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AYVAKIT® (avapritinib) 25 mg white logo

Dosing and administration information for patients with Advanced SM taking AYVAKIT1

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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.

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Below is helpful information for starting treatment, monitoring treatment response, and recommended dose modifications for adverse reactions if necessary.
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Patient monitoring for initiating and continuing treatment with AYVAKIT1

PLATELET MONITORING

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 therapyMonitoring planTreatment plan
Prior to initiationPerform platelet count.AYVAKIT is not recommended in Advanced SM patients with platelet counts <50 x 109/L.
First 8 weeksPerform 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 weeksMonitor platelet counts:
  • Every 2 weeks if values are <75 x 109/L (or more frequently as clinically indicated)
  • Every 4 weeks if values are 75-100 x 109/L
  • As clinically indicated if values are >100 x 109/L

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.

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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.

60%
Dose interruption
68%
Dose reduction (median time to reduction: 6.9 weeks)7
10%
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:

  • Thrombocytopenia
  • Neutropenia
  • Anemia
  • Elevated blood alkaline phosphatase
  • Cognitive disorder
  • Peripheral edema
  • Periorbital edema
  • Fatigue
  • Arthralgia
RECOMMENDED DOSE REDUCTIONS FROM THE 200 MG ONCE-DAILY STARTING DOSE1
Recommended dose reductions for adverse reactions
Dose ReductionStarting Dose (200 mg)a
First100 mg once daily
Second50 mg once daily
Third25 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
Adverse ReactionSeveritybDosage Modification
Intracranial HemorrhageAny GradePermanently discontinue AYVAKIT.
Cognitive EffectsGrade 1Continue 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 3Withhold AYVAKIT until improvement to baseline, Grade 1, or resolution. Resume at same dose or reduced dose.
Grade 4Permanently discontinue AYVAKIT.
Thrombocytopenia<50 x 109/LInterrupt 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.
OtherGrade 3 or Grade 4Withhold 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.

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For further information on dose modifications and patient monitoring, review the Prescribing Information and download the AYVAKIT Dosing and Administration Guide

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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.

Intracranial Hemorrhage (ICH)1
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Thrombocytopenia1
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Cognitive Effects1
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Other Adverse Reactions1
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See hypothetical profiles of patients taking AYVAKIT

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INDICATION

AYVAKIT® (avapritinib) 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.

IMPORTANT SAFETY INFORMATION
INDICATION & IMPORTANT SAFETY INFORMATION

Intracranial Hemorrhage—Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (e.g., subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. 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 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. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. 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 Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including 28% of 148 AdvSM patients (3% were Grade ≥3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

Photosensitivity—AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.

Embryo-Fetal Toxicity—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 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 following the final dose.

Adverse Reactions—The most common adverse reactions (≥20%) were edema, diarrhea, nausea, and fatigue/asthenia.

Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers.

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here to see the full Prescribing Information for AYVAKIT.

References:

  1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Mastocytosis V.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 20, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  3. Gilreath JA et al. Clin Pharmacol. 2019;11:77-92.
  4. Verstovsek S. Eur J Haematol. 2013;90(2):89-98.
  5. Garcia-Montero AC et al. Blood. 2006;108(7):‍2366-2372.
  6. Kristensen T et al. Am J Hematol. 2014;89(5):493-498.
  7. Data on file. Blueprint Medicines Corporation, Cambridge, MA. 2021.
  8. Gotlib J et al. Blood. 2013;121(13):‍2393-2401.
  9. WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022 [cited September 20, 2023]. (WHO Classification of Tumours Series. 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63
  10. Pardanani A. Am J Hematol. 2023;98(7):1097-1116.
  11. Theoharides TC et al. N Engl J Med. 2015;373(2):163-172.
  12. Pardanani A et al. Blood. 2009;114(18):‍3769-3772.
  13. Passamonti F, Maffioli M. Hematology Am Soc Hematol Educ Program. 2016;2016(1):534-542.
  14. Valent P et al. Blood. 2017;129(11):1420-1427.
  15. Stoecker MM, Wang E. Arch Pathol Lab Med. 2012;136(7):832-838.
  16. Arber DA et al. Blood. 2016;127(20):‍2391-2405.
  17. Greiner G et al. Clin Chem. 2018;64(3):547-555.
  18. Gotlib J et al. Nat Med. 2021;27(12):‍2192-2199.
  19. Kwon J. Blood Res. 2021;56(suppl 1):S5-S16.
  20. Meggendorfer M et al. Blood. 2012;120(15):‍3080-3088.
  21. Greenberg PL et al. Blood. 2012;120(12):‍2454-2465.
  22. Malcovati L et al. Blood. 2020;136(2):157-170.