Crizotinib interactions

Food & lifestyle

• grapefruit juice

  Major

  Metabolism

  Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

  What to do: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

Conditions

Conditions in which Crizotinib needs care, as documented in this source.

• Long QT Syndrome

  Major

  The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Use with caution when using this drug in patients with a history or predisposition to QTc prolongation. Withhold in patients who develop QTc greater than 500 ms on at least 2 separate ECGs until recovery to a QTc less than or equal to 480 ms and resume drug treatment at a reduced dose. Permanently discontinue in patients who develop QTc greater than 500 ms, or greater than or equal to 60 ms change from baseline with torsade de pointes, polymorphic ventricular tachycardia, or signs of serious arrhythmia. Consider obtaining ECGs and electrolytes as close as possible prior to the first dose and periodic monitoring in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, history or predisposition for QTc prolongation, and taking medications that prolong the QT interval.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

• Bradycardia

  Moderate

  Crizotinib can cause symptomatic bradycardia. It is recommended to monitor heart rate and blood pressure regularly. It might be necessary to withhold crizotinib in cases of symptomatic bradycardia that is not life-threatening until recovery occurs and then resume treatment at an appropriate dose. Permanently discontinue therapy for life-threatening bradycardia due to crizotinib treatment; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold crizotinib until recovery and if concomitant medications can be adjusted or discontinued, restart treatment with crizotinib at 250 mg once daily with frequent monitoring. Close monitoring is recommended.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

• Hepatic Insufficiency

  Moderate

  Crizotinib is extensively metabolized in the liver, and hepatic impairment is likely to increase plasma crizotinib concentrations. Cases of drug-induced hepatotoxicity with fatal outcomes have been reported with the use of crizotinib. It is recommended to monitor liver function tests, regularly as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations and to temporarily suspend, reduce the dose, or permanently discontinue therapy as per recommended by the manufacturer. Caution is recommended in patients with hepatic impairment.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

• Kidney Diseases

  Moderate

  Based on a population pharmacokinetic analysis of crizotinib no starting dose adjustment is needed for patients with mild or moderate renal impairment. Care should be exercised when using this agent in patients with severe renal impairment as the exposure to crizotinib is increased in these patients. It is recommended to administer crizotinib at a dose of 250 mg taken orally once daily in patients with severe renal impairment not requiring dialysis.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

• Lung Diseases

  Moderate

  The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue these agents and institute appropriate measures. Immediately withhold treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue therapy if no other potential causes of ILD/pneumonitis have been identified.

  7 sources

  1. "Product Information. Vandetanib (vandetanib)." Astra-Zeneca Pharmaceuticals (2011):
  2. "Product Information. Zelboraf (vemurafenib)." Genentech (2011):
  3. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):
  4. "Product Information. Mekinist (trametinib)." GlaxoSmithKline (2013):
  5. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):
  6. "Product Information. Zydelig (idelalisib)." Gilead Sciences (2014):
  7. "Product Information. Alecensa (alectinib)." Genentech (2015):

• Peptic Ulcer Perforation

  Moderate

  The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):

• Vision Disorders

  Moderate

  Cases of optic atrophy and optic nerve disorder leading to vision loss have been reported with the use of crizotinib. It is recommended to perform an ophthalmological evaluation consisting of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT) and other evaluations as appropriate for new onset of severe visual loss. Discontinue crizotinib in patients with new onset of severe visual loss. There is insufficient information to characterize the risks of resumption of crizotinib in patients with a severe visual loss; a decision to resume treatment with crizotinib should consider the potential benefits to the patient. Care should be exercised when prescribing crizotinib in these patients.

  1 source

  1. "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group (2011):