Tasigna

Name: Tasigna

What Is Nilotinib?

Nilotinib is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Nilotinib is used to treat a type of blood cancer called Philadelphia chromosome positive chronic myeloid leukemia (CML).

Nilotinib is usually given after other medications have been tried without success.

Nilotinib may also be used for purposes not listed in this medication guide.

You should not use nilotinib if you have low blood levels of potassium or magnesium, or a heart rhythm disorder called Long QT syndrome.

Before and during your treatment with nilotinib, your heart function may be checked with an electrocardiograph or ECG (sometimes called an EKG), and you may need frequent blood tests.

Some medicines can cause unwanted or dangerous effects when used with nilotinib. Your doctor may need to change your treatment plan if you use any of the following drugs: chloroquine, methadone, nefazodone, an antibiotic--clarithromycin, moxifloxacin, telithromycin; antifungal medication--itraconazole, ketoconazole, voriconazole; heart rhythm medicine--amiodarone, disopyramide, dronedarone, procainamide, quinidine, sotalol; HIV or AIDS medicine--atazanavir, indinavir, nelfinavir, ritonavir, saquinavir; or medicine to treat a psychiatric disorder--haloperidol, pimozide, thioridazine, ziprasidone.

Take nilotinib on an empty stomach. Avoid eating anything for at least 2 hours before and 1 hour after you take nilotinib.

You should not use nilotinib if you are allergic to it, or if you have:

  • low blood levels of potassium or magnesium; or
  • a heart rhythm disorder called long QT syndrome.

Some medicines can cause unwanted or dangerous effects when used with nilotinib. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • chloroquine, methadone, nefazodone; or
  • an antibiotic--clarithromycin, moxifloxacin, telithromycin; antifungal medication--itraconazole, ketoconazole, voriconazole; heart rhythm medicine--amiodarone, disopyramide, dronedarone, procainamide, quinidine, sotalol; HIV or AIDS medicine--atazanavir, indinavir, nelfinavir, ritonavir, saquinavir; or medicine to treat a psychiatric disorder--haloperidol, pimozide, thioridazine, ziprasidone.

To make sure nilotinib is safe for you, tell your doctor if you have any of these conditions:

  • heart disease, heart rhythm problems;
  • a personal or family history of Long QT syndrome;
  • liver disease;
  • a history of pancreatitis; or
  • if your stomach has been surgically removed (total gastrectomy).

Nilotinib capsules may contain lactose. Talk to your doctor before using this medication if you have galactose intolerance, or severe problems with lactose (milk sugar).

Do not use nilotinib if you are pregnant. It could harm the unborn baby. Use effective birth control to avoid pregnancy, and tell your doctor if you become pregnant during treatment.

It is not known whether nilotinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking nilotinib.

Nilotinib Dosage

Nilotinib is usually taken every 12 hours. Follow the directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with a full glass of water. Swallow the nilotinib capsule whole.

Take nilotinib on an empty stomach, at least 1 hour before or 2 hours after a meal. Do not take with food. Food can increase your blood levels of nilotinib and may increase your risk of harmful side effects.

To make swallowing easier, you may open the nilotinib capsule and sprinkle the medicine into no more than 1 teaspoon of applesauce. Swallow right away without chewing. Do not save the mixture for later use.

Avoid eating anything for at least 2 hours before and 1 hour after you take nilotinib.

Nilotinib is to be taken long-term. You should not stop using nilotinib suddenly. Stopping suddenly may make your condition worse.

Nilotinib can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Your heart function may be checked with an electrocardiograph or ECG (sometimes called an EKG).

Store at room temperature away from moisture and heat.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include drowsiness and vomiting.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Side Effects of Tasigna

Tasigna may cause serious side effects including: See the “Tasigna Drug Precautions” section.

The most common side effects of Tasigna include:

  • low blood count 
  • rash
  • nausea 
  • fever
  • headache
  • itching
  • tiredness
  • stomach (abdominal) pain
  • diarrhea
  • constipation
  • muscle and joint pain
  • back pain
  • muscle spasms
  • weakness
  • hair loss
  • runny or stuffy nose, sneezing, sore throat
  • cough

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all of the possible side effects of Tasigna. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Uses for Tasigna

Chronic Myelogenous Leukemia (CML)

Treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) CML in adults who are in chronic phase of the disease.1 16 Efficacy based on molecular and cytogenetic response rates at 12 months; additional data needed to establish long-term efficacy.1 16

Treatment of Ph+ CML in adults who are in chronic or accelerated phase of the disease, after failure (secondary to resistance or intolerance) of prior therapy that included imatinib.1 4 20 Efficacy based on hematologic and cytogenetic response rates.1

Designated an orphan drug by FDA for use in the treatment of CML.2

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Actions

  • Inhibits Bcr-Abl tyrosine kinase, an abnormal protein created by the Philadelphia chromosome abnormality in CML.1 3 8

  • Competitively inhibits the ATP-binding site of Bcr-Abl tyrosine kinase, leading to inhibition of tyrosine phosphorylation of proteins involved in the intracellular signal transduction that Bcr-Abl mediates.4 5

  • Binds to and stabilizes the inactive conformation of the Abl kinase; inhibits proliferation of murine leukemic cells as well as human cell lines derived from Ph+ CML patients.1

