Nilotinib
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: QT PROLONGATION and SUDDEN DEATHS Tasigna prolongs the QT interval. Prior to Tasigna administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies [see Warnings and Precautions (5.2)] . Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments [see Warnings and Precautions (5.2, 5.3, 5.7, 5.12)] . Sudden deaths have been reported in patients receiving Tasigna [see Warnings and Precautions (5.3)] . Do not administer Tasigna to patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Contraindications (4), Warnings and Precautions (5.2)] .
Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions (7.1, 7.2)] . Avoid food 2 hours before and 1 hour after taking the dose [see Dosage and Administration (2.1)] . WARNING: QT PROLONGATION and SUDDEN DEATHS See full prescribing information for complete boxed warning. Tasigna prolongs the QT interval. Prior to Tasigna administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. ( 5.2 ) Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments.
( 5.2 , 5.3 , 5.7 , 5.12) Sudden deaths have been reported in patients receiving Tasigna. ( 5.3) Do not administer Tasigna to patients with hypokalemia, hypomagnesemia, or long QT syndrome. ( 4 , 5.2) Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. ( 7.1 , 7.2) Avoid food 2 hours before and 1 hour after taking the dose. ( 2.1 )
Dosing in kidney impairment
In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality/fetal effects (small renal papilla, fetal edema, and skeletal variations) in rats and increased resorptions of fetuses and fetal skeletal variations in rabbits at maternal area under the curve (AUCs) approximately 2 and 0.5 times, respectively, the AUC in patients receiving the recommended dose.
Dosing in liver impairment
Dosage Modification for Hepatic Impairment If possible, consider alternative therapies. If Tasigna must be administered to patients with hepatic impairment, consider the following dose reduction [see Use in Specific Populations] : [See table below.] Resistant or intolerant Ph+ CML in chronic phase or accelerated phase Mild or Moderate Reduce dosage to 300 mg twice daily.
Increase dosage to 400 mg twice daily based on tolerability. Severe Reduce dosage to 200 mg twice daily. Increase dosage to 300 mg twice daily and then to 400 mg twice daily based on tolerability.
| Degree of non-hematologic laboratory abnormality | Dosage adjustment |
| Elevated serum lipase or amylase greater than or equal to Grade 3 | Adult patients: 1. Withhold Tasigna, and monitor serum lipase or amylase. 2. Resume treatment at 400 mg once daily if serum lipase or amylase returns to less than or equal to Grade 1. |
| Pediatric patients: 1. Interrupt Tasigna until the event returns to less than or equal to Grade 1. 2. Resume treatment at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue treatment if prior dose was 230 mg/m2 once daily. | |
| Elevated bilirubin greater than or equal to Grade 3 in adult patients and greater than or equal to Grade 2 in pediatric patients | Adult patients: 1. Withhold Tasigna, and monitor bilirubin. 2. Resume treatment at 400 mg once daily if bilirubin returns to less than or equal to Grade 1. |
| Pediatric patients: 1. Interrupt Tasigna until the event returns to less than or equal to Grade 1. 2. Resume treatment at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue treatment if prior dose was 230 mg/m2 once daily, and recovery to less than or equal to Grade 1 takes longer than 28 days. | |
| Elevated hepatic transaminases greater than or equal to Grade 3 | Adult patients: 1. Withhold Tasigna, and monitor hepatic transaminases. 2. Resume treatment at 400 mg once daily if hepatic transaminases returns to less than or equal to Grade 1. |
| Pediatric patients: 1. Interrupt Tasigna until the event returns to less than or equal to Grade 1. 2. Resume treatment at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue treatment if prior dose was 230 mg/m2 once daily, and recovery to less than or equal to Grade 1 takes longer than 28 days. |
| Diagnosis | Degree of hepatic impairment | Dosage adjustment |
| Newly diagnosed Ph+ CML in chronic phase | Mild (Child-Pugh A), Moderate (Child-Pugh B), or Severe (Child-Pugh C) | Reduce dosage to 200 mg twice daily. Increase dosage to 300 mg twice daily based on tolerability. |
| Resistant or intolerant Ph+ CML in chronic phase or accelerated phase | Mild or Moderate | Reduce dosage to 300 mg twice daily. Increase dosage to 400 mg twice daily based on tolerability. |
| Severe | Reduce dosage to 200 mg twice daily. Increase dosage to 300 mg twice daily and then to 400 mg twice daily based on tolerability. |
Drug interactions
Check nilotinib against a medication listLabel text (5 paragraphs)
5.8 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) cases have been reported in Tasigna treated patients with resistant or intolerant CML. Malignant disease progression, high white blood cell (WBC) counts and/or dehydration were present in the majority of these cases. Due to potential for TLS, maintain adequate hydration and correct uric acid levels prior to initiating therapy with Tasigna. 7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with Tasigna, or reduce Tasigna dose if coadministration cannot be avoided. ( 7.1 ) Strong CYP3A Inducers: Avoid concomitant use with Tasigna.
( 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 Tasigna Strong CYP3A Inhibitors Concomitant use with a strong CYP3A inhibitor increased nilotinib concentrations compared to Tasigna alone [see Clinical Pharmacology (12.3)] , 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 (2.8)] . Strong CYP3A Inducers Concomitant use with a strong CYP3A inducer decreased nilotinib concentrations compared to Tasigna alone [see Clinical Pharmacology (12.3)] , 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 (12.3)] , 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.
7.2 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 (2.4), Warnings and Precautions (5.2), Drug Interactions (7.1), Clinical Pharmacology (12.2)] .
Contraindications
Tasigna is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Boxed Warning]. Tasigna is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, Tasigna 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…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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