Drug Interactions between acalabrutinib and avapritinib
This report displays the potential drug interactions for the following 2 drugs:
- acalabrutinib
- avapritinib
Interactions between your drugs
acalabrutinib avapritinib
Applies to: acalabrutinib and avapritinib
MONITOR CLOSELY: Coadministration of acalabrutinib 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 acalabrutinib therapy. In the combined safety database of 1040 patients with hematologic malignancies treated with acalabrutinib monotherapy, major hemorrhage (serious or >= Grade 3 bleeding events or any central nervous system bleeding) occurred in 3.6% of patients, with fatalities occurring in 0.1% of patients. Overall, bleeding events of any grade, including bruising and petechiae, occurred in 46% of patients. The mechanism is not well understood, as bleeding events have occurred in patients both with and without thrombocytopenia. In clinical trials, major hemorrhagic events were experienced by 3% of patients taking acalabrutinib without concurrent antithrombotic agents. The addition of antithrombotic agents increased this percentage to 4.3%.
MANAGEMENT: Concomitant use of acalabrutinib with antithrombotic agents or other drugs that increase bleeding risk 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. Refer to the product labeling for guidance on acalabrutinib dosage adjustments in patients with concurrent Grade 3 thrombocytopenia and bleeding.
References
- (2019) "Product Information. Calquence (acalabrutinib)." AstraZeneca Pty Ltd
- (2023) "Product Information. Calquence (acalabrutinib)." AstraZeneca Canada Inc
- (2021) "Product Information. Calquence (acalabrutinib)." AstraZeneca UK Ltd
- (2022) "Product Information. Calquence (acalabrutinib)." Astra-Zeneca Pharmaceuticals
Drug and food interactions
acalabrutinib food
Applies to: acalabrutinib
GENERALLY AVOID: Consumption of grapefruit and/or grapefruit juice may increase the plasma concentrations of acalabrutinib. 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 specifically, but has been reported for other CYP450 3A4 inhibitors. When acalabrutinib was administered with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 5 days) in 17 healthy subjects, acalabrutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.9- and 5.1-fold, respectively. Physiologically based pharmacokinetic (PBPK) simulations showed that moderate CYP450 3A4 inhibitors (erythromycin, fluconazole, diltiazem) increased acalabrutinib Cmax and AUC by 2- to nearly 3-fold. In healthy subjects, administration of acalabrutinib with the moderate CYP450 3A4 inhibitors fluconazole (400 mg as a single dose) or isavuconazole (200 mg as a repeated dose for 5 days) increased acalabrutinib Cmax and AUC by 1.4- to 2-fold, while the Cmax and AUC of the active metabolite, ACP-5862, was decreased by 0.65- to 0.88-fold. 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 acalabrutinib exposure may potentiate the risk of toxicities such as hemorrhage, infection, cytopenias, malignancies, and atrial fibrillation or flutter.
Food may delay the absorption of acalabrutinib, but does not appear to affect the overall extent of absorption. When a single 100 mg tablet or a 75 mg developmental formulation of acalabrutinib was administered with a high-fat, high-calorie meal (approximately 918 calories; 59 grams carbohydrate, 59 grams fat, 39 grams protein) in healthy study subjects, mean acalabrutinib Cmax was decreased by 54% and 73%, respectively, while time to reach Cmax was delayed by 1 to 2 hours compared to administration under fasted conditions. However, mean AUC was not affected.
MANAGEMENT: Acalabrutinib may be administered with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with acalabrutinib.
References
- (2019) "Product Information. Calquence (acalabrutinib)." AstraZeneca Pty Ltd
- (2023) "Product Information. Calquence (acalabrutinib)." AstraZeneca Canada Inc
- (2021) "Product Information. Calquence (acalabrutinib)." AstraZeneca UK Ltd
- (2022) "Product Information. Calquence (acalabrutinib)." Astra-Zeneca Pharmaceuticals
- Chen B, Zhou D, Wei H, et al. (2022) "Acalabrutinib CYP3A-mediated drug-drug interactions: clinical evaluations and physiologically based pharmacokinetic modelling to inform dose adjustment strategy" Br J Clin Pharmacol, 88, p. 3716-29
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
- (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.