Nilotinib
Capsule · Oral
Uses
Nilotinib Capsules is a kinase inhibitor indicated for the treatment of: Adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. ( 1.1 ) Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. ( 1.2 ) 1.1 Adult Patients With Newly Diagnosed Ph+ CML-CP Nilotinib Capsules is indicated for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna ® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 1.2 Adult Patients With Resistant or Intolerant Ph+ CML-CP and CML-AP Nilotinib Capsules is indicated for the treatment of adult patients with chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) resistant or intolerant to prior therapy that included imatinib. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna ® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Dosage and administration
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. ( 2.1 ) See Dosage and Administration for full dosing instructions and dose-reduction instructions for toxicity. ( 2.1 ) Reduce starting dose in patients with baseline hepatic impairment. ( 2.7 ) Eligible newly diagnosed adult patients with Ph+ CML-CP who have received Nilotinib Capsules 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 Nilotinib Capsules for at least 3 years and have achieved a sustained molecular response (MR4.5) may be considered for treatment discontinuation. ( 2.2 , 2.3 , 5.16 ) 2.1 Recommended Dosage Dosage in Adult Patients with Newly Diagnosed Ph+ CML-CP The recommended dosage of Nilotinib Capsules is 300 mg orally twice daily. Dosage in Adult Patients with Resistant or Intolerant Ph+ CML-CP and CML-AP The recommended dosage of Nilotinib Capsules is 400 mg orally twice daily . Additional Administration Instructions Dose Nilotinib Capsules twice daily at approximately 12-hour intervals 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. Advise patients to swallow the capsules whole with water and not open the capsules [see Boxed Warning, Clinical Pharmacology ( 12.3 )] . If a dose of Nilotinib Capsules is missed, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time. Optional Concomitant Therapy Nilotinib Capsules may be given in combination with hematopoietic growth factors, such as erythropoietin or G-CSF if clinically indicated. Nilotinib Capsules may be given with hydroxyurea or anagrelide if clinically indicated. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna ® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 2.2 Discontinuation of Treatment After a Sustained Molecular Response (MR4.5) on Nilotinib Capsules Patient Selection Eligibility for Discontinuation of Treatment Ph+ CML-CP patients with typical BCR-ABL transcripts, who have been taking Nilotinib Capsules for a minimum of 3 years and have achieved a sustained molecular response (MR4.5, corresponding to = BCR-ABL/ABL ≤ 0.0032% IS), may be eligible for treatment discontinuation [see Clinical Studies ( 14.3 , 14.4 )] . Information on FDA authorized tests for the detection and quantitation of BCR-ABL transcripts to determine eligibility for treatment discontinuation is available at http://www.fda.gov/CompanionDiagnostics. Patients with typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), who achieve the sustained MR4.5 criteria, are eligible for discontinuation of Nilotinib Capsules. Patients must continue to be monitored for possible loss of molecular remission after treatment discontinuation. Use the same FDA-authorized test to consistently monitor molecular response levels while on and off treatment. Consider discontinuation in patients with newly diagnosed Ph+ CML-CP who have: been treated with Nilotinib Capsules for at least 3 years maintained a molecular response of at least MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) for one year prior to discontinuation of therapy achieved an MR4.5 for the last assessment taken immediately prior to discontinuation of therapy been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2) no history of accelerated phase or blast crisis no history of prior attempts of treatment-free remission discontinuation that resulted in relapse. Consider discontinuation in patients with Ph+ CML-CP that are resistant or intolerant to imatinib who have achieved a sustained molecular response (MR4.5) on Nilotinib Capsules who have: been treated with Nilotinib Capsules for a minimum of 3 years been treated with imatinib only prior to treatment with Nilotinib Capsules achieved a molecular response of MR4.5 (corresponding to = BCR-ABL/ABL ≤ 0.0032% IS) sustained an MR4.5 for a minimum of one year immediately prior to discontinuation of therapy been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2) no history of accelerated phase or blast crisis no history of prior attempts of treatment-free remission discontinuation that resulted in relapse. Monitor BCR-ABL transcript levels and complete blood count (CBC) with differential in patients who have discontinued Nilotinib Capsules therapy monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter [see Warnings and Precautions ( 5.16 )]. Upon the loss of MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) during the treatment-free phase, monitor BCR-ABL transcript levels every 2 weeks until BCR-ABL levels remain lower than major molecular response [(MMR), corresponding to MR3.0 or = BCR-ABL/ABL ≤ 0.1% IS] for 4 consecutive measurements. The patient can then proceed to the original monitoring schedule. 2.3 Reinitiation of Treatment in Patients Who Lose Molecular Response After Discontinuation of Therapy With Nilotinib Capsules Newly diagnosed patients who lose MMR must reinitiate treatment within 4 weeks at the dose level prior to discontinuation of therapy [see Warnings and Precautions ( 5.16 )] . Patients who reinitiate Nilotinib Capsules therapy should have their BCR-ABL transcript levels monitored monthly until major molecular response is re-established and every 12 weeks thereafter .
