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.
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.v
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]
- Central nervous system 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 335 patients enrolled in one of three clinicals trials conducted in patients with advanced malignancies, including NAVIGATOR [see Clinical Studies]. Among the 335 patients receiving AYVAKIT, 49% 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 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 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. | ||
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.