  • Overcomes imatinib resistance resulting from Bcr-Abl kinase domain mutations in vitro.1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nilotinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

150 mg

Tasigna

Novartis

200 mg

Tasigna

Novartis

Tasigna Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Abdominal or stomach pain or tenderness
  • black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • blurred vision
  • bone pain
  • clay colored stools
  • confusion
  • convulsions
  • cough or hoarseness
  • dark urine
  • decreased appetite
  • difficult or labored breathing
  • dry mouth
  • fainting
  • fever or chills
  • flushed, dry skin
  • fruit-like breath odor
  • headache
  • increased hunger
  • increased thirst
  • increased urination
  • irregular heartbeat, recurrent
  • loss of appetite
  • lower back or side pain
  • muscle aches, cramps, or pain
  • nausea and vomiting
  • no blood pressure
  • no breathing
  • no pulse
  • numbness, tingling, pain, or weakness in the hands or feet
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • seizures
  • skin rash or itching
  • sore throat
  • stuffy or runny nose
  • sweating
  • swelling of the hands, ankles, feet, or lower legs
  • tightness in the chest
  • trembling
  • troubled breathing with exertion
  • ulcers, sores, or white spots in the mouth
  • unexplained weight loss
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • weakness and heaviness of the legs
  • yellow eyes or skin
Less common
  • Coma
  • decreased urine output
  • dizziness
  • fast heartbeat
  • muscle cramps in the hands, arms, feet, legs, or face
  • nervousness
  • numbness and tingling around the mouth, fingertips, or lips
  • rapid weight gain
  • tremor
Less common or rare
  • Bladder pain
  • bloody or cloudy urine
  • body aches or pain
  • constipation
  • cough producing mucus
  • depressed mood
  • difficult, burning, or painful urination
  • dry skin and hair
  • ear congestion
  • feeling cold
  • frequent urge to urinate
  • hair loss
  • loss of voice
  • muscle stiffness
  • pain or tenderness around the eyes and cheekbones
  • sensitivity to heat
  • slowed heartbeat
  • sneezing
  • swelling or puffiness of the face
  • tender, swollen glands in the neck
  • trouble sleeping
  • trouble swallowing
  • weight changes
  • white patches in the mouth or throat or on the tongue
  • white patches with diaper rash
Incidence not known
  • Pain or swelling of the treated skin
  • rapid, shallow breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Back pain
  • burning, itching, and pain in hairy areas
  • diarrhea
  • difficulty with moving
  • lack or loss of strength
  • muscle spasms
  • pain in the arms or legs
  • pain in the joints
  • pus at the root of the hair
  • swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dosage forms and strengths

150 mg red opaque hard gelatin capsules with black axial imprint “NVR/BCR.”

200 mg light-yellow opaque hard gelatin capsules with a red axial imprint “NVR/TKI.”

Contraindications

Tasigna is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Boxed Warning].

Adverse reactions

The following serious adverse reactions can occur with Tasigna and are discussed in greater detail in other sections of the package insert [see Boxed Warning, Warnings and Precautions (5)].

  • Myelosuppression [see Warnings and Precautions (5.1)]
  • QT Prolongation [see Boxed Warning, Warnings and Precautions (5.2)]
  • Sudden Deaths [see Boxed Warning, Warnings and Precautions (5.3)]
  • Cardiac and Arterial Vascular Occlusive Events [see Warnings and Precautions (5.4)]
  • Pancreatitis and Elevated Serum Lipase [see Warnings and Precautions (5.5)]
  • Hepatotoxicity [see Warnings and Precautions (5.6)]
  • Electrolyte Abnormalities [see Boxed Warning, Warnings and Precautions (5.7)]
  • Hemorrhage [see Warnings and Precautions (5.12)]
  • Fluid Retention [see Warnings and Precautions (5.17)]

      Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In Patients with Newly Diagnosed Ph+ CML-CP

The data below reflect exposure to Tasigna from a randomized trial in patients with newly diagnosed Ph+ CML in chronic phase treated at the recommended dose of 300 mg twice daily (n=279). The median time on treatment in the nilotinib 300 mg twice daily group was 61 months (range 0.1 to 71 months). The median actual dose intensity was 593 mg/day in the nilotinib 300 mg twice daily group.

The most common (greater than 10%) non-hematologic adverse drug reactions were rash, pruritus, headache, nausea, fatigue, alopecia, myalgia, and upper abdominal pain. Constipation, diarrhea, dry skin, muscle spasms, arthralgia, abdominal pain, peripheral edema, vomiting, and asthenia were observed less commonly (less than or equal to 10% and greater than 5%) and have been of mild-to-moderate severity, manageable and generally did not require dose reduction.

Increase in QTcF greater than 60 msec from baseline was observed in 1 patient (0.4%) in the 300 mg twice daily treatment group. No patient had an absolute QTcF of greater than 500 msec while on study drug.

The most common hematologic adverse drug reactions (all grades) were myelosuppression including: thrombocytopenia (18%), neutropenia (15%) and anemia (8%). See Table 7 for Grade 3/4 laboratory abnormalities.

Discontinuation due to adverse reactions, regardless of relationship to study drug, was observed in 10% of patients.

