AYVAKYT: Uses, Dosage & Side Effects
A selective kinase inhibitor targeting KIT and PDGFRA mutations for the treatment of GIST and advanced systemic mastocytosis
AYVAKYT (avapritinib) is a prescription oral kinase inhibitor used to treat adults with specific types of gastrointestinal stromal tumor (GIST) and advanced systemic mastocytosis (AdvSM). It works by selectively inhibiting mutant forms of KIT and platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are the molecular drivers of these diseases. AYVAKYT was specifically designed to target activation loop mutations, including the PDGFRA D842V mutation found in approximately 5–6% of GIST patients, and the KIT D816V mutation that drives over 90% of systemic mastocytosis cases. By blocking these aberrant kinase signaling pathways, avapritinib inhibits tumor cell proliferation and survival. AYVAKYT represents a breakthrough in precision oncology, offering targeted therapy for patients who previously had limited treatment options.
Quick Facts: AYVAKYT
Key Takeaways
- AYVAKYT (avapritinib) is a precision-targeted kinase inhibitor approved for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation (including D842V) and for adults with advanced systemic mastocytosis (AdvSM).
- The recommended starting dose differs by indication: 300 mg once daily for GIST with PDGFRA exon 18 mutations, and 200 mg once daily for advanced systemic mastocytosis. Tablets should be taken on an empty stomach.
- Key safety concerns include intracranial hemorrhage, cognitive effects (memory impairment, confusion, cognitive disturbance), and fluid retention — patients require regular monitoring during treatment.
- AYVAKYT has significant drug interactions with CYP3A4 inhibitors and inducers; co-administration with strong CYP3A4 inhibitors or inducers should be avoided.
- In the pivotal NAVIGATOR trial for PDGFRA D842V-mutant GIST, avapritinib achieved an overall response rate of 88%, representing a major advance for patients who were previously resistant to standard imatinib therapy.
What Is AYVAKYT and What Is It Used For?
AYVAKYT contains the active substance avapritinib, a potent and highly selective inhibitor of mutant forms of KIT and platelet-derived growth factor receptor alpha (PDGFRA) kinases. These receptor tyrosine kinases are transmembrane proteins that play critical roles in cell growth, differentiation, and survival. When mutations occur in the genes encoding KIT or PDGFRA, the resulting kinases become constitutively activated, meaning they signal continuously without the need for their normal ligands (stem cell factor for KIT, and platelet-derived growth factor for PDGFRA). This uncontrolled signaling drives the proliferation and survival of tumor cells in gastrointestinal stromal tumors (GIST) and the abnormal accumulation and activation of mast cells in systemic mastocytosis.
Avapritinib was specifically engineered using structure-based drug design to target the activation loop mutations of KIT and PDGFRA. The activation loop is a critical regulatory region within these kinases. When mutations occur in this domain, the kinase adopts an active conformation that is resistant to many existing kinase inhibitors, including imatinib. The PDGFRA D842V mutation, which occurs in approximately 5–6% of all GIST cases, is the most common PDGFRA mutation and is associated with primary resistance to imatinib, sunitinib, and regorafenib — the standard-of-care treatments for most GIST patients. Similarly, the KIT D816V mutation is the hallmark genetic abnormality in systemic mastocytosis, found in over 90% of patients with this condition.
Avapritinib binds with high affinity to the ATP-binding pocket of mutant KIT and PDGFRA kinases in their active conformation. By occupying this site, avapritinib prevents the transfer of phosphate groups from ATP to downstream signaling proteins, effectively blocking the cascade of intracellular events that promote cell proliferation, survival, and migration. In preclinical studies, avapritinib demonstrated potent inhibitory activity against PDGFRA D842V with an IC50 (half-maximal inhibitory concentration) approximately 30-fold lower than that of imatinib, explaining its superior clinical activity in this patient population.
