Nilotinib Zentiva (Nilotinib)

Nilotinib is a BCR‑ABL tyrosine kinase inhibitor used in the management of chronic myeloid leukemia.

• Chronic myeloid leukemia – chronic phase: achieves hematologic and cytogenetic remission in patients with Philadelphia chromosome‑positive disease.
• Chronic myeloid leukemia – accelerated phase: provides disease control when prior tyrosine kinase inhibitor therapy has failed or is not tolerated.
• Chronic myeloid leukemia – blast phase: offers a therapeutic option to reduce leukemic blasts and improve survival in resistant cases.

• Nilotinib selectively binds to the ATP‑binding site of the BCR‑ABL tyrosine kinase, stabilizing the inactive conformation of the enzyme. By preventing phosphorylation of downstream substrates, it blocks the signaling pathways that drive proliferation and survival of leukemic cells. The drug also inhibits several other kinases, such as KIT and PDGFR, contributing to its antineoplastic activity. These actions result in cell‑cycle arrest and apoptosis of malignant progenitors.

Nilotinib may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Rash: mild to moderate skin eruption.
• Nausea: transient gastrointestinal discomfort.
• Diarrhea: watery stools, often self‑limiting.
• Elevated liver enzymes: mild transaminase increase.
• Fatigue: generalized tiredness.
• Pruritus: itching sensation.
• Headache: mild to moderate head pain.

Serious or Rare Side Effects

• Cardiovascular events: arterial occlusive disease, myocardial infarction.
• Pancreatitis: acute inflammation of the pancreas.
• Severe hepatotoxicity: marked elevation of liver enzymes or liver failure.
• QT prolongation: cardiac rhythm disturbance that may lead to arrhythmia.
• Severe neutropenia: significant reduction in white blood cells increasing infection risk.

When prescribing Nilotinib, clinicians should observe several precautionary measures to minimize risks.

• Cardiac assessment: evaluate baseline ECG and monitor for QT prolongation.
• Hepatic function: check liver enzymes before initiation and periodically during therapy.
• Pancreatic monitoring: assess serum amylase/lipase if abdominal symptoms develop.
• Drug interactions: avoid concomitant use with strong CYP3A4 inhibitors or inducers.
• Pregnancy and lactation: contraindicated; advise effective contraception for women of childbearing potential.
• Store at ambient temperature: keep below 25 °C, protect from moisture and light in the original container.

Nilotinib interacts with several medicines, requiring careful management to avoid reduced efficacy or increased toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may raise Nilotinib plasma levels, increasing toxicity risk.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may lower drug exposure, reducing therapeutic effect.
• Antacids containing aluminum or magnesium: can decrease absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors (e.g., omeprazole): may modestly reduce Nilotinib absorption; separate dosing by at least 2 hours.
• Statins metabolized by CYP3A4 (e.g., simvastatin, atorvastatin): increased risk of statin‑related muscle toxicity; consider dose adjustment.
• Anticoagulants (e.g., warfarin): monitor INR more frequently due to potential interaction.