In Patients with Resistant or Intolerant Ph+ CML-CP and CML-AP

In the single open-label multicenter clinical trial, a total of 458 patients with Ph+ CML-CP and CML-AP resistant to or intolerant to at least one prior therapy including imatinib were treated (CML-CP=321; CML-AP=137) at the recommended dose of 400 mg twice daily.

The median duration of exposure in days for CML-CP and CML-AP patients is 561 (range 1 to 1096) and 264 (range 2 to 1160), respectively. The median dose intensity for patients with CML-CP and CML-AP is 789 mg/day (range 151 to 1110) and 780 mg/day (range 150 to 1149), respectively and corresponded to the planned 400 mg twice daily dosing.

The median cumulative duration in days of dose interruptions for the CML-CP patients was 20 (range 1 to 345), and the median duration in days of dose interruptions for the CML-AP patients was 23 (range 1 to 234).

In patients with CML-CP, the most commonly reported non-hematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus, nausea, fatigue, headache, constipation, diarrhea, vomiting and myalgia. The common serious drug-related adverse reactions (greater than or equal to 1% and less than 10%) were thrombocytopenia, neutropenia and anemia.

In patients with CML-AP, the most commonly reported non-hematologic adverse drug reactions (greater than or equal to 10%) were rash, pruritus and fatigue. The common serious adverse drug reactions (greater than or equal to 1% and less than 10%) were thrombocytopenia, neutropenia, febrile neutropenia, pneumonia, leukopenia, intracranial hemorrhage, elevated lipase and pyrexia.

Sudden deaths and QT prolongation were reported. The maximum mean QTcF change from baseline at steady-state was 10 msec. Increase in QTcF greater than 60 msec from baseline was observed in 4.1% of the patients and QTcF of greater than 500 msec was observed in 4 patients (less than 1%) [see Boxed Warning, Warnings and Precautions (5.2, 5.3), Clinical Pharmacology (12.6)].

Discontinuation due to adverse drug reactions was observed in 16% of CML-CP and 10% of CML-AP patients.

Most Frequently Reported Adverse Reactions

Tables 5 and 6 show the percentage of patients experiencing non-hematologic adverse reactions (excluding laboratory abnormalities) regardless of relationship to study drug. Adverse reactions reported in greater than 10% of patients who received at least 1 dose of Tasigna are listed.

Table 5: Most Frequently Reported Non-hematologic Adverse Reactions (Regardless of Relationship to Study Drug) in Patients with Newly Diagnosed Ph+ CML-CP (Greater than or equal to 10% in Tasigna 300 mg Twice Daily or Imatinib 400 mg Once Daily Groups) 60-Month Analysisa
Patients with Newly Diagnosed Ph+ CML-CP
Tasigna
300 mg
twice daily
Imatinib
400 mg
once daily
Tasigna
300 mg
twice daily
Imatinib
400 mg
once daily
N=279 N=280 N=279 N=280
Body System and Preferred Term All Grades (%) CTC Gradesb 3/4 (%)
Skin and subcutaneous tissue disorders Rash 38 19 <1 2
Pruritus 21 7 <1 0
Alopecia 13 7 0 0
Dry skin 12 6 0 0
Gastrointestinal disorders Nausea 22 41 2 2
Constipation 20 8 <1 0
Diarrhea 19 46 1 4
Vomiting 15 27 <1 <1
Abdominal pain upper 18 14 1 <1
Abdominal pain 15 12 2 0
Dyspepsia 10 12 0 0
Nervous system disorders Headache 32 23 3 <1
Dizziness 12 11 <1 <1
General disorders and administration site conditions Fatigue 23 20 1 1
Pyrexia 14 13 <1 0
Asthenia 14 12 <1 0
Peripheral edema 9 20 <1 0
Face edema <1 14 0 <1
Musculoskeletal and connective tissue disorders Myalgia 19 19 <1 <1
Arthralgia 22 17 <1 <1
Muscle spasms 12 34 0 1
Pain in extremity 15 16 <1 <1
Back pain 19 17 1 1
Respiratory, thoracic and mediastinal disorders Cough 17 13 0 0
Oropharyngeal pain 12 6 0 0
Dyspnea 11 6 2 <1
Infections and infestations Nasopharyngitis                   27 21 0 0
Upper respiratory tract infection 17 14 <1 0
Influenza 13 9 0 0
Gastroenteritis 7 10 0 <1
Eye disorders Eyelid edema 1 19 0 <1
Periorbital edema <1 15 0 0
Psychiatric disorders Insomnia 11 9 0 0
Vascular disorder Hypertension 10 4 1 <1

aExcluding laboratory abnormalities
bNCI Common Terminology Criteria for Adverse Events, Version 3.0