GIST with PDGFRA Exon 18 Mutations
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract, with an estimated annual incidence of 10–15 cases per million population. GIST most commonly arise in the stomach (60%) and small intestine (30%), but can occur anywhere in the gastrointestinal tract. The majority of GIST (approximately 75–80%) harbor gain-of-function mutations in the KIT gene, while approximately 5–10% carry mutations in PDGFRA. About 10–15% of GIST are wild-type for both KIT and PDGFRA.
Among PDGFRA-mutant GIST, the D842V substitution in exon 18 is the most prevalent, accounting for approximately 60–70% of all PDGFRA mutations and about 5–6% of all GIST. This single amino acid change (aspartic acid to valine at position 842) stabilizes the activation loop of PDGFRA in an active conformation, rendering the kinase constitutively active and resistant to imatinib. Before the approval of avapritinib, patients with PDGFRA D842V-mutant GIST had no approved targeted therapy and faced a poor prognosis with conventional treatments.
The pivotal evidence for AYVAKYT in GIST came from the NAVIGATOR trial (Study BLU-285-1101), an open-label, single-arm, multicenter, phase I/II clinical trial. In the NAVIGATOR trial, patients with PDGFRA D842V-mutant unresectable or metastatic GIST treated with avapritinib 300 mg once daily achieved a remarkable overall response rate (ORR) of 88% (95% CI: 78–95%), including a complete response rate of 9% and a partial response rate of 79%. The median duration of response had not been reached at the time of the primary analysis, indicating durable clinical benefit. These results represented an unprecedented level of activity in a tumor type that had previously been considered resistant to kinase inhibitor therapy.
Advanced Systemic Mastocytosis (AdvSM)
Systemic mastocytosis is a rare myeloid neoplasm characterized by the abnormal proliferation and accumulation of clonal mast cells in various organs, including the bone marrow, liver, spleen, and gastrointestinal tract. Advanced systemic mastocytosis (AdvSM) encompasses three clinical subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). AdvSM is a life-threatening condition with a median survival ranging from approximately 2 years for MCL to 3–4 years for ASM and SM-AHN.
The KIT D816V mutation is the primary oncogenic driver in over 90% of systemic mastocytosis cases. This activating mutation in the KIT activation loop leads to constitutive kinase activation and uncontrolled mast cell proliferation and survival. The KIT D816V mutation confers resistance to imatinib, making it essential to develop inhibitors specifically designed to target this variant.
The efficacy of AYVAKYT in AdvSM was demonstrated in the PATHFINDER trial (Study BLU-285-2002) and the EXPLORER trial (Study BLU-285-1101). In the PATHFINDER trial, a single-arm, open-label, multicenter study, patients with AdvSM treated with avapritinib 200 mg once daily achieved an overall response rate of 75% (95% CI: 64–84%), with 36% achieving a complete remission with full or partial hematologic recovery. Responses were observed across all AdvSM subtypes and were accompanied by significant reductions in serum tryptase levels, reduction in bone marrow mast cell burden, and improvement in organ damage measures.
AYVAKYT represents a landmark in precision oncology. For PDGFRA D842V-mutant GIST, it is the first and only approved targeted therapy, transforming an imatinib-resistant disease into one with high response rates. For advanced systemic mastocytosis, it provides a potent and selective option targeting the KIT D816V mutation that drives over 90% of cases. Both indications highlight the power of mutation-specific drug design in modern oncology.
What Should You Know Before Taking AYVAKYT?
Contraindications
AYVAKYT is contraindicated in patients with known hypersensitivity to avapritinib or to any of the excipients in the formulation. The inactive ingredients include microcrystalline cellulose, copovidone, croscarmellose sodium, magnesium stearate, and a film coating consisting of polyvinyl alcohol, talc, macrogol, titanium dioxide, and iron oxide yellow (for the 25 mg tablet). Patients with a documented allergy to any of these components should not take AYVAKYT.
