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Drug Interactions between avapritinib and deferiprone

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

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Interactions between your drugs

Major

deferiprone avapritinib

Applies to: deferiprone and avapritinib

GENERALLY AVOID: Coadministration of deferiprone and other drugs that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Serious infection and death have been reported. The mechanism by which deferiprone leads to neutropenia or agranulocytosis is unknown. In pooled clinical trials of 642 patients with thalassemia syndromes, neutropenia occurred in 6.2% and agranulocytosis in 1.7% of deferiprone-treated patients. Similarly, agranulocytosis occurred in 1.5% of deferiprone-treated patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. Pediatric patients experienced a higher rate of decreases in neutrophil count when compared to adults being treated with deferiprone for the same condition. Neutropenia and agranulocytosis generally resolve upon discontinuation of deferiprone.

MANAGEMENT: Concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis should generally be avoided. Some authorities consider this combination to be contraindicated. If coadministration is unavoidable, the patient's baseline absolute neutrophil count (ANC) should be measured and then closely monitored during deferiprone therapy according to the manufacturer's product labeling. If neutropenia or infection develops, deferiprone and any other concomitant therapy associated with neutropenia or agranulocytosis should be discontinued. A complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an ANC, and a platelet count should be obtained daily until recovery. Patients should be advised to seek immediate medical assistance if they develop symptoms of infection (e.g., fever, sore throat, flu-like symptoms). For patients who develop agranulocytosis (ANC less than 0.5 x 10^9/L), hospitalization should be considered, and deferiprone should not be resumed following recovery unless potential benefits outweigh the risks. Likewise, patients who develop neutropenia with deferiprone should not be rechallenged unless potential benefits outweigh the risks.

References

  1. (2023) "Product Information. Ferriprox (deferiprone)." Chiesi Ltd
  2. (2022) "Product Information. Ferriprox (deferiprone)." Apotex Pty Ltd, 2.0
  3. (2023) "Product Information. Ferriprox MR (deferiprone)." Chiesi Canada Corp
  4. (2023) "Product Information. Ferriprox (deferiprone)." Chiesi USA, Inc
View all 4 references

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Drug and food interactions

Major

avapritinib food

Applies to: avapritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. 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. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% 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 exposure to avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.

ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.

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

References

  1. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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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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