Table 6: Most Frequently Reported Non-hematologic Adverse Reactions in Patients with Resistant or Intolerant Ph+ CML Receiving Tasigna 400 mg Twice Daily (Regardless of Relationship to Study Drug) (Greater than or equal to 10% in any Group) 24-Month Analysisa
Body System and Preferred Term CML-CP CML-AP
N=321 N=137
All Grades (%) CTC Gradesb 3/4 (%) All Grades (%) CTC Gradesb 3/4 (%)
Skin and subcutaneous tissue disorders Rash 36 2 29 0
Pruritus 32 <1 20 0
Night sweat 12 <1 27 0
Alopecia 11 0 12 0
Gastrointestinal disorders Nausea 37 1 22 <1
Constipation 26 <1 19 0
Diarrhea 28 3 24 2
Vomiting 29 <1 13 0
Abdominal pain 15 2 16 3
Abdominal pain upper 14 <1 12 <1
Dyspepsia 10 <1 4 0
Nervous system disorders Headache 35 2 20 1
General disorders and administration site conditions Fatigue 32 3 23 <1
Pyrexia 22 <1 28 2
Asthenia 16 0 14 1
Peripheral edema 15 <1 12 0
Musculoskeletal and connective tissue disorders Myalgia 19 2 16 <1
Arthralgia  26 2 16 0
Muscle spasms 13 <1 15 0
Bone pain 14 <1 15 2
Pain in extremity 20 2 18 1
Back pain 17 2 15 <1
Musculoskeletal pain 11 <1 12 1
Respiratory, thoracic and mediastinal disorders Cough 27 <1 18 0
Dyspnea 15 2 9 2
Oropharyngeal pain 11 0 7 0
Infections and infestations Nasopharyngitis 24 <1 15 0
Upper respiratory tract infection 12 0 10 0
Metabolism and nutrition disorders Decreased appetitec 15 <1 17 <1
Psychiatric disorders Insomnia 12 1 7 0
Vascular disorders Hypertension 10 2 11 <1

aExcluding laboratory abnormalities   bNCI Common Terminology Criteria for Adverse Events, Version 3.0 cAlso includes preferred term anorexia

Laboratory Abnormalities

Table 7 shows the percentage of patients experiencing treatment-emergent Grade 3/4 laboratory abnormalities in patients who received at least one dose of Tasigna.

Table 7: Percent Incidence of Clinically Relevant Grade 3/4* Laboratory Abnormalities
Patient Population
Newly Diagnosed Ph+ CML-CP Resistant or Intolerant Ph+
CML-CP CML-AP
Tasigna 300 mg
twice daily
N=279
(%)
Imatinib 400 mg
once daily
N=280
(%)
Tasigna 400 mg
twice daily
N=321
(%)
Tasigna 400 mg
twice daily
N=137
(%)
Hematologic Parameters
Thrombocytopenia 10 9 301 423
Neutropenia 12 22 312 424
Anemia 4 6 11 27
Biochemistry Parameters
Elevated lipase 9 4 18 18
Hyperglycemia 7 <1 12 6
Hypophosphatemia 8 10 17 15
Elevated bilirubin (total) 4 <1 7 9
Elevated SGPT (ALT) 4 3 4 4
Hyperkalemia 2 1 6 4
Hyponatremia 1 <1 7 7
Hypokalemia <1 2 2 9
Elevated SGOT (AST) 1 1 3 2
Decreased albumin 0 <1 4 3
Hypocalcemia <1 <1 2 5
Elevated alkaline phosphatase 0 <1 <1 1
Elevated creatinine  0 <1 <1 <1

*NCI Common Terminology Criteria for Adverse Events, version 3.0

1CML-CP: Thrombocytopenia: 12% were Grade 3, 18% were Grade 4

2CML-CP: Neutropenia: 16% were Grade 3, 15% were Grade 4

3CML-AP: Thrombocytopenia: 11% were Grade 3, 32% were Grade 4

4CML-AP: Neutropenia: 16% were Grade 3, 26% were Grade 4

Elevated total cholesterol (all grades) occurred in 28% (Tasigna 300 mg bid) and 4% (imatinib). Elevated triglycerides (all grades) occurred in 12% and 8% of patients in the Tasigna and imatinib arms, respectively. Hyperglycemia (all grades) occurred in 50% and 31% of patients in the Tasigna and imatinib arms, respectively.

Most common biochemistry laboratory abnormalities (all grades) were alanine aminotransferase increased (72%), blood bilirubin increased (59%), aspartate aminotransferase increased (47%), lipase increased (28%), blood glucose increased (50%), blood cholesterol increased (28%), and blood triglyceride increased (12%).

Additional Data from Clinical Trials

The following adverse drug reactions were reported in patients in the Tasigna clinical studies at the recommended doses. These adverse drug reactions are ranked under a heading of frequency, the most frequent first using the following convention: common (greater than or equal to1% and less than 10%), uncommon (greater than or equal to 0.1% and less than 1%), and unknown frequency (single events). For laboratory abnormalities, very common events (greater than or equal to 10%), which were not included in Tables 5 and 6, are also reported. These adverse reactions are included based on clinical relevance and ranked in order of decreasing seriousness within each category, obtained from 2 clinical studies:

1. Newly diagnosed Ph+ CML-CP 60 month analysis and,

2. Resistant or intolerant Ph+ CML-CP and CMP-AP 24 months’ analysis.

Infections and Infestations: Common: folliculitis. Uncommon: pneumonia, bronchitis, urinary tract infection, candidiasis (including oral candidiasis). Unknown frequency: hepatitis B reactivation, sepsis, subcutaneous abscess, anal abscess, furuncle, tinea pedis.

