Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.3 · PDF-Seite 4

HOS-109649 · Präparat HOS-093221

Hypersensitivity to the active substance 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.

Wechselwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-109650 · Präparat HOS-093221

No formal assessments of pharmacokinetic interactions between TRISENOX and other therapeutic medicinal products have been conducted.

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

Wechselwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6

HOS-109651 · Präparat HOS-093221

Medicinal products known to cause QT/QTc interval prolongation, hypokalaemia or hypomagnesaemia QT/QTc prolongation is expected during treatment with arsenic trioxide, and torsade de pointes and complete heart block have been reported. Patients who are receiving, or who have received, medicinal products known to cause hypokalaemia or hypomagnesaemia, such as diuretics or amphotericin B,

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): amphotericin B (HOS-109312)

Wechselwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 6–7

HOS-109652 · Präparat HOS-093221

6 may be at higher risk for torsade de pointes. Caution is advised when TRISENOX is co-administered with other medicinal products known to cause QT/QTc interval prolongation such as macrolide antibiotics, the antipsychotic thioridazine, or medicinal products known to cause hypokalaemia or hypomagnesaemia. Additional information about QT prolonging medicinal agents, is provided in 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): thioridazine (HOS-086281)

Wechselwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 7

HOS-109654 · Präparat HOS-093221

Medicinal products known to cause hepatotoxic effects Hepatotoxic effects may occur during the treatment with arsenic trioxide, caution is advised when TRISENOX is co-administered with other medicinal products known to cause hepatotoxic effects (see section 4.4 and 4.8).

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

Wechselwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 7

HOS-109655 · Präparat HOS-093221

Other antileukaemic medicinal products The influence of TRISENOX on the efficacy of other antileukaemic medicinal products is unknown.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7

HOS-109656 · Präparat HOS-093221

Summary of the safety profile Related adverse reactions of CTC grade 3 and 4 occurred in 37 % of relapsed/refractory APL patients in clinical trials. The most commonly reported reactions were hyperglycaemia, hypokalaemia, neutropenia, and increased alanine amino transferase (ALT). Leucocytosis occurred in 50 % of patients with relapsed/refractory APL, as determined by haematology assessments.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7

HOS-109657 · Präparat HOS-093221

Serious adverse reactions were common (1-10 %) and not unexpected in the relapsed/refractory population. Those serious adverse reactions attributed to arsenic trioxide included APL differentiation syndrome (3), leucocytosis (3), prolonged QT interval (4, 1 with torsade de pointes), atrial fibrillation/atrial flutter (1), hyperglycaemia (2) and a variety of serious adverse reactions related to haemorrhage, infections, pain, diarrhoea, nausea.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 7–8

HOS-109658 · Präparat HOS-093221

7 In general, treatment-emergent adverse events tended to decrease over time, in relapsed/refractory APL patients perhaps accounted for by amelioration of the underlying disease process. Patients tended to tolerate consolidation and maintenance treatment with less toxicity than in induction. This is probably due to the confounding of adverse events by the uncontrolled disease process early on in the treatment course and the myriad concomitant medicinal products required to control symptoms and morbidity.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-109659 · Präparat HOS-093221

In a phase 3, multicentre, non-inferiority trial comparing all-trans-retinoic acid (ATRA) plus chemotherapy with ATRA plus arsenic trioxide in newly diagnosed low-to-intermediate risk APL patients (Study APL0406; see also section 5.1), serious adverse reactions including hepatic toxicity, thrombocytopenia, neutropenia and QTc prolongation were observed in patients treated with arsenic trioxide.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-109660 · Präparat HOS-093221

Tabulated list of adverse reactions The following undesirable effects have been reported in clinical trials and/or post-marketing experience in newly diagnosed and relapsed/refractory APL patients. Undesirable effects are listed in table 2 below as MedDRA preferred term by system organ class and frequencies observed during TRISENOX clinical trials in 52 patients with refractory/relapsed APL. Frequencies are defined as: (very common ≥ 1/10), (common ≥ 1/100 to < 1/10), (uncommon ≥ 1/1,000 to < 1/100), 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.

