Nilotinib Viatris (Nilotinib)

• Nilotinib is a tyrosine kinase inhibitor used in the management of chronic myeloid leukemia.
• Chronic phase CML: helps achieve cytogenetic and molecular responses, slowing disease progression and extending overall survival in patients with BCR‑ABL positive disease.
• Accelerated phase CML: provides disease control by inhibiting proliferative signaling, aiming to achieve hematologic remission and prevent transformation to blast phase.
• Blast phase CML: used as part of combination therapy to reduce leukemic blast counts and improve response rates in advanced disease.

• Nilotinib selectively inhibits the BCR‑ABL tyrosine kinase, as well as the related c‑KIT and platelet‑derived growth factor receptors (PDGFR). By binding to the ATP‑binding site of these enzymes, it blocks downstream signaling pathways that drive uncontrolled proliferation and survival of malignant hematopoietic cells, thereby inducing apoptosis and reducing tumor growth. The inhibition is sustained at therapeutic plasma concentrations, allowing continuous suppression of oncogenic signaling.

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

Common Side Effects

• Elevated liver enzymes: mild to moderate increases in ALT/AST.
• Nausea and vomiting: gastrointestinal discomfort.
• Diarrhea: loose stools, usually transient.
• Rash: mild skin eruptions.
• Fatigue: generalized tiredness.
• Peripheral edema: swelling of extremities.

Serious or Rare Side Effects

• Cardiac arrhythmias: QT interval prolongation that can lead to serious rhythm disturbances.
• Pancreatitis: inflammation of the pancreas, presenting with abdominal pain and elevated enzymes.
• Severe hepatic toxicity: marked elevation of liver enzymes or hepatitis.

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

• Cardiac monitoring: baseline and periodic ECGs to detect QT prolongation.
• Hepatic function: assess liver enzymes before initiation and during treatment.
• Pancreatic enzymes: monitor amylase and lipase levels regularly.
• Drug interactions: avoid concomitant use with strong CYP3A4 inhibitors.
• Pregnancy and lactation: contraindicated; discuss risks with women of childbearing potential.
• Store at ambient temperature: keep below 25 °C, in the original container, protected from moisture and light.

Nilotinib interacts with several medicines that can alter its plasma concentration or increase toxicity.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may raise Nilotinib levels and heighten cardiac risk.
• QT‑prolonging agents (e.g., amiodarone, fluoroquinolones): can exacerbate arrhythmia potential.
• Antacids containing aluminum or magnesium: reduce absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inducers (e.g., rifampin, carbamazepine): may lower efficacy by decreasing drug exposure.
• Warfarin: may require INR monitoring due to potential pharmacodynamic changes.
• Statins metabolized by CYP3A4 (e.g., simvastatin): consider dose adjustment to avoid increased toxicity.