Avapritinib – Uses, Dosage, Side Effects, Interactions

Use in Cancer

Avapritinib is approved to treat adults with:

• A gastrointestinal stromal tumor (GIST) that cannot be removed by surgery or has metastasized (spread to other parts of the body) and has certain mutations in the PDGFRA gene.
• Systemic mastocytosis that is advanced, including the following types:
  • Aggressive systemic mastocytosis.
  • Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN).
  • Mast cell leukemia. Avapritinib is not recommended for the treatment of advanced systemic mastocytosis in people with low platelet counts (less than 50 × 109/L).

Avapritinib is also being studied in the treatment of other conditions and other types of cancer.

Contraindications

The following conditions are contraindicated? with this drug. Check with your physician if you have any of the following:

• decreased blood platelets
• bleeding within the skull?
• pregnancy
• a patient who is producing milk and breastfeeding

Dosage?

Strengths: 100 mg; 200 mg; 25 mg; 300 mg; 50 mg

Stomach Cancer

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

Renal? Dose Adjustments

• Mild? (60 to less than 90 mL/min) to moderate? (30 to less than 60 mL/min) renal impairment: No adjustment recommended.
  Severe? (15 to less than 30 mL/min) or end-stage? (less than 15 mL/min) renal impairment: Data not available

Liver? Dose Adjustments

• Mild (total bilirubin? less than or equal to upper limit of normal [ULN] and aspartate aminotransferase [AST] greater than ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: No adjustment recommended.
  Severe hepatic impairment: Data not available

Dose Adjustments

RECOMMENDED DOSE REDUCTIONS:

• First dose reduction: 200 mg orally once a day
• Second dose reduction: 100 mg orally once a day
• Permanently discontinue therapy in patients unable to tolerate 100 mg orally once a day.

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS:
INTRACRANIAL HEMORRHAGE:
Grade 1 or 2:

• First occurrence: Withhold this drug until resolution; resume at reduced dose.
• Subsequent occurrence: Permanently discontinue this drug.

Grade 3 or 4:

• Permanently discontinue this drug.

CENTRAL NERVOUS SYSTEM EFFECTS:

• Grade 1: Continue at same dose or withhold until improvement to baseline? or resolution; resume at same OR reduced dose.
• Grade 2 or 3: Withhold this drug until improvement to baseline, Grade 1, or resolution; resume at same OR reduced dose.

Grade 4:

• Permanently discontinue therapy.

Side Effects

The Most Common

• stomach pain?
• vomiting?
• nausea?
• diarrhea?
• heartburn?
• headache?
• tiredness
• difficulty falling asleep or staying asleep
• hair loss
• hair color changes
• weight loss?
• teary eyes
• taste changes
• swelling? of face, eyes, mouth, or throat?
• swelling of hands, ankles, or feet
• vomiting blood or material that looks like coffee grounds or red or tarry black stools
• severe headache, vomiting, confusion, vision problems, drowsiness, extreme tiredness, or weakness on one side of your body
• forgetfulness, confusion, drowsiness, dizziness, difficulty sleeping, difficulty speaking, hallucinations, or changes in mood or behavior
• rash
• shortness of breath
• fever or other signs of infection

More Common

• 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.
• 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.

Rare

• 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

Drug Interactions

Pregnanct and Lactations

US FDA pregnancy category: Not assigned

Pregnancy

Based on findings from animal studies and its mechanism of action, AYVAKIT can cause fetal harm when administered to a pregnant woman. There are no available data on AYVAKIT use in pregnant women. Oral administration of avapritinib to pregnant animals during the period of organogenesis was teratogenic and embryotoxic in rats at exposure levels approximately 6.3 and 2.7 times the human exposure based on AUC at the 200 mg and 300 mg dose, respectively. Advise pregnant women of the potential risk to a fetus.

Lactation

Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks following the final dose

References