Medical Editor: John P. Cunha, DO, FACOEP
What Is Tasigna?
Tasigna (nilotinib) is a kinase inhibitor that interferes with a protein that signals cancer cells to multiply used to treat adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in the chronic phase of the disease; it is also used to treat both chronic and accelerated Philadelphia chromosome positive myeloid leukemia in adults that are resistant or intolerant to prior therapy, including imatinib. Tasigna is available in generic form.
What Are Side Effects of Tasigna?
Common side effects of Tasigna include:
- skin rash,
- joint or muscle aches or pain,
- back pain,
- temporary hair loss, or
- cold symptoms (stuffy nose, sneezing, cough, or sore throat).
Tell your doctor if you have serious side effects of Tasigna including:
- severe stomach or abdominal pain,
- toe or joint pain,
- painful urination,
- a change in the amount of urine,
- swelling hands/ankles/feet,
- unusual or rapid weight gain,
- symptoms of high blood sugar (such as increased thirst or urination), or
- signs of liver disease (such as persistent vomiting, stomach or abdominal pain, yellowing eyes or skin, or dark urine).
Dosage for Tasigna
Tasigna comes in a gelatin capsule at strengths of 150 and 200 mg. It is usually taken without food twice a day, at least 1 hour before or 2 hours after eating any food. The dosage is usually 300 mg per day, or 400 mg per day in those patients that are resistant or intolerant to prior therapy. However, because of the extensive and dire side effects in persons with underlying problems such as sudden death, hepatotoxicity, QT prolongation, myelosupression and other electrolyte and enzyme abnormalities, physicians often need to adjust the dose depending on several health factors; patients and physicians need to check the multiple tables available to develop a safe dose according to the patient's concurrent health problems and medications they take.
What Drugs, Substances, or Supplements Interact with Tasigna?
Tasigna may interact with esomeprazole (Nexium) and other stomach acid reducers, ergotamine, dihydroergotamine, St. John's wort, theophylline, blood thinners or medication to prevent blood clots, antibiotics, tuberculosis medicine, antifungals, anti-malaria medication, cancer medication, immunosuppressants, medicine to prevent organ transplant rejection, heart or blood pressure medications, heart rhythm medications, medications to treat HIV/AIDS or hepatitis C, medicine to treat depression or mental illness, medicine to treat or prevent nausea, narcotics, sedatives, narcolepsy medication, seizure medication, or steroids. Tell your doctor all medications and supplements you use.
Tasigna During Pregnancy or Breastfeeding
Women who are pregnant should not take this drug; women who are breastfeeding should be cautioned that benefits to the mother must be weighed against the relatively unstudied risks to the infant. Safety and effectiveness of Tasigna use in pediatrics has not been established.
Our Tasigna Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Contact your doctor right away or get emergency medical help if you have symptoms of a serious heart problem: fast or pounding heartbeats and sudden dizziness (like you might pass out).
Call your doctor at once if you have:
- unusual bleeding (bruises, blood in your urine or stools);
- swelling, rapid weight gain, feeling short of breath;
- bleeding in the brain--sudden headache, confusion, vision problems, and dizziness;
- signs of liver or pancreas problems--upper stomach pain (that may spread to your back), nausea or vomiting, dark urine, jaundice (yellowing of the skin or eyes);
- low blood cell counts--fever, chills, night sweats, mouth sores, pale skin, unusual weakness;
- signs of decreased blood flow--leg pain or cold feeling, chest pain, numbness, trouble walking, speech problems; or
- signs of tumor cell breakdown--confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth.
Nilotinib can affect growth in children and teenagers. Tell your doctor if your child is not growing at a normal rate while using this medicine.
Common side effects may include:
- nausea, vomiting, diarrhea, constipation;
- rash, temporary hair loss;
- night sweats;
- pain in your bones, spine, joints, or muscles;
- headache, feeling tired; or
- runny or stuffy nose, sneezing, cough, sore throat.