There are no additional absolute contraindications listed in the current prescribing information. However, the serious risks associated with AYVAKYT, particularly intracranial hemorrhage, mean that careful risk-benefit assessment is essential before initiating treatment, especially in patients with additional risk factors for bleeding.
Warnings and Precautions
AYVAKYT can cause intracranial hemorrhage (bleeding in the brain), which can be fatal. In clinical trials for GIST, intracranial hemorrhage occurred in approximately 2–3% of patients. Immediately seek medical attention if you experience sudden severe headache, vision changes, confusion, weakness on one side of the body, difficulty speaking, or loss of consciousness. Treatment should be permanently discontinued if Grade 3 or higher intracranial hemorrhage occurs.
Cognitive adverse reactions, including memory impairment, cognitive disorder, confusional state, and encephalopathy, have been reported in clinical trials. These effects occurred in approximately 40% of patients in the NAVIGATOR trial. Most cognitive effects were Grade 1 or 2, but Grade 3 events occurred in approximately 5–6% of patients. Patients should be monitored for changes in cognitive function, and dose modifications may be necessary.
Before starting AYVAKYT, your healthcare provider should discuss the following important considerations:
- Bleeding risk: In addition to intracranial hemorrhage, AYVAKYT can cause other bleeding events, including gastrointestinal hemorrhage, tumor hemorrhage, and epistaxis (nosebleeds). Patients taking anticoagulants or antiplatelet agents may be at increased risk. Regular monitoring of platelet counts is essential, as avapritinib can cause thrombocytopenia (low platelet counts), which increases bleeding risk.
- Cognitive function: Cognitive adverse reactions are common with AYVAKYT treatment. These can manifest as memory problems, difficulty concentrating, confusion, speech difficulties, or changes in mental status. Patients should inform their doctor if they notice any cognitive changes, and caregivers should be alert to potential behavioral or cognitive alterations in patients.
- Fluid retention: Edema (swelling) is common with AYVAKYT, including periorbital edema (swelling around the eyes), peripheral edema (swelling of the hands, feet, or ankles), ascites (fluid in the abdomen), pleural effusion (fluid around the lungs), and generalized edema. Patients should be monitored for signs of fluid retention, and weight should be assessed regularly.
- Liver function: AYVAKYT has not been studied in patients with severe hepatic impairment. Patients with moderate hepatic impairment require a dose reduction. Liver function tests should be monitored during treatment.
- Bone marrow suppression: AYVAKYT can cause cytopenias, including anemia, neutropenia, and thrombocytopenia. Complete blood counts should be monitored regularly during treatment, and dose adjustments should be made as clinically indicated.
Pregnancy and Breastfeeding
AYVAKYT should not be used during pregnancy. Based on its mechanism of action and findings from animal reproduction studies, avapritinib can cause embryo-fetal harm. In animal studies, avapritinib caused adverse developmental effects at doses below the human therapeutic exposure. Women of reproductive potential should be advised of the potential risk to a fetus and should use effective contraception during treatment with AYVAKYT and for at least 6 weeks after the last dose.
Male patients with female partners of reproductive potential should use effective contraception during treatment and for at least 2 weeks after the last dose of AYVAKYT. Avapritinib may impair male fertility based on findings from animal studies, in which effects on male reproductive organs were observed at clinically relevant exposures.
It is not known whether avapritinib or its metabolites are excreted in human breast milk. Because of the potential for serious adverse reactions in breastfed infants from AYVAKYT, women should not breastfeed during treatment and for at least 2 weeks after the last dose. If you are currently breastfeeding, discuss alternative feeding options with your doctor before starting AYVAKYT.
Driving and Operating Machinery
AYVAKYT may affect your ability to drive and use machines. Given the risk of cognitive effects (including memory impairment, confusion, and cognitive disturbance), patients should be cautious when driving or operating machinery, particularly early in treatment or after dose increases. If you experience any cognitive symptoms that could impair your ability to concentrate or react, you should refrain from driving or operating machinery until these symptoms resolve.
