Dosing and administration information for patients with Advanced SM taking AYVAKIT1
Starting AYVAKIT—one tablet, once-daily dosing1
The recommended dosage of AYVAKIT for Advanced SM is 200 mg orally once daily.
AYVAKIT should be taken1:
One tablet orally
One time day
On an empty stomach, at least 1 hour before or 2 hours after a meal
Do not initiate AYVAKIT in patients with platelet counts <50 x 109/L.
Treatment should continue until disease progression or unacceptable toxicity.
Do not take an additional dose if vomiting occurs after AYVAKIT has been taken, but continue with the next scheduled dose.
AYVAKIT is also available in dose strengths of 100 mg, 50 mg, and 25 mg for dose modification for adverse reactions or drug interactions (for example, CYP3A inhibitors).
Avoid concomitant use of AYVAKIT with strong or moderate CYP3A inhibitors or inducers. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the recommended starting dosage of AYVAKIT is 50 mg orally once daily.
Watch Dr McCloskey review information about managing patients who have started treatment with AYVAKIT.
Patient monitoring for initiating and continuing treatment with AYVAKIT1
A platelet count must be performed prior to initiation of therapy, during the first 8 weeks of treatment, and potentially longer depending on what is clinically indicated. AYVAKIT is not recommended for patients with platelet counts <50 x 109/L.1
|Time on therapy
|Prior to initiation
|Perform platelet count.
|AYVAKIT is not recommended in Advanced SM patients with platelet counts <50 x 109/L.
|First 8 weeks
|Perform platelet count every 2 weeks regardless of baseline platelet count.
If platelet count <50 x 109/L occurs, interrupt AYVAKIT until platelet count is ≥50 x 109/L, then resume at reduced dose.
If platelet counts do not recover above 50 x 109/L, platelet support may be necessary.
|After 8 weeks
|Monitor platelet counts:
Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia.
If any ICH occurs, permanently discontinue AYVAKIT.
Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction of AYVAKIT. Platelet support may be necessary.
It was common to modify AYVAKIT dosage1
MANY PATIENTS IN THE EXPLORER AND PATHFINDER TRIALS HAD THEIR DOSE REDUCED OR INTERRUPTED DUE TO ADVERSE REACTIONS1
AYVAKIT DOSE REDUCTIONS AND INTERRUPTIONS IN CLINICAL TRIALS1
Among patients with Advanced SM in clinical trials who started at 200 mg (N=80), many patients had their dose modified.
Dose reduction (median time to reduction: 6.9 weeks)7
Permanent discontinuation due to adverse reaction
Adverse reactions requiring dosage interruption or dose reduction in >2% of patients who received AYVAKIT at 200 mg once daily:
- Elevated blood alkaline phosphatase
- Cognitive disorder
- Peripheral edema
- Periorbital edema
RECOMMENDED DOSE REDUCTIONS FROM THE 200 MG ONCE-DAILY STARTING DOSE1
|Recommended dose reductions for adverse reactions
|Starting Dose (200 mg)a
|100 mg once daily
|50 mg once daily
|25 mg once daily
aPermanently discontinue AYVAKIT in patients who are unable to tolerate a dose of 25 mg daily.
RECOMMENDED DOSE MODIFICATIONS FOR PATIENTS EXPERIENCING ADVERSE REACTIONS1
|Permanently discontinue AYVAKIT.
|Continue AYVAKIT at same dose or reduced dose or withhold until improvement to baseline or resolution. Resume at same dose or reduced dose.
|Grade 2 or Grade 3
|Withhold AYVAKIT until improvement to baseline, Grade 1, or resolution. Resume at same dose or reduced dose.
|Permanently discontinue AYVAKIT.
|<50 x 109/L
|Interrupt AYVAKIT until platelet count is ≥50 x 109/L, then resume at reduced dose per the recommended reductions. If platelet counts do not recover above 50 x 109/L, consider platelet support.
|Grade 3 or Grade 4
|Withhold AYVAKIT until improvement to Grade ≤2. Resume at same dose or reduced dose, as clinically appropriate.
bSeverity as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
For patients experiencing adverse reactions, dose modification may be necessary1
For patients who experience certain adverse reactions, additional information is provided below and in the AYVAKIT Prescribing Information to help guide in modifying and managing their treatment.