Imatinib Krka D.D. (Imatinib)

Imatinib is a targeted therapy used in hematologic malignancies and selected solid tumours that depend on specific tyrosine‑kinase signalling pathways.

• Chronic myeloid leukemia (CML): achieves disease control by suppressing BCR‑ABL‑driven leukemic cell proliferation.
• Philadelphia chromosome‑positive acute lymphoblastic leukemia (Ph+ ALL): helps attain remission through inhibition of the same BCR‑ABL driver.
• Gastrointestinal stromal tumor (GIST): reduces tumour growth by blocking c‑KIT and PDGFR signalling.

• Imatinib binds to the ATP‑binding site of BCR‑ABL, c‑KIT and PDGFR tyrosine kinases, stabilising them in an inactive conformation. This blocks downstream phosphorylation cascades that drive uncontrolled cell proliferation, thereby inducing apoptosis or growth arrest in malignant cells that rely on these pathways.

Imatinib may cause a range of adverse reactions, from mild to severe.

Common Side Effects

• Nausea
• Edema (peripheral swelling)
• Muscle cramps or pain
• Fatigue
• Diarrhoea
• Rash or skin irritation

Serious or Rare Side Effects

• Hepatotoxicity (elevated liver enzymes, hepatitis)
• Severe neutropenia or thrombocytopenia
• Cardiac failure or reduced left‑ventricular ejection fraction
• Pulmonary arterial hypertension
• Severe skin reactions (Stevens‑Johnson syndrome, toxic epidermal necrolysis)
• Tumour lysis syndrome

Before initiating therapy, clinicians should assess baseline organ function and monitor patients regularly.

• Blood counts: monitor complete blood count weekly during the first month, then periodically.
• Liver function: check hepatic enzymes before treatment and at regular intervals.
• Cardiac assessment: evaluate cardiac status in patients with pre‑existing heart disease.
• Drug interactions: review concomitant medications that affect CYP3A4 metabolism.
• Pregnancy and lactation: avoid use unless the potential benefit justifies the risk; safety data are limited.
• Store below 25°C: keep in the original packaging, protect from moisture and direct light.

Imatinib interacts with several medicines that influence its metabolism or increase toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may raise imatinib plasma levels.
• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine): may markedly reduce efficacy.
• Antacids containing aluminium or magnesium: can impair absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Warfarin: may enhance anticoagulant effect; monitor INR.
• Diuretics (e.g., furosemide): increased risk of fluid retention and electrolyte imbalance.
• QT‑prolonging agents (e.g., sotalol, quinidine): monitor cardiac rhythm for arrhythmias.