Dosage forms and strengths
Capsules: 50 mg: light yellow colored blend filled in hard gelatin capsule size 4 cap red opaque linear imprinted with 'Cipla' in black ink and body white opaque linear imprinted with ‘030 50 mg’ in black ink. Each capsule contains the equivalent of 50 mg of nilotinib. 150 mg: light yellow colored blend filled in hard gelatin capsule size 1, cap red opaque linear imprinted with 'Cipla' in black ink and body red opaque linear imprinted with ‘031 150 mg’ in black ink. Each capsule contains the equivalent of 150 mg of nilotinib. 200 mg: light yellow colored blend filled in hard gelatin capsule size 0, cap white opaque linear imprinted with ‘Cipla’ in black ink and body white opaque linear imprinted with ‘032 200 mg’ in black ink. Each capsule contains the equivalent of 200 mg of nilotinib. Capsules: 50 mg, 150 mg, and 200 mg of nilotinib ( 3 )
Contraindications
Nilotinib Capsules is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Boxed Warning and Warnings and Precautions (5.2)]. Nilotinib Capsules is contraindicated in patients with,
• hypokalemia ( 4 )
• hypomagnesemia ( 4 )
• long QT syndrome ( 4 )
Warnings and precautions
Myelosuppression : Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction. ( 5.1 ) Cardiac and Arterial Vascular Occlusive Events : Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during Nilotinib Capsules therapy. ( 5.4 ) Pancreatitis and Elevated Serum Lipase : Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis. ( 5.5 ) Hepatotoxicity : Monitor hepatic function tests monthly or as clinically indicated. ( 5.6 ) Electrolyte Abnormalities : Nilotinib Capsules can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating Nilotinib Capsules and monitor periodically during therapy. ( 5.7 ) Tumor Lysis Syndrome: Maintain adequate hydration and correct uric acid levels prior to initiating therapy with Nilotinib Capsules. ( 5.8 ) Hemorrhage: Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed. ( 5.9 ) Fluid Retention: Monitor patients for unexpected rapid weight gain, swelling, and shortness of breath. Manage medically. ( 5.13 ) Effects on Growth and Development in Pediatric Patients : Growth retardation has been reported in pediatric patients treated with nilotinib. Monitor growth and development in pediatric patients. ( 5.14 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.15 , 8.1 , 8.3 ) Treatment Discontinuation : 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. ( 5.16 ) 5.1 Myelosuppression Treatment with Nilotinib Capsules can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Perform CBCs every 2 weeks for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding Nilotinib Capsules temporarily or dose reduction [see Dosage and Administration ( 2.5 )]. 5.2 QT Prolongation Nilotinib has been shown to prolong cardiac ventricular repolarization as measured by the QT interval on the surface electrocardiogram (ECG) in a concentration-dependent manner [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.2 )]. Prolongation of the QT interval can result in a type of ventricular tachycardia called torsade de pointes, which may result in syncope, seizure, and/or death. Electrocardiograms should be performed at baseline, 7 days after initiation of Nilotinib Capsules, and periodically as clinically indicated and following dose adjustments [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.12 )]. Nilotinib Capsules should not be used in patients who have hypokalemia, hypomagnesemia, or long QT syndrome. Before