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Imatinib Accord is a brand name for Imatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Imatinib Accord is indicated for the treatment of • adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. • adult and paediatric patients with Ph+ CML in…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy should be initiated by a physician experienced in the treatment of patients with haematological malignancies and malignant sarcomas, as appropriate. Posology for CML in adult patients The recommended dosage of Imatib Accord is 400 mg/day for adult patients in chronic phase CML.
Chronic phase CML is defined when all of the following criteria are met: blasts < 15% in blood and bone marrow, peripheral blood basophils < 20%, platelets > 100 x 109/l. The recommended dosage of Imatinib Accord is 600 mg/day for adult patients in accelerated phase.
Accelerated phase is defined by the presence of any of the following: blasts ≥ 15% but < 30% in blood or bone marrow, blasts plus promyelocytes ≥ 30% in blood or bone marrow (providing < 30% blasts), peripheral blood basophils ≥ 20%, platelets < 100 x 109/l unrelated to therapy.
The recommended dose of Imatinib is 600 mg/day for adult patients in blast crisis. Blast crisis is defined as blasts ≥ 30% in blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Treatment duration:
In clinical trials, treatment with imatinib was continued until disease progression. The effect of stopping treatment after the achievement of a complete cytogenetic response has not been investigated. Dose increases from 400 mg to 600 mg or 800 mg in patients with chronic phase disease, or from 600 mg to a maximum of 800 mg (given as 400 mg twice daily) in patients with accelerated phase or blast crisis may be considered in the absence of severe adverse drug reaction and severe non- leukaemia-related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time); failure to achieve a satisfactory haematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved haematological and/or cytogenetic response.
Patients should be monitored closely following dose escalation given the potential for an increased incidence of adverse reactions at higher dosages. Posology for CML in children Dosing for children should be on the basis of body surface area (mg/m2).
The dose of 340 mg/m2 daily is recommended for children with chronic phase CML and advanced phase CML (not to exceed the total dose of 800 mg). Treatment can be given as a once daily dose or alternatively the daily dose may be split into two administrations – one in the morning and one in the evening.
Summary of the safety profile Patients with advanced stages of malignancies may have numerous confounding medical conditions that make causality of adverse reactions difficult to assess due to the variety of symptoms related to the underlying disease, its progression, and the co-administration of numerous medicinal products.
4% of newly diagnosed patients, 4% of patients in late chronic phase after failure of interferon therapy, 4% of patients in accelerated phase after failure of interferon therapy and 5% of blast crisis patients after failure of interferon therapy.
In GIST the study drug was discontinued for drug-related adverse reactions in 4% of patients. The adverse reactions were similar in all indications, with two exceptions. There was more myelosuppression seen in CML patients than in GIST, which is probably due to the underlying disease.
In the study in patients with unresectable and/or metastatic GIST, 7 (5%) patients experienced CTC grade 3/4 GI bleeds (3 patients), intra-tumoural bleeds (3 patients) or both (1 patient). 4). GI and tumoural bleeding may be serious and sometimes fatal.
The most commonly reported (≥ 10%) drug-related adverse reactions in both settings were mild nausea, vomiting, diarrhoea, abdominal pain, fatigue, myalgia, muscle cramps and rash. Superficial oedemas were a common finding in all studies and were described primarily as periorbital or lower limb oedemas.
However, these oedemas were rarely severe and may be managed with diuretics, other supportive measures, or by reducing the dose of imatinib. When imatinib was combined with high dose chemotherapy in Ph+ ALL patients, transient liver toxicity in the form of transaminase elevation and hyperbilirubinaemia were observed.
Considering the limited safety database, the adverse events thus far reported in children are consistent with the known safety profile in adult patients with Ph+ ALL. The safety database for children with Ph+ALL is very limited though no new safety concerns have been identified.
When imatinib is co-administered with other medicinal products, there is a potential for drug interactions. g. 5). g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or Hypericum perforatum, also known as St. John’s Wort) may significantly reduce exposure to imatinib, potentially increasing the risk of therapeutic failure.
5). 5). Thyroid-stimulating hormone (TSH) levels should be closely monitored in such patients. Hepatotoxicity 8 Metabolism of imatinib is mainly hepatic, and only 13% of excretion is through the kidneys. 2). It should be noted that GIST patients may have hepatic metastases which could lead to hepatic impairment.