How Does AYVAKYT Interact with Other Drugs?
Unlike monoclonal antibody therapies, avapritinib is a small-molecule drug that is extensively metabolized by hepatic cytochrome P450 (CYP) enzymes, primarily CYP3A4, with minor contributions from CYP2C9. This metabolic profile results in clinically significant drug-drug interactions that require careful management. Understanding these interactions is critical for safe and effective use of AYVAKYT.
Avapritinib is also a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters, although the clinical significance of transporter-mediated interactions is considered less impactful than CYP3A4-mediated interactions. At clinically relevant concentrations, avapritinib does not meaningfully inhibit or induce major CYP enzymes, meaning it is unlikely to affect the metabolism of other drugs through CYP-mediated pathways.
Major Interactions (Avoid)
| Drug Category | Examples | Effect on AYVAKYT | Recommendation |
|---|---|---|---|
| Strong CYP3A4 inhibitors | Ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, ritonavir, cobicistat | Increases avapritinib AUC by approximately 4.2-fold | Avoid — use alternative agents |
| Strong CYP3A4 inducers | Rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s wort, enzalutamide | Decreases avapritinib AUC by approximately 73% | Avoid — use alternative agents |
Moderate Interactions (Dose Adjustment Required)
| Drug Category | Examples | Effect on AYVAKYT | Recommendation |
|---|---|---|---|
| Moderate CYP3A4 inhibitors | Fluconazole, erythromycin, diltiazem, verapamil, ciprofloxacin, aprepitant, grapefruit juice | Increases avapritinib exposure (predicted ~2-fold increase in AUC) | Reduce AYVAKYT dose if co-administration cannot be avoided |
| Moderate CYP3A4 inducers | Efavirenz, modafinil, bosentan | Decreases avapritinib exposure | Use with caution — monitor efficacy |
Additional Considerations
In addition to CYP3A4-mediated interactions, patients should be aware of the following:
- Acid-reducing agents: Co-administration with proton pump inhibitors (PPIs), H2-receptor antagonists, or antacids does not significantly affect the bioavailability of avapritinib. No dose adjustment is required when taking AYVAKYT with acid-reducing medications.
- Anticoagulants and antiplatelet agents: While not a direct pharmacokinetic interaction, the concurrent use of anticoagulants (warfarin, DOACs) or antiplatelet agents (aspirin, clopidogrel) with AYVAKYT may increase the risk of bleeding, given that avapritinib can cause thrombocytopenia and has been associated with hemorrhagic events, including intracranial hemorrhage.
- Grapefruit and Seville oranges: These fruits and their juices contain compounds that inhibit CYP3A4 in the gastrointestinal tract. Patients should avoid consuming large quantities of grapefruit or Seville oranges during AYVAKYT treatment, as this could increase avapritinib plasma levels.
Always inform your doctor, pharmacist, and other healthcare providers about all medications you are taking, including prescription drugs, over-the-counter medications, vitamins, herbal supplements, and dietary products. Your oncologist can help identify potential interactions and make appropriate adjustments to your treatment plan.
Before starting AYVAKYT, provide your doctor with a complete list of all medications, supplements, and herbal products you are taking. CYP3A4 inhibitors and inducers are found in many common medications, and even some foods (grapefruit). Your pharmacist can help identify potential interactions.
What Is the Correct Dosage of AYVAKYT?
AYVAKYT should always be used exactly as prescribed by your oncologist or hematologist. The dosing regimen depends on the specific indication for which AYVAKYT is being used, and dose modifications may be required based on individual tolerability, adverse reactions, and concomitant medications.
