Pronunciation:

a-va-PRI-ti-nib

Brand Names:

• Ayvakit

Dosage Forms:

• Tablet

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Tyrosine Kinase Inhibitor

Uses of This Medicine:

Avapritinib is used to treat 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 a certain platelet-derived growth factor receptor alpha (PDGFRA) gene mutation.

This medicine is also used to treat advanced systemic mastocytosis (AdvSM), including aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). It is also used to treat indolent systemic mastocytosis (ISM).

Avapritinib belongs to the group of medicines known as antineoplastics. It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by sunitinib, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with avapritinib, you should talk to your doctor about the benefits as well as the risks of using this medicine.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of avapritinib in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of avapritinib in the elderly.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Levoketoconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adagrasib
• Apalutamide
• Aprepitant
• Atazanavir
• Boceprevir
• Bosentan
• Carbamazepine
• Cenobamate
• Ciprofloxacin
• Clarithromycin
• Cobicistat
• Conivaptan
• Crizotinib
• Cyclosporine
• Dabrafenib
• Diltiazem
• Dronedarone
• Duvelisib
• Efavirenz
• Enzalutamide
• Erythromycin
• Etravirine
• Fedratinib
• Fexinidazole
• Fluconazole
• Fluvoxamine
• Fosnetupitant
• Fosphenytoin
• Idelalisib
• Imatinib
• Indinavir
• Itraconazole
• Ketoconazole
• Larotrectinib
• Lenacapavir
• Letermovir
• Lopinavir
• Lorlatinib
• Lumacaftor
• Mavacamten
• Mitotane
• Modafinil
• Nafcillin
• Nefazodone
• Nelfinavir
• Netupitant
• Nilotinib
• Olutasidenib
• Omaveloxolone
• Pacritinib
• Phenobarbital
• Phenytoin
• Pirtobrutinib
• Posaconazole
• Primidone
• Rifabutin
• Rifampin
• Ritlecitinib
• Ritonavir
• Saquinavir
• St John's Wort
• Telaprevir
• Telithromycin
• Trofinetide
• Verapamil
• Voriconazole

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Kidney disease, severe (eg, end-stage kidney disease) or
• Liver disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of This Medicine:

Medicines used to treat cancer are very strong and can have many side effects. Before using this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with patient information insert. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Take this medicine with an empty stomach, at least 1 hour before or 2 hours after a meal.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of gastrointestinal stromal tumor (GIST):
    • Adults—300 milligrams (mg) once a day. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.
  • For treatment of advanced systemic mastocytosis (AdvSM):
    • Adults—200 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.
  • For treatment of indolent systemic mastocytosis (ISM):
    • Adults—25 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose and it is less than 8 hours until your next dose, skip the missed dose and go back to your regular dosing schedule. If you miss a dose and it is more than 8 hours until your next dose, take it as soon as possible, and then go back to your regular dosing schedule.

If you vomit after taking a dose, take the next dose at the regular time.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly.

Using this medicine while you are pregnant can harm your unborn baby. If you are a woman who can get pregnant, your doctor may do tests to make sure you are not pregnant before starting avapritinib treatment. Men and women should use an effective form of birth control during treatment and for up to 6 weeks after treatment. If you think you have become pregnant while using this medicine or within 6 weeks after the last dose, tell your doctor right away.

This medicine may cause intracranial hemorrhage (bleeding in the brain). Make sure your doctor knows if you have a bleeding disorder, or any medical condition that increases your chance of bleeding. Call your doctor right away if you have confusion, headache, sudden, severe weakness, nausea, or vomiting.

This medicine may cause changes in mood or behavior, trouble sleeping, or hallucinations (seeing, hearing, or feeling things that are not there). It may also make you drowsy, dizzy, confused, or less alert than you are normally. Do not drive or do anything else that could be dangerous until you know this medicine affects you.

This medicine may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds.

If you plan to have children, talk with your doctor before using this medicine. Some men and women using this medicine have become infertile (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bladder pain

bloody or cloudy urine

blurred vision

body aches or pain

chest tightness

defects in intelligence, short-term memory, learning ability, and attention

dizziness

ear congestion

headache

loss of voice

lower back or side pain

mood or mental changes

nervousness

pale skin

pounding in the ears

runny or stuffy nose

slow or fast heartbeat

sneezing

sore throat

trouble sleeping

trouble with breathing

unusual bleeding or bruising

unusual tiredness or weakness

Less common

Agitation

black, tarry stools

bloody stools

chest pain

chills

confusion

constipation

cough

decreased awareness or responsiveness

decreased urine output

depressed mood

difficult, burning, or painful urination

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

dry skin and hair

dilated neck veins

fainting

feeling cold

fever

frequent urge to urinate

gaseous stomach pain

hair loss

hoarseness or husky voice

hostility

increased sensitivity of the skin to sunlight

irritability

lightheadedness

loss of consciousness

muscle cramps, stiffness, and twitching

nausea

pounding in the ears

rapid weight gain

rapid, shallow breathing

redness or other discoloration of the skin

seizures

sensitivity to heat

severe sleepiness

severe sunburn

skin rash

sneezing

sore throat

stomach pain and bloating

sweating

swelling of the face, ankles, or hands

swelling of the finger, feet, or lower legs

unusual drowsiness, dullness, or feeling of sluggishness

vomiting of blood or material that looks like coffee grounds

weight gain or loss

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Bad unusual or unpleasant (after)taste

belching

change in taste

decreased appetite

diarrhea

difficulty in moving

feeling of warmth

redness of the face, neck, arms and occasionally, upper chest

hair color changes

heartburn

increased tearing

indigestion

muscle pain or stiffness

pain in the joints

skin rash

stomach discomfort, upset, or pain

swelling of the eye, eyelid, or inner lining of the eyelid

vomiting

Less common

Redness or pain of the skin

scaling of the skin on the hands and feet

tingling of the hands and feet

ulceration of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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