DOSAGE AND ADMINISTRATION
The recommended dose of Tasigna (nilotinib) is 400 mg orally twice daily. [ See Clinical Pharmacology (12. 3 ) ]. Treatment should continue as long as the patient does not show evidence of progression or unacceptable toxicity.
Tasigna should be taken twice daily at approximately 12 hour intervals and should not be taken with food. The capsules should be swallowed whole with water. No food should be consumed for at least 2 hours before the dose is taken and no food should be consumed for at least one hour after the dose is taken . [ See Box ed Warning, Warnings and Precautions (5. 8 ), Clinical Pharmacology ( 12. 3 ) and Clinical Studies (14) ].
If a dose is missed, the patient should not take a make-up dose, but should resume taking the next prescribed daily dose.
Tasigna may be given in combination with hematopoietic growth factors such as erythropoietin or G-CSF if clinically indicated. Tasigna may be given with hydroxyurea or anagrelide if clinically indicated.
Dose Adjustments or Modifications
QT interval prolongation:
Table 1 Dose Adjustments for QT prolongation
|ECGs with a QTc > 480 msec||1. Withhold Tasigna, and perform an analysis of serum potassium and magnesium, and if below lower limit of normal, correct with supplements to within normal limits. Concomitant medication usage must be reviewed.|
2. Resume within 2 weeks at prior dose if QTcF returns to <450msec and to within 20 msec of baseline.
3. If QTcF is between 450 msec and 480 msec after 2 weeks reduce the dose to 400 mg once daily.
4. If, following dose-reduction to 400 mg once daily, QTcF returns to >480 msec, Tasigna should be discontinued.
5. An ECG should be repeated approximately 7 days after any dose adjustment.
Myelosuppression: Tasigna may need to be withheld and/or dose reduced for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia (Table 2).
Table 2 Dose Adjustments for Neutropenia and Thrombocytopenia
|Chronic Phase or Accelerated Phase CML at 400 mg twice daily||ANC* < 1.0 x 109/L and/or platelet counts < 50 x 109/L||1. Stop Tasigna, and monitor blood counts|
2. Resume within 2 weeks at prior dose if ANC >1.0 x 109/L and platelets >50 x 109/L
3. If blood counts remain low for > 2 weeks, reduce the dose to 400 mg once daily
*ANC = absolute neutrophil count
See Table 3 for dose adjustments for elevations of lipase, amylase, bilirubin, and/or hepatic transaminases. [ See Adverse R eactions (6.1) ] .
Table 3 Dose Adjustments for selected non-hematologic laboratory abnormalities
|Elevated serum lipase or amylase ≥ Grade 3||1. Withhold Tasigna, and monitor serum lipase or amylase|
2. Resume treatment at 400 mg once daily if serum lipase or amylase return to ≤ Grade 1
|Elevated bilirubin ≥ Grade 3||1. Withhold Tasigna, and monitor bilirubin|
2. Resume treatment at 400 mg once daily if bilirubin return to ≤ Grade 1
|Elevated hepatic transaminases ≥ Grade 3||1. Withhold Tasigna, and monitor hepatic transaminases |
2. Resume treatment at 400 mg once daily if hepatic transaminases return to ≤ Grade 1
Other n o n-hematologic t oxicities: If other clinically significant moderate or severe non-hematologic toxicity develops, dosing should be withheld, and may be resumed at 400 mg once daily when the toxicity has resolved. If clinically appropriate, escalation of the dose back to 400 mg twice daily should be considered. [ See Warnings and Precautions (5) and Use in Specific Populations (8) ] .
Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). Grapefruit products may also increase serum concentrations of nilotinib and should be avoided. Should treatment with any of these agents be required, it is recommended that therapy with Tasigna be interrupted. If patients must be co-administered a strong CYP3A4 inhibitor, based on pharmacokinetic studies, 400 mg once daily (a dose reduction to 1/2 of the original daily dose) is predicted to adjust the nilotinib AUC to the AUC observed without inhibitors. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inhibitors. If the strong inhibitor is discontinued, a washout period should be allowed before the Tasigna dose is adjusted upward to the indicated dose. Close monitoring for prolongation of the QT interval is indicated for patients who cannot avoid strong CYP3A4 inhibitors . [ See Boxed Warning, Warnings and Precautions (5. 2 and 5.7 ) and Drug Interactions (7. 2 ) ].
Concomitant Strong CYP3A4 Inducers: The concomitant use of strong CYP3A4 inducers should be avoided (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital). Patients should also refrain from taking St. John’s Wort. If patients must be co-administered a strong CYP3A4 inducer, the dose of Tasigna may need to be increased, depending on patient tolerability. If the strong inducer is discontinued the nilotinib dose should be reduced to the indicated dose. [ See Drug Interactions (7. 2 ) ] .
DOSAGE FORMS AND STRENGTHS
200 mg light yellow opaque hard gelatin capsules with a red axial imprint “NVR/TKI”.
HOW SUPPLIED/STORAGE AND HANDLING
Tasigna (nilotinib) capsules are light yellow opaque hard gelatin capsules, size 0 with the red axial imprint “NVR/TKI.” Tasigna capsules are supplied in blister packs.
Carton of 4 blister packs of (4x28) ………………………….…….NDC 0078-0526-87
Blisters of 28 capsules……………………………………….…….NDC 0078-0526-51
Each blister pack contains one folded blister card of 28 capsules each, for dosing two in the morning and two in the evening at 12 hour intervals over a 7 day period.
Tasigna (nilotinib) Capsules, 200 mg, should be stored at 25º C (77º F); excursions permitted between 15°–30° C (59º–86º F) [see USP Controlled Room Temperature].