initiating Nilotinib Capsules and periodically, test electrolyte, calcium, and magnesium blood levels. Hypokalemia or hypomagnesemia must be corrected prior to initiating Nilotinib Capsules and these electrolytes should be monitored periodically during therapy [see Warnings and Precautions ( 5.12 )]. Significant prolongation of the QT interval may occur when Nilotinib Capsules is inappropriately taken with food and/or strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT. Therefore, avoid coadministration with food and concomitant Nilotinib Capsules use with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 , 7.2 )] . The presence of hypokalemia and hypomagnesemia may further prolong the QT interval [see Warnings and Precautions ( 5.7 , 5.12 )] . 5.3 Sudden Deaths Sudden deaths have been reported in 0.3% of patients with CML treated with nilotinib in clinical studies of 5661 patients. The relative early occurrence of some of these deaths relative to the initiation of nilotinib suggests the possibility that ventricular repolarization abnormalities may have contributed to their occurrence. 5.4 Cardiac and Arterial Vascular Occlusive Events Cardiovascular events, including arterial vascular occlusive events, were reported in a randomized, clinical trial in newly diagnosed CML patients and observed in the postmarketing reports of patients receiving nilotinib therapy [see Adverse Reactions ( 6.1 )] . With a median time on therapy of 60 months in the clinical trial, cardiovascular events, including arterial vascular occlusive events, occurred in 9% and 15% of patients in the nilotinib 300 and 400 mg twice daily arms, respectively, and in 3.2% in the imatinib arm. These included cases of cardiovascular events, including ischemic heart disease-related cardiac events (5% and 9% in the nilotinib 300 mg and 400 mg twice daily arms, respectively, and 2.5% in the imatinib arm), peripheral arterial occlusive disease (3.6% and 2.9% in the nilotinib 300 mg and 400 mg twice daily arms, respectively, and 0% in the imatinib arm), and ischemic cerebrovascular events (1.4% and 3.2% in the nilotinib 300 mg and 400 mg twice daily arms, respectively, and 0.7% in the imatinib arm). If acute signs or symptoms of cardiovascular events occur, advise patients to seek immediate medical attention. The cardiovascular status of patients should be evaluated and cardiovascular risk factors should be monitored and actively managed during Nilotinib Capsules therapy according to standard guidelines [see Dosage and Administration ( 2.4 )] . 5.5 Pancreatitis and Elevated Serum Lipase Nilotinib can cause increases in serum lipase [see Adverse Reactions ( 6.1 )] .
Side effects
The following clinically significant adverse reactions can occur with Nilotinib Capsules and are discussed in greater detail in other sections of labeling:
• 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 ( 5.9 )]
• Fluid Retention [see Warnings and Precautions ( 5.13 )] The most commonly reported non-hematologic adverse reactions (≥ 20%) in adult patients are nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, and night sweats. Hematologic adverse drug reactions include myelosuppression: thrombocytopenia, neutropenia, and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 nilotinib 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%). 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 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 ( 12.2 )] . 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 nilotinib are listed.