Read the entire detailed patient monograph for Tasigna (Nilotinib Capsules)
The following clinically significant adverse reactions can occur with Tasigna and are discussed in greater detail in other sections of labeling:
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- QT Prolongation [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Sudden Deaths [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Cardiac and Arterial Vascular Occlusive Events [see WARNINGS AND PRECAUTIONS]
- Pancreatitis and Elevated Serum Lipase [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Electrolyte Abnormalities [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Hemorrhage [see WARNINGS AND PRECAUTIONS]
- Fluid Retention [see WARNINGS AND PRECAUTIONS]
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 Adult 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 Tasigna 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 Tasigna 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 9 for Grade 3/4 laboratory abnormalities.
Discontinuation due to adverse reactions, regardless of relationship to study drug, was observed in 10% of patients.
In Adult Patients With Resistant Or Intolerant Ph+ CML-CP And CML-AP
In the single-arm, 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, CLINICAL PHARMACOLOGY].
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 7 and 8 show the percentage of adult patients experiencing non-hematologic adverse reactions (excluding laboratory abnormalities) regardless of relationship to study drug. Adverse reactions reported in greater than 10% of adult patients who received at least 1 dose of Tasigna are listed.
Table 7: Most Frequently Reported Non-Hematologic Adverse Reactions (Regardless of Relationship to Study Drug) in Adult 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
|Body System and Adverse Reaction||Patients with Newly Diagnosed Ph+ CML-CP|
|Tasigna 300 mg Twice Daily
N = 279
|imatinib 400 mg Once Daily
N = 280
|Tasigna 300 mg Twice Daily
N = 279
|imatinib 400 mg Once Daily
N = 280
|All Grades (%)||CTC Gradesb 3/4 (%)|
|Skin and subcutaneous tissue disorders||Rash||38||19||< 1||2|
|Vomiting||15||27||< 1||< 1|
|Abdominal pain upper||18||14||1||< 1|
|Nervous system disorders||Headache||32||23||3||< 1|
|Dizziness||12||11||< 1||< 1|
|General disorders and administration-site conditions||Fatigue||23||20||1||1|
|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|
|Pain in extremity||15||16||< 1||< 1|
|Respiratory, thoracic, and mediastinal disorders||Cough||17||13||0||0|
|Infections and infestations||Nasopharyngitis||27||21||0||0|
|Upper respiratory tract infection||17||14||< 1||0|
|Eye disorders||Eyelid edema||1||19||0||< 1|
|Periorbital edema||< 1||15||0||0|
|Vascular disorder||Hypertension||10||4||1||< 1|
|Abbreviations: CML-CP, chronic myeloid leukemia-chronic phase; Ph+, Philadelphia chromosome positive.
aExcluding laboratory abnormalities.
bNCI Common Terminology Criteria (CTC) for Adverse Events, version 3.0.
Table 8: Most Frequently Reported Non-Hematologic Adverse Reactions in Adult 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 Adverse Reaction||CML-CP
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|
|Night sweat||12||< 1||27||0|
|Gastrointestinal disorders||Nausea||37||1||22||< 1|
|Abdominal pain upper||14||< 1||12||< 1|
|Nervous system disorders||Headache||35||2||20||1|
|General disorders and administration-site conditions||Fatigue||32||3||23||< 1|
|Peripheral edema||15||< 1||12||0|
|Musculoskeletal and connective tissue disorders||Myalgia||19||2||16||< 1|
|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|
|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|
|Vascular disorders||Hypertension||10||2||11||< 1|
|Abbreviations: CML-AP, chronic myeloid leukemia-accelerated phase; CML-CP, chronic myeloid leukemia-chronic phase; Ph+, Philadelphia chromosome positive.
aExcluding laboratory abnormalities.
bNCI Common Terminology Criteria for Adverse Events, version 3.0.
cAlso includes preferred term anorexia.
Table 9 shows the percentage of adult patients experiencing treatment-emergent Grade 3/4 laboratory abnormalities in patients who received at least one dose of Tasigna.
