Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Blueprint Medicines (Netherlands) B.V., Gustav Mahlerplein 2, 1082 MA Amsterdam, Netherlands
AYVAKYT is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.
Therapy should be initiated by a physician experienced in the administration of anticancer therapy.
Patient selection for treatment of unresectable or metastatic GIST harbouring the PDGFRA D842V mutation should be based on a validated test method.
The recommended starting dose of avapritinib is 300 mg orally once daily, on an empty stomach (see Method of administration). The dose should be adjusted based on safety and tolerability.
Treatment should be continued until disease progression or unacceptable toxicity.
Concomitant use of avapritinib with strong or moderate CYP3A inhibitors should be avoided. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dose of avapritinib should be reduced from 300 mg orally once daily to 100 mg orally once daily (see section 4.5).
If vomiting occurs after taking a dose of avapritinib, the patient should not take an additional dose but continue with the next scheduled dose.
If a dose of avapritinib is missed, the patient should make up for the missed dose unless the next scheduled dose is within 8 hours (see Method of administration). If the dose has not been taken at least 8 hours prior to the next dose, then that dose should be omitted and the patient should resume treatment with the next scheduled dose.
Interruption of treatment with or without dose reduction may be considered to manage adverse reactions based on severity and clinical presentation. Patients may have their dose reduced by 100 mg increments to a minimum dose of 100 mg once daily.
Recommended dose modifications are indicated in Table 1.
Table 1. Recommended dose modifications for AYVAKYT for adverse reactions:
| Adverse reaction | Severity* | Dosage modification |
|---|---|---|
| Intracranial haemorrhage (see section 4.4) | All Grades | Permanently discontinue AYVAKYT. |
| Cognitive effects** (see section 4.4) | Grade 1 | Continue at the same dose or interrupt until improvement to baseline or resolution. Resume at the same dose or a reduced dose. |
| Grade 2 or Grade 3 | Interrupt therapy until improved to baseline, Grade 1, or resolution. Resume at the same dose or at a reduced dose. | |
| Grade 4 | Permanently discontinue AYVAKYT. | |
| Other (also see section 4.4 and section 4.8) | Grade 3 or Grade 4 | Interrupt therapy until less than or equal to Grade 2. Resume at the same dose or at a reduced dose, if warranted. |
* The severity of adverse reactions graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0
** Adverse reactions with impact on Activities of Daily Living (ADLs) for Grade 2 or higher adverse reactions
No dose adjustment is recommended for patients aged 65 years and above. Hepatic impairment No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin within upper limit of normal [ULN] and aspartate aminotransferase (AST) > ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST) and moderate hepatic impairment (total bilirubin >1.5 to 3.0 times ULN and any AST). Avapritinib has not been studied in subjects with severe (Child-Pugh class C) hepatic impairment and therefore its use in patients with severe hepatic impairment cannot be recommended (see section 5.2).
No dose adjustment is recommended for patients with mild and moderate renal impairment [creatinine clearance (CLcr) 30-89 mL/min estimated by Cockcroft-Gault]. Avapritinib has not been studied in patients with severe renal impairment (CLcr 15-29 mL/min) or end-stage renal disease (CLcr <15 mL/min), therefore its use in patients with severe renal impairment or end-stage renal disease cannot be recommended (see section 5.2).
The safety and efficacy of AYVAKYT in children aged 0 to 18 years have not yet been established.
No data are available.
AYVAKYT is for oral use. The tablets should be taken on an empty stomach at least 1 hour before or at least 2 hours after a meal (see section 5.2). Patients should swallow the tablet(s) whole with a glass of water.
No cases of overdose have been reported in clinical trials with avapritinib. The maximum dose of AYVAKYT studied clinically is 600 mg orally once daily. Adverse reactions observed at this dose were consistent with the safety profile at 300 mg or 400 mg once daily (see section 4.8).
There is no known antidote for AYVAKYT overdose. In the event of suspected overdose, AYVAKYT should be interrupted and supportive care instituted. Based on the large volume of distribution of avapritinib and extensive protein binding, dialysis is unlikely to result in significant removal of avapritinib.
30 months.
This medicinal product does not require any special storage conditions.
High-density polyethylene (HDPE) bottle with child-resistant cap with foiled induction seal liner and a desiccant in canister.
Each carton contains one bottle with 30 film-coated tablets.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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