Intracranial hemorrhage may occur with AYVAKIT treatment.In clinical trials:
- ICH occurred in 2 out of 75 patients (2.7%) with Advanced SM who received AYVAKIT at 200 mg daily and had platelet counts ≥50 x 109/L prior to initiation of therapy
- For all patients with Advanced SM receiving AYVAKIT at 200 mg daily, 3 of 80 (3.8%) experienced ICH regardless of platelet counts
Monitor patients closely for the risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year.
Advise patients to contact their healthcare provider immediately if experiencing neurological signs and symptoms that may be associated with intracranial hemorrhage (ie, severe headache, vomiting, drowsiness, dizziness, confusion, slurred speech, or paralysis).
- 18/80 (23%) of patients experienced a Grade ≥3 adverse event of thrombocytopenia or platelet count decrease
- Median time to onset: 3.1 weeks
- Median time to improvement: 3.3 weeks*
Thrombocytopenia was generally reversible by reducing or interrupting treatment with AYVAKIT. Dose interruptions and dose reductions for thrombocytopenia occurred in 20% and 22% of AYVAKIT-treated patients, respectively.
If your patient experiences platelet counts <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.
Use with caution in patients with potential increased risk of ICH. AYVAKIT is not recommended for use in patients with platelet counts <50 x 109/L.1
*Defined as improvement to Grade 0-2. Not all patients showed improvement; 4 patients were censored.Get more details on platelet monitoring
Cognitive adverse reactions can occur in patients taking AYVAKIT.In clinical trials:
- Cognitive adverse reactions occurred in 28% of 148 patients with systemic mastocytosis (3% were Grade ≥3). These reactions included:
- Memory impairment (16%)
- Cognitive disorder (10%)
- Confusional state (6%)
- Other cognitive effects that occurred in <2% of patients
- Median time to onset of first cognitive adverse reaction was 13.3 weeks (range 1 day to 1.8 years)
- Median time to improvement for patients experiencing cognitive effects ≥ Grade 2 to Grade 1 or complete resolution was 8.1 weeks
Dose modifications in clinical trials due to cognitive adverse reactions:
- 2% of patients required permanent discontinuation
- 8.1% of patients required dose interruption
- 8.8% of patients required dose reduction
Dose modifications for 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.|
Advise patients and caregivers to notify their healthcare provider if they experience new or worsening cognitive symptoms. Patients should not drive or operate hazardous machinery if they are experiencing cognitive adverse reactions.
- Serious adverse reactions occurred in 34% of patients receiving the recommended starting dose of 200 mg once daily
- Serious reactions occurring in ≥1% of patients were: anemia (5%), subdural hematoma (4%), pleural effusion, ascites, and pneumonia (3% each), acute kidney injury, gastrointestinal hemorrhage, intracranial hemorrhage, encephalopathy, gastric hemorrhage, large intestine perforation, pyrexia, and vomiting (2% each)
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.
Access more resources for you and your patients taking AYVAKIT.