Neoplasms Benign, Malignant, and Unspecified: Common: skin papilloma. Unknown frequency: oral papilloma, paraproteinemia.

Blood and Lymphatic System Disorders: Common: leukopenia, eosinophilia, febrile neutropenia, pancytopenia, lymphopenia. Unknown frequency: thrombocythemia, leukocytosis.

Immune System Disorders: Unknown frequency: hypersensitivity.

Endocrine Disorders: Uncommon: hyperthyroidism, hypothyroidism. Unknown frequency: hyperparathyroidism secondary, thyroiditis.

Metabolism and Nutrition Disorders: Very Common: hypophosphatemia. Common: electrolyte imbalance (including hypomagnesemia, hyperkalemia, hypokalemia, hyponatremia, hypocalcemia, hypercalcemia, hyperphosphatemia), diabetes mellitus, hyperglycemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia. Uncommon: gout, dehydration, increased appetite. Unknown frequency: hyperuricemia, hypoglycemia.

Psychiatric Disorders: Common: depression, anxiety. Unknown frequency: disorientation, confusional state, amnesia, dysphoria.

Nervous System Disorders: Common: peripheral neuropathy, hypoesthesia, paresthesia. Uncommon: intracranial hemorrhage, ischemic stroke, transient ischemic attack, cerebral infarction, migraine, loss of consciousness (including syncope), tremor, disturbance in attention, hyperesthesia. Unknown frequency: basilar artery stenosis, brain edema, optic neuritis, lethargy, dysesthesia, restless legs syndrome.

Eye Disorders: Common: eye hemorrhage, eye pruritus, conjunctivitis, dry eye (including xerophthalmia). Uncommon: vision impairment, vision blurred, visual acuity reduced, photopsia, hyperemia (scleral, conjunctival, ocular), eye irritation, conjunctival hemorrhage. Unknown frequency: papilloedema, diplopia, photophobia, eye swelling, blepharitis, eye pain, chorioretinopathy, conjunctivitis allergic, ocular surface disease.

Ear and Labyrinth Disorders: Common: vertigo. Unknown frequency: hearing impaired, ear pain, tinnitus.

Cardiac Disorders: Common: angina pectoris, arrhythmia (including atrioventricular block, cardiac flutter, extrasystoles, atrial fibrillation, tachycardia, bradycardia), palpitations, electrocardiogram QT prolonged. Uncommon: cardiac failure, myocardial infarction, coronary artery disease, cardiac murmur, coronary artery stenosis, myocardial ischemia, pericardial effusion, cyanosis. Unknown frequency: ventricular dysfunction, pericarditis, ejection fraction decrease.

Vascular Disorders: Common: flushing. Uncommon: hypertensive crisis, peripheral arterial occlusive disease, intermittent claudication, arterial stenosis limb, hematoma, arteriosclerosis. Unknown frequency: shock hemorrhagic, hypotension, thrombosis, peripheral artery stenosis.

Respiratory, Thoracic and Mediastinal Disorders: Common: dyspnea exertional, epistaxis, dysphonia. Uncommon: pulmonary edema, pleural effusion, interstitial lung disease, pleuritic pain, pleurisy, pharyngolaryngeal pain, throat irritation. Unknown frequency: pulmonary hypertension, wheezing.

Gastrointestinal Disorders: Common: pancreatitis, abdominal discomfort, abdominal distension, dysgeusia, flatulence. Uncommon: gastrointestinal hemorrhage, melena, mouth ulceration, gastroesophageal reflux, stomatitis, esophageal pain, dry mouth, gastritis, sensitivity of teeth. Unknown frequency: gastrointestinal ulcer perforation, retroperitoneal hemorrhage, hematemesis, gastric ulcer, esophagitis ulcerative, subileus, enterocolitis, hemorrhoids, hiatus hernia, rectal hemorrhage, gingivitis.

Hepatobiliary Disorders: Very Common: hyperbilirubinemia. Common: hepatic function abnormal. Uncommon: hepatotoxicity, toxic hepatitis, jaundice. Unknown frequency: cholestasis, hepatomegaly.

Skin and Subcutaneous Tissue Disorders: Common: eczema, urticaria, erythema, hyperhidrosis, contusion, acne, dermatitis (including allergic, exfoliative and acneiform). Uncommon: exfoliative rash, drug eruption, pain of skin, ecchymosis. Unknown frequency: psoriasis, erythema multiforme, erythema nodosum, skin ulcer, palmar-plantar erythrodysesthesia syndrome, petechiae, photosensitivity, blister, dermal cyst, sebaceous hyperplasia, skin atrophy, skin discoloration, skin exfoliation, skin hyperpigmentation, skin hypertrophy, hyperkeratosis.

Musculoskeletal and Connective Tissue Disorders: Common: bone pain, musculoskeletal chest pain, musculoskeletal pain, back pain, neck pain, flank pain, muscular weakness. Uncommon: musculoskeletal stiffness, joint swelling. Unknown frequency: arthritis.

Renal and Urinary Disorders: Common: pollakiuria. Uncommon: dysuria, micturition urgency, nocturia. Unknown frequency: renal failure, hematuria, urinary incontinence, chromaturia.