Drug interactions
Strong CYP3A Inhibitors : Avoid concomitant use with Nilotinib Capsules or reduce Nilotinib Capsules dose if concomitant use cannot be avoided. ( 7.1 ) Strong CYP3A Inducers: Avoid concomitant use with Nilotinib Capsules. ( 7.1 ) Proton Pump Inhibitors: Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors. ( 7.1 ) 7.1 Effect of Other Drugs on Nilotinib Capsules Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors with Nilotinib Capsules. If concomitant use cannot be avoided, reduce Nilotinib Capsules dose [see Dosage and Administration (2.8)]. Nilotinib is a CYP3A substrate [see Clinical Pharmacology (12.3)]. Concomitant use with a strong CYP3A inhibitor increases nilotinib exposure [see Clinical Pharmacology (12.3)], which may increase the risk of Nilotinib Capsules adverse reactions. Strong CYP3A Inducers Avoid concomitant use of strong CYP3A inducers with Nilotinib Capsules. Nilotinib is a CYP3A substrate [see Clinical Pharmacology (12.3)]. Concomitant use with a strong CYP3A inducer decreases nilotinib exposure [see Clinical Pharmacology (12.3)], which may reduce Nilotinib Capsules efficacy. Proton Pump Inhibitors Avoid concomitant use of proton pump inhibitors (PPI) with Nilotinib Capsules. As an alternative to PPIs, use H2 blockers approximately 10 hours before or approximately 2 hours after the dose of Nilotinib Capsules, or use antacids approximately 2 hours before or approximately 2 hours after the dose of Nilotinib Capsules. Nilotinib displays pH-dependent aqueous solubility [see Description (11)]. Concomitant use with a PPI decreases nilotinib concentrations [see Clinical Pharmacology (12.3)], which may reduce Nilotinib Capsules efficacy. 7.2 Drugs That Prolong the QT Interval Avoid coadministration of Nilotinib Capsules with agents that may prolong the QT interval, such as anti-arrhythmic drugs [see Boxed Warning , Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.2 )] . Nilotinib is associated with a clinically significant concentration-dependent QT prolongation [see Clinical Pharmacology (12.2)].
Use in specific populations
Lactation: Advise women not to breastfeed. ( 8.2 ) Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna ® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information 8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, Nilotinib Capsules can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, the exposures in patients at the recommended dose ( see Data ). Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of nilotinib up to 100 mg/kg/day and 300 mg/kg/day, respectively, during the period of organogenesis. In rats, oral administration of nilotinib produced embryo-lethality/fetal effects at doses ≥ 30 mg/kg/day. At ≥ 30 mg/kg/day, skeletal variations of incomplete ossification of the frontals and misshapen sternebra were noted, and there was an increased incidence of small renal papilla and fetal edema. At 100 mg/kg/day, nilotinib was associated with maternal toxicity (decreased gestation weight, gravid uterine weight, net weight gain, and food consumption) and resulted in a single incidence of cleft palate and two incidences of pale skin were noted in the fetuses. A single incidence of dilated ureters was noted in a fetus also displaying small renal papilla at 100 mg/kg/day. Additional variations of forepaw and hindpaw phalanx unossified, fused sternebra, bipartite sternebra ossification, and incomplete ossification of the cervical vertebra were noted at 100 mg/kg/day. In rabbits, oral administration of nilotinib resulted in the early sacrifice of two females, maternal toxicity and increased resorption of fetuses at 300 mg/kg/day. Fetal skeletal variations (incomplete ossification of the hyoid, bent hyoid, supernumerary short detached ribs and the presence of additional ossification sites near the nasals, frontals and in the sternebral column) were also increased at this dose in the presence of maternal toxicity. Slight maternal toxicity was evident at 100 mg/kg/day but there were no reproductive or embryo-fetal effects at this dose. At 30 mg/kg/day in rats and 300 mg/kg/day in rabbits, the maternal systemic exposure (AUC) were 72700 ng*hr/mL and 17100 ng*hr/mL, respectively, representing approximately 2 and 0.5 times the exposure in humans at the highest recommended dose 400 mg twice daily. When pregnant rats were dosed with nilotinib during organogenesis and through lactation, the adverse effects included a longer gestational period, lower pup body weights until weaning and decreased fertility indices in the pups when they reached maturity, all at a maternal dose of 60 mg/kg (i.e., 360 mg/m 2 , approximately 0.7 times the clinical dose of 400 mg twice daily based on body surface area) . At doses up to 20 mg/kg (i.e., 120 mg/m 2 , approximately 0.25 times the clinical dose of 400 mg twice daily based on body surface area) no adverse effects were seen in the maternal animals or the pups. 8.2 Lactation Risk Summary There are no data on the presence of nilotinib or its metabolites in human milk or its effects on a breastfed child or on milk production. However, nilotinib is present in the milk of lactating rats. