Nilotinib

Approved Uses

Nilotinib is primarily used to treat adults and children aged 1 year and older with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This condition is a type of cancer where the bone marrow produces too many white blood cells.

Specific situations where nilotinib may be prescribed include:

• Newly diagnosed chronic phase: For patients who have recently been diagnosed with Ph+ CML in the chronic phase.
• Resistant or intolerant cases: For adults with Ph+ CML in the chronic or accelerated phase who have not responded to or could not tolerate previous treatments, such as imatinib.
• Pediatric use: For children 1 year of age and older with Ph+ CML in the chronic phase, whether they are newly diagnosed or have shown resistance or intolerance to other tyrosine kinase inhibitor therapies.

Nilotinib belongs to a class of drugs known as kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which helps slow or stop the spread of leukemia cells.

Targeting Cancer Cells

Nilotinib is a type of targeted therapy known as a kinase inhibitor. It works by interfering with the signals that tell cancer cells to grow and divide. Specifically, it targets a protein called BCR-ABL.

This protein is created by the Philadelphia chromosome, which is an abnormal gene found in the leukemia cells of people with certain types of chronic myeloid leukemia (CML). The BCR-ABL protein acts as a signal that causes the bone marrow to produce too many abnormal white blood cells.

When nilotinib enters the body, it blocks the BCR-ABL protein from sending these signals. By blocking this protein, the medication helps to:

• Stop the uncontrolled growth of leukemia cells.
• Reduce the number of abnormal white blood cells in the bloodstream.
• Slow the progression of the cancer.

Because nilotinib is a targeted therapy, it is designed to focus on the specific proteins that allow cancer cells to thrive, rather than affecting all rapidly dividing cells in the body.

Common Side Effects

• Nausea and vomiting
• Diarrhea or constipation
• Stomach pain
• Headache
• Fatigue or weakness
• Muscle, bone, or joint pain
• Itching or rash
• Hair loss
• Night sweats
• Symptoms of a cold, such as a runny nose, sneezing, or cough

Serious Side Effects

Contact a healthcare provider immediately if you notice any of the following:

• Signs of low blood cell counts, such as fever, chills, sore throat, or unusual bleeding and bruising
• Heart rhythm changes, including a fast, pounding, or irregular heartbeat, dizziness, or fainting
• Liver problems, such as yellowing of the skin or eyes, dark urine, or pain in the upper right stomach area
• Inflammation of the pancreas, characterized by severe upper stomach pain that may spread to the back
• Fluid retention, causing swelling in the hands, ankles, or feet, or shortness of breath
• Signs of decreased blood flow, such as leg pain, coldness, or numbness in the arms or legs
• High blood sugar, which may cause increased thirst or frequent urination

Boxed Warning: QT Prolongation

Nilotinib can cause a life-threatening heart rhythm problem called QT prolongation, which may lead to sudden death. This risk is significantly increased if the medication is taken with food or certain other drugs that affect heart rhythm. It should not be used by individuals with low blood levels of potassium or magnesium, or those with a history of long QT syndrome.

Cardiovascular Risks

Serious and sometimes fatal cardiovascular problems have been reported, including narrowing or blockage of the arteries in the limbs, heart, or brain. These events can occur even in people without a prior history of heart disease. Immediate medical attention is needed for symptoms such as chest pain, shortness of breath, numbness, weakness, or changes in speech.

Blood and Organ Function

• Myelosuppression: Treatment may cause severe decreases in white blood cells, red blood cells, and platelets. Regular blood tests are required to monitor for infection, anemia, or bleeding risks.
• Pancreatitis: Nilotinib can cause inflammation of the pancreas. Patients are monitored for elevated lipase levels and symptoms like severe abdominal pain, nausea, and vomiting.
• Liver Toxicity: This medication may cause liver damage or elevated bilirubin levels. Liver function tests are typically performed before starting the drug and monthly during treatment.
• Electrolyte Imbalances: Low levels of phosphorus, potassium, calcium, or sodium may occur. These imbalances must be corrected before starting therapy and monitored throughout treatment.

