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Arsenic Trioxide Mylan is a brand name for Arsenic Trioxide. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Arsenic trioxide Mylan is indicated for induction of remission, and consolidation in adult patients with: - Newly diagnosed low-to-intermediate risk acute promyelocytic leukaemia (APL) (white blood cell count, ≤ 10 x 103/μl) in combination with all-trans-retinoic acid (ATRA) - Relapsed/refractory acute promyelocytic…
Verbatim from this product's EMA label. Tap a section to expand.
4 must be followed. Posology The same dose is recommended for adults and elderly. 15 mg/kg/day, given daily until complete remission is achieved. If complete remission has not occurred by day 60, dosing must be discontinued. 15 mg/kg/day, 5 days per week.
Treatment should be continued for 4 weeks on and 4 weeks off, for a total of 4 cycles. 15 mg/kg/day given daily until complete remission is achieved (less than 5% blasts present in cellular bone marrow with no evidence of leukaemic cells).
If complete remission has not occurred by day 50, dosing must be discontinued. Consolidation schedule Consolidation treatment must begin 3 to 4 weeks after completion of induction therapy. 15 mg/kg/day for 25 doses given 5 days per week, followed by 2 days interruption, repeated for 5 weeks.
Dose delay, modification and reinitiation Treatment with Arsenic trioxide Mylan must be temporarily interrupted before the scheduled end of therapy at any time that a toxicity grade 3 or greater on the National Cancer Institute Common Toxicity Criteria is observed and judged to be possibly related to Arsenic trioxide Mylan treatment.
Patients who experience such reactions that are considered arsenic trioxide related must resume treatment only after resolution of the toxic event or after recovery to baseline status of the abnormality that prompted the interruption.
In such cases, treatment must resume at 50% of the preceding daily dose. If the toxic event does not recur within 7 days of restarting treatment at the reduced dose, the daily dose can be escalated back to 100% of the original dose.
Patients who experience a recurrence of toxicity must be removed from treatment. For ECG, electrolytes abnormalities and hepatotoxicity see section
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).
Leukocytosis occurred in 50% of patients with relapsed/refractory APL, as determined by haematology assessments. 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), leukocytosis (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.
In general, treatment-emergent adverse reactions 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 reactions by the uncontrolled disease process early on in Medicinal product no longer authorised 8 the treatment course and the myriad concomitant medicinal products required to control symptoms and morbidity.
1), serious adverse reactions including hepatic toxicity, thrombocytopenia, neutropenia and QTc prolongation were observed in patients treated with arsenic trioxide. Tabulated list of adverse reactions The following undesirable effects have been reported in the APL0406 study in newly diagnosed patients and in clinical trials and/or post-marketing experience in relapsed/refractory APL patients.
Undesirable effects are listed in table 2 below as MedDRA preferred term by system organ class and frequencies observed during arsenic trioxide 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).
4. 8). Renal impairment Since no data are available across all renal impairment groups, caution is advised in the use of Arsenic trioxide Mylan in patients with renal impairment. Paediatric population The safety and efficacy of Arsenic trioxide Mylan in children aged up to 17 years has not been established.
1 but no recommendation on a posology can be made. No data are available for children under 5 years. Method of administration Arsenic trioxide Mylan must be administered intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if vasomotor reactions are observed.
A central venous catheter is not required. Patients must be hospitalised at the beginning of treatment due to symptoms of disease and to ensure adequate monitoring. 6. 1. 4 Special warnings and precautions for use Clinically unstable APL patients are especially at risk and will require more frequent monitoring of electrolyte and glycaemia levels as well as more frequent haematologic, hepatic, renal and coagulation parameter tests.
Leukocyte activation syndrome (APL differentiation syndrome) 27% of patients with APL, in the relapsed/refractory setting, treated with arsenic trioxide have experienced symptoms similar to a syndrome called the retinoic-acid-acute promyelocytic leukaemia (RA-APL) or APL differentiation syndrome, characterised by fever, dyspnoea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis.
This syndrome can be fatal. In newly diagnosed APL patients treated with arsenic trioxide and all-trans-retinoic acid (ATRA), APL differentiation syndrome was observed in 19% including 5 severe cases. At the first signs that could suggest the syndrome (unexplained fever, dyspnoea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), treatment with arsenic trioxide must be temporarily discontinued and high-dose steroids (dexamethasone 10 mg intravenously twice a day) must be immediately initiated, irrespective of the leukocyte count and continued for at least 3 days or longer until signs and symptoms have abated.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 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 Leukocytosis 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 Encephalopathy, Wernicke encephalopathy Not known Not known Eye disorders Vision blurred Common Not known Medicinal product no longer authorised 9 All grades Grades ≥ 3 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* *In the CALGB study C9710, 2 cases of grade ≥3 increased GGT were reported out of the 200 patients who received arsenic trioxide consolidation cycles (cycle 1 and cycle 2) versus none in the control arm.
4). Twenty-seven patients had leukocytosis (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 […]
If clinically justified/required, concomitant diuretic therapy is also recommended. The majority of patients do not require permanent termination of arsenic trioxide therapy during treatment of the APL differentiation syndrome. As soon as signs and symptoms have subsided, treatment with arsenic trioxide can be resumed at 50% of the previous dose during the first 7 days.
Thereafter, in the absence of worsening of the previous toxicity, arsenic trioxide might be resumed at full dosage. In the case of the reappearance of symptoms arsenic trioxide should be reduced to the previous dosage. 5 mg/kg body weight per day throughout induction treatment) may be administered from day 1 of arsenic trioxide application to the end of induction therapy in APL patients.
It is recommended that chemotherapy not be added to treatment with steroids since there is no experience with administration of both steroids and chemotherapy during treatment of the leukocyte activation syndrome due to arsenic trioxide.
Post--marketing experience suggests that a similar syndrome may occur in patients with other types of malignancy. Monitoring and management for these patients should be as described above. Electrocardiogram (ECG) abnormalities Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block.
QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. Previous treatment with anthracyclines may increase the risk of QT prolongation. g. g. g. g. g. g. g. cisapride)), a history of torsade de pointes, pre-existing QT interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, amphotericin B or other conditions that result in hypokalemia or hypomagnesaemia.
In clinical trials, in the relapsed/refractory setting, 40% of patients treated with arsenic trioxide experienced at least one QT corrected (QTc) interval prolongation greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after arsenic trioxide infusion, and then returned to baseline by the end of 8 weeks after arsenic trioxide infusion.
One patient (receiving multiple, concomitant medicinal products, including amphotericin B) had asymptomatic torsade de pointes during induction therapy for relapsed APL with arsenic trioxide. 8). In one newly diagnosed patient induction treatment was terminated because of severe prolongation of the QTc interval and electrolyte abnormalities on day 3 of induction treatment.
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