Imatinib

Gleevec (Imatinib)

🔴 Red Flags (Key Points When Using Imatinib)

• Fluid retention and oedema (including pleural effusions, ascites, pericardial effusions)
• Hepatotoxicity → monitor LFTs regularly
• Myelosuppression (neutropenia, thrombocytopenia) → FBC monitoring required
• Cardiac toxicity (rare but reported, especially in advanced disease)
• Severe GI bleeding risk, particularly in GIST
• Drug–drug interactions via CYP3A4
• Avoid pregnancy and breastfeeding

🔹 1. Basic Information

Generic name: Imatinib (as mesylate)
Brand name: Gleevec®
Drug class: Tyrosine kinase inhibitor (TKI)
Formulation: Film-coated tablets
Strengths: 100 mg, 400 mg

Mechanism of Action:
Imatinib selectively inhibits BCR-ABL, KIT, and PDGFR tyrosine kinases, blocking malignant cell proliferation and inducing apoptosis in susceptible tumours.

🔹 2. Indications (ONCOLOGY ONLY – FULL, AS PER PI)

A. Chronic Myeloid Leukaemia (CML)

Gleevec is indicated for the treatment of Philadelphia chromosome–positive (Ph+) Chronic Myeloid Leukaemia in the following settings:

• Newly diagnosed Ph+ CML
• Chronic phase CML after failure of interferon-alpha therapy
• Accelerated phase CML
• Blast crisis CML

B. Acute Lymphoblastic Leukaemia (ALL)

• Philadelphia chromosome–positive (Ph+) Acute Lymphoblastic Leukaemia, in combination with chemotherapy

C. Myelodysplastic / Myeloproliferative Diseases

• MDS/MPD associated with PDGFR gene rearrangements

D. Hypereosinophilic Syndrome (HES) / Chronic Eosinophilic Leukaemia (CEL)

• HES or CEL associated with PDGFR gene rearrangements

E. Gastrointestinal Stromal Tumours (GIST)

• Unresectable or metastatic GIST expressing KIT (CD117)
• Adjuvant treatment of adult patients following resection of KIT-positive GIST

F. Dermatofibrosarcoma Protuberans (DFSP)

• Unresectable, recurrent or metastatic DFSP

🔹 3. Dosing & Administration (Oncology)

CML / ALL / MDS/MPD / HES / CEL:
• 400–800 mg once daily depending on disease phase and response

GIST:
• Metastatic/unresectable: 400 mg once daily (may increase to 800 mg)
• Adjuvant: 400 mg once daily

Administration:
• Oral
• Take with a meal and a large glass of water
• Swallow tablets whole

🔹 4. Dose Modifications

• Haematologic toxicity: Interrupt and resume at reduced dose when recovered
• Hepatic toxicity: Interrupt if severe; resume at reduced dose once resolved
• Fluid retention: Manage symptomatically or interrupt if severe

🔹 5. Contraindications

• Hypersensitivity to imatinib or excipients
• Pregnancy and breastfeeding

🔹 6. Monitoring Requirements

• FBC: Baseline and regularly
• Liver function tests: Baseline and ongoing
• Renal function: Baseline and periodically
• Body weight and fluid status: Monitor for fluid retention
• Cardiac monitoring: In patients with risk factors

🔹 7. Side Effects (Oncology-Relevant)

Very Common / Common:
• Oedema (periorbital, peripheral)
• Nausea, vomiting, diarrhoea
• Muscle cramps, musculoskeletal pain
• Rash
• Fatigue
• Cytopenias

Serious:
• Severe myelosuppression
• Hepatotoxicity
• Congestive heart failure
• GI bleeding (especially GIST)
• Severe skin reactions

🔹 8. Drug Interactions

• CYP3A4 inhibitors → ↑ imatinib levels
• CYP3A4 inducers → ↓ efficacy
• Warfarin → increased bleeding risk
• Avoid strong enzyme inducers where possible

🔹 9. Use in Special Populations

• Pregnancy: Contraindicated
• Breastfeeding: Contraindicated
• Elderly: No routine dose adjustment
• Renal impairment: Use with caution
• Hepatic impairment: Dose reduction may be required

🔹 10. Duration of Use / When to Stop

Continue until:
• Disease progression, or
• Unacceptable toxicity

Discontinue permanently if:
• Severe, recurrent toxicity despite dose reductions
• Life-threatening adverse events

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2024/10/Gleevec-Professional-Information-16-09-2024.pdf