Tasigna

Tasigna Manufacturers

• Novartis Pharmaceuticals Corporation
  

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  Tasigna | Novartis Pharmaceuticals Corporation

  

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  2.1     Recommended Dosing

  Tasigna should be taken twice-daily at approximately 12-hour intervals and must be taken 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 [see Boxed Warning, Warnings and Precautions (5.9), Clinical Pharmacology (12.3)].

  For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple). The mixture should be taken immediately (within 15 minutes) and should not be stored for future use [see Clinical Pharmacology (12.3)].

  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.

  Newly Diagnosed Ph+ CML-CP

  The recommended dose of Tasigna is 300 mg orally twice-daily [see Clinical Pharmacology (12.3)].

  Resistant or Intolerant Ph+ CML-CP and CML-AP

  The recommended dose of Tasigna (nilotinib) is 400 mg orally twice-daily [see Clinical Pharmacology (12.3)].

  2.2     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 <450 msec 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 

  Withhold or dose reduce Tasigna for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia (Table 2).

  Table 2: Dose Adjustments for Neutropenia and Thrombocytopenia *ANC=absolute neutrophil count Newly diagnosed Ph+ CML in chronic phase at 300 mg twice-daily
  
  
  Resistant or intolerant Ph+ CML in chronic phase or accelerated phase 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
  
  
  
  
  

  See Table 3 for dose adjustments for elevations of lipase, amylase, bilirubin, and/or hepatic transaminases [see Adverse Reactions (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 returns to ≤Grade 1 Elevated bilirubin ≥Grade 3 1. Withhold Tasigna, and monitor bilirubin
  2. Resume treatment at 400 mg once-daily if bilirubin returns 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 returns to ≤Grade 1

  Other Non-hematologic Toxicities 

  If other clinically significant moderate or severe non-hematologic toxicity develops, withhold dosing, and resume at 400 mg once-daily when the toxicity has resolved. If clinically appropriate, escalation of the dose back to 300 mg (newly diagnosed Ph+ CML-CP) or 400 mg (resistant or intolerant Ph+ CML-CP and CML-AP) twice-daily should be considered. For Grade 3 to 4 lipase elevations, dosing should be withheld, and may be resumed at 400 mg once-daily. Test serum lipase levels monthly or as clinically indicated. For Grade 3 to 4 bilirubin or hepatic transaminase elevations, dosing should be withheld, and may be resumed at 400 mg once-daily. Test bilirubin and hepatic transaminases levels monthly or as clinically indicated [see Warnings and Precautions (5.5, 5.6), Use in Specific Populations (8.7)].

  Hepatic Impairment 

  If possible, consider alternative therapies. If Tasigna must be administered to patients with hepatic impairment, consider the following dose reduction:

  Table 4: Dose Adjustments for Hepatic Impairment (At Baseline) *Mild=mild hepatic impairment (Child-Pugh Class A); Moderate=moderate hepatic impairment (Child-Pugh Class B); Severe=severe hepatic impairment (Child-Pugh Class C) [see Warnings and Precautions (5.10), Use in Specific Populations (8.7)]. Newly diagnosed Ph+ CML in chronic phase at 300 mg twice-daily Mild, Moderate, or Severe* An initial dosing regimen of 200 mg twice-daily followed by dose escalation to 300 mg twice-daily based on tolerability
  
  
  Resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 400 mg twice-daily Mild or Moderate* An initial dosing regimen of 300 mg twice-daily followed by dose escalation to 400 mg twice-daily based on tolerability Severe* A starting dose of 200 mg twice-daily followed by a sequential dose escalation to 300 mg twice-daily and then to 400 mg twice-daily based on tolerability

  Concomitant Strong CYP3A4 Inhibitors 

  Avoid the concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). Avoid grapefruit products since they may also increase serum concentrations of nilotinib. Should treatment with any of these agents be required, therapy with Tasigna should be interrupted. If patients must be coadministered a strong CYP3A4 inhibitor, based on pharmacokinetic studies, consider a dose reduction to 300 mg once-daily in patients with resistant or intolerant Ph+ CML or to 200 mg once-daily in patients with newly diagnosed Ph+ CML-CP. 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. For patients who cannot avoid use of strong CYP3A4 inhibitors, monitor closely for prolongation of the QT interval [see Boxed Warning, Warnings and Precautions (5.2, 5.8), Drug Interactions (7.2)].

  Concomitant Strong CYP3A4 Inducers 

  Avoid the concomitant use of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). Also inform patients not to take St. John’s Wort since these agents may reduce the concentration of Tasigna. Based on the nonlinear pharmacokinetic profile of nilotinib, increasing the dose of Tasigna when coadministered with such agents is unlikely to compensate for the loss of exposure [see Drug Interactions (7.2)].

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