Cases of liver injury, including hepatic failure and hepatic necrosis, have been observed with imatinib. When imatinib is combined with high dose chemotherapy regimens, an increase in serious hepatic reactions has been detected. 8). 5% of newly diagnosed CML patients taking imatinib.
Therefore, it is highly recommended that patients be weighed regularly. An unexpected rapid weight gain should be carefully investigated and if necessary appropriate supportive care and therapeutic measures should be undertaken. In clinical trials, there was an increased incidence of these events in elderly and those with a prior history of cardiac disease.
Therefore, caution should be exercised in patients with cardiac dysfunction. Patients with cardiac disease Patients with cardiac disease, risk factors for cardiac failure or history of renal failure should be monitored carefully, and any patient with signs or symptoms consistent with cardiac failure or renal failure should be evaluated and treated.
In patients with hypereosinophilic syndrome (HES) with occult infiltration of HES cells within the myocardium, isolated cases of cardiogenic shock/left ventricular dysfunction have been associated with HES cell degranulation upon the initiation of imatinib therapy.
1.
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2). There is no experience with the treatment of children below 2 years of age. 4 Dose increases from 340 mg/m2 daily to 570 mg/m2 daily (not to exceed the total dose of 800 mg) may be considered in children in the absence of severe adverse drug reaction and severe non-leukaemia-related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time); failure to achieve a satisfactory haematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved haematological and/or cytogenetic response.
Patients should be monitored closely following dose escalation given the potential for an increased incidence of adverse reactions at higher dosages. Posology for Ph+ ALL in adult patients The recommended dose of Imatinib is 600 mg/day for adults patients with Ph+ ALL.
Haematological experts in the management of this disease should supervise the therapy throughout all phases of care. 1) for adult patients with newly diagnosed Ph+ ALL. The duration of imatinib therapy can vary with the treatment programme selected, but generally longer exposures to imatinib have yielded better results.
For adult patients with relapsed or refractory Ph+ALL Imatinib monotherapy at 600 mg/day is safe, effective and can be given until disease progression occurs. Posology for Ph+ ALL in children Dosing for children should be on the basis of body surface area (mg/m2).
The dose of 340 mg/m2 daily is recommended for children with Ph+ ALL (not to exceed the total dose of 600 mg). Posology for MDS/MPD The recommended dose of Imatinib Accord is 400 mg/day for adult patients with MDS/MPD. 1). At the time of analysis, the treatment duration was a median of 47 months (24 days - 60 months).
Posology for HES/CEL The recommended dose of Imatinib Accord is 100 mg/day for adult patients with HES/CEL. Dose increase from 100 mg to 400 mg may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
Treatment should be continued as long as the patient continues to benefit. Posology for GIST The recommended dose of Imatinib Accord is 400 mg/day for adult patients with unresectable and/or metastatic malignant GIST. 1).
Treatment duration:
In clinical trials in GIST patients, treatment with Imatinib was continued until disease progression. At the time of analysis, the treatment duration was a median of 7 months (7 days to 13 months). The effect of stopping treatment after achieving a response has not been investigated.
5 The recommended dose of Imatinib Accord is 400 mg/day for the adjuvant treatment of adult patients following resection of GIST. Optimal treatment duration is not yet established. Length of treatment in the clinical trial supporting this indication was 36 months (see […]
Miscellaneous adverse reactions such as pleural effusion, ascites, pulmonary oedema and rapid weight gain with or without superficial oedema may be collectively described as “fluid retention”. These reactions can usually be managed by withholding imatinib temporarily and with diuretics and other appropriate supportive care measures.
However, some of these reactions may be serious or life-threatening and several patients with blast crisis died with a complex clinical history of pleural effusion, congestive heart failure and renal failure. There were no special safety findings in paediatric clinical trials.
