Imatinib Accord 100 & 400 100 mg/400 mg FC tablets.

• Adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukaemia (CML).
• Adult and paediatric patients with CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
• Adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.
• Adult patients with relapsed or refractory Ph+ ALL as monotherapy.
• Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene rearrangements.
• Adult patients with systemic mastocytosis (SM) without the D816V c-Kit mutation and eosinophilia.
• Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRu03b1 rearrangement.
• Adult patients with unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).
• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).

Therapy should be initiated by a medical practitioner experienced in the treatment of patients with chronic myeloid leukaemia or GIST respectively.

Adult Dosage in CML

The recommended dosage of IMATINIB ACCORD is 400 mg daily for patients in chronic phase CML and 600 mg daily for patients in accelerated phase or blast crisis. Treatment should be continued as long as the patient continues to benefit.

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Dosage in DFSP

The recommended dose of IMATINIB ACCORD is 800 mg daily for patients with DFSP.

Method of administration

The prescribed dose should be administered orally, once daily with a meal and a large glass of water, to minimize the risk of gastrointestinal disturbances.

Hypersensitivity to imatinib, the metabolite N-demethylated piperazine derivative, or to any of the inactive ingredients of IMATINIB ACCORD listed in section 6.1. Pregnancy and lactation (see section 4.6).

When IMATINIB ACCORD is co-administered with other medications, there is a potential for drug interactions (see section 4.5).

Caution should be exercised when taking IMATINIB ACCORD with protease inhibitors, azole antifungals, certain macrolides (see section 4.5), CYP3A4 substrates with a narrow therapeutic window (e.g. cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel, quinidine) or warfarin and other coumarin derivatives (see section 4.5).

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Medicines that may increase IMATINIB ACCORD plasma concentrations include substances that inhibit the cytochrome P-450 isoenzyme CYP3A4 activity (e.g. protease inhibitors such as indinavir, lopinavir/ritonavir, ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir; azole antifungals including ketoconazole, itraconazole, posaconazole, voriconazole; certain macrolides such as erythromycin, clarithromycin and telithromycin).

Medicines that may decrease IMATINIB ACCORD plasma concentrations include substances that are inducers of CYP3A4 activity (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, fosphenytoin, primidone or Hypericum perforatum).

IMATINIB ACCORD should not be taken during pregnancy or lactation (see section 4.3). Women of childbearing potential must be advised to use highly effective contraception during treatment and for 15 days after stopping treatment to avoid pregnancy. Use in pregnancy may lead to foetal abortion or malformation. Patients should not breastfeed during treatment.

Patients should be advised that they may experience undesirable effects such as dizziness, somnolence or blurred vision during treatment with IMATINIB ACCORD. Therefore, caution should be recommended when driving a car or operating machinery.

Tabulated summary of adverse reactions:

SYSTEM ORGAN CLASS FREQUENCY ADVERSE REACTION

Infections and infestations: Less frequent - Sepsis, pneumonia, herpes simplex, herpes zoster, upper respiratory tract infection, gastroenteritis, sinusitis, cellulitis, influenza, urinary tract infections, nasopharyngitis, fungal infection.

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Symptoms: Severe muscle cramps, elevations of serum creatinine, ascites and elevated liver transaminase levels, and elevations of bilirubin. A general exacerbation of symptoms listed as side effects may be seen in the event of overdosage (see section 4.8).

Treatment: Patients should be observed and appropriate symptomatic and supportive treatment given.