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Nilotinib Capsules and for 14 days after the last dose. Animal Data After a single 20 mg/kg of [ 14 C] nilotinib dose to lactating rats, the transfer of parent drug and its metabolites into milk was observed. The overall milk-to-plasma exposure ratio of total radioactivity was approximately 2, based on the AUC 0-24h or AUC 0-INF values. No rat metabolites of nilotinib were detected that were unique to milk. 8.3 Females and Males of Reproductive Potential Based on animal studies, Nilotinib Capsules can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Females of reproductive potential should have a pregnancy test prior to starting treatment with Nilotinib Capsules. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Nilotinib Capsules and for 14 days after the last dose. Infertility The risk of infertility in females or males of reproductive potential has not been studied in humans. In studies in rats and rabbits, the fertility in males and females was not affected [see Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use The frequency, type, and severity of adverse reactions observed were generally consistent with those observed in adults, with the exception of the laboratory abnormalities of hyperbilirubinemia (Grade 3/4: 16%) and transaminase elevation (AST Grade 3/4: 2.9%, ALT Grade 3/4: 10%), which were reported at a higher frequency in pediatric patients than in adults [see Adverse Reactions (6.1)].
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, Nilotinib Capsules can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, the exposures in patients at the recommended dose ( see Data ). Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of nilotinib up to 100 mg/kg/day and 300 mg/kg/day, respectively, during the period of organogenesis. In rats, oral administration of nilotinib produced embryo-lethality/fetal effects at doses ≥ 30 mg/kg/day. At ≥ 30 mg/kg/day, skeletal variations of incomplete ossification of the frontals and misshapen sternebra were noted, and there was an increased incidence of small renal papilla and fetal edema. At 100 mg/kg/day, nilotinib was associated with maternal toxicity (decreased gestation weight, gravid uterine weight, net weight gain, and food consumption) and resulted in a single incidence of cleft palate and two incidences of pale skin were noted in the fetuses. A single incidence of dilated ureters was noted in a fetus also displaying small renal papilla at 100 mg/kg/day. Additional variations of forepaw and hindpaw phalanx unossified, fused sternebra, bipartite sternebra ossification, and incomplete ossification of the cervical vertebra were noted at 100 mg/kg/day. In rabbits, oral administration of nilotinib resulted in the early sacrifice of two females, maternal toxicity and increased resorption of fetuses at 300 mg/kg/day. Fetal skeletal variations (incomplete ossification of the hyoid, bent hyoid, supernumerary short detached ribs and the presence of additional ossification sites near the nasals, frontals and in the sternebral column) were also increased at this dose in the presence of maternal toxicity. Slight maternal toxicity was evident at 100 mg/kg/day but there were no reproductive or embryo-fetal effects at this dose. At 30 mg/kg/day in rats and 300 mg/kg/day in rabbits, the maternal systemic exposure (AUC) were 72700 ng*hr/mL and 17100 ng*hr/mL, respectively, representing approximately 2 and 0.5 times the exposure in humans at the highest recommended dose 400 mg twice daily. When pregnant rats were dosed with nilotinib during organogenesis and through lactation, the adverse effects included a longer gestational period, lower pup body weights until weaning and decreased fertility indices in the pups when they reached maturity, all at a maternal dose of 60 mg/kg (i.e., 360 mg/m 2 , approximately 0.7 times the clinical dose of 400 mg twice daily based on body surface area) . At doses up to 20 mg/kg (i.e., 120 mg/m 2 , approximately 0.25 times the clinical dose of 400 mg twice daily based on body surface area) no adverse effects were seen in the maternal animals or the pups.
