Ceritinib interactions

Food & lifestyle

• grapefruit juice

  Major

  Metabolism

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

  What to do: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

Conditions

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

• Long QT Syndrome

  Major

  Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• Bradycardia

  Moderate

  The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• Gastrointestinal Diseases

  Moderate

  Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• Hepatic Insufficiency

  Moderate

  Ceritinib is eliminated primarily via the liver. Patients with hepatic impairment may have increased exposure and drug-induced hepatotoxicity. Based on results of population pharmacokinetic analysis no dose adjustment is needed for patients with mild hepatic impairment. The pharmacokinetics of ceritinib has not been studied in patients with moderate to severe hepatic impairment; therefore, a recommended dose has not been determined for these patients. It is recommended to monitor liver function tests including ALT, AST, and total bilirubin once a month and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. In some cases, it might be necessary to withhold ceritinib and resume therapy at a reduced dose, or permanently discontinue treatment.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• Hyperglycemia

  Moderate

  The use of ceritinib causes hyperglycemia. It is recommended to monitor fasting serum glucose prior to the start of therapy and periodically thereafter as clinically indicated. Initiate or optimize antihyperglycemic medications as clinically appropriate, and withhold therapy until hyperglycemia is adequately controlled, then resume at a reduced dose as clinically appropriate. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue treatment with ceritinib. Care should be exercised when using this agent in diabetic patients.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• Kidney Diseases

  Moderate

  Based on results of population pharmacokinetic analyses ceritinib exposures are similar between patients with mild to moderate renal impairment and patients with normal renal function. No dose adjustment is needed for these patients. Caution and monitoring is needed when using this agent in patients with severe renal impairment as no information is available.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

• 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):

• Pancreatitis

  Moderate

  Pancreatitis, including a fatal case has occurred in patients receiving ceritinib. It is recommended to monitor lipase and amylase prior to the start of therapy with ceritinib and periodically thereafter as clinically indicated. It might be necessary to withhold the dose of ceritinib based on the severity of the laboratory abnormalities and resume therapy at a reduced dose per clinical guidelines. Care is recommended when using this agent in patients at risk.

  1 source

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):