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Drug Interactions between crizotinib and Lytgobi

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

crizotinib futibatinib

Applies to: crizotinib and Lytgobi (futibatinib)

MONITOR: Coadministration with inhibitors of CYP450 3A4 that can also inhibit P-glycoprotein (P-gp) may increase the plasma concentrations of futibatinib. Futibatinib is a substrate of both the CYP450 3A4 isoenzyme and P-gp efflux transporter. Drug interaction studies have shown that single dose administration of futibatinib with multiple doses of itraconazole, a combined potent P-gp and CYP450 3A4 inhibitor, increased futibatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 41%, respectively, compared to futibatinib alone. Increased exposure to futibatinib may increase the risk and severity of adverse effects such as retinal pigment epithelial detachment, dry eye/corneal keratitis, pyrexia, hyperphosphatemia and soft tissue mineralization, palmar-plantar erythrodysesthesia syndrome, fatigue, nail toxicity, urinary tract infection, constipation, diarrhea, dry mouth, increased liver function tests (ALT and AST), stomatitis, abdominal pain, ascites, bile duct obstruction, and musculoskeletal pain. The interaction has not been studied with other, less potent dual inhibitors of CYP450 3A4 and P-gp.

MANAGEMENT: Caution is advised when futibatinib is used with inhibitors of CYP450 3A4 that can also inhibit P-gp. Clinical and laboratory monitoring for the development of adverse effects is recommended and the futibatinib dosage adjusted as necessary.

References (1)
  1. (2022) "Product Information. Lytgobi (futibatinib)." Taiho Oncology, Inc., 1

Drug and food interactions

Major

crizotinib food

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
Major

futibatinib food

Applies to: Lytgobi (futibatinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of futibatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to futibatinib may increase the risk of adverse effects such as retinal pigment epithelial detachment, dry eye/corneal keratitis, pyrexia, hyperphosphatemia and soft tissue mineralization, palmar-plantar erythrodysesthesia syndrome, fatigue, nail toxicity, urinary tract infection, constipation, diarrhea, dry mouth, increased liver function tests (ALT and AST), stomatitis, abdominal pain, ascites, bile duct obstruction, and musculoskeletal pain.

MANAGEMENT: Patients should be advised to avoid consumption of grapefruit or grapefruit juice during treatment with futibatinib.

References (1)
  1. (2022) "Product Information. Lytgobi (futibatinib)." Taiho Oncology, Inc., 1

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • crizotinib
  • Lytgobi (futibatinib)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.