Ayvakit

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 9/1/2021
Ayvakit Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Ayvakit?

Ayvakit (avapritinib) is a kinase inhibitor used to treat adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. Ayvakit is also used to treat adult patients with advanced systemic mastocytosis (AdvSM), which includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

What Are Side Effects of Ayvakit?

Side effects of Ayvakit include:

Dosage for Ayvakit

The recommended dosage of Ayvakit is 300 mg orally once daily on an empty stomach, at least one hour before and two hours after a meal in patients with GIST.

The recommended dosage of Ayvakit is 200 mg orally once daily in patients with AdvSM.

Ayvakit In Children

The safety and effectiveness of Ayvakit in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Ayvakit?

Ayvakit may interact with other medicines such as:

  • strong and moderate CYP3A inhibitors (such as itraconazole and fluconazole) and
  • strong and moderate CYP3A inducers (such as rifampin and efavirenz).

Tell your doctor all medications and supplements you use.

Ayvakit During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Ayvakit; it may harm a fetus. Females of reproductive potential and males with female partners of reproductive potential are advised to use effective contraception during treatment with Ayvakit and for 6 weeks after the final dose. It is unknown if Ayvakit passes into breast milk. Because of the potential for serious adverse reactions in breastfed children, breastfeeding is not recommended while using Ayvakit and for 2 weeks following the final dose.

Additional Information

Our Ayvakit (avapritinib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow
Ayvakit Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • a severe headache, vision problems;
  • unusual changes in mood or behavior;
  • problems with speech, thinking, or memory;
  • confusion, hallucinations (seeing objects or hearing things that are not real);
  • severe drowsiness or dizziness;
  • trouble sleeping; or
  • severe weakness on one side of your body.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, loss of appetite, stomach pain;
  • diarrhea, constipation;
  • fluid retention, swelling;
  • feeling dizzy, weak, or tired;
  • muscle weakness;
  • watery eyes;
  • rash; or
  • hair color changes.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Ayvakit (Avapritinib Tablets)

Ayvakit Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Intracranial hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Cognitive effects [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data in the WARNINGS AND PRECAUTIONS reflect exposure to AYVAKIT at 30 mg to 600 mg orally once daily in 749 patients enrolled in one of four clinicals trials conducted in patients with advanced malignancies and systemic mastocytosis, including NAVIGATOR, EXPLORER and PATHFINDER [see Clinical Studies]. These patients included 601 patients with GIST and 148 patients with systemic mastocytosis. Among the 749 patients receiving AYVAKIT, 46% were exposed for 6 months or longer and 23% were exposed for greater than 1 year.

Gastrointestinal Stromal Tumors

Unresectable Or Metastatic GIST

The safety of AYVAKIT in patients with unresectable or metastatic GIST was evaluated in NAVIGATOR [see Clinical Studies]. The trial excluded patients with history of cerebrovascular accident or transient ischemic attacks, known risk of intracranial bleeding, and metastases to the brain. Patients received AYVAKIT 300 mg or 400 mg orally once daily (n = 204). Among patients receiving AYVAKIT, 56% were exposed for 6 months or longer and 44% were exposed for greater than one year.

The median age of patients who received AYVAKIT was 62 years (range: 29 to 90 years), 60% were <65 years, 62% were male, and 69% were White. Patients had received a median of 3 prior kinase inhibitors (range: 0 to 7).

Serious adverse reactions occurred in 52% of patients receiving AYVAKIT. Serious adverse reactions occurring in ≥1% of patients who received AYVAKIT were anemia (9%), abdominal pain (3%), pleural effusion (3%), sepsis (3%), gastrointestinal hemorrhage (2%), vomiting (2%), acute kidney injury (2%), pneumonia (1%), and tumor hemorrhage (1%). Fatal adverse reactions occurred in 3.4% of patients. Fatal adverse reactions that occurred in more than one patient were sepsis and tumor hemorrhage (1% each).

Permanent discontinuation due to adverse reactions occurred in 16% of patients who received AYVAKIT. Adverse reactions requiring permanent discontinuation in more than one patient were fatigue, abdominal pain, vomiting, sepsis, anemia, acute kidney injury, and encephalopathy.

Dosage interruptions due to an adverse reaction occurred in 57% of patients who received AYVAKIT. Adverse reactions requiring dosage interruption in >2% of patients who received AYVAKIT were anemia, fatigue, nausea, vomiting, hyperbilirubinemia, memory impairment, diarrhea, cognitive disorder, and abdominal pain.

Dose reduction due to an adverse reaction occurred in 49% of patients who received AYVAKIT. Median time to dose reduction was 9 weeks. Adverse reactions requiring dosage reduction in more than 2% of patients who received AYVAKIT were fatigue, anemia, hyperbilirubinemia, memory impairment, nausea, and periorbital edema.

The most common adverse reactions (≥ 20%) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness. Table 3 summarizes the adverse reactions observed in NAVIGATOR.

