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:
- fluid retention (edema),
- nausea,
- vomiting,
- fatigue,
- weakness/lethargy,
- cognitive impairment,
- decreased appetite,
- diarrhea,
- hair color changes,
- increased tearing,
- abdominal pain,
- constipation,
- rash, and
- dizziness
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 SlideshowGet 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)
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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