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Drug Interactions between avapritinib and bivalirudin

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

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Interactions between your drugs

Major

bivalirudin avapritinib

Applies to: bivalirudin and avapritinib

MONITOR CLOSELY: Coadministration of avapritinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Serious and fatal hemorrhagic events have been reported during avapritinib therapy, including gastrointestinal, hepatic, tumor, ocular, and intracranial hemorrhages. In clinical studies, intracranial hemorrhage (e.g., subdural hematoma, cerebral hemorrhage, cerebral hematoma) occurred in 1% to 3% of patients, with onset ranging from 1.7 to 19.3 months after initiating avapritinib. Overall, 0.9% of patients receiving avapritinib required permanent discontinuation for an intracranial hemorrhage, and 1.2% required treatment interruption followed by dosage reduction. The mechanism for the bleeding events is not well understood, although treatment with avapritinib commonly causes thrombocytopenia.

MANAGEMENT: Concomitant use of avapritinib with other drugs that increase the risk of bleeding should be approached with caution. Close clinical and laboratory monitoring for bleeding complications is recommended during therapy. Patients should be advised to promptly report any signs and symptoms of bleeding to their physician. Patients should also seek immediate medical attention if they experience neurological signs and symptoms that may be associated with intracranial hemorrhage such as severe headache, vision problems, somnolence, or focal weakness. Brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) may be performed at the discretion of the physician based on severity and clinical presentation. For patients with observed intracranial hemorrhage during treatment with avapritinib, some authorities recommend that avapritinib be discontinued permanently regardless of Grade. Others suggest withholding avapritinib for Grade 1 or 2 reactions until resolution, then resuming at a reduced dosage. However, avapritinib should be permanently discontinued upon recurrence of Grade 1 or 2 reactions or first occurrence of Grade 3 or 4 reactions.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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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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