Ayvakit (avapritinib)

Brand name: Ayvakit

Generic: avapritinib

Ayvakit is a prescription medicine used to treat adults with a certain type of stomach, bowel, or esophagus cancer called gastrointestinal stromal tumor (GIST) that cannot be treated with surgery or that has spread to other parts of the body (metastatic), and that is caused by certain abnormal platelet-derived growth factor receptor alpha (PDGFRA) genes.

Your healthcare provider will perform a test to make sure that you have this abnormal PDGFRA gene and that Ayvakit is right for you.

It is not known if Ayvakit is safe and effective in children.

What are the serious side effects of Ayvakit?

Ayvakit may cause serious side effects, including:

• Bleeding in your brain. Serious bleeding in the brain may happen during treatment with Ayvakit and may lead to death. Stop taking Ayvakit and tell your healthcare provider right away if you develop any symptoms such as severe headache, vomiting, drowsiness, dizziness, confusion, or severe weakness on one or more side of your body.
  If you have AdvSM, your healthcare provider will check your platelet counts before and during treatment with Ayvakit.
• Cognitive effects. Cognitive side effects are common with Ayvakit and can be severe. Tell your healthcare provider if you develop any new or worsening cognitive symptoms including:
  • forgetfulness
  • confusion
  • getting lost
  • trouble thinking
  • drowsiness
  • trouble staying awake (somnolence)
  • word finding problems
  • seeing objects or hearing things that are not there (hallucinations)
  • change in mood or behavior

What are the common side effects of Ayvakit?

The most common side effects of Ayvakit in people with GIST include:

• fluid retention or swelling
• nausea
• tiredness
• muscle weakness
• vomiting
• decreased appetite
• diarrhea
• increased eye tearing
• stomach area (abdominal) pain
• constipation
• rash
• dizziness
• hair color changes
• changes in certain blood tests

The most common side effects of Ayvakit in people with AdvSM include:

• fluid retention or swelling
• diarrhea
• nausea
• tiredness
• changes in certain blood tests

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Ayvakit if you develop certain side effects.

Ayvakit may cause fertility problems in females and may decrease sperm production in males, which may affect your ability to have a child. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of Ayvakit.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Patient Selection For GIST Harboring PDGFRA Exon 18 Mutations

• Select patients for treatment with Ayvakit based on the presence of a PDGFRA exon 18 mutation. An FDA-approved test for the detection of exon 18 mutations is not currently available.

Recommended Dosage For GIST Harboring PDGFRA Exon 18 Mutations

• The recommended dosage of Ayvakit is 300 mg orally once daily in patients with GIST. Continue treatment until disease progression or unacceptable toxicity.

Recommended Dosage For Advanced Systemic Mastocytosis

• The recommended dosage of Ayvakit is 200 mg orally once daily in patients with AdvSM. Continue treatment until disease progression or unacceptable toxicity.
• Modify dosage for adverse reactions as outlined in Table 2.

Recommended Administration

• Administer Ayvakit orally on an empty stomach, at least 1 hour before or 2 hours after a meal. Do not make up for a missed dose within 8 hours of the next scheduled dose. Do not repeat dose if vomiting occurs after Ayvakit but continue with the next scheduled dose.

Dosage Modifications For Adverse Reactions

• The recommended dose reductions and dosage modifications for adverse reactions are provided in Tables 1 and 2.

Table 1: Recommended Dose Reductions for Ayvakit for Adverse Reactions

Table 2: Recommended Dosage Modifications for Ayvakit for Adverse Reactions

Concomitant Use Of Strong Or Moderate CYP3A Inhibitors

Avoid concomitant use of Ayvakit with strong or moderate CYP3A inhibitors. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dosage of Ayvakit is as follows:

• GIST: 100 mg orally once daily
• AdvSM: 50 mg orally once daily

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, 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.

Strong And Moderate CYP3A Inducers

• Coadministration of Ayvakit with a strong or moderate CYP3A inducer decreases avapritinib plasma concentrations, which may decrease efficacy of Ayvakit. Avoid coadministration of Ayvakit with strong or moderate CYP3A inducers.

Before taking Ayvakit, tell your healthcare provider about all of your medical conditions, including if you:

• have low platelet counts
• bulging or weakening of a blood vessel wall (aneurysm) or history of bleeding in your brain
• history of stroke within the last year
• are pregnant or plan to become pregnant. Ayvakit can cause harm to your unborn baby.
  Females who are able to become pregnant:
  • Your healthcare provider should do a pregnancy test before you start treatment with Ayvakit.
  • You should use effective birth control (contraception) during treatment with Ayvakit and for 6 weeks after the final dose of Ayvakit. Talk to your healthcare provider about birth control methods that may be right for you.
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Ayvakit.
    Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment and for 6 weeks after the final dose of Ayvakit.
• are breastfeeding or plan to breastfeed. It is not known if Ayvakit passes into your breast milk. Do not breastfeed during treatment with Ayvakit and for at least 2 weeks after the final dose of Ayvakit. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

Ayvakit may affect the way other medicines work, and certain other medicines may affect how Ayvakit works. Talk to your healthcare provider prior to starting a new medicine.