Nilotinib

What is Nilotinib?

• Nilotinib (Tasigna) is a kinase inhibitor used to treat chronic myelogenous leukemia (CML) which has the Philadelphia chromosome.

Nilotinib

What are the uses of this medicine?

Nilotinib (Tasigna) used to treat:

• adults and children who have been newly diagnosed with a certain type of leukemia called Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

adults with chronic phase Ph+ CML or accelerated phase Ph+ CML who:

• are no longer benefiting from other treatments, including imatinib (Gleevec), or
• have taken other treatments, including imatinib (Gleevec), and cannot tolerate them.

children with chronic phase Ph+ CML or accelerated phase Ph+ CML who:

• are no longer benefiting from treatment with a tyrosine-kinase inhibitor medicine, or
• have taken a tyrosine-kinase inhibitor medicine and cannot tolerate it.

Limitations of use:

• It is not known if Tasigna is safe and effective in children younger than 1 year of age with newly diagnosed, resistant, or intolerant Ph+ CML in chronic phase.
• The long-term effects of treating children with Tasigna for a long period of time are not known.

How does this medicine work?

• Nilotinib (nye loe' ti nib) is a selective inhibitor of the abnormal tyrosine kinase receptor known as bcr-abl, formed by the reciprocal translocation between chromosome 9 and 22, which creates the Philadelphia chromosome that is associated with chronic myelogenous leukemia (CML).
• The bcr-abl tyrosine kinase receptor is constitutively expressed in leukemic cells and causes unregulated cell growth and proliferation.
• Nilotinib is a specific inhibitor of bcr-abl and structurally related to imatinib.
• Like imatinib, nilotinib also blocks the tyrosine kinase activity of the abnormal tyrosine kinase (cKit) that is found in gastrointestinal stromal tumors (GIST) and platelet derived growth factor (PDGF), which is commonly mutated in renal cell carcinoma.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• hypokalemia,or low levels of potassium or magnesium in your blood
• hypomagnesemia, or long QT syndrome

What drug interactions can this medicine cause?

• Avoid concomitant use of strong CYP3A inhibitors with Tasigna. If patients must be coadministered a strong CYP3A4 inhibitor, reduce Tasigna dose.
• Avoid concomitant use of strong CYP3A inducers with Tasigna.
• Avoid concomitant use of PPI with Tasigna.
• Avoid coadministration of Tasigna with agents that may prolong the QT interval, such as anti-arrhythmic drugs.

Is this medicine FDA approved?

• Nilotinib received approval for use in the United States in 2007 for treatment of Philadelphia chromosome-positive CML resistant to or intolerant of prior treatment that included imatinib.
• Indications were subsequently expanded to include newly diagnosed cases of CML in the chronic phase.

How should this medicine be used?

Recommended dosage: Recommended Adult Dose:

• Newly diagnosed Ph+ CML-CP: 300 mg orally twice daily.
• Resistant or intolerant Ph+ CML-CP and CML-AP: 400 mg orally twice daily.

Recommended Pediatric Dose:

• Newly Diagnosed Ph+ CML-CP or Ph+ CML-CP and CML-AP resistant or intolerant to prior TKI therapy: 230 mg/m2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg).

• Eligible newly diagnosed adult patients with Ph+ CML-CP who have received Tasigna for a minimum of 3 years and have achieved a sustained molecular response (MR4.5) and patients with Ph+ CML-CP resistant or intolerant to imatinib who have received Tasigna for at least 3 years and have achieved a sustained molecular response (MR4.5) may be considered for treatment discontinuation.

Administration:

