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Interactions between Crizotinib and Triclabendazole

1 drug interaction and 13 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

triclabendazole crizotinib

Applies to: triclabendazole and crizotinib
Generally avoid

Crizotinib can cause prolongation of the QT interval, which pharmacokinetic/pharmacodynamic modeling indicate may be concentration-dependent. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials done in adults on crizotinib (250 mg twice daily) QTcF (Fridericia corrected QT interval) prolongation greater than or equal to 500 msec was observed in 34 of 1619 (2.1%) and an increase from baseline QTcF greater than or equal to 60 msec was observed in 79 of 1585 patients (5%). In clinical studies of pediatric patients (dosed according to body surface area), a prolonged QT interval was observed in approximately 4% of patients. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

Management

Concomitant use of crizotinib with drugs that prolong the QT interval should generally be avoided. ECG and serum electrolytes, including potassium, magnesium, and calcium, should be monitored before starting crizotinib therapy and periodically during treatment according to the manufacturer's labeling. Electrolytes should be replaced as clinically indicated. Crizotinib should not be started if baseline QTc (QT corrected for heart rate) is greater than 500 msec. Likewise, treatment should be interrupted in patients who develop a QTc greater than 500 msec on at least 2 separate ECGs. Once the QTc has recovered to baseline or less than 481 msec, crizotinib can be resumed at the next lower dosage recommended in the manufacturer's labeling. Crizotinib should be permanently discontinued if the patient has a QTc greater than 500 msec or a change greater than or equal to 60 msec from baseline with torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of a serious arrhythmia. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (3)
  1. (2022) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group, SUPPL-33
  2. (2022) "Product Information. Xalkori (crizotinib)." Pfizer Australia Pty Ltd, pfpxalkc11122
  3. (2023) "Product Information. Xalkori (crizotinib)." Pfizer Ltd, XI 36_1

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

crizotinib Food/Lifestyle

Applies to: crizotinib
Generally avoid

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. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

Management

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.

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

Disease interactions

12 potential interactions Applies to: 11 conditions, including Heart Failure, Arrhythmia, Diverticulitis, Liver Disease, and Interstitial Lung Disease.

Arrhythmia

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Arrhythmia.

Crizotinib can cause symptomatic bradycardia. Heart rate and blood pressure should be monitored regularly. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for bradycardia as recommended.

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Arrhythmia.

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. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Diverticulitis

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Diverticulitis.

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.

Electrolyte Abnormalities

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Electrolyte Abnormalities.

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. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Gastrointestinal Obstruction

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Gastrointestinal Obstruction.

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.

Gastrointestinal Perforation

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Gastrointestinal Perforation.

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.

Heart Failure

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Heart Failure.

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. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Interstitial Lung Disease

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Interstitial Lung Disease.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

Liver Disease

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Liver Disease.

Crizotinib concentrations increased in patients with preexisting moderate (any AST and total bilirubin greater than 1.5 to 3 times the upper limit of normal [1.5 to 3 x ULN]) or severe (any AST and total bilirubin greater than 3 x ULN) liver dysfunction; a reduced dosage of crizotinib is recommended in these patients. Caution is recommended in patients with moderate or severe liver dysfunction. No dose adjustment is recommended in patients with preexisting mild liver dysfunction (AST greater than ULN and total bilirubin up to 1 x ULN or any AST and total bilirubin greater than 1 to 1.5 x ULN).

Cases of drug-induced hepatotoxicity with fatal outcomes have been reported with the use of crizotinib. It is recommended to monitor liver function tests (including ALT, AST, total bilirubin) every 2 weeks during the first 2 months of therapy, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for hepatotoxicity as recommended.

Pulmonary Impairment

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Pulmonary Impairment.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

Renal Dysfunction

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Renal Dysfunction.

The exposure to crizotinib is increased in patients with preexisting severe renal dysfunction (CrCl less than 30 mL/min [calculated using the modified Cockcroft-Gault equation for adult patients and the Schwartz equation for pediatric patients]) not requiring dialysis; a reduced dosage of crizotinib is recommended in these patients. Care should be exercised when using this drug in patients with severe renal dysfunction not requiring dialysis. No dose adjustment is recommended in patients with mild to moderate renal dysfunction (CrCl 30 to 89 mL/min).

Visual Defect/Disturbance

Moderate:

crizotinib

Crizotinib has a moderate potential interaction with Visual Defect/Disturbance.

Cases of optic atrophy and optic nerve disorder leading to vision loss have been reported with the use of crizotinib. Assessment of visual symptoms for all patients is recommended monthly during therapy; new visual symptoms should be reported to an eye specialist. For pediatric and young adult patients with anaplastic large cell lymphoma or inflammatory myofibroblastic tumor, baseline and follow-up ophthalmologic examinations (including retinal examination) should be obtained within 1 month of starting crizotinib and every 3 months thereafter. The ophthalmological evaluation should consist of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT), and other evaluations as appropriate. Crizotinib should be permanently discontinued for grade 3 or 4 ocular disorders or severe visual loss (best corrected vision less than 20/200 in 1 or both eyes) unless another cause is identified. There is insufficient information to characterize the risks of resumption of crizotinib in patients who develop visual symptoms or visual loss; a decision to resume treatment with crizotinib should consider the potential benefits versus risks to the patient.

More resources

crizotinib

A total of 860 drugs are known to interact with crizotinib.

triclabendazole

A total of 252 drugs are known to interact with triclabendazole.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.