Table 3: Adverse Reactions (≥ 10%) in Patients with GIST Receiving AYVAKIT in NAVIGATOR

Adverse Reactions AYVAKIT
N=204
All Grades % Grade ≥ 3 %
General
Edemaa 72 2
Fatigue/asthenia 61 9
Pyrexia 14 0.5
Gastrointestinal
Nausea 64 2.5
Vomiting 38 2
Diarrhea 37 4.9
Abdominal painb 31 6
Constipation 23 1.5
Dyspepsia 16 0
Nervous System
Cognitive impairmentc 48 4.9
Dizziness 22 0.5
Headache 17 0.5
Sleep disordersd 16 0
Taste effectse 15 0
Mood disordersf 13 1
Metabolism and nutrition
Decreased appetite 38 2.9
Eye
Increased lacrimation 33 0
Skin and subcutaneous tissue
Rashg 23 2.1
Hair color changes 21 0.5
Alopecia 13 -
Respiratory, thoracic and mediastinal
Dyspnea 17 2.5
Pleural effusion 12 2
Investigations
Weight decreased 13 1
*Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0
a Edema includes face swelling, conjunctival edema, eye edema, eyelid edema, orbital edema, periorbital edema, face edema, mouth edema, pharyngeal edema, peripheral edema, edema, generalized edema, localized edema, peripheral swelling, testicular edema.
b Abdominal pain includes abdominal pain, upper abdominal pain, abdominal discomfort, lower abdominal pain, abdominal tenderness, and epigastric discomfort.
c Cognitive impairment includes memory impairment, cognitive disorder, confusional state, disturbance in attention, amnesia, mental impairment, mental status changes, encephalopathy, dementia, abnormal thinking, mental disorder, and retrograde amnesia.
d Sleep disorders includes insomnia, somnolence, and sleep disorder.
e Taste effects include dysgeusia and ageusia.
f Mood disorders includes agitation, anxiety, depression, depressed mood, dysphoria, irritability, mood altered, nervousness, personality change, and suicidal ideation.
g Rash includes rash, rash maculo-papular, rash erythematous, rash macular, rash generalized, and rash papular.

Clinically relevant adverse reactions occurring in <10% of patients were:

Vascular: hypertension (8%)

Endocrine: thyroid disorders (hyperthyroid, hypothyroid) (3%)

Skin and subcutaneous: palmar-plantar erythrodysesthesia (1%)

Table 4 summarizes the laboratory abnormalities observed in NAVIGATOR.

Table 4: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients with GIST Receiving AYVAKIT in NAVIGATOR

Laboratory Abnormality AYVAKITa
N=204
All Grades (%) Grade ≥ 3 (%)
Hematology
Decreased hemoglobin 81 28
Decreased leukocytes 62 5
Decreased neutrophils 43 6
Decreased platelets 27 0.5
Increased INR 24 0.6
Increased activated partial thromboplastin time 13 0
Chemistry
Increased bilirubin 69 9
Increased aspartate aminotransferase 51 1.5
Decreased phosphate 49 13
Decreases potassium 34 6
Decreased albumin 31 2
Decreased magnesium 29 1
Increased creatinine 29 0
Decreased sodium 28 7
Increased alanine aminotransferase 19 0.5
Increased alkaline phosphatase 14 1
a The denominator used to calculate the rate varied from 154 to 201 based on the number of patients with a baseline value and at least one post-treatment value.

Advanced Systemic Mastocytosis

The safety of AYVAKIT in patients with AdvSM was evaluated in EXPLORER and PATHFINDER [see Clinical Studies]. Patients received a starting dose of AYVAKIT ranging from 30 mg to 400 mg orally once daily (n = 131), including 80 patients who received the recommended starting dose of 200 mg once daily. Among patients receiving AYVAKIT, 70% were treated for 6 months or longer and 37% were exposed for greater than one year.

The median age of patients who received AYVAKIT was 68 years (range: 31 to 88 years), 38% were <65 years, 57% were male, and 88% were White.

Serious adverse reactions occurred in 34% of patients receiving the recommended starting dose of 200 mg once daily and in 50% of patients receiving AYVAKIT at all doses. Serious adverse reactions occurring in ≥1% of patients who received AYVAKIT 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). Fatal adverse reactions occurred in 2.5% of patients receiving the recommended starting dose of 200 mg once daily and in 5.3% of patients receiving AYVAKIT at all doses. No specific adverse reaction leading to death was reported in more than one patient.

Permanent discontinuation due to adverse reactions occurred in 10% of patients receiving the recommended starting dose of 200 mg once daily and in 15% of patients who received AYVAKIT at all doses. Of patients receiving 200 mg once daily, subdural hematoma was the only adverse reaction requiring permanent discontinuation in more than one patient.

Dosage interruptions due to an adverse reaction occurred in 60% of patients receiving the recommended starting dose of 200 mg once daily and in 67% of patients who received AYVAKIT at all doses. Adverse reactions requiring dosage interruption in >2% of patients who received AYVAKIT at 200 mg once daily were thrombocytopenia, neutropenia, neutrophil count decreased, platelet count decreased, anemia, white blood cell decreased, cognitive disorder, blood alkaline phosphatase increased, and edema peripheral.