Table 9: Percent Incidence of Clinically Relevant Grade 3/4* Laboratory Abnormalities
|Newly Diagnosed Adult Ph+ CML-CP||Resistant or Intolerant Adult Ph+|
|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 (%)
|Elevated bilirubin (total)||4||< 1||7||9|
|Elevated SGPT (ALT)||4||3||4||4|
|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|
|Abbreviations: ALT alanine aminotransferase; AST, aspartate aminotransferase; CML-AP, chronic myeloid leukemia-accelerated phase; CML-CP, chronic myeloid leukemia-chronic phase; Ph+, Philadelphia chromosome positive. *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 twice daily) 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%).
Treatment Discontinuation In Ph+ CML-CP Patients Who Have Achieved A Sustained Molecular Response (MR4.5)
In eligible patients who discontinued Tasigna therapy after attaining a sustained molecular response (MR4.5), musculoskeletal symptoms (e.g., myalgia, pain in extremity, arthralgia, bone pain, spinal pain, or musculoskeletal pain), were reported more frequently than before treatment discontinuation in the first year, as noted in Table 10. The rate of new musculoskeletal symptoms generally decreased in the second year after treatment discontinuation.
In the newly diagnosed population in whom musculoskeletal symptoms occurred at any time during the TFR phase, 23/53 (43.4%) had not resolved by the TFR end date or data cut-off date. In the population previously treated with imatinib in whom musculoskeletal events occurred at any time during the TFR phase, 32/57 (56.1%) had not resolved by the data cut-off date.
The rate of musculoskeletal symptoms decreased in patients who entered the Tasigna treatment reinitiation (NTRI) phase, at 11/88 (12.5%) in the newly diagnosed population and 14/56 (25%) in the population previously treated with imatinib. Other adverse reactions observed in the Tasigna re-treatment phase were similar to those observed during Tasigna use in patients with newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP.
Table 10: Musculoskeletal Symptoms Occurring Upon Treatment Discontinuation in the Context of Treatment-Free Remission (TFR)
|Ph+ CML-CP patients||Entire TFR period in all TFR patients||By time interval, in subset of patients in TFR greater than 48 weeks|
|N||Median follow-up in TFR||Patients with musculoskeletal symptoms||N||Year prior to Tasigna discontinuation||1st year after Tasigna discontinuation||2nd year after Tasigna discontinuation|
|All Grades||Grade 3/4||All Grades||Grade 3/4||All Grades||Grade 3/4||All Grades||Grade 3/4|
|Newly Diagnosed||190||76 weeks||28%||1%||100||17%||0%||34%||2%||9%||0%|
|Previously treated with imatinib||126||99 weeks||45%||2%||73||14%||0%||48%||3%||15%||1%|
|Abbreviations: CML-CP, chronic myeloid leukemia-chronic phase; Ph+, Philadelphia chromosome positive ;TFR, treatment-free remission.|
Additional Data From Clinical Trials
The following adverse drug reactions were reported in adult 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 to 1% 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 7 and 8, 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:
- Adult patients with newly diagnosed Ph+ CML-CP 60 month analysis and,
- Adult patients with 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.
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.
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, facial paralysis. Unknown frequency: basilar artery stenosis, brain edema, optic neuritis, lethargy, dysesthesia, restless legs syndrome.
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: papilledema, 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.
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.
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.
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.
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.
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, gammaglutamyltransferase 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.
In Pediatric Patients With Newly Diagnosed Ph+ CML-CP Or Resistant Or Intolerant Ph+ CML-CP
The data below reflect exposure to Tasigna from two studies in pediatric patients from 2 to less than 18 years of age with either newly diagnosed Ph+ CML-CP or imatinib/dasatinib resistant or intolerant Ph+ CML-CP treated at the recommended dose of 230 mg/m² twice daily (n = 69) [see Clinical Studies]. The median time on treatment with Tasigna was 13.8 months (range, 0.7 to 30.9 months). The median actual dose intensity was 435.5 mg/m²/day (range, 149 to 517 mg/m²/day), and the median relative dose intensity was 94.7% (range, 32 to 112%). Forty patients (58.0%) had relative dose intensity superior to 90%.
