Avapritinib
Avapritinib Uses, Dosage, Side Effects, Food Interaction and all others data.
Avapritinib, or BLU-285, is a selective tyrosine kinase inhibitor of KIT and platelet derived growth factor receptor alpha indicated for the treatment of unresectable, metastatic gastrointestinal stromal tumors. It is one of the first medications available for the treatment of multidrug resistant cancers. Avapritinib shares a similar mechanism with ripretinib.
Avapritinib was granted FDA approval on 9 January 2020.
Avapritinib is a selective kinase inhibitor that negatively modulates the action of cell transporters to resensitize them to other chemotherapies. It has a long duration of action as it is given once daily. Patients should be counselled regarding the risk of intracranial hemorrhage, CNS effects, and embryo-fetal toxicity.
| Trade Name | Avapritinib |
| Availability | Prescription only |
| Generic | Avapritinib |
| Avapritinib Other Names | Avapritinib |
| Related Drugs | omeprazole, Prilosec, lansoprazole, Prevacid, imatinib, Gleevec, sunitinib, Sutent, Stivarga, regorafenib |
| Weight | 100mg, 200mg, 300mg |
| Type | Oral tablet |
| Formula | C26H27FN10 |
| Weight | Average: 498.57 Monoisotopic: 498.240419072 |
| Protein binding | Avapritinib is 98.8% protein bound in serum. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Avapritinib is a selective tyrosine kinase inhibitor being investigated for the treatment of multidrug resistant gastrointestinal tumors.
Avapritinib is indicated for the treatment of unresectable, metastatic gastrointestinal stromal tumors with a platelet-derived growth factor receptor alpha exon 18 mutation.
Avapritinib is also used to associated treatment for these conditions: Metastatic Gastrointestinal Stromal Tumor, Unresectable Gastrointestinal stromal tumor
How Avapritinib works
Avapritinib has a negative modulating effect on the transporters ABCB1 and ABCG2, which mediate the multidrug resistance phenotype of some cancers. This modulation may be due to interactions of avapritinib with the drug binding pocket of these transporters. Negative modulation of these transporters, resensitizes cancerous cells to treatment with chemotherapeutic agents like paclitaxel.
Toxicity
Data regarding overdoses of avapritinib are not readily available.
Food Interaction
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of avapritinib.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of avapritinib.
- Take on an empty stomach. Take more than 1 hour before or 2 hours after a meal.
[Major] 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
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.
Avapritinib Disease Interaction
Volume of Distribution
The mean apparent volume of distribution is 1200L.
Elimination Route
A 300mg oral dose of avapritinib reaches a Cmax of 813ng/mL with a Tmax of 2.0-4.1h and an AUC of 15400h*ng/mL.
Half Life
The half life of avapritinib is 32-57h.
Clearance
The mean apparent oral clearance of avapritinib is 19.5L/h.
Elimination Route
Avapritinib is 70% eliminated in the feces with 11% as the unchanged drug and 18% eliminated in the urine with 0.23% as the unchanged drug.
Innovators Monograph
You find simplified version here Avapritinib