Pediatric use
8.4 Pediatric Use The frequency, type, and severity of adverse reactions observed were generally consistent with those observed in adults, with the exception of the laboratory abnormalities of hyperbilirubinemia (Grade 3/4: 16%) and transaminase elevation (AST Grade 3/4: 2.9%, ALT Grade 3/4: 10%), which were reported at a higher frequency in pediatric patients than in adults [see Adverse Reactions (6.1)]. For pediatric growth and development, growth retardation has been reported in pediatric patients with Ph+ CML-CP treated with nilotinib [see Warnings and Precautions (5.14 and 5.12), Adverse Reactions (6.1)]. The safety and effectiveness of nilotinib 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. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna ® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Geriatric use
8.5 Geriatric Use In the clinical trials of nilotinib (patients with newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP), approximately 12% and 30% of patients were 65 years or over, respectively. Patients with newly diagnosed Ph+ CML-CP: There was no difference in major molecular response between patients aged less than 65 years and those greater than or equal to 65 years. Patients with resistant or intolerant CML-CP: There was no difference in major cytogenetic response rate between patients aged less than 65 years and those greater than or equal to 65 years. Patients with resistant or intolerant CML-AP: The hematologic response rate was 44% in patients less than 65 years of age and 29% in patients greater than or equal to 65 years. No major differences for safety were observed in patients greater than or equal to 65 years of age as compared to patients less than 65 years.
Overdosage
Overdose with nilotinib has been reported, where an unspecified number of nilotinib were ingested in combination with alcohol and other drugs. Events included neutropenia, vomiting, and drowsiness. In the event of overdose, observe the patient and provide appropriate supportive treatment.
Description
Nilotinib Capsules contains nilotinib d-tartrate, which belongs to a pharmacologic class of drugs known as kinase inhibitors. Nilotinib d-tartrate is a white to yellow powder with the molecular formula and weight, respectively, of C 32 H 28 F 3 N 7 O 7 and 679.61 g/mol (corresponding molecular formula and weight of nilotinib base, anhydrous are C 28 H 22 F 3 N 7 O and 529 g/mol, respectively). The solubility of nilotinib d-tartrate in aqueous solutions decreases with increasing pH. The pK a 1 of nilotinib d-tartrate was determined to be 4.0. The chemical name of nilotinib d-tartrate is 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide D-Tartrate . Its structure is shown below: Nilotinib Capsules, for oral use, contain 50 mg, 150 mg, or 200 mg nilotinib, anhydrous (equivalent to 64.172 mg, 192.517 mg, and 256.689 mg nilotinib d-tartrate, respectively). The inactive ingredients of Nilotinib Capsules are colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium aluminometasilicate, magnesium stearate, and polysorbate 80. The inactive ingredients in the empty capsules contain gelatin, iron oxide (black), iron oxide (red), iron oxide (yellow), and titanium dioxide. The black ink contains iron oxide (black), potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. structure
Mechanism of action
12.1 Mechanism of Action Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro , nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20 to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).
How supplied