Reproductive System and Breast Disorders: Uncommon: breast pain, gynecomastia, erectile dysfunction. Unknown frequency: breast induration, menorrhagia, nipple swelling.

General Disorders and Administration Site Conditions: Common: pyrexia, chest pain (including non-cardiac chest pain), pain, chest discomfort, malaise. Uncommon: gravitational edema, influenza-like illness, chills, feeling body temperature change (including feeling hot, feeling cold). Unknown frequency: localized edema.

Investigations: Very Common: alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, lipoprotein cholesterol (including very low density and high density) increased, total cholesterol increased, blood triglycerides increased. Common: hemoglobin decreased, blood amylase increased, gamma-glutamyltransferase increased, blood creatinine phosphokinase increased, blood alkaline phosphatase increased, weight decreased, weight increased, globulins decreased. Uncommon: blood lactate dehydrogenase increased, blood urea increased. Unknown frequency: troponin increased, blood bilirubin unconjugated increased, insulin C-peptide decreased, blood parathyroid hormone increased.

Patient counseling information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

A Medication Guide is required for distribution with Tasigna. The complete text of the Medication Guide is reprinted at the end of this document.

Myelosuppression

Advise patients that treatment with Tasigna can cause serious thrombocytopenia, neutropenia, and anemia. Advise patients to seek immediate medical attention if symptoms suggestive of low blood counts occur, such as fever, chills or other signs of infection, unexplained bleeding or bruising, or unexplained weakness or shortness of breath [see Warnings and Precautions (5.1)].

QT Prolongation

Advise patients that Tasigna can cause possibly life-threatening, abnormal heart beat. Advise patients to seek immediate medical attention if symptoms of abnormal heart beat occur, such as feeling light-headed, faint or experiencing an irregular heartbeat [see Warnings and Precautions (5.2)].

Cardiac and Arterial Vascular Occlusive Events

Advise patients that cardiovascular events (including ischemic heart disease, peripheral arterial occlusive disease, and ischemic cerebrovascular events) have been reported. Advise patients to seek immediate medical attention if any symptoms suggestive of a cardiovascular event occur, such as chest or leg pain, numbness or weakness, or problems walking or speaking occur suddenly [see Warnings and Precautions (5.4)].

Pancreatitis and Elevated Serum Lipase

Advise patients that Tasigna can increase the risk of pancreatitis and that patients with a previous history of pancreatitis may be at greater risk. Advise patients to seek immediate medical attention if symptoms suggestive of pancreatitis occur, such as sudden stomach area pain with accompanying nausea and vomiting [see Warnings and Precautions (5.5)].

Taking Tasigna

Advise patients to take Tasigna doses twice daily approximately 12 hours apart. The capsules should be swallowed whole with water.

Advise patients to take Tasigna on an empty stomach. No food should be consumed for at least 2 hours before the dose is taken and for at least 1 hour after the dose is taken. Patients should not consume grapefruit products and other foods that are known to inhibit CYP3A4 at any time during Tasigna treatment [see Dosage and Administration (2.1), Warnings and Precautions (5.8, 5.9) and Medication Guide].

If the patient missed a dose of Tasigna, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time. 

Should patients be unable to swallow capsules, the contents of each capsule may be dispersed in one teaspoon of applesauce and the mixture swallowed immediately (within 15 minutes).

Tumor Lysis Syndrome

Advise patients that Tasigna can cause tumor lysis syndrome and to seek immediate medical attention if any symptoms suggestive of tumor lysis syndrome occur such as an abnormal heartbeat or less urine production [see Warnings and Precautions (5.11)].

Fluid Retention

Advise patients that Tasigna can cause fluid retention and to seek immediate medical attention if any symptoms suggestive of fluid retention such as shortness of breath, rapid weight gain, or swelling occur [see Warnings and Precautions (5.17)].

Drug Interactions

Advise patients that Tasigna and certain other medicines, including over the counter medications or herbal supplements (such as St. John’s Wort), can interact with each other [see Warnings and Precautions (5.8) and Drug Interactions (7)].

Pregnancy

Advise patients that the use of Tasigna during pregnancy may cause harm to the fetus and that Tasigna should not be taken during pregnancy unless necessary. Women of childbearing potential should use highly effective contraceptives while taking Tasigna. Sexually active female patients taking Tasigna should use adequate contraception [see Warnings and Precautions (5.16) and Use in Specific Populations (8.1)].

Nursing Mothers

It is not known whether nilotinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Tasigna, decide whether to advise discontinuing nursing or discontinuing the drug, taking into account the importance of the drug to the mother [see Use in Specific Populations (8.3)].

Compliance

Advise patients of the following:

  • Continue taking Tasigna every day for as long as their doctor tells them.
  • This is a long-term treatment.
  • Do not change dose or stop taking Tasigna without first consulting their doctor.
  • If a dose is missed, take the next dose as scheduled. Do not take a double dose to make up for the missed capsules.