Other Precautions

Nilotinib can cause significant fluid retention, resulting in swelling or fluid accumulation around the lungs and heart. It may also cause tumor lysis syndrome, a condition where rapidly dying cancer cells release their contents into the bloodstream, potentially causing kidney failure. Hemorrhage, including bleeding in the brain or gastrointestinal tract, has also been reported.

Because nilotinib can harm a developing fetus, effective contraception is recommended during treatment and for a period after the final dose. Breastfeeding is not advised during treatment and for at least two weeks after the last dose. The medication must be taken on an empty stomach, as food increases the concentration of the drug in the body and raises the risk of dangerous side effects.

Pregnancy

Nilotinib can cause fetal harm when administered to a pregnant woman. Healthcare providers typically require a pregnancy test before starting treatment to ensure the patient is not pregnant. If you are pregnant or planning to become pregnant, it is important to discuss the potential risks to the fetus with your medical team.

Contraception

Individuals who are able to become pregnant should use effective birth control during treatment with nilotinib. This contraception should be continued for at least 14 days after the final dose of the medication.

Breastfeeding

It is not known whether nilotinib passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 14 days after the last dose.

Available Forms

Nilotinib is provided in the following oral dosage forms:

• Capsules
• Tablets

The different formulations of this medication may have different instructions regarding administration and food intake. It is important to follow the specific directions provided for the prescribed form, as some versions are taken on an empty stomach while others may have different requirements.

FDA Approval Status

Nilotinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic phase. Its approved uses include:

• Newly diagnosed adults with Ph+ CML-CP.
• Adults with Ph+ CML-CP who are resistant or intolerant to prior therapies, including imatinib.
• Pediatric patients aged 1 year and older with newly diagnosed Ph+ CML-CP or those who are resistant or intolerant to prior tyrosine kinase inhibitor therapy.

Boxed Warning

The FDA has issued a boxed warning for nilotinib due to the risk of QT interval prolongation, a heart rhythm abnormality that can lead to sudden death. Regulatory requirements for safe use include:

• ECG Monitoring: Healthcare providers must perform an electrocardiogram (ECG) to monitor heart rhythm before starting treatment, seven days after starting, and periodically thereafter.
• Electrolyte Correction: Patients must have normal blood levels of potassium and magnesium before starting nilotinib. These levels must be monitored and maintained during treatment.
• Drug and Food Interactions: Nilotinib should not be taken with strong CYP3A4 inhibitors or certain foods, such as grapefruit products, which can increase drug levels and the risk of heart rhythm issues.
• Dosing Requirements: To avoid dangerous increases in drug absorption, nilotinib must be taken on an empty stomach. Patients should not eat for at least two hours before and one hour after taking a dose.

Safety Communications

The FDA warns that nilotinib should not be used in patients with long QT syndrome or those with uncorrected low blood potassium or magnesium. Because of the potential for severe cardiovascular events, including arterial blockage, the FDA requires ongoing monitoring for signs of vascular issues and regular blood tests to check liver function and blood cell counts.

FDA-Approved Indications

The U.S. Food and Drug Administration (FDA) has approved nilotinib for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the following populations:

• Adults: For newly diagnosed chronic phase Ph+ CML, as well as chronic and accelerated phase Ph+ CML in patients who are resistant or intolerant to prior therapies.
• Pediatric Patients: For children 1 year of age and older with newly diagnosed chronic phase Ph+ CML or those with chronic phase Ph+ CML who are resistant or intolerant to prior tyrosine kinase inhibitor therapy.

Boxed Warning

The FDA has issued a boxed warning for nilotinib due to the risk of QT prolongation, a serious heart rhythm condition that can lead to sudden death. The FDA advises that the medication should not be used in patients with certain electrolyte imbalances, such as low blood levels of potassium or magnesium, or in those with long QT syndrome.

Regulatory History

Nilotinib received its initial FDA approval in 2007. In 2018, the FDA expanded the approval to include pediatric patients. In 2024, a new formulation of nilotinib was approved that provides different bioavailability, allowing for administration with or without food compared to the original formulation which requires fasting.