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Drug Interactions between Nexium and selpercatinib

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

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Interactions between your drugs

Major

esomeprazole selpercatinib

Applies to: Nexium (esomeprazole) and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When selpercatinib was administered under fasted conditions with multiple daily doses of omeprazole, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. These changes may result in diminished anti-tumor activity of selpercatinib. By contrast, when selpercatinib was administered with a high-fat meal (approximately 800 to 1000 calories;150 calories from protein, 250 calories from carbohydrate, 500 to 600 calories from fat) or a low-fat meal (approximately 390 calories; 10 g fat) in combination with multiple daily doses of omeprazole, selpercatinib Cmax was reduced by 49% and 22%, respectively, but AUC was not significantly altered.

MANAGEMENT: Concomitant use of selpercatinib with proton pump inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib with food or a meal to minimize the clinical impact of the interaction.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Drug and food interactions

Major

selpercatinib food

Applies to: selpercatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When selpercatinib was coadministered with multiple doses of itraconazole, a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of selpercatinib with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem, fluconazole, or verapamil is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. 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 selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).

MANAGEMENT: Patients should limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company

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Moderate

esomeprazole food

Applies to: Nexium (esomeprazole)

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

References

  1. (2001) "Product Information. Nexium (esomeprazole)." Astra-Zeneca Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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

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