Ayvakit

Ayvakit is used in adults to treat:

• gastrointestinal stromal tumor (GIST) that cannot be removed by surgery (unresectable) or that is metastatic (has spread), and that is caused by an abnormal PDGFRA exon 18 gene, including PDGFRA D842V mutations. Your healthcare provider will test for this abnormal gene to make sure Ayvakit is right for you.
• Advanced systemic mastocytosis (AdvSM), including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
• Indolent systemic mastocytosis (ISM).

Ayvakit (avapritinib) is a tyrosine kinase inhibitor. It blocks specific abnormal proteins that drive the growth of certain tumors: mutated PDGFRA in GIST, and mutated KIT (D816V) in systemic mastocytosis. By targeting these specific mutations, Ayvakit slows or stops the growth of cells that depend on them.

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

Ayvakit (avapritinib) received FDA approval on January 9, 2020.

Ayvakit at a glance

Take Ayvakit exactly as your healthcare provider tells you to. Do not change your dose or stop taking it unless your provider tells you to. Your provider may change your dose, pause treatment, or stop it if you have side effects.

• Take Ayvakit tablets one time each day.
• Take the tablet(s) on an empty stomach, at least 1 hour before or at least 2 hours after a meal.
• If you miss a dose, take it as soon as you remember, unless your next dose is due within 8 hours. In that case, skip the missed dose and take the next one at your regular time.
• If you vomit after a dose, do not take an extra dose. Take your next dose at the usual time.

There are no contraindications to Ayvakit. Before you start treatment, tell your healthcare provider about all of your medical conditions, including if you:

• have a history of a bulging or weakened blood vessel wall (aneurysm) or bleeding in your brain
• have had a stroke within the last year
• have low platelet counts
• have or have had liver problems.

Pregnancy

Ayvakit can harm an unborn baby. Tell your healthcare provider if you are pregnant or plan to become pregnant.

• Females who can become pregnant should have a pregnancy test before starting, use effective birth control during treatment and for 6 weeks after the final dose, and tell their provider right away if they become pregnant or think they may be.
• Males with female partners who can become pregnant should use effective birth control during treatment and for 6 weeks after the final dose.

Breastfeeding

It is not known if Ayvakit passes into breast milk. Do not breastfeed during treatment and for at least 2 weeks after the final dose. Talk to your healthcare provider about how to feed your baby during this time.

Serious side effects

Ayvakit may cause serious side effects, including:

• Bleeding in the brain (intracranial hemorrhage). Serious bleeding in the brain can happen and may lead to death. Stop treatment and tell your healthcare provider right away if you have symptoms such as severe headache, nausea, vomiting, vision changes, drowsiness, dizziness, confusion, or severe weakness on one or more sides of your body. If you have AdvSM, your provider will check your platelet counts before and during treatment. Bleeding in the brain has not been seen in people treated for ISM.
• Cognitive effects. Cognitive side effects are common and can be severe. Tell your provider about any new or worsening symptoms such as forgetfulness, confusion, getting lost, trouble thinking, drowsiness, trouble staying awake, word-finding problems, hallucinations (seeing or hearing things that are not there), or changes in mood or behavior.
• Skin sensitivity to sunlight (photosensitivity).

Ayvakit may also cause fertility problems in females and may decrease sperm production in males, which could affect your ability to have a child.

Common side effects

The most common side effects depend on the condition being treated:

• GIST: fluid retention or swelling, nausea, tiredness or weakness, trouble thinking, vomiting, decreased appetite, diarrhea, increased eye tearing, abdominal pain, constipation, rash, dizziness, hair color changes, and changes in certain blood tests.
• AdvSM: fluid retention or swelling, diarrhea, nausea, tiredness or weakness, and changes in certain blood tests.
• ISM: swelling around the eyes, dizziness, swelling of the arms and legs, and flushing.

These are not all of the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual adult dose for GIST

300 mg orally once a day, until the disease worsens or side effects become unacceptable. Patients are selected for treatment based on the presence of a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

Usual adult dose for advanced systemic mastocytosis (AdvSM)

200 mg orally once a day, until the disease worsens or side effects become unacceptable. Not recommended if the platelet count is below 50 x 10(9)/L.

Usual adult dose for indolent systemic mastocytosis (ISM)

25 mg orally once a day to start. After at least 6 months of treatment, the dose may be increased to 50 mg once a day if clinically appropriate. Not recommended if the platelet count is below 50 x 10(9)/L.

Dose adjustments

Lower starting doses are recommended for people with severe liver (hepatic) impairment, and when Ayvakit must be taken with a moderate CYP3A inhibitor. Your provider may also reduce the dose, pause, or stop Ayvakit to manage side effects.

Do not drive or operate heavy machinery if you have confusion or trouble thinking during treatment.

Your skin may be more sensitive to the sun or other light (photosensitivity) during treatment. Avoid or limit direct sunlight, sunlamps, and other sources of ultraviolet light during treatment and for 1 week after stopping. Use sunscreen or wear clothing that covers your skin if you need to be in the sun.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Ayvakit can affect how other medicines work, and some medicines can change the level of Ayvakit in your body. Especially tell your provider if you take:

• Strong or moderate CYP3A inhibitors (for example, certain antifungal and antibiotic medicines): these can raise Ayvakit levels and should be avoided. If a moderate inhibitor cannot be avoided, your Ayvakit dose may be lowered.
• Strong or moderate CYP3A inducers (for example, rifampin, some seizure medicines, and the herbal supplement St. John's wort): these can lower Ayvakit levels and should be avoided.
• Hormonal birth control that contains ethinyl estradiol: Ayvakit may make it less effective, so an additional or non-hormonal method may be needed.
• Medicines that prevent blood clots (anticoagulants): these may add to the risk of bleeding.

This is not a complete list of interactions.

• Store the tablets at room temperature between 68 and 77 degrees Fahrenheit (20 and 25 degrees Celsius).
• Keep all medicines out of the reach of children and pets.

Active ingredient: avapritinib.

Inactive ingredients: copovidone, croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. Film coat: polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. Blue printing ink: ammonium hydroxide, black iron oxide, esterified shellac, FD&C blue 1, isopropyl alcohol, n-butyl alcohol, propylene glycol, and titanium dioxide.

Ayvakit is manufactured for Blueprint Medicines Corporation, Cambridge, MA 02139, USA.