Adults — GIST with PDGFRA Exon 18 Mutations
Recommended Dose for PDGFRA-Mutant GIST
The recommended starting dose is 300 mg orally once daily on an empty stomach. Treatment should continue until disease progression or unacceptable toxicity.
| Dose Level | Daily Dose | Context |
|---|---|---|
| Starting dose | 300 mg once daily | Standard starting dose |
| First dose reduction | 200 mg once daily | For adverse reactions or moderate CYP3A4 inhibitors |
| Second dose reduction | 100 mg once daily | For persistent adverse reactions |
| Minimum dose | 100 mg once daily | Discontinue if unable to tolerate 100 mg |
Adults — Advanced Systemic Mastocytosis
Recommended Dose for AdvSM
The recommended starting dose is 200 mg orally once daily on an empty stomach. Treatment should continue until disease progression or unacceptable toxicity.
| Dose Level | Daily Dose | Context |
|---|---|---|
| Starting dose | 200 mg once daily | Standard starting dose |
| First dose reduction | 100 mg once daily | For adverse reactions or moderate CYP3A4 inhibitors |
| Second dose reduction | 50 mg once daily | For persistent adverse reactions |
| Third dose reduction | 25 mg once daily | Discontinue if unable to tolerate 25 mg |
How to Take AYVAKYT
AYVAKYT tablets should be taken under specific conditions to ensure optimal absorption and therapeutic effectiveness:
- Empty stomach: Take AYVAKYT on an empty stomach, at least 1 hour before or at least 2 hours after a meal. Food significantly increases the absorption of avapritinib (by approximately 2-fold increase in AUC), which could increase the risk of side effects.
- Swallow whole: Tablets should be swallowed whole with a glass of water. Do not break, crush, or chew the tablets, as this could alter the drug release characteristics and potentially increase exposure.
- Consistent timing: Take AYVAKYT at approximately the same time each day to maintain consistent drug levels in the blood.
- Do not open capsules: If you have difficulty swallowing tablets, discuss alternative options with your doctor. Do not crush or dissolve AYVAKYT tablets.
Children and Adolescents
AYVAKYT is not indicated for use in children and adolescents under 18 years of age. The safety and efficacy of avapritinib have not been established in pediatric patients. GIST in children is rare and typically driven by different molecular mechanisms (SDH-deficient GIST) than in adults, and systemic mastocytosis is also uncommon in pediatric populations.
Elderly Patients
No dose adjustment is required based on age alone. Clinical trials included patients aged 65 and older, and no clinically meaningful differences in safety or efficacy were observed between older and younger patients. However, elderly patients may be more susceptible to certain adverse effects, particularly cognitive effects and bleeding, and should be monitored closely.
Renal and Hepatic Impairment
No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 30–89 mL/min). AYVAKYT has not been studied in patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease. For hepatic impairment, no dose adjustment is needed for mild hepatic impairment (Child-Pugh A). Patients with moderate hepatic impairment (Child-Pugh B) should receive a reduced starting dose. AYVAKYT has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended in this population.
Missed Dose
If you miss a dose of AYVAKYT or vomit after taking a dose, do not take an additional dose. Simply take the next scheduled dose at the regular time. Do not double the dose to make up for a missed one. If you frequently miss doses, discuss strategies with your healthcare team to help improve adherence, such as setting daily reminders or using a pill organizer.
Overdose
There is no specific antidote for avapritinib overdose. In the event of suspected overdose, AYVAKYT should be withheld, and the patient should receive supportive care with monitoring of vital signs and clinical status. Given the elimination half-life of approximately 32–57 hours, patients may require prolonged monitoring. Hemodialysis is unlikely to be effective in removing avapritinib due to its high protein binding (approximately 98.8%).
What Are the Side Effects of AYVAKYT?
Like all medicines, AYVAKYT can cause side effects, although not everyone who takes it will experience them. The safety profile of AYVAKYT has been characterized through clinical trials involving hundreds of patients with GIST and advanced systemic mastocytosis. The types and frequencies of adverse reactions can differ somewhat between the two indications, primarily due to differences in dosing (300 mg for GIST vs. 200 mg for AdvSM) and the underlying disease biology.