Dose reduction due to an adverse reaction occurred in 68% of patients receiving the recommended starting dose of 200 mg once daily and 70% of patients who received AYVAKIT at all doses. Median time to dose reduction was 1.7 months. Adverse reactions requiring dosage reduction in more than 2% of patients who received AYVAKIT at 200 mg once daily were thrombocytopenia, neutropenia, edema peripheral, neutrophil count decreased, platelet count decreased, periorbital edema, cognitive disorder, anemia, fatigue, arthralgia, blood alkaline phosphatase increased, and white blood cell count decreased.

The most common adverse reactions (≥ 20%) at all doses were edema, diarrhea, nausea, and fatigue/asthenia. Table 5 summarizes the adverse reactions observed in EXPLORER and PATHFINDER.

Table 5: Adverse Reactions (≥ 10%) in Patients with AdvSM Receiving AYVAKIT in EXPLORER and PATHFINDER

Adverse Reactions AYVAKIT (200 mg once daily)
N=80
All Grades % Grade ≥ 3 %
General
Edemaa 79 5
Fatigue/asthenia 23 4
Gastrointestinal
Diarrhea 28 1
Nausea 24 1
Vomiting 18 3
Abdominal painb 14 1
Constipation 11 0
Nervous system
Headache 15 0
Cognitive effectsc 14 1
Taste effectsd 13 0
Dizziness 13 0
Musculoskeletal and connective tissue
Arthralgia 10 1
Respiratory, thoracic and mediastinal
Epistaxis 11 0
*Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0
a Edema includes face swelling, eyelid edema, orbital edema, periorbital edema, face edema, peripheral edema, edema, generalized edema, and peripheral swelling.
b Abdominal pain includes abdominal pain, upper abdominal pain, and abdominal discomfort.
c Cognitive effects include memory impairment, cognitive disorder, confusional state, delirium, and disorientation.
d Taste effects include dysgeusia.

Clinically relevant adverse reactions occurring in <10% of patients were:

Cardiac: cardiac failure (2.5%), and cardiac failure congestive (1.3%)

Gastrointestinal: ascites (5%), gastrointestinal hemorrhage (1.3%), and large intestine perforation (1.3%)

Hepatobiliary: cholelithiasis (1.3%) Infections and infestations: upper respiratory tract infection (6%), urinary tract infection (6%), and herpes zoster (2.5%)

Vascular: flushing (3.8%), hypertension (3.8%), hypotension (3.8%), and hot flush (2.5%)

Nervous: insomnia (6%)

Musculoskeletal and connective tissue: pain in extremity (6%)

Respiratory, thoracic and mediastinal: dyspnea (9%), and cough (2.5%)

Skin and subcutaneous tissue: rasha (8%), alopecia (9%), pruritus (8%), and hair color changes (6%)

Metabolism and nutrition: decreased appetite (8%)

Eye: lacrimation increased (9%)

Laboratory abnormality: decreased phosphate (9%)

aGrouped terms

Rash includes rash and rash maculo-papular

Table 6 summarizes the laboratory abnormalities observed in EXPLORER and PATHFINDER.

Table 6: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients with AdvSM Receiving AYVAKIT in EXPLORER and PATHFINDER

Laboratory Abnormality AYVAKIT (200 mg once daily)
N=80
All Grades (%) Grade ≥ 3 (%)
Hematology
Decreased platelets 64 21
Decreased hemoglobin 55 23
Decreased neutrophils 54 25
Decreased lymphocytes 34 11
Increased activated partial thromboplastin time 14 1
Increased lymphocytes 10 0
Chemistry
Decreased calcium 50 3
Increased bilirubin 41 3
Increased aspartate aminotransferase 38 1
Decreased potassium 26 4
Increased alkaline phosphatase 24 5
Increased creatinine 20 0
Increased alanine aminotransferase 18 1
Decreased sodium 18 1
Decreased albumin 15 1
Decreased magnesium 14 1
Increased potassium 11 0

DRUG INTERACTIONS

Effects Of Other Drugs On AYVAKIT

Strong And Moderate CYP3A Inhibitors

Coadministration of AYVAKIT with a strong or moderate CYP3A inhibitor increases avapritinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may increase the incidence and severity of adverse reactions of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration of AYVAKIT with a moderate CYP3A inhibitor cannot be avoided, reduce the dose of AYVAKIT [see DOSAGE AND ADMINISTRATION].

Strong And Moderate CYP3A Inducers

Coadministration of AYVAKIT with a strong or moderate CYP3A inducer decreases avapritinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may decrease efficacy of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers.

Read the entire FDA prescribing information for Ayvakit (Avapritinib Tablets)

© Ayvakit Patient Information is supplied by Cerner Multum, Inc. and Ayvakit Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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