Avapritinib

Avapritinib is a prescription medication used for the treatment of gastrointestinal stromal tumors and systemic mastocytosis. 

• Avapritinib is available under the following different brand names: Ayvakit.

Common side effects of Avapritinib include:

• Nausea,
• Vomiting,
• Loss of appetite,
• Stomach pain,
• Diarrhea,
• Constipation,
• Fluid retention,
• Swelling,
• Dizziness,
• Weakness,
• Tiredness,
• Muscle weakness,
• Water eyes,
• Rash, and
• Hair color changes

Serious side effects of Avapritinib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Severe headache,
• Vision problems,
• Unusual changes in mood or behavior,
• Problems with speech, thinking, or memory,
• Confusion,
• Hallucinations,
• Severe drowsiness,
• Dizziness,
• Trouble sleeping, and
• Severe weakness on one side of your body

Rare side effects of Avapritinib include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats;fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 25 mg
• 50 mg
• 100 mg
• 200 mg
• 300 mg

Gastrointestinal Stromal Tumors

Adult dosage

• 300 mg orally once a day
• Continue until disease progression or unacceptable toxicity.

Systemic Mastocytosis

Adult dosage

• 200 mg orally once a day
• Continue until disease progression or unacceptable toxicity.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Avapritinib has severe interactions with the following drug:
  • thalidomide
• Avapritinib has serious interactions with at least 110 other drugs.
• Avapritinib has moderate interactions with at least 257 other drugs.
• Avapritinib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Avapritinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Avapritinib?”

Cautions

• A broad spectrum of CNS adverse reactions was reported; these include, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations.
• Cognitive adverse reactions reported; depending on severity, withhold treatment and then resume at the same dose or a reduced dose upon improvement, or permanently discontinue treatment.
• Fetal harm can occur when administered to pregnant females.
• Therapy may cause photosensitivity reactions; in all patients treated in clinical trials, photosensitivity reactions occurred in 2.5% of patients; advise patients to limit direct ultraviolet exposure during treatment and for one week after discontinuation of treatment
• Intracranial hemorrhage
  • Intracranial hemorrhage (. g, subdural hematoma, intracranial hemorrhage, cerebral hemorrhage) occurred; thrombocytopenia was generally reversible by dose reduction or interruption.
  • Monitor patients closely for the risk of intracranial hemorrhage including those with thrombocytopenia, vascular aneurysm, or a history of intracranial hemorrhage or cerebrovascular accident within the prior year.
  • Permanently discontinue therapy if intracranial hemorrhage of any grade occurs.
• Advanced systemic mastocytosis
  • Platelet count must be performed before initiating therapy; drug not recommended in patients with AdvSM with platelet counts below 50 X 109/L
  • Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks regardless of baseline platelet count
  • After 8 weeks of treatment, monitor platelet counts every 2 weeks (or more frequently as clinically indicated) if values are less than 75 X 109/L, every 4 weeks if values are between 75 and 100 X 109/L, and as clinically indicated if values are greater than 100 X 109/L
  • Manage platelet counts of below 50 X 109/L by treatment interruption or dose-reduction; platelet support may be necessary
  • Dose interruptions and dose reduction for thrombocytopenia occurred in 20% and 22% of treated patients, respectively; thrombocytopenia was generally reversible by reducing or interrupting the drug.
• Drug interaction overview
  • Substrate of CYP3A4 and CYP2C9
    • Strong and moderate CYP3A inhibitors
    • Avoid coadministration; reduce dose if unable to avoid it.
    • Strong or moderate CYP3A inhibitor increases Avapritinib plasma concentrations and adverse reactions.
  • Strong and moderate CYP3A inducers
    • Avoid coadministration.
    • Strong or moderate CYP3A inducer decreases plasma concentrations and efficacy of Avapritinib.

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
• No data available on use in pregnant women
• Verify the pregnancy status of females of reproductive potential before initiation.
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose.
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose.
• Infertility
  • Based on findings from animal studies, may impair fertility for both males and females
• Lactation
  • There are no data on the presence of Avapritinib or its metabolites in human milk or the effects of Avapritinib on the breastfed child or milk production
  • Advise women not to breastfeed during treatment and for 2 weeks following the final dose.