• Tasigna is a long-term treatment.
• Your healthcare provider will tell you how many Tasigna capsules to take and when to take them.
• If your child takes Tasigna, your healthcare provider will change the dose as your child grows.
• Tasigna must be taken on an empty stomach.
• Avoid eating food for at least 2 hours before the dose is taken, and
• Avoid eating food for at least 1 hour after the dose is taken.
• Swallow Tasigna capsules whole with water. If you cannot swallow Tasigna capsules whole, tell your healthcare provider.
• If you cannot swallow Tasigna capsules whole:
• Open the Tasigna capsules and sprinkle the contents in 1 teaspoon of applesauce (puréed apple).
• Do not use more than 1 teaspoon of applesauce.
• Only use applesauce. Do not sprinkle Tasigna onto other foods.
• Swallow the mixture right away (within 15 minutes).
• Do not drink grapefruit juice, eat grapefruit, or take supplements containing grapefruit extract at any time during treatment. See “What is the most important information I should know about Tasigna?”
• If you miss a dose, just take your next dose at your regular time. Do not take 2 doses at the same time to make up for a missed dose.
• If you take too much Tasigna, call your healthcare provider or go to the nearest hospital emergency room right away. Symptoms may include vomiting and drowsiness.
• During treatment with Tasigna your healthcare provider will do tests to check for side effects and to see how well Tasigna is working for you. The tests will check your:
• heart
• blood cells (white blood cells, red blood cells, and platelets). Your blood cells should be checked every 2 weeks for the first 2 months and then monthly.
• electrolytes (potassium, magnesium)
• pancreas and liver function
• bone marrow samples
• Your healthcare provider may change your dose. Your healthcare provider may have you stop Tasigna for some time or lower your dose if you have side effects with it.
• Your healthcare provider will monitor your CML during treatment with Tasigna to see if you are in a remission. After at least 3 years of treatment with Tasigna, your healthcare provider may do certain tests to determine if you continue to be in remission. Based on your test results, your healthcare provider may decide if you may be eligible to try stopping treatment with Tasigna. This is called Treatment Free Remission (TFR).
• Your healthcare provider will carefully monitor your CML during and after you stop taking Tasigna. Based on your test results, your healthcare provider may need to re-start your Tasigna if your CML is no longer in remission.
• It is important that you are followed by your healthcare provider and undergo frequent monitoring to find out if you need to re-start your Tasigna treatment because you are no longer in TFR. Follow your healthcare provider’s instructions about re-starting Tasigna if you are no longer in TFR.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 50 mg, 150 mg, and 200 mg

This medicine is available in fallowing brand namesː

• Tasigna

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• rash
• headache
• tiredness
• itching
• vomiting
• diarrhea
• cough
• constipation
• muscle and joint pain
• runny or stuffy nose, sneezing, sore throat
• fever
• night sweats

Tasigna may cause serious side effects, including:

• QTc prolongation
• Low blood cell counts
• Decreased blood flow to the leg, heart, or brain
• pancreatitis
• Liver problems

What special precautions should I follow?

• Treatment with Tasigna can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction.
• Tasigna has been shown to prolong cardiac ventricular repolarization as measured by the QT interval on the surface electrocardiogram (ECG) in a concentration-dependent manner.
• Sudden deaths have been reported in 0.3% of patients with CML treated with Tasigna.
• Cardiovascular events, including arterial vascular occlusive events, were reported. Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during Tasigna therapy.
• Tasigna can cause increases in serum lipase. Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis.
• Tasigna may result in hepatotoxicity as measured by elevations in bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Monitor hepatic function tests monthly or as clinically indicated.
• Tasigna can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating Tasigna and monitor periodically during therapy.
• Tumor lysis syndrome (TLS) cases have been reported in Tasigna treated patients with resistant or intolerant CML. Maintain adequate hydration and correct uric acid levels prior to initiating therapy with Tasigna.
• Serious hemorrhagic events, including fatal events, have occurred in patients with CML treated with Tasigna. Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed.
• Since the exposure of Tasigna is reduced in patients with total gastrectomy, perform more frequent monitoring of these patients.
• Since the capsules contain lactose, Tasigna is not recommended for patients with rare hereditary problems of galactose intolerance.
• Complete blood counts should be performed every 2 weeks for the first 2 months and then monthly thereafter.
• Growth retardation has been reported in pediatric patients treated with Tasigna. Monitor growth and development in pediatric patients.
• In the randomized trial in patients with newly diagnosed Ph+ CML in chronic phase, severe (Grade 3 or 4) fluid retention occurred.
• Based on findings from animal studies and its mechanism of action, Tasigna can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.
• Patients must have typical BCR-ABL transcripts. An FDA-authorized test with a detection limit below MR4.5 must be used to determine eligibility for discontinuation. Patients must be frequently monitored by the FDA authorized test to detect possible loss of remission.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• neutropenia
• vomiting
• drowsiness

Treatment of overdose:

• In the event of overdose, observe the patient and provide appropriate supportive treatment.

Can this medicine be used in pregnancy?

• Based on findings from animal studies and the mechanism of action, Tasigna can cause fetal harm when administered to a pregnant woman.
• There are no available data in pregnant women to inform the drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Tasigna have been established in pediatric patients greater than or equal to 1 year of age with newly diagnosed and resistant or intolerant Ph+ CML in chronic phase.
• The safety and effectiveness of Tasigna in pediatric patients below the age of 1 year with newly diagnosed, or resistant or intolerant Ph+ CML in chronic phase and accelerated phase, have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: nilotinib
• Inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate and poloxamer 188.

The capsules contain gelatin, iron oxide (red), iron oxide (yellow), iron oxide (black), and titanium dioxide.

Who manufactures and distributes this medicine?

Distributed by:

• Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store Tasigna at room temperature between 68°F to 77°F (20°C to 25°C).
• Safely throw away medicine that is out of date or no longer needed.

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• Dailymed label info on Nilotinib
• FDA Nilotinib

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