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Drug Interactions between daprodustat and pralsetinib

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

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Interactions between your drugs

Moderate

pralsetinib daprodustat

Applies to: pralsetinib and daprodustat

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations and the risk of adverse effects associated with daprodustat, which is primarily metabolized by the isoenzyme. When gemfibrozil (600 mg twice daily for 5 days), a potent CYP450 2C8 inhibitor, was administered with a single daprodustat dose of 100 mg on day 4 of gemfibrozil administration, daprodustat peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.9-fold and 18.6-fold, respectively. In addition, daprodustat Cmax and AUC are predicted to increase by at least 3-fold and 4-fold, respectively, following concomitant administration with clopidogrel 75 mg once daily (a moderate CYP450 2C8 inhibitor). When trimethoprim (200 mg twice daily for 5 days), a weak CYP450 2C8 inhibitor, was coadministered with a single daprodustat dose of 25 mg on day 4 of trimethoprim administration, daprodustat Cmax and AUC increased by 1.3-fold and 1.5-fold, respectively.

MANAGEMENT: Caution is recommended when daprodustat is coadministered with CYP450 2C8 inhibitors. Monitoring of hemoglobin levels and adjusting the dose of daprodustat may be considered following initiation or discontinuation of treatment with CYP450 2C8 inhibitors.

References

  1. (2023) "Product Information. Jesduvroq (daprodustat)." GlaxoSmithKline

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Drug and food interactions

Major

pralsetinib food

Applies to: pralsetinib

ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 to 8.5 hours.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pralsetinib. 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 pralsetinib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, constipation, hypertension, and pneumonia.

MANAGEMENT: Pralsetinib should be administered on an empty stomach, at least 2 hours after or 1 hour before a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with pralsetinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
  3. (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406

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Moderate

daprodustat food

Applies to: daprodustat

MONITOR: Smoking and alcohol consumption during therapy with daprodustat may increase the risk of gastric or esophageal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during daprodustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if daprodustat is prescribed to current tobacco smokers or alcohol drinkers. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.

References

  1. (2023) "Product Information. Jesduvroq (daprodustat)." GlaxoSmithKline

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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

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

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