Nilotinib

Nilotinib is used in the treatment of chronic myeloid leukemia, a BCR‑ABL driven hematologic malignancy.

• Chronic phase CML: achieves deeper molecular response and prolongs remission.
• Accelerated phase CML: helps obtain cytogenetic response when other TKIs have failed.
• Philadelphia chromosome‑positive CML resistant to imatinib: provides an alternative targeted therapy.

• Nilotinib binds competitively to the ATP‑binding site of the BCR‑ABL tyrosine kinase, inhibiting its activity. By blocking this constitutively active kinase, the drug prevents downstream signaling that drives proliferation and survival of leukemic cells. It also inhibits related kinases such as KIT and PDGFR, contributing to its antineoplastic effect in chronic myeloid leukemia.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Diarrhea: watery stools, usually transient.
• Rash: erythematous skin eruptions.
• Fatigue: generalized tiredness.
• Headache: mild to moderate intensity.
• Arthralgia: joint pain without swelling.

Serious or Rare Side Effects

• QT interval prolongation: may predispose to cardiac arrhythmias.
• Pancreatitis: abdominal pain with elevated enzymes.
• Severe hepatic injury: marked elevation of transaminases.
• Severe neutropenia: increased infection risk.
• Thrombocytopenia: bleeding tendency.
• Stevens‑Johnson syndrome: severe skin and mucosal reactions.

Before initiating therapy, clinicians should assess baseline cardiac, hepatic and hematologic status.

• Cardiac monitoring: obtain baseline ECG and monitor QT interval during treatment.
• Hematologic monitoring: perform regular complete blood counts to detect neutropenia or thrombocytopenia.
• Hepatic monitoring: check liver function tests periodically.
• Drug hypersensitivity: discontinue if severe rash or allergic reaction occurs.
• Pregnancy and lactation: avoid use unless benefits outweigh potential risks.
• Store at room temperature: keep in the original packaging, protect from moisture and direct sunlight.

Nilotinib may interact with several concomitant medications, altering its plasma concentration or cardiac safety.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): increase nilotinib exposure and risk of QT prolongation.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): reduce nilotinib levels, compromising efficacy.
• Antacids that raise gastric pH: decrease nilotinib absorption.
• Other QT‑prolonging agents (e.g., amiodarone, fluoroquinolones): additive risk of arrhythmia.

Moderate Interactions (Monitor Closely)

• St. John’s wort: moderate CYP3A4 induction may lower nilotinib concentrations.
• Warfarin: nilotinib can affect INR; monitor coagulation parameters.
• Digoxin: potential increase in serum levels; assess renal function and drug levels.