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Drug Interactions between fedratinib and Ubrelvy

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

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Interactions between your drugs

Moderate

fedratinib ubrogepant

Applies to: fedratinib and Ubrelvy (ubrogepant)

ADJUST DOSE: Coadministration with moderate or weak inhibitors of CYP450 3A4 may increase the plasma concentrations of ubrogepant, which is primarily metabolized by the isoenzyme. When ubrogepant was administered with the moderate CYP450 3A4 inhibitor verapamil during in vivo studies, ubrogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 3.5-fold, respectively. Dedicated drug interaction studies have not been conducted to assess concomitant use of ubrogepant with weak CYP450 3A4 inhibitors. Ubrogepant exposure is not expected to increase by more than 2-fold when used with weak CYP450 3A4 inhibitors, per a conservative prediction from the manufacturer.

MANAGEMENT: The manufacturer recommends an initial ubrogepant dose of 50 mg when coadministered with moderate or weak CYP450 3A4 inhibitors. If needed, a second ubrogepant dose should be avoided within 24 hours of the initial dose when used with moderate CYP450 3A4 inhibitors. When used with weak CYP450 3A4 inhibitors, a second 50 mg dose of ubrogepant may be administered at least 2 hours after the initial dose, if needed.

References

  1. (2019) "Product Information. Ubrelvy (ubrogepant)." Allergan Inc

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Drug and food interactions

Moderate

fedratinib food

Applies to: fedratinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of fedratinib. 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 a single 300 mg oral dose of fedratinib (0.75 times the recommended dose) was coadministered with 200 mg twice daily ketoconazole, a potent CYP450 3A4 inhibitor, fedratinib total systemic exposure (AUC(inf)) increased by approximately 3-fold. Using physiologically based pharmacokinetic (PBPK) simulations, coadministration of fedratinib 400 mg once daily and ketoconazole 400 mg once daily is predicted to increase fedratinib AUC at steady state by 2-fold. Coadministration with the moderate CYP450 3A4 inhibitors, erythromycin (500 mg three times daily) or diltiazem (120 mg twice daily), is predicted to increase fedratinib AUC by approximately 1.5- to 2-fold following single-dose administration and by approximately 1.2-fold at steady state. 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 fedratinib exposure may potentiate the risk of adverse reactions such as nausea, vomiting, diarrhea, anemia, thrombocytopenia, neutropenia, encephalopathy (including Wernicke's), liver (ALT, AST) and pancreatic (amylase, lipase) enzyme elevations, increased blood creatinine, and secondary malignancies.

Food does not affect the oral bioavailability of fedratinib to a clinically significant extent. Administration of a single 500 mg dose (1.25 times the recommended dose) with a low-fat, low-calorie meal (162 calories; 6% from fat, 78% from carbohydrate, 16% from protein) or a high-fat, high-calorie meal (815 calories; 52% from fat, 33% from carbohydrate, 15% from protein) increased fedratinib peak plasma concentration (Cmax) and systemic exposure (AUC) by up to 14% and 24%, respectively.

MANAGEMENT: Fedratinib may be taken with or without food. However, administration with a high-fat meal may help reduce the incidence of nausea and vomiting. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with fedratinib.

References

  1. Wu F, Krishna G, Surapaneni S (2020) "Physiologically based pharmacokinetic modeling to assess metabolic drug-drug interaction risks and inform the drug label for fedratinib." Cancer Chemother Pharmacol, 86, p. 461-73
  2. (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
  3. (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals Ltd

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Moderate

ubrogepant food

Applies to: Ubrelvy (ubrogepant)

ADJUST DOSE: Grapefruit and grapefruit juice may increase the plasma concentrations of ubrogepant. 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 but has been reported for other CYP450 3A4 inhibitors. When ubrogepant was administered with the moderate CYP450 3A4 inhibitor verapamil during in vivo studies, ubrogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 3.5-fold, respectively. 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.

When administered with a high-fat meal, ubrogepant time to maximum plasma concentration (Tmax) was delayed by 2 hours, which resulted in a 22% decrease in Cmax and no change in AUC. Ubrogepant was administered without regard to food in clinical efficacy studies.

MANAGEMENT: Ubrogepant may be administered with or without food. Per the manufacturer, when coadministered with grapefruit or grapefruit juice, the initial ubrogepant dose should be 50 mg, and if needed, a second ubrogepant dose should be avoided within 24 hours of the initial dose.

References

  1. (2019) "Product Information. Ubrelvy (ubrogepant)." Allergan Inc

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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.