Nilotinib

Nilotinib is a targeted therapy that acts on the BCR‑ABL tyrosine‑kinase pathway in chronic myeloid leukemia.

• Chronic phase CML: reduces leukemic cell proliferation and achieves hematologic and cytogenetic responses.
• Accelerated phase CML: helps attain disease control when resistance to prior TKIs occurs.
• Blast phase CML: used in combination regimens to improve response rates in advanced disease.

• Nilotinib selectively inhibits the BCR‑ABL tyrosine kinase by binding to its ATP‑binding site, preventing downstream signaling that drives proliferation and survival of leukemic cells. This blockade leads to apoptosis of abnormal progenitors while sparing most normal hematopoietic cells.

Common side effects are generally mild to moderate and reflect the drug’s impact on gastrointestinal and metabolic systems.

Common Side Effects

• Nausea: mild to moderate stomach upset.
• Diarrhea: loose stools, often transient.
• Rash: skin erythema or pruritus.
• Headache: mild tension‑type pain.
• Fatigue: reduced energy levels.
• Myalgia: muscle aches.

Serious or Rare Side Effects

• QT interval prolongation: may predispose to cardiac arrhythmias.
• Pancreatitis: inflammation of the pancreas with abdominal pain.
• Hepatic toxicity: elevated liver enzymes or hepatitis.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Tumor lysis syndrome: rapid cell breakdown causing metabolic disturbances.
• Severe neutropenia: markedly low white‑blood‑cell count increasing infection risk.

Nilotinib requires careful monitoring and patient education to minimise risks.

• Cardiac monitoring: assess baseline ECG and monitor QT interval during therapy.
• Liver function: check hepatic enzymes before initiation and periodically thereafter.
• Blood glucose: monitor fasting glucose as hyperglycaemia may occur.
• Drug interactions: avoid concomitant strong CYP3A4 inhibitors or inducers.
• Dose adjustments: consider reduced dosing in patients with hepatic impairment.
• Store at room temperature: keep in the original container, protect from moisture and light.

Nilotinib interacts with several drug classes that can alter its plasma concentration or cardiac safety.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may raise nilotinib levels and increase toxicity.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): can lower exposure and reduce efficacy.
• QT‑prolonging agents (e.g., amiodarone, sotalol): additive risk of arrhythmia.
• Antacids that raise gastric pH (e.g., aluminum‑magnesium hydroxide): may reduce absorption.
• St John’s wort: potent CYP3A4 induction leading to sub‑therapeutic levels.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole): may modestly increase exposure.
• Warfarin: potential alteration of anticoagulant effect, requiring INR monitoring.
• Diuretics (e.g., furosemide): may exacerbate electrolyte disturbances that affect QT interval.
• Other tyrosine‑kinase inhibitors: overlapping toxicity profiles warrant close observation.