Clinical trial data from the NAVIGATOR, PATHFINDER, and EXPLORER studies form the foundation of the known safety profile. In these trials, the most frequently reported adverse reactions leading to dose reduction were cognitive effects, periorbital edema, nausea, and increased bilirubin. The most common reasons for permanent discontinuation included cognitive effects and intracranial hemorrhage.
Side Effects in GIST (PDGFRA Exon 18 Mutation)
Very Common
May affect more than 1 in 10 people
- Periorbital edema (swelling around the eyes)
- Increased lacrimation (watery eyes)
- Nausea
- Diarrhea
- Fatigue
- Decreased appetite
- Memory impairment
- Cognitive disorder
- Peripheral edema (swelling of hands/feet)
- Facial edema
- Anemia (low red blood cells)
- Vomiting
- Hair color changes
- Abdominal pain
- Dizziness
- Increased bilirubin
Common
May affect up to 1 in 10 people
- Thrombocytopenia (low platelet count)
- Neutropenia (low white blood cells)
- Confusional state
- Encephalopathy
- Speech disorder
- Rash
- Constipation
- Dry mouth
- Taste disturbance (dysgeusia)
- Weight gain
- Headache
- Insomnia
Uncommon
May affect up to 1 in 100 people
- Intracranial hemorrhage (bleeding in the brain)
- Gastrointestinal hemorrhage
- Tumor hemorrhage
- Pleural effusion (fluid around the lungs)
- Ascites (fluid in the abdomen)
Rare
May affect up to 1 in 1,000 people
- Fatal intracranial hemorrhage
- Severe hepatotoxicity
Side Effects in Advanced Systemic Mastocytosis
Very Common
May affect more than 1 in 10 people
- Periorbital edema (swelling around the eyes)
- Diarrhea
- Nausea
- Fatigue
- Peripheral edema
- Thrombocytopenia (low platelet count)
- Anemia
- Neutropenia
- Vomiting
- Dizziness
- Decreased appetite
- Cognitive effects (memory impairment, confusion)
Common
May affect up to 1 in 10 people
- Facial edema
- Increased lacrimation
- Abdominal pain
- Hair color changes
- Rash
- Weight gain
- Headache
- Increased bilirubin
- Increased liver enzymes (ALT/AST)
It is important to understand that many of these side effects are dose-dependent and can often be managed through dose reductions or temporary treatment interruptions. The side effect profile of AYVAKYT in AdvSM at the 200 mg dose is generally more favorable than at the 300 mg dose used for GIST. Your oncologist will monitor you regularly with blood tests and clinical assessments to detect and manage adverse effects early.
Cognitive effects deserve special attention. In the NAVIGATOR trial, approximately 40% of patients experienced some form of cognitive adverse reaction, with the most common being memory impairment (22%), cognitive disorder (12%), and confusional state (7%). Most cognitive effects were mild to moderate (Grade 1–2) and were managed with dose reductions. Grade 3 cognitive effects occurred in approximately 5–6% of patients. The onset of cognitive effects was typically within the first several months of treatment. Most patients who experienced cognitive effects had improvement or resolution with dose reduction or discontinuation.
Hematologic toxicities, including thrombocytopenia, anemia, and neutropenia, are common with AYVAKYT, particularly in the AdvSM population where bone marrow involvement by disease is common. Regular complete blood count monitoring is essential, typically weekly for the first 4 weeks, then every 2 weeks for the next 8 weeks, and monthly thereafter or as clinically indicated.
Seek emergency medical attention immediately if you experience: sudden severe headache, vision changes or loss of vision, confusion or inability to think clearly, weakness or numbness on one side of the body, difficulty speaking, unexplained bruising or bleeding, blood in stool or vomit, or signs of severe allergic reaction (difficulty breathing, facial swelling, severe rash).
How Should You Store AYVAKYT?
