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Drug Interactions between crizotinib and morphine

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

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Interactions between your drugs

Moderate

morphine crizotinib

Applies to: morphine and crizotinib

MONITOR: Coadministration with crizotinib may theoretically increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 2B6 (e.g., bupropion), P-glycoprotein (P-gp) (e.g., dabigatran), and/or the organic cation transporters 1 and 2 (OCT1, OCT2) (e.g., metformin). The proposed mechanism, based on in vitro data, is decreased clearance due to crizotinib-mediated inhibition of CYP450 2B6, P-gp, and/or OCT1 or OCT2.

MANAGEMENT: Although the clinical significance is unknown, caution is advised if crizotinib is used concomitantly with drugs that are substrates of CYP450 2B6, P-gp, and/or OCT1 or OCT2, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever crizotinib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group

Drug and food interactions

Major

morphine food

Applies to: morphine

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.

References (4)
  1. (2005) "Product Information. Avinza (morphine)." Ligand Pharmaceuticals
  2. Ghalie R (2005) Dear Health Care Professional. http://www.fda.gov/medwatch/safety/2005/AVINZA_DHCP_Letter_Oct2005.pdf
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. (2015) "Canadian Product Information."
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

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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.

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