Nilotinib Viatris (Nilotinib)

• Nilotinib is a targeted therapy that inhibits the BCR‑ABL tyrosine kinase pathway in chronic myeloid leukemia.
• Chronic myeloid leukemia (chronic phase): achieves cytogenetic and molecular remission by suppressing BCR‑ABL activity.
• Chronic myeloid leukemia (accelerated phase): reduces disease progression and improves survival when used as first‑line or second‑line therapy.
• Chronic myeloid leukemia after imatinib resistance: provides an alternative kinase inhibition strategy to overcome resistance.

• Nilotinib binds competitively to the ATP‑binding site of the BCR‑ABL fusion protein, stabilizing the inactive conformation of the kinase. By preventing ATP access, it blocks phosphorylation of downstream substrates, halting the proliferative signaling cascade that drives leukemic cell growth. This selective inhibition results in reduced clonal expansion of malignant progenitors while sparing most normal hematopoietic cells.

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

Common Side Effects

• Nausea: mild to moderate stomach upset.
• Diarrhea: loose stools, often transient.
• Headache: mild headache.
• Fatigue: general tiredness.
• Rash: skin erythema or itching.
• Elevated lipase: increase in pancreatic enzymes without symptoms.

Serious or Rare Side Effects

• QT interval prolongation: can lead to serious cardiac arrhythmias.
• Pancreatitis: inflammation of the pancreas, may be severe.
• Hepatotoxicity: significant liver enzyme elevation or liver injury.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Myelosuppression: marked decrease in blood cell counts.
• Arterial occlusive events: peripheral arterial disease or ischemia.

When prescribing nilotinib, clinicians should consider several safety precautions to minimize risk.

• Cardiac monitoring: assess baseline ECG and monitor QT interval during therapy.
• Electrolyte balance: correct hypokalemia, hypomagnesemia, and hypocalcemia before and during treatment.
• Liver function: evaluate hepatic enzymes regularly and adjust dose if significant elevation occurs.
• Pancreatic enzymes: monitor serum lipase and amylase for signs of pancreatitis.
• Drug interactions: avoid concomitant use with strong CYP3A4 inhibitors or inducers without dose adjustment.
• Store at ambient temperature: keep below 25 °C, retain in original packaging, protect from moisture.

Nilotinib interacts with several medicines through metabolic pathways and cardiac effects.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may markedly increase nilotinib plasma levels.
• QT‑prolonging agents (e.g., amiodarone, sotalol): additive risk of serious arrhythmias.
• Antacids containing aluminum or magnesium: reduce nilotinib absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• CYP3A4 inducers (e.g., rifampin, carbamazepine): may reduce drug exposure, requiring dose adjustment.
• Warfarin: may enhance anticoagulant effect, monitor INR closely.
• Statins metabolized by CYP3A4 (e.g., simvastatin): increased risk of myopathy, consider alternative lipid‑lowering agents.