Nilotinib Capsules are supplied as follows: Capsule Strength Description Package Configuration NDC Code 50 mg Light yellow colored blend filled in hard gelatin capsule size 4 cap red opaque linear imprinted with 'Cipla' in black ink and body white opaque linear imprinted with ‘030 50 mg’ in black ink. Bottle of 120 capsules NDC 69097-030-08 Carton of 7 blister packs of 4 capsules NDC 69097-030-63 Blister of 4 capsules NDC 69097-030-16 150 mg Light yellow colored blend filled in hard gelatin capsule size 1, cap red opaque linear imprinted with 'Cipla' in black ink and body red opaque linear imprinted with ‘031 150 mg’ in black ink. Carton of 4 individual packs of 28 (4 X 7’s) capsules each NDC 69097-031-74 Carton of 4 blister packs of 7 capsules NDC 69097-031-56 Blister of 7 capsules NDC 69097-031-17 Carton of 4 individual packs of 28 (2 X 14’s) capsules each NDC 69097-031-91 Carton of 2 blister packs of 14 capsules NDC 69097-031-73 Blister of 14 capsules NDC 69097-031-76 200 mg Light yellow colored blend filled in hard gelatin capsule size 0, cap white opaque linear imprinted with ‘Cipla’ in black ink and body white opaque linear imprinted with ‘032 200 mg’ in black ink. Carton of 4 individual packs of 28 (4 X 7’s) capsules each NDC 69097-032-74 Carton of 4 blister packs of 7 capsules NDC 69097-032-56 Blister of 7 capsules NDC 69097-032-17 Carton of 4 individual packs of 28 (2 X 14’s) capsules each NDC 69097-032-91 Carton of 2 blister packs of 14 capsules NDC 69097-032-73 Blister of 14 capsules NDC 69097-032-76 Nilotinib Capsules should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Taking Nilotinib Capsules Advise patients to take Nilotinib Capsules doses twice daily approximately 12 hours apart. Advise patients to swallow the capsules whole with water and not open the capsules. Advise patients to take Nilotinib Capsules 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 Nilotinib Capsules treatment [see Dosage and Administration (2.1), Drug Interactions (7.1, 7.2)] . If the patient misses a dose of Nilotinib Capsules, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time. Compliance Advise patients of the following: Continue taking Nilotinib Capsules every day for as long as their doctor tells them. This is a long-term treatment. Do not change dose or stop taking Nilotinib Capsules without first consulting their doctor. Myelosuppression Advise patients that treatment with Nilotinib Capsules 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 Nilotinib Capsules 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 Nilotinib Capsules 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 )] . Hepatotoxicity Advise patients that Nilotinib Capsules can increase the risk of hepatotoxicity and that patients with previous history of liver diseases may be at risk. Advise patients to seek immediate medical attention if any symptoms suggestive of hepatotoxicity occur, such as stomach pain, yellow skin and eyes, and dark-colored urine [see Warnings and Precautions ( 5.6 )]. Tumor Lysis Syndrome Advise patients that Nilotinib Capsules can cause TLS and to seek immediate medical attention if any symptoms suggestive of TLS occur, such as an abnormal heartbeat or less urine production [see Warnings and Precautions ( 5.8 )] . Hemorrhage Advise patients that serious hemorrhagic events, including fatal events, have occurred in patients with CML treated with Nilotinib Capsules. Advise patients to seek immediate medical attention if symptoms suggestive of hemorrhage occur, such as uncontrolled bleeding, changes in eyesight, unconsciousness, or sudden headache or sudden confusion in surroundings [see Warnings and Precautions ( 5.9 )] . Fluid Retention Advise patients that Nilotinib Capsules 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 ( 5.13 )] . Effects on Growth and Development in Pediatric Patients Inform pediatric patients and their caregivers of the possibility of developing growth abnormalities. Growth retardation has been reported in pediatric patients treated with nilotinib. Therefore, monitor growth and development in pediatric patients [see Warnings and Precautions ( 5.14 )] . Treatment-Free Remission (TFR) Advise patients that frequent monitoring is required to detect possible loss of remission if TFR is attempted. Advise patients that musculoskeletal symptoms, such as muscle pain, pain in extremity, joint pain, bone pain, or spinal pain, may occur more frequently than before treatment discontinuation [see Warnings and Precautions ( 5.16 )]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.15 ), Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during treatment and for 14 days after receiving the last dose of Nilotinib Capsules [see Use