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Generic Gleevec ( Imatinib )
Gleevec (imatinib mesylate) is a tyrosine kinase inhibitor indicated for the treatment of Philadelphia chromosome‑positive chronic myeloid leukemia (CML) in chronic, accelerated, or blast phase, Philadelphia chromosome‑positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases associated with platelet‑derived growth factor receptor gene rearrangements, aggressive systemic mastocytosis, hypereosinophilic syndrome, unresectable or metastatic gastrointestinal stromal tumours (GIST), and dermatofibrosarcoma protuberans. Imatinib works by selectively inhibiting the BCR‑ABL tyrosine kinase, the abnormal enzyme produced by the Philadelphia chromosome, as well as c‑KIT and platelet‑derived growth factor receptors. This blocks downstream signalling pathways that drive the uncontrolled proliferation of malignant cells.
Usual adult dose: For chronic phase CML, the recommended dose is 400 mg taken orally once daily with a meal and a large glass of water. For accelerated or blast phase CML, the dose is 600 mg once daily. For GIST, the dose is 400 mg once daily; in progressive disease, 400 mg twice daily may be considered. The tablets should be swallowed whole; they may be dispersed in a glass of water or apple juice if swallowing is difficult. The 100 mg tablet is used for dose reductions, paediatric dosing, and for patients intolerant to the 400 mg strength. Treatment continues as long as clinical benefit is observed and unacceptable toxicity does not occur. Dose modifications may be required for hematologic or hepatic toxicity. If a dose is missed, the patient should take the next dose at the usual time; two doses must not be taken on the same day. No dose adjustment is required in mild‑to‑moderate renal impairment; caution is advised in severe renal impairment. In hepatic impairment, dose reduction may be necessary.
Dosage form: Film‑coated tablets: 100 mg (orange‑brown, round, imprinted with "NVR" and "SA") and 400 mg (orange‑brown, oval, imprinted with "NVR" and "400"). Available in bottles or blister packs of 30, 60, or 90 tablets.
Onset of action: Hematologic response in chronic phase CML is typically observed within 1 to 2 months, with complete hematologic response achieved in up to 95% of patients within 3 months. Cytogenetic and major molecular responses develop more gradually, usually within 6 to 12 months of continuous therapy. For GIST, tumour shrinkage or stabilization may be seen within 2 to 3 months.
Duration of action: The elimination half‑life of imatinib is approximately 18 hours, with its major active metabolite having a half‑life of about 40 hours, supporting once‑daily dosing. The therapeutic effect is maintained with continuous daily treatment. Long‑term therapy is generally required to sustain remission; discontinuation can be considered only in selected patients with deep and sustained molecular response under specialist supervision.
Alcohol recommendation: Alcohol should be avoided or strictly limited during treatment with Gleevec. Alcohol may increase the risk of hepatotoxicity and gastrointestinal irritation, and can contribute to dehydration, which may worsen renal function in patients receiving imatinib. Patients with liver impairment or those taking other hepatotoxic medications should exercise particular caution.
Most common side effects: Fluid retention (periorbital edema, peripheral edema), nausea, vomiting, diarrhea, muscle cramps, musculoskeletal pain, fatigue, rash, and headache. Myelosuppression, including neutropenia, thrombocytopenia, and anemia, is common and requires regular complete blood count monitoring, especially during the first few months of therapy. Hepatotoxicity, ranging from transaminase elevations to rare cases of severe hepatitis, necessitates periodic liver function tests. Cardiotoxicity, including congestive heart failure, has been reported; patients with pre‑existing cardiac disease should be monitored closely. Hypothyroidism can occur in patients who have undergone thyroidectomy. Gastrointestinal irritation can be reduced by taking the tablets with food and water. Serious skin reactions, including Stevens‑Johnson syndrome, have been reported; imatinib should be discontinued if severe dermatologic toxicity develops. Tumour lysis syndrome may occur in patients with high tumour burden; adequate hydration and uric acid control are important. Women of childbearing potential must use effective contraception during treatment, as imatinib may cause fetal harm. Gleevec is available only by prescription and must be prescribed and supervised by a healthcare professional experienced in oncology or hematology.
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