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-109661 · Präparat HOS-093221

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 · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8

HOS-109662 · Präparat HOS-093221

Table 2 All grades Grades ≥ 3 Infections and infestations Herpes zoster Common Not known Sepsis Not known Not known Pneumonia Not known Not known Blood and lymphatic system disorders Febrile neutropenia Common Common Leucocytosis Common Common Neutropenia Common Common Pancytopenia Common Common Thrombocytopenia Common Common Anaemia Common Not known Leukopenia Not known Not known Lymphopenia Not known Not known Metabolism and nutrition disorders Hyperglycaemia Very Common Very Common Hypokalaemia Very Common Very Common Hypomagnesaemia Very Common Common Hypernatraemia Common Common Ketoacidosis Common Common Hypermagnesaemia Common Not known Dehydration Not known Not known Fluid retention Not known Not known Psychiatric disorders Confusional state Not known Not known Nervous system disorders Paraesthesia Very Common Common Dizziness Very Common Not known Headache Very Common Not known Convulsion Common Not known

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 8–9

HOS-109663 · Präparat HOS-093221

8  All grades Grades ≥ 3 Encephalopathy, Wernicke Not known Not known encephalopathy Eye disorders Vision blurred Common Not known Cardiac disorders Tachycardia Very Common Common Pericardial effusion Common Common Ventricular extrasystoles Common Not known Cardiac failure Not known Not known Ventricular tachycardia Not known Not known Vascular disorders Vasculitis Common Common Hypotension Common Not known Respiratory, thoracic and mediastinal disorders Differentiation syndrome Very Common Very Common Dyspnoea Very Common Common Hypoxia Common Common Pleural effusion Common Common Pleuritic pain Common Common Pulmonary alveolar haemorrhage Common Common Pneumonitis Not known Not known Gastrointestinal disorders Diarrhoea Very Common Common Vomiting Very Common Not known Nausea Very Common Not known Abdominal pain Common Common Skin and subcutaneous tissue disorders Pruritus Very Common Not known Rash Very Common Not known Erythema Common Common Face oedema Common Not known Musculoskeletal and connective tissue disorders Myalgia Very Common Common Arthralgia Common Common Bone pain Common Common Renal and urinary disorders Renal failure Common Not known General disorders and administration site conditions Pyrexia Very Common Common Pain Very Common Common Fatigue Very Common Not known Oedema Very Common Not known Chest pain Common Common Chills Common Not known Investigations Alanine amino transferase increased Very Common Common Aspartate amino transferase increased Very Common Common Electrocardiogram QT prolonged Very Common Common Hyperbilirubinaemia Common Common Blood creatinine increased Common Not known Weight increased Common Not known Gamma-glutamyltransferase increased* Not known* Not known*

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 9–10

HOS-109664 · Präparat HOS-093221

9 *In the CALGB study C9710, 2 cases of grade ≥3 increased GGT were reported out of the 200 patients who received TRISENOX consolidation cycles (cycle 1 and cycle 2) versus none in the control arm.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-109665 · Präparat HOS-093221

Description of selected adverse reactions

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-109666 · Präparat HOS-093221

Differentiation syndrome During TRISENOX treatment, 14 of the 52 patients in the APL studies in the relapsed setting had one or more symptoms of APL differentiation syndrome, characterised by fever, dyspnoea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leucocytosis (see section 4.4). Twenty-seven patients had leucocytosis (WBC ≥ 10 x 103/µl) during induction, 4 of whom had values above 100,000/µl. Baseline white blood cell (WBC) counts did not correlate with development of leucocytosis on study, and WBC counts during consolidation therapy were not as high as during induction. In these studies, leucocytosis was not treated with chemotherapeutic medicinal products. Medicinal products that are used to lower the white blood cell count often exacerbate the toxicities associated with leucocytosis, and no standard approach has proven effective. One patient treated under a compassionate use program died from cerebral infarct due to leucocytosis, following treatment with chemotherapeutic medicinal products to lower WBC count. Observation is the recommended approach with intervention only in selected cases.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-109667 · Präparat HOS-093221

Mortality in the pivotal studies in the relapsed setting from disseminated intravascular coagulation (DIC) associated haemorrhage was very common (> 10 %), which is consistent with the early mortality reported in the literature.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-109668 · Präparat HOS-093221

In newly diagnosed patients with low to intermediate risk APL, differentiation syndrome was observed in 19 % including 5 severe cases.

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

Nebenwirkungen · Trisenox

TRISENOX 1 mg/ml concentrate for solution for infusion TRISENOX 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-109669 · Präparat HOS-093221

In post marketing experience, a differentiation syndrome, like retinoic acid syndrome, has also been reported for the treatment of malignancies other than APL with TRISENOX.

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