Proper storage of AYVAKYT is important to maintain the stability, quality, and effectiveness of the medication. As a small-molecule kinase inhibitor in tablet form, avapritinib is generally more stable than biological products but still requires appropriate storage conditions to ensure pharmaceutical integrity throughout the shelf life.
Follow these storage guidelines:
- Temperature: Store AYVAKYT at room temperature below 25°C (77°F). Brief excursions to temperatures up to 40°C (104°F) are permissible but should be minimized. Avoid prolonged exposure to heat or direct sunlight.
- Moisture protection: Keep the tablets in the original blister packaging until you are ready to take a dose. The blister pack provides protection from moisture. Do not transfer tablets to pill organizers for extended periods unless they include a desiccant.
- Keep out of reach of children: AYVAKYT is a cytotoxic medication and should be stored in a secure location inaccessible to children and pets.
- Check expiration date: Do not use AYVAKYT after the expiration date printed on the blister pack and outer carton. The expiration date refers to the last day of that month.
- Inspection: Before each dose, visually inspect the tablet. Do not use tablets that appear damaged, discolored, or have an unusual appearance.
- Disposal: Do not throw unused AYVAKYT tablets in household waste or flush them down the toilet. Return any unused or expired tablets to your pharmacist for safe disposal. As a cytotoxic agent, special disposal procedures should be followed.
When traveling with AYVAKYT, keep the medication in its original packaging and carry it in your hand luggage. Avoid exposing the medication to extreme temperatures, such as those in a car glovebox during hot weather or in checked airline baggage in cold temperatures. If you are traveling across time zones, maintain your regular dosing interval as closely as possible and consult your doctor or pharmacist for guidance on adjusting your dosing schedule.
What Does AYVAKYT Contain?
Understanding the composition of your medication is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. AYVAKYT tablets are available in multiple strengths, each identified by a distinctive color and marking.
Active Ingredient
The active substance is avapritinib, a synthetic small-molecule kinase inhibitor. Avapritinib has the molecular formula C26H27FN6O2 and a molecular weight of 474.53 g/mol. It is a white to slightly yellow powder that is practically insoluble in water. AYVAKYT tablets are available in the following strengths:
| Strength | Tablet Color | Debossing | Shape |
|---|---|---|---|
| 25 mg | Yellow | BLU 25 | Round |
| 50 mg | Orange | BLU 50 | Round |
| 100 mg | Green | BLU 100 | Round |
| 200 mg | Purple | BLU 200 | Oval |
| 300 mg | White to off-white | BLU 300 | Oval |
Inactive Ingredients (Excipients)
The tablet core contains the following inactive ingredients:
- Microcrystalline cellulose: Binder and filler that gives the tablet its structure
- Copovidone: Binder that helps hold the tablet together
- Croscarmellose sodium: Disintegrant that helps the tablet break down in the gastrointestinal tract
- Magnesium stearate: Lubricant used in the manufacturing process
The film coating contains:
- Polyvinyl alcohol: Film-forming agent
- Talc: Anti-tacking agent
- Macrogol (polyethylene glycol): Plasticizer
- Titanium dioxide (E171): White colorant and opacifier
- Iron oxide yellow (E172): Colorant (in 25 mg tablets)
- Iron oxide red (E172): Colorant (in certain tablet strengths)
AYVAKYT does not contain lactose, gluten, or animal-derived ingredients. If you have known allergies or sensitivities to any of the excipients listed above, inform your healthcare provider before starting treatment.
Frequently Asked Questions About AYVAKYT
AYVAKYT is approved for two different conditions at different doses. For GIST with PDGFRA exon 18 mutations (including D842V), the starting dose is 300 mg once daily. For advanced systemic mastocytosis (AdvSM), the starting dose is 200 mg once daily. While the drug is the same (avapritinib), it targets different mutations in each disease: PDGFRA D842V in GIST and KIT D816V in AdvSM. The side effect profiles are similar but can differ in severity due to the different doses and underlying diseases.
