Zykadia

Zykadia Manufacturers

• Novartis Pharmaceuticals Corporation
  

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  Zykadia | Novartis Pharmaceuticals Corporation

  

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  2.1     Dosing and Administration

  The recommended dose of ZYKADIA is 750 mg orally once daily until disease progression or unacceptable toxicity. Administer ZYKADIA on an empty stomach (i.e., do not administer within 2 hours of a meal) [see Clinical Pharmacology (12.3)].

  A recommended dose has not been determined for patients with moderate to severe hepatic impairment [see Use in Specific Populations (8.6)].

  If a dose of ZYKADIA is missed, make up that dose unless the next dose is due within 12 hours.

  If vomiting occurs during the course of treatment, do not administer an additional dose and continue with the next scheduled dose of ZYKADIA.

  2.2     Dose Modifications for Adverse Reactions

  Recommendations for dose modifications of ZYKADIA for adverse reactions are provided in Table 1.

  Approximately 58% of patients initiating treatment at the recommended dose required at least one dose reduction and the median time to first dose reduction was 7 weeks.

  Discontinue ZYKADIA for patients unable to tolerate 300 mg daily.

  Table 1: ZYKADIA Dose Interruption, Reduction, or Discontinuation Recommendations Criteria ZYKADIA Dosing ALT or AST elevation greater than 5 times ULN with total bilirubin elevation less than or equal to 2 times ULN Withhold until recovery to baseline or less than or equal to 3 times ULN, then resume ZYKADIA with a 150 mg dose reduction. ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis Permanently discontinue ZYKADIA. Any Grade treatment-related ILD/pneumonitis Permanently discontinue ZYKADIA. QTc interval greater than 500 msec on at least 2 separate ECGs Withhold until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec, then resume ZYKADIA with a 150 mg dose reduction. QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia Permanently discontinue ZYKADIA. Severe or intolerable nausea, vomiting or diarrhea despite optimal anti-emetic or anti-diarrheal therapy Withhold until improved, then resume ZYKADIA with a 150 mg dose reduction. Persistent hyperglycemia greater than 250 mg/dL despite optimal anti-hyperglycemic therapy Withhold until hyperglycemia is adequately controlled, then resume ZYKADIA with a 150 mg dose reduction.
  
  If adequate hyperglycemic control cannot be achieved with optimal medical management, discontinue ZYKADIA. Symptomatic bradycardia that is not life-threatening Withhold until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, evaluate concomitant medications known to cause bradycardia, and adjust the dose of ZYKADIA. Clinically significant bradycardia requiring intervention or life-threatening bradycardia in patients taking a concomitant medication also known to cause bradycardia or a medication known to cause hypotension Withhold until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
  
  If the concomitant medication can be adjusted or discontinued, resume ZYKADIA with a 150 mg dose reduction, with frequent monitoring. Life-threatening bradycardia in patients who are not taking a concomitant medication also known to cause bradycardia or known to cause hypotension Permanently discontinue ZYKADIA.

  Lipase or amylase elevation greater than 2 times ULN

  Withhold and monitor serum lipase and amylase.
  Resume ZYKADIA with a 150 mg dose reduction after recovery to less than 1.5 times ULN.

  ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal; ILD, interstitial lung disease;
  ECG, electrocardiogram 2.3     Dose Modification for Strong CYP3A4 Inhibitors

  Avoid concurrent use of strong CYP3A inhibitors during treatment with ZYKADIA [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

  If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the ZYKADIA dose by approximately one-third, rounded to the nearest multiple of the 150 mg dosage strength. After discontinuation of a strong CYP3A inhibitor, resume the ZYKADIA dose that was taken prior to initiating the strong CYP3A4 inhibitor.

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