TASIGNA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TASIGNA (TASIGNA).
Nilotinib is a tyrosine kinase inhibitor that binds to and inhibits the activity of BCR-ABL, the constitutively activated fusion protein responsible for chronic myeloid leukemia (CML). It also inhibits other kinases including KIT, PDGFR, and DDR1.
| Metabolism | Nilotinib is primarily metabolized by CYP3A4, with minor contributions from CYP2C8 and flavin-containing monooxygenase (FMO). It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily fecal (approximately 66-93% of the dose) as unchanged drug and metabolites; renal excretion is minimal (<5% of the dose). |
| Half-life | Terminal elimination half-life is approximately 90-120 hours, supporting once-daily dosing. |
| Protein binding | Approximately 99% bound to human serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1000 L (not weight-normalized), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 30% (range 10-50%) under fasting conditions; absorption is decreased with high-fat meal (by ~20%). |
| Onset of Action | Oral: Inhibition of BCR-ABL phosphorylation observed within 1-2 hours; maximal inhibition at 2-6 hours. |
| Duration of Action | Sustained BCR-ABL inhibition for the entire 24-hour dosing interval; chronic therapy required for sustained response. |
| Action Class | Tyrosine kinase inhibitors |
400 mg orally twice daily approximately every 12 hours. Administer on an empty stomach (no food for at least 2 hours before and 1 hour after dose). Swallow whole with water; do not crush or chew.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment is required for mild to severe renal impairment (CrCL ≥15 mL/min). For end-stage renal disease (CrCL <15 mL/min) not on dialysis, no data; use with caution. |
| Liver impairment | Child-Pugh A: 400 mg twice daily. Child-Pugh B: Reduce starting dose to 300 mg twice daily. Child-Pugh C: Reduce starting dose to 200 mg twice daily. Monitor liver function. |
| Pediatric use | Approved for newly diagnosed Ph+ CML-CP in pediatric patients aged 1 year and older: Body surface area ≥0.47 m²: 230 mg/m² orally twice daily. Maximum dose 400 mg twice daily. Round to nearest 50 mg capsule strength. |
| Geriatric use | No specific dose adjustment based solely on age. Monitor renal function (CrCL may decline) and hepatic function; consider increased susceptibility to QT prolongation and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TASIGNA (TASIGNA).
| Breastfeeding | No data on the presence of nilotinib in human milk, effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions, women should not breastfeed during treatment and for at least 14 days after the last dose. |
| Teratogenic Risk | Based on animal studies, Tasigna (nilotinib) is embryotoxic and fetotoxic at clinically relevant exposures. There are no adequate and well-controlled studies in pregnant women. The drug should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Avoid pregnancy during treatment. |
■ FDA Black Box Warning
WARNING: QT PROLONGATION AND SUDDEN DEATH. Tasigna has been associated with QT interval prolongation, which can lead to torsade de pointes and sudden death. Do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Correct electrolytes prior to use and monitor ECG at baseline, after 7 days, and periodically thereafter.
| Serious Effects |
["Hypokalemia, hypomagnesemia, or long QT syndrome (QTcF > 480 msec)","Concurrent use with strong CYP3A4 inhibitors","Concurrent use with drugs known to prolong QT interval","Hypersensitivity to nilotinib or any component of the formulation"]
| Precautions | ["QT prolongation and sudden death: Monitor electrolytes and ECG.","Myelosuppression: Neutropenia, thrombocytopenia, anemia may occur; monitor blood counts regularly.","Pancreatitis: Elevated lipase and amylase; monitor closely.","Hepatotoxicity: Elevated liver enzymes, bilirubin; monitor hepatic function.","Hypophosphatemia, hyperkalemia, and electrolyte imbalances: Monitor and correct.","Fluid retention: Edema, pleural effusion, pericardial effusion, ascites; manage as needed.","Cardiovascular events: Peripheral arterial occlusive disease, ischemic heart disease, stroke; evaluate risk and monitor.","Hemorrhage: Fatal and non-fatal bleeding events reported.","Lipodystrophy: Reversible posterior leukoencephalopathy syndrome (RPLS) reported; discontinue if severe.","Fetal harm: Can cause fetal harm; advise women of reproductive potential of effective contraception."] |
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| Fetal Monitoring | Monitor complete blood counts (CBCs) regularly due to risk of myelosuppression. Monitor liver function tests (LFTs) and serum lipase/amylase for hepatotoxicity and pancreatitis. Monitor ECG for QTc prolongation, especially in the presence of electrolyte abnormalities. Monitor serum electrolytes (potassium, magnesium) prior to therapy and periodically. |
| Fertility Effects | Based on animal studies, nilotinib may impair male and female fertility. Decreased sperm count and motility observed in male rats. Ovarian atrophy and decreased corpora lutea in female rats. Effects may be reversible upon discontinuation. |