AYVAKYT is typically taken for as long as it continues to provide clinical benefit without unacceptable side effects. For GIST, this means treatment continues until the tumor progresses or side effects become too severe despite dose adjustments. For AdvSM, treatment duration depends on the response and tolerability. Some patients with AdvSM may achieve deep molecular responses, and your doctor will discuss whether treatment continuation or potential dose reduction is appropriate based on your individual response.
You should avoid consuming grapefruit, Seville oranges, and their juices while taking AYVAKYT. These fruits contain compounds called furanocoumarins that inhibit the CYP3A4 enzyme in your gut, which is the main enzyme responsible for metabolizing avapritinib. Consuming grapefruit could increase the amount of AYVAKYT absorbed into your bloodstream, potentially leading to increased side effects. If you enjoy citrus fruits, regular oranges, lemons, and limes are safe alternatives.
Cognitive effects, including memory impairment, are among the most common side effects of AYVAKYT. If you notice changes in your memory, thinking, concentration, or experience confusion, inform your oncologist promptly. Mild cognitive effects (Grade 1–2) may be managed with dose reduction. More severe cognitive effects may require temporary treatment interruption. It can be helpful to keep a daily journal or ask a family member to monitor for cognitive changes. Most cognitive effects improve with dose adjustment or discontinuation of treatment.
If your GIST has a PDGFRA D842V mutation, it was likely resistant to imatinib from the start, as this specific mutation is inherently resistant to imatinib. AYVAKYT was specifically designed to target this mutation, and in the NAVIGATOR trial it achieved an overall response rate of 88% in patients with PDGFRA D842V-mutant GIST. However, if your GIST has a different mutation (such as a KIT exon 11 mutation) and has become resistant to imatinib, AYVAKYT may not be the appropriate treatment. Molecular testing of your tumor is essential to determine whether AYVAKYT is right for you.
Taking AYVAKYT with food significantly increases the absorption of avapritinib, leading to higher blood levels (approximately 2-fold increase in AUC compared to the fasted state). While this might seem beneficial, higher-than-intended blood levels increase the risk of side effects, including cognitive effects, edema, and bleeding. The approved dose was determined based on studies where the drug was taken on an empty stomach. To ensure you receive the right amount of medication, take AYVAKYT at least 1 hour before or at least 2 hours after eating.
References
- European Medicines Agency (EMA). AYVAKYT (avapritinib) — Summary of Product Characteristics. Last updated 2025. Available at: EMA EPAR: AYVAKYT.
- U.S. Food and Drug Administration (FDA). AYVAKYT (avapritinib) — Prescribing Information. Revised 2024. Available at: FDA: AYVAKYT Label.
- Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020;21(7):935–946. doi:10.1016/S1470-2045(20)30269-2.
- Gotlib J, Reiter A, Radia DH, et al. Avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis (PATHFINDER): primary analysis of an open-label, single-arm, phase 2 trial. Lancet. 2024;403(10434):1341–1352. doi:10.1016/S0140-6736(24)00212-9.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Gastrointestinal Stromal Tumors (GIST). Version 1.2024. Available at: NCCN Guidelines.
- Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2024;33(1):20–33. doi:10.1016/j.annonc.2021.09.005.
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd list, 2023. Geneva: World Health Organization; 2023.
- DeAngelo DJ, Radia DH, George TI, et al. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med. 2021;27(12):2183–2191. doi:10.1038/s41591-021-01538-9.
Editorial Team
Medical Writer
iMedic Medical Editorial Team — Specialists in Clinical Oncology and Pharmacology
Medical Reviewer
iMedic Medical Review Board — Board-certified oncologists and hematologists
Evidence Standard
Level 1A — Based on systematic reviews, randomized controlled trials, and regulatory guidelines (EMA, FDA, NCCN, ESMO)
Independence
No commercial funding. No pharmaceutical industry sponsorship. Independent medical editorial content.
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