AYVAKYT – one tablet, once-daily dosing, with a starting dose of 200 mg that can be modified to optimise patient management1
Managing your patients taking AYVAKYT1
The recommended dose of AYVAKYT is 200 mg orally, once daily
AYVAKYT should be taken as follows:1
One tablet orally
One time each day
On an empty stomach, at least 1 hour before or 2 hours after a meal
- Patients with Advanced SM must not exceed the recommended starting dose of 200 mg once daily
- Treatment should continue until disease progression or unacceptable toxicity occurs
- AYVAKYT is also available in dose strengths of 100 mg, 50 mg and 25 mg
- Concomitant use of AYVAKYT with potent or moderate CYP3A inhibitors should be avoided. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dose of AYVAKYT must be reduced from 200 mg to 50 mg orally once daily
Treatment with AYVAKYT is not recommended in patients with a platelet count <50 x 109/L
Additional instructions:
- AYVAKYT tablets should be swallowed whole with a glass of water
- Do not take an extra dose if vomiting occurs after taking a dose
- Do not make up for the missed dose within 8 hours of the next scheduled dose
Monitor your patients at initiation and as indicated during treatment to help reduce and manage potential adverse reactions1
Platelet monitoring1
| Time on therapy | Monitoring plan | Treatment plan |
| Prior to initiation | Perform platelet count | AYVAKYT is not recommended in Advanced SM patients with platelet count <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 AYVAKYT until platelet count is ≥50 x 109/L, then resume at reduced dose
If platelet count does not recover above 50 x 109/L, consider platelet support |
| After 8 weeks | Monitor platelet counts:
|
- Thrombocytopenia is generally reversible by reducing or interrupting treatment with AYVAKYT
- 23% of patients treated with AYVAKYT experienced a Grade ≥3 thrombocytopenia in clinical studies
- Use AYVAKYT with caution in patients with potential increased risk of intracranial haemorrhage (ICH), including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year
Monitor for cognitive effects1
- It is recommended that patients are clinically monitored for signs and symptoms of cognitive events such as new or increased forgetfulness, confusion and/or difficulty with cognitive functioning. Patients must notify their healthcare professional immediately if they experience new or worsening cognitive symptoms
- Manage cognitive effects by temporary treatment interruption or dose modification. Cognitive effects (Grade ≥2) are generally reversible by reducing or interrupting treatment with AYVAKYT
Interruption of treatment with or without dose reduction may be considered to manage adverse reactions based on severity and clinical presentation1
The dose should be adjusted based on safety and tolerability1
Recommended dose modifications for patients experiencing adverse reactions1
| Adverse reactions | Severity* | Dose modification |
| Intracranial haemorrhage | All grades | Permanently discontinue AYVAKYT |
| Cognitive effects** | Grade 1 | Continue at the same dose or reduced dose, or interrupt until improvement to baseline or resolution. Resume at the same dose or at a reduced dose |
| Grade 2 or 3 | Interrupt treatment until improved to baseline, Grade 1 or resolution. Resume at the same dose or at a reduced dose | |
| Grade 4 | Permanently discontinue AYVAKYT | |
| Thrombocytopenia | <50 x 109/L | Interrupt dosing until platelet count is ≥50 x 109/L, then resume at reduced dose as per the recommended dose reductions. If platelet count does not rise above 50 x 109/L, consider platelet support |
| Other | Grade 3 or 4 | Interrupt treatment until ≤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.
Recommended dose reductions from the 200 mg once-daily starting dose1
| Dose reduction | Starting dose (200 mg) |
| First | 100 mg once daily |
| Second | 50 mg once daily |
| Third | 25 mg once daily |
Dose modifications in clinical trials1
EXPLORER & PATHFINDER
Advanced SM patients treated with 200 mg AYVAKYT (n=126):
7.1%
Permanent treatment discontinuation due to adverse reactions
PATHFINDER
Advanced SM patients who received at least one prior systemic therapy and a starting dose of 200 mg AYVAKYT (n=47):
79%
One or more dose reductions, with a median time to dose reductions of 6 weeks
Adverse reactions leading to a dose reduction included:1
Thrombocytopenia, neutropenia, periorbital oedema, cognitive disorder, oedema peripheral, platelet count decreased, neutrophil count decreased, anaemia, asthenia, fatigue, arthralgia, blood alkaline phosphatase increased, blood bilirubin increased, white blood cell count decreased
