affected (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115564 · Präparat HOS-094307

Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years than in older patients.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115565 · Präparat HOS-094307

Renal tubulopathy has been mainly reported in children and adolescents with beta-thalassaemia treated with deferasirox. In post-marketing reports, a high proportion of cases of metabolic acidosis occurred in children in the context of Fanconi syndrome.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115566 · Präparat HOS-094307

Acute pancreatitis has been reported, particularly in children and adolescents.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-115567 · Präparat HOS-094307

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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

Nebenwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.8 · PDF-Seite 33

HOS-115581 · Präparat HOS-094307

Summary of the safety profile The most frequent reactions reported during chronic treatment in clinical studies conducted with deferasirox dispersible tablets in adult and paediatric patients include gastrointestinal disturbances (mainly nausea, vomiting, diarrhoea or abdominal pain) and skin rash. Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years and in the elderly. These reactions are dose- dependent, mostly mild to moderate, generally transient and mostly resolve even if treatment is continued.

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

Nebenwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.8 · PDF-Seite 33

HOS-115582 · Präparat HOS-094307

During clinical studies dose-dependent increases in serum creatinine occurred in about 36% of patients, though most remained within the normal range. Decreases in mean creatinine clearance have been observed in both paediatric and adult patients with beta-thalassemia and iron overload during the first year of treatment, but there is evidence that this does not decrease further in subsequent years of treatment. Elevations of liver transaminases have been reported. Safety monitoring schedules for renal and liver parameters are recommended. Auditory (decreased hearing) and ocular (lens opacities) disturbances are uncommon, and yearly examinations are also recommended (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.8 · PDF-Seite 33

HOS-115583 · Präparat HOS-094307

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of EXJADE (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.8 · PDF-Seite 33

HOS-115584 · Präparat HOS-094307

Tabulated list of adverse reactions Adverse reactions are ranked below using the following convention: 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.