Tabulated list of adverse reactions Adverse reactions reported as more than an isolated case are listed below, by system organ class and by frequency. Frequency categories are defined 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, undesirable effects are presented in order of frequency, the most frequent first. Adverse reactions and their frequencies are reported in Table 1. Table 1 Tabulated summary of adverse reactions Infections and infestations 13 Uncommon Herpes zoster, herpes simplex, nasopharyngitis, pneumonia1, sinusitis,cellulitis, upper respiratory tract infection, influenza, urinary tract infection, gastroenteritis, sepsis Rare Fungal infection Not known Hepatitis B reactivation* Neoplasm benign, malignant and unspecified (incl cysts and polyps) Rare Tumour lysis syndrome Not known Tumour haemorrhage/tumour necrosis* Immune system disorders Not known Anaphylactic shock* Blood and lymphatic system disorders Very common Neutropenia, thrombocytopenia, anaemia Common Pancytopenia, febrile neutropenia Uncommon Thrombocythaemia, lymphopenia, bone marrow depression, eosinophilia, lymphadenopathy Rare Haemolytic anaemia, thrombotic microangiopathy Metabolism and nutrition disorders Common Anorexia Uncommon Hypokalaemia, increased appetite, hypophosphataemia, decreased appetite, dehydration, gout, hyperuricaemia, hypercalcaemia, hyperglycaemia, hyponatraemia Rare Hyperkalaemia, hypomagnesaemia Psychiatric disorders Common Insomnia Uncommon Depression, libido decreased, anxiety Rare Confusional state Nervous system disorders Very common Headache2 Common Dizziness, paraesthesia, taste disturbance, hypoaesthesia Uncommon Migraine, somnolence, syncope, peripheral neuropathy, memory impairment, sciatica, restless leg syndrome, tremor, cerebral haemorrhage Rare Increased intracranial pressure, convulsions, optic neuritis Not known Cerebral oedema* Eye disorders Common Eyelid oedema, lacrimation increased, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision Uncommon Eye irritation, eye pain, orbital oedema, scleral haemorrhage, retinal haemorrhage, blepharitis, macular oedema Rare Cataract, glaucoma, papilloedema Not known Vitreous haemorrhage* Ear and labyrinth disorders Uncommon Vertigo, tinnitus, hearing loss Cardiac disorders Uncommon Palpitations, tachycardia, cardiac failure congestive3, pulmonary oedema Rare Arrhythmia, atrial fibrillation, cardiac arrest, myocardial infarction, angina pectoris, pericardial effusion Not known Pericarditis*, cardiac tamponade* Vascular disorders4 Common Flushing, haemorrhage Uncommon Hypertension, haematoma, subdural haematoma, peripheral coldness, hypotension, Raynaud’s phenomenon Not known Thrombosis/embolism* Respiratory, thoracic and mediastinal disorders Common Dyspnoea, epistaxis, cough Uncommon Pleural effusion5, pharyngolaryngeal pain, pharyngitis 14 Rare Pleuritic pain, pulmonary fibrosis, pulmonary hypertension, pulmonary haemorrhage Not known Acute respiratory […]
The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding imatinib. As cardiac adverse events have been reported uncommonly with imatinib, a careful assessment of the benefit/risk of imatinib therapy should be considered in the HES/CEL population before treatment initiation.
Myelodysplastic/myeloproliferative diseases with PDGFR gene re-arrangements could be associated with high eosinophil levels. Evaluation by a cardiology specialist, performance of an echocardiogram and determination of serum troponin should therefore be considered in patients with HES/CEL, and in patients with MDS/MPD associated with high eosinophil levels before imatinib is administered.
If either is abnormal, follow-up with a cardiology specialist and the prophylactic use of systemic steroids (1-2 mg/kg) for one to two weeks concomitantly with imatinib should be considered at the initiation of therapy. 8). g. tumour size, tumour location, coagulation disorders) have been identified that place patients with GIST at a higher risk of either type of haemorrhage.
Since increased vascularity and propensity for bleeding is a part of the nature and clinical course of GIST, standard practices and procedures for the monitoring and management of haemorrhage in all patients should be applied. When needed,discontinuation of Imatinib treatment may be considered.
8). Hepatitis B reactivation Reactivation of hepatitis B in patients who are chronic carriers of this virus has occurred after these patients received BCR-ABL tyrosine kinase inhibitors. Some cases resulted in acute hepatic failure or fulminant hepatitis leading to liver transplantation or a fatal outcome.
Patients should be tested for HBV infection before initiating treatment with Imatinib Accord. Experts in liver disease and in the treatment of hepatitis B should be consulted before treatment is initiated in patients with positive hepatitis B serology (including those with active disease) and for patients who test positive for HBV infection during treatment.
Carriers of HBV who require treatment with […]