T2017-24
February 2017

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: February 2017
Medication Guide
Tasigna® (ta-sig-na)
(nilotinib)
capsules
What is the most important information I should know about Tasigna?
Tasigna can cause a possible life-threatening heart problem called QTc prolongation. QTc prolongation causes an irregular heartbeat, which may lead to sudden death.
Your healthcare provider should check the electrical activity of your heart with a test called an electrocardiogram (ECG):
• before starting Tasigna
• 7 days after starting Tasigna
• with any dose changes
• regularly during Tasigna treatment
You may lower your chances for having QTc prolongation with Tasigna if you:
  • Take Tasigna 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.
  • Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract while taking Tasigna. Food and grapefruit products increase the amount of Tasigna in your body.
  • Avoid taking other medicines or supplements with Tasigna that can also cause QTc prolongation.
  • Tasigna can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects.
  • Do not take any other medicine while taking Tasigna unless your healthcare provider tells you it is okay to do so.
  • If you cannot swallow Tasigna capsules whole, you may open the Tasigna capsule and sprinkle the contents of each capsule in 1 teaspoon of applesauce (puréed apple). Swallow the mixture right away (within 15 minutes). For more information, see “How should I take Tasigna?”

Call your healthcare provider right away if you feel lightheaded, faint, or have an irregular heartbeat while taking Tasigna. These can be symptoms of QTc prolongation.

What is Tasigna?
Tasigna is a prescription medicine used to treat a type of leukemia called Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in adults who:
  • are newly diagnosed, or
  • are no longer benefiting from previous other treatments, including treatment with imatinib (Gleevec), or
  • have taken other treatments, including imatinib (Gleevec), and cannot tolerate them

It is not known if Tasigna is safe and effective in children.

Who should not take Tasigna?
Do not take if you have:
  • low levels of potassium or magnesium in your blood
  • long QTc syndrome
What should I tell my healthcare provider before starting Tasigna?
Before taking Tasigna, tell your healthcare provider about all of your medical conditions, including if you :
  • have heart problems
  • have had a stroke or other problems due to decreased blood flow to the brain
  • have problems with decreased blood flow to your legs
  • have irregular heartbeat
  • have QTc prolongation or a family history of it
  • have liver problems
  • have had pancreatitis
  • have low blood levels of potassium or magnesium in your blood
  • have a severe problem with lactose (milk sugar) or other sugars. Tasigna capsules contain lactose. Most people who have mild or moderate lactose intolerance can take Tasigna.
  • have bleeding problems
  • had a surgical procedure involving the removal of the entire stomach (total gastrectomy)
  • are pregnant or plan to become pregnant. Tasigna may harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment with Tasigna. Talk to your healthcare provider about the best birth control methods to prevent pregnancy while you are taking Tasigna.
  • are breastfeeding or plan to breastfeed. It is not known if Tasigna passes into your breast milk. You and your healthcare provider should decide if you will take Tasigna or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

If you need to take antacids (medicines to treat heartburn) do not take them at the same time that you take Tasigna. If you take:

  • a medicine to block the amount of acid produced in the stomach (H2 blocker): Take these medicines about 10 hours before you take Tasigna, or about 2 hours after you take Tasigna.
  • an antacid that contains aluminum hydroxide, magnesium hydroxide, and simethicone to reduce the amount of acid in the stomach: Take these medicines about 2 hours before or about 2 hours after you take Tasigna.

Tasigna can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects. See “What is the most important information I should know about Tasigna?”

How should I take Tasigna?
  • Take Tasigna exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking Tasigna unless your healthcare provider tells you.
  • Tasigna is a long-term treatment.
  • Your healthcare provider will tell you how many Tasigna capsules to take and when to take them.
  • 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 poison control center 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.

What are the possible side effects of Tasigna?
Tasigna may cause serious side effects, including:
  • See “What is the most important information I should know about Tasigna?”
  • Decreased blood flow to the leg, heart, or brain. People who have recently been diagnosed with Ph+ CML and take Tasigna may develop decreased blood flow to the leg, the heart, or brain.
    Get medical help right away if you suddenly develop any of the following symptoms:
    • chest pain or discomfort
    • numbness or weakness
    • problems walking or speaking
    • leg pain
    • your leg feels cold
    • change in the skin color of your leg
  • Low blood counts. Low blood counts are common with Tasigna. Your healthcare provider will check your blood counts regularly during treatment with Tasigna. Symptoms of low blood counts include:
    • unexplained bleeding or bruising
    • blood in urine or stool
    • unexplained weakness
  • Liver problems. Symptoms include yellow skin and eyes.
  • Pancreas inflammation (pancreatitis). Symptoms include sudden stomach area pain with nausea and vomiting.
  • Bleeding in the brain. Symptoms include sudden headache, changes in your eyesight, not being aware of what is going on around you and becoming unconscious.
  • Tumor Lysis Syndrome (TLS). TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have:
    • kidney failure and the need for dialysis treatment
    • an abnormal heart beat
      Your healthcare provider may do blood tests to check you for TLS.
  • Bleeding. Tell your healthcare provider right away if you develop any signs and symptoms of bleeding during treatment with Tasigna.
  • Fluid retention. Your body may hold too much fluid (fluid retention). Symptoms of fluid retention include shortness of breath, rapid weight gain, and swelling.
The most common side effects of Tasigna include:
• low blood count
• nausea
• rash
• headache
• tiredness
• itching
• vomiting
• diarrhea
• cough
• constipation
• muscle and joint pain
• runny or stuffy nose, sneezing, sore throat
• fever
• night sweats

These are not all of the possible side effects of Tasigna.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Tasigna?
  • 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.