in Specific Populations ( 8.3 )]. Lactation Advise women not to breastfeed during treatment with Nilotinib Capsules and for 14 days after the last dose [see Use in Specific Populations ( 8.2 )]. Drug Interactions Advise patients that Nilotinib Capsules and certain other medicines, including over the counter medications or herbal supplements (such as St. John’s Wort), can interact with each other [see Drug Interactions ( 7 )] . Manufactured by: Cipla Ltd., Verna- 403722, Goa, India. or Cipla Ltd. At M/s Genvion Corporation, Winnipeg, Manitoba R2J 4K2, Canada (CAN) Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059
Label text from the FDA structured product label by Cipla USA Inc. (revised Jul 2, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Nilotinib in 16 products
- Nilotinib Hydrochloride Monohydrate in 5 products
Nilotinib NDC products (21)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60505-3803 | Nilotinib 50 mg/1 Capsule | Apotex Corp. | ANDA |
| 60505-3802 | Nilotinib 200 mg/1 Capsule | Apotex Corp. | ANDA |
| 60505-3801 | Nilotinib 150 mg/1 Capsule | Apotex Corp. | ANDA |
| 73190-034 | Nilotinib 200 mg/1 Capsule | AvKARE | ANDA |
| 73190-033 | Nilotinib 150 mg/1 Capsule | AvKARE | ANDA |
| 31722-779 | Nilotinib 150 mg/1 Capsule | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-780 | Nilotinib 200 mg/1 Capsule | Camber Pharmaceuticals, Inc. | ANDA |
| 43598-055 | Nilotinib Hydrochloride Monohydrate 50 mg/1 Capsule | Dr. Reddy's Laboratories Inc | ANDA |
| 43598-455 | Nilotinib Hydrochloride Monohydrate 150 mg/1 Capsule | Dr. Reddy's Laboratories Inc | ANDA |
| 43598-456 | Nilotinib Hydrochloride Monohydrate 200 mg/1 Capsule | Dr. Reddy's Laboratories Inc | ANDA |
| 72205-237 | Nilotinib 50 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-238 | Nilotinib 150 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-239 | Nilotinib 200 mg/1 Capsule | Novadoz Pharmaceuticals LLC | ANDA |
| 13668-711 | Nilotinib Hydrochloride Monohydrate 200 mg/1 Capsule | Torrent Pharmaceuticals Limited | ANDA |
| 13668-710 | Nilotinib Hydrochloride Monohydrate 150 mg/1 Capsule | Torrent Pharmaceuticals Limited | ANDA |
| 17088-0240 | Nilotinib 50 mg/1 Capsule | Novartis Pharma Stein AG | DRUG FOR FURTHER PROCESSING |
| 17088-0233 | Nilotinib 200 mg/1 Capsule | Novartis Pharma Stein AG | DRUG FOR FURTHER PROCESSING |
| 17088-0226 | Nilotinib 150 mg/1 Capsule | Novartis Pharma Stein AG | DRUG FOR FURTHER PROCESSING |
| 69097-030 | Nilotinib 50 mg/1 Capsule | Cipla USA Inc. | NDA |
| 69097-031 | Nilotinib 150 mg/1 Capsule | Cipla USA Inc. | NDA |
| 69097-032 | Nilotinib 200 mg/1 Capsule | Cipla USA Inc. | NDA |
Nilotinib recalls
- D-0381-2026 Mar 11, 2026 · Class III · Ongoing
Failed Tablet/Capsule Specifications: Observed OOS results at 6-months long-term stability condition for Description test and Appearance by Visual Inspection test. - D-0382-2026 Mar 11, 2026 · Class III · Ongoing
Failed Tablet/Capsule Specifications: Observed OOS results at 6-months long-term stability condition for Description test and Appearance by Visual Inspection test.
Frequently asked questions
What is Nilotinib used for?
Nilotinib Capsules is a kinase inhibitor indicated for the treatment of: Adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. ( 1.1 ) Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. ( 1.2 ) 1.1 Adult Patients With Newly Diagnosed Ph+…
What are the side effects of Nilotinib?
The following clinically significant adverse reactions can occur with Nilotinib Capsules and are discussed in greater detail in other sections of labeling: • 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… See the full label for the complete list.
Who makes Nilotinib?
Nilotinib is listed by 8 labelers in the FDA NDC directory, including Apotex Corp., AvKARE, Camber Pharmaceuticals, Inc., Dr. Reddy's Laboratories Inc.
Has Nilotinib been recalled?
The FDA enforcement database lists 2 recalls for Nilotinib, most recently D-0381-2026 (class iii): Failed Tablet/Capsule Specifications: Observed OOS results at 6-months long-term stability condition for Description test and Appearance by Visual Inspection…