• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Safety

  • Print
  • Share
  • E-mail

Xalkori (crizotinib) Capsules

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  

 

May 2014

Summary View

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy...updated safety margins
8.4 Pediatric Use...updated safety margins

 

November 2013

Summary View

WARNINGS AND PRECAUTIONS

Hepatotoxicity
  • Drug-induced hepatotoxicity with fatal outcome occurred in 2 (0.2%) of the 1225 patients treated with Xalkori across three main clinical trials…
Interstitial Lung Disease (Pneumonitis)
  • Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Xalkori...
QT Interval Prolongation
  • QTc prolongation can occur in patients treated with Xalkori…
Bradycardia
  • Symptomatic bradycardia can occur in patients receiving Xalkori… 

 

October 2013

Summary View

WARNINGS AND PRECAUTIONS

Bradycardia
  • Symptomatic bradycardia can occur in patients receiving Xalkori. Bradycardia with a heart rate <50 beats per minute occurred in 10% of 890 patients and 14% of 114 patients treated with Xalkori in Studies A and B, respectively. Avoid using Xalkori in combination with other agents known to cause bradycardia (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, clonidine and digoxin) to the extent possible. Monitor heart rate and blood pressure regularly. In cases of Grade 2 and 3 symptomatic bradycardia hold Xalkori, re-evaluate the use of concomitant medications, and adjust the dose of Xalkori …

USE IN SPECIFIC POPULATIONS

Renal Impairment
  • No starting dose adjustment is needed for patients with mild (creatinine clearance [CLcr] 60 to 89 mL/min) and moderate (CLcr 30 to 59 mL/min) renal impairment, as steady-state trough concentrations in these two groups were similar to those in patients with normal renal function (CLcr =90 mL/min) in Study B. Increased exposure to crizotinib occurred in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis.
  • Administer Xalkori at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment not requiring dialysis.

PATIENT COUNSELING INFORMATION

  • Inform patients that symptoms of bradycardia including dizziness, lightheadedness, and syncope can occur while taking Xalkori. Advise patients to report dizziness or lightheadedness and to inform their physician about the use of any heart or blood pressure medications. 

 

February 2012

Summary View

WARNINGS AND PRECAUTIONS

Hepatotoxicity
  • Drug-induced hepatotoxicity with fatal outcome has occurred. These cases have occurred during Xalkori treatment in less than 1% of patients in clinical trials. Concurrent elevations in ALT greater than 3 times the upper limit of normal and total bilirubin greater than 2 times the upper limit of normal, with normal alkaline phosphatase, occurred in less than 1% of patients in clinical trials…

 

PATIENT COUNSELING INFORMATION

Hepatotoxicity
  • Inform patients that symptoms of weakness, fatigue, anorexia, nausea, vomiting, abdominal pain (especially RUQ abdominal pain), jaundice, dark urine, generalized pruritus, and bleeding diathesis, especially in combination with fever and rash, should be reported immediately