Keep Tasigna and all medicines out to the reach of children.

General information about the safe and effective use of Tasigna.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Tasigna for a condition for which it was not prescribed. Do not give Tasigna to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Tasigna that is written for health professionals.
What are the ingredients in Tasigna?
Active ingredient: nilotinib
Inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate and poloxamer 188.
The capsule shell contains gelatin, iron oxide (red), iron oxide (yellow), iron oxide (black), and titanium dioxide.

Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936 © Novartis

For more information, go to www.Tasigna.com or call 1-866-411-8274.

T2017-25

PRINCIPAL DISPLAY PANEL

Package Label – 150 mg

Rx Only             NDC 0078-0592-87

Tasigna® (nilotinib) capsules

Contents: 4 individual blister packs containing 28 capsules each.

For oral use.

Dosage: See package insert

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

1 capsule contains 150 mg nilotinib

Keep this and all drugs out of the reach of children.

For more information, visit www.US.Tasigna.com or call 1-866-411-Tasigna

PHARMACIST: DISPENSE WITH MEDICATION GUIDE ATTACHED OR PROVIDED SEPARATELY.

Take Tasigna on empty stomach. Avoid food for at least 2 hours before taking a dose of Tasigna and at least 1 hour after the dose is taken.

PRINCIPAL DISPLAY PANEL

Package Label – 200 mg

Rx Only             NDC 0078-0526-87

Tasigna® (nilotinib) capsules

Contents: 4 individual blister packs containing 28 capsules each.

For oral use.

Dosage: See package insert

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

1 capsule contains 200 mg nilotinib

Keep this and all drugs out of the reach of children.

For more information, visit www.US.Tasigna.com or call 1-866-411-Tasigna

PHARMACIST: DISPENSE WITH MEDICATION GUIDE ATTACHED OR PROVIDED SEPARATELY.

Take Tasigna on empty stomach. Avoid food for at least 2 hours before taking a dose of Tasigna and at least 1 hour after the dose is taken.

Tasigna 
nilotinib capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0078-0526
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NILOTINIB (NILOTINIB) NILOTINIB 200 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSPOVIDONE  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
POLOXAMER 188  
GELATIN  
FERRIC OXIDE RED  
FERRIC OXIDE YELLOW  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (light yellow opaque) Score no score
Shape CAPSULE Size 22mm
Flavor Imprint Code NVR;TKI
Contains     
Packaging
# Item Code Package Description
1 NDC:0078-0526-87 4 BLISTER PACK in 1 CARTON
1 28 CAPSULE in 1 BLISTER PACK
2 NDC:0078-0526-51 28 CAPSULE in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022068 10/29/2007
Tasigna 
nilotinib capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0078-0592
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NILOTINIB (NILOTINIB) NILOTINIB 150 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSPOVIDONE  
LACTOSE MONOHYDRATE  
MAGNESIUM STEARATE  
POLOXAMER 188  
GELATIN  
FERRIC OXIDE RED  
FERRIC OXIDE YELLOW  
TITANIUM DIOXIDE  
Product Characteristics
Color RED Score no score
Shape CAPSULE Size 22mm
Flavor Imprint Code NVR;BCR
Contains     
Packaging
# Item Code Package Description
1 NDC:0078-0592-87 4 BLISTER PACK in 1 CARTON
1 28 CAPSULE in 1 BLISTER PACK
2 NDC:0078-0592-51 28 CAPSULE in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022068 10/29/2007
Labeler - Novartis Pharmaceuticals Corporation (002147023)
Revised: 02/2017   Novartis Pharmaceuticals Corporation

What is Tasigna?

Tasigna (nilotinib) is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Tasigna is used to treat a type of blood cancer called Philadelphia chromosome positive chronic myeloid leukemia (CML). It is usually given after other medications have been tried without success.

Tasigna may also be used for purposes not listed in this medication guide.

What other drugs will affect Tasigna?

Many drugs can interact with Tasigna, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all medicines you use, and those you start or stop using during your treatment. Not all possible interactions are listed in this medication guide.

How to Take Tasigna (Dosage)

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take Tasigna will depend on:

  • your age
  • the condition being treated
  • how severe or resistant your condition is
  • other medical conditions you have
  • how you react to the first dose

What are you taking this medication for?

Chronic myeloid leukemia

Brand: Tasigna

Form: oral capsule Strengths: 150 mg, 200 mg Adult dosage (ages 18 years and older)

The typical starting dosage is 300–400 mg twice per day in doses that are 12 hours apart.

Child dosage (ages 0–17 years)

It has not been confirmed that Tasigna is safe and effective for use in people younger than 18 years.

Special considerations

People with liver damage: Your starting dosage is typically 200–300 mg twice per day.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always to speak with your doctor or pharmacist about dosages that are right for you. Important considerations for taking this drug

Do not take this drug with food

See Details

Take this drug every 12 hours

Do not cut or crush the capsule

See Details

Store this drug carefully

See Details

A prescription for this medication is refillable

See Details

Travel

See Details

Clinical monitoring

See Details

Sun sensitivity

See Details

Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead

Insurance

See Details

Are there any alternatives?

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