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Drug Interactions between atazanavir and pralsetinib

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

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Interactions between your drugs

Major

atazanavir pralsetinib

Applies to: atazanavir and pralsetinib

GENERALLY AVOID: Coadministration with potent CYP450 3A inhibitors may significantly increase the plasma concentrations of pralsetinib, which is primarily metabolized by the isoenzyme. Drug interactions studies have shown single dose administration of pralsetinib 200 mg with itraconazole, a potent CYP450 3A4 inhibitor, increased pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 84% and 251%, respectively. Increased exposure to pralsetinib may increase the risk of serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, hypertension, and hemorrhage.

MANAGEMENT: Concomitant use of pralsetinib with potent CYP450 3A inhibitors should generally be avoided.

References

  1. (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation

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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

atazanavir food

Applies to: atazanavir

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb

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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.

See also

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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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