for your patients
AYVAKIT SHOULD BE TAKEN1:
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. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the recommended starting dosage of AYVAKIT is 50 mg orally once daily.
Below is helpful information for starting your patient’s treatment, monitoring their response, and recommended dose modifications for adverse reactions, if necessary.
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||Monitoring plan||Treatment plan|
|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, consider platelet support.
|After 8 weeks||Monitor platelet counts:
Monitor patients closely for the risk of ICH, including those with thrombocytopenia, vascular aneurysm or a history of intracranial hemorrhage or cerebrovascular accident within the prior year.
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.
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 Advanced SM patients in clinical trials who started at 200 mg (N=80), many patients had their dose modified.
(median time to
reduction: 6.9 weeks)6
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|
|Dose Reduction||Starting Dose (200 mg)a|
|First||100 mg once daily|
|Second||50 mg once daily|
|Third||25 mg once daily|
a Permanently discontinue AYVAKIT in patients who are unable to tolerate a dose of 25 mg daily.
Recommended dose modifications for patients experiencing adverse reactions1
|Adverse Reaction||Severityb||Dosage Modification|
|Intracranial Hemorrhage||Any Grade||Permanently discontinue AYVAKIT.|
|Cognitive Effects||Grade 1||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.|
|Grade 4||Permanently discontinue AYVAKIT.|
|ThrombocytopeniaThrombo-cytopenia||<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.|
|Other||Grade 3 or Grade 4||Withhold AYVAKIT until improvement to Grade ≤2. Resume at same dose or reduced dose, as clinically appropriate.|
IMPORTANT SAFETY INFORMATION
There are no contraindications for AYVAKIT.
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In AdvSM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in AdvSM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were Grade >3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; <1% of these events were Grade 3. Confusional state occurred in 6% of patients; <1% of these events were Grade 3. Other events occurred in < 2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
The most common adverse reactions (≥20%) at all doses were edema, diarrhea, nausea and fatigue/asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.
Please click here to see the full Prescribing Information for AYVAKIT.
AYVAKIT is indicated for the treatment of adult patients with Advanced SM (AdvSM) including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of <50 x 109/L.
- AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; June 2021.
- Gilreath JA, et al. Clin Pharmacol. 2019;11:77-92.
- Garcia-Montero AC, et al. Blood. 2006;108(7):2366-2372.
- Verstovsek S. Eur J Haematol. 2013;90(2):89-98.
Additional information for managing and modifying treatment for patients experiencing specific adverse events.