In pediatric patients with Ph+ CML-CP, the most common (greater than 20%) non-hematologic adverse drug reactions were headache, rash, hyperbilirubinemia, alanine aminotransferase increased, pyrexia, nausea, upper respiratory tract infection, aspartate aminotransferase increased, and vomiting. The most common (greater than 5%) Grade 3/4 non-hematologic adverse drug reactions were alanine aminotransferase increased and hyperbilirubinemia.
Laboratory abnormalities of hyperbilirubinemia (Grade 3/4: 13%) and transaminase elevation (AST Grade 3/4: 1%, ALT Grade 3/4: 9%), were reported at a higher frequency than in adult patients.
The most common hematological adverse drug reactions (greater than or equal to 30% of patients, of all Grades) were decreases in total white blood cells (54%), platelet count (44%), absolute neutrophils (41%), absolute lymphocytes (32%), and hemoglobin (30%).
Discontinuation due to adverse reactions occurred in 9 patients (13%). The adverse reactions leading to discontinuation were hyperbilirubinemia (6%) and rash (4%).
Increase in QTcF greater than 30 msec from baseline was observed in 17 patients (25%). No patient had an absolute QTcF of greater than 500 msec or QTcF increase of greater than 60 msec from baseline.
Growth Retardation In Pediatric Population
In a multicenter, open-label, single-arm study of 58 pediatric patients with newly diagnosed or resistant Ph+ CML-CP treated with Tasigna, with a median exposure of 33 months in each cohort, adverse reactions associated with growth and deceleration of growth in regard to height were reported in 3 patients (5%). The adverse reactions include growth retardation in 2 adolescent patients and growth hormone deficiency with body height below normal in the remaining patient (age category: child). Of the 58 pediatric patients, 12% (n = 7) experienced a decrease of two main height percentiles compared with baseline (percentile lines: 5th, 10th, 25th, 50th, 75th, 90th, and 95th). Close monitoring of growth in pediatric patients under Tasigna treatment is recommended [see WARNINGS AND PRECAUTIONS].
The following adverse reactions have been identified during postapproval use of Tasigna. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: thrombotic microangiopathy
Nervous System Disorders: facial paralysis
Effect Of Other Drugs On Tasigna
Strong CYP3A Inhibitors
Concomitant use with a strong CYP3A inhibitor increased nilotinib concentrations compared to Tasigna alone [see CLINICAL PHARMACOLOGY], which may increase the risk of Tasigna toxicities. Avoid concomitant use of strong CYP3A inhibitors with Tasigna. If patients must be coadministered a strong CYP3A4 inhibitor, reduce Tasigna dose [see DOSAGE AND ADMINISTRATION].
Strong CYP3A Inducers
Concomitant use with a strong CYP3A inducer decreased nilotinib concentrations compared to Tasigna alone [see CLINICAL PHARMACOLOGY], which may reduce Tasigna efficacy. Avoid concomitant use of strong CYP3A inducers with Tasigna.
Proton Pump Inhibitors
Concomitant use with a proton pump inhibitor (PPI) decreased nilotinib concentrations compared to Tasigna alone [see CLINICAL PHARMACOLOGY], which may reduce Tasigna efficacy. Avoid concomitant use of PPI with Tasigna. As an alternative to PPIs, use H2 blockers approximately 10 hours before or approximately 2 hours after the dose of Tasigna, or use antacids approximately 2 hours before or approximately 2 hours after the dose of Tasigna.
Drugs That Prolong The QT Interval
Avoid coadministration of Tasigna with agents that may prolong the QT interval, such as anti-arrhythmic drugs [see BOXED WARNING, DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].
Read the entire FDA prescribing information for Tasigna (Nilotinib Capsules)
© Tasigna Patient Information is supplied by Cerner Multum, Inc. and Tasigna Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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