Avapritinib Dosage

Medically reviewed by Drugs.com. Last updated on Feb 20, 2025.

Usual Adult Dose for Gastrointestinal Stromal Tumor

300 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Select patients for treatment based on the presence of a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.
• A test approved by the US FDA for the detection of exon 18 mutations is not currently available.

Use: For the treatment of unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations

Usual Adult Dose for Systemic Mastocytosis

ADVANCED SYSTEMIC MASTOCYTOSIS (AdvSM): 200 mg orally once a day

• Duration of therapy: Until disease progression or unacceptable toxicity

INDOLENT SYSTEMIC MASTOCYTOSIS (ISM): 25 mg orally once a day

Comments:

• Limitation of use: This drug is not recommended for the treatment of patients with AdvSM or ISM with platelet counts of less than 50 x 10(9)/L.
• Ensure a platelet count is performed prior to initiating therapy.
• This drug should be taken on an empty stomach.

Uses:

• For the treatment of AdvSM, including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia
• For the treatment of adult patients with ISM

Renal Dose Adjustments

Mild to Moderate Renal Dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended
Severe Renal Dysfunction (CrCl 15 to 29 mL/min): Data not available
End-Stage Renal Disease ([ESRD]; CrCl less than 15 mL/min): Data not available

Liver Dose Adjustments

Mild Liver Dysfunction (total bilirubin at the upper limit of normal [ULN] or less and AST greater than ULN, or total bilirubin greater than 1 to 1.5 times ULN and any AST): No adjustment recommended.

Moderate Liver Dysfunction (total bilirubin greater than 1.5 to 3 times ULN and any AST): No adjustment recommended.

Severe Liver Dysfunction (Child-Pugh C): Exposure is increased; a lower starting dose is recommended:

• In patients with GIST: 200 mg orally once a day
• In patients with AdvSM: 100 mg orally once a day
• In patients with ISM: 25 mg orally every other a day

Dose Adjustments

STEPWISE DOSE REDUCTION RECOMMENDATIONS:
Patients with GIST:

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

Patients with AdvSM:

• First dose reduction: 100 mg orally once a day
• Second dose reduction: 50 mg orally once a day
• Third dose reduction: 25 mg orally once a day
• Permanently discontinue this drug in patients unable to tolerate 25 mg orally once a day.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
Patients with GIST or AdvSM:

• Intracranial Hemorrhage (Any grade): Permanently discontinue treatment.
• Cognitive Effects:
• Grade 1: Continue therapy at the same or reduced dose, or withhold until improvement to baseline or resolution. Then, resume therapy at same or reduced dose.
• Grade 2 or 3: Withhold therapy until improvement to baseline, grade 1, or resolution. Then, resume therapy at same or reduced dose.
• Grade 4: Permanently discontinue treatment.
• Other Adverse Reactions (Grade 3 or 4): Withhold therapy until improvement Grade 2 or less. Then, resume therapy at the same dose or reduced dose, as clinically appropriate.

Patients with AdvSM:

• Thrombocytopenia (Platelets less than 50 x 10(9)/L): Interrupt therapy until platelet count is 50 x 10(9)/L or greater; then, resume at a reduced dose. If platelet counts do not recover above 50 x 10 (9)/L, consider platelet support.

CONCOMITANT USE WITH STRONG AND MODERATE CYP450 3A INHIBITORS:
Strong CYP450 3A Inhibitors: Avoid concomitant use

Moderate CYP450 3A Inhibitors: In general, avoid concomitant use, especially in patients with ISM; however, if concomitant use cannot be avoided, a reduced starting dose of this drug is recommended as follows:

• In patients with GIST: 100 mg orally once a day
• In patients with AdvSM: 50 mg orally once a day
• In patients with ISM: Concomitant use should be avoided.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For oral use.
• Administer this drug 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.
• If vomiting occurs after administration, do not repeat the dose; continue with the next scheduled dose.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions are permitted from 15C to 30C (59F to 86F).

Monitoring:

• Hematologic: Platelet counts in patients with AdvSM (at baseline, every 2 weeks for the first 8 weeks of therapy, and then as recommended based on platelet count values that follow)
• For platelets less than 75 x 10(9)/L: Monitor every 2 weeks, or as clinically indicated
• For platelets between 75 and 100 x 10(9)/L: Monitor every 4 weeks
• For platelets greater than 100 x 10(9)/L: Monitor as clinically indicated
• Neurologic: For intracranial hemorrhage risk factors (prior to and during therapy); cognitive effects (during therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Take this medication on an empty stomach, at least 1 hour before or 2 hours after a meal.
• Seek immediate medical attention if neurological signs/symptoms of intracranial hemorrhage occur; platelet counts are recommended before and during treatment.
• Notify healthcare provider if new or worsening cognitive symptoms; do not drive or operate heavy machinery if experiencing cognitive adverse reactions.
• Limit direct ultraviolet light exposure by using sunscreen and protective clothing during treatment.
• Inform health care provider of all other concomitant medications, including over-the-counter products.
• Patients of childbearing potential:
• Understand the potential risk to a fetus and notify health care provider of a known/suspected pregnancy.
• Recognize that this drug may impair fertility or decrease sperm production, especially at higher doses.
• Females: Use effective contraception during treatment and for 6 weeks after last dose.
• Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 weeks after last dose.
• Breastfeeding patients: Do not breastfeed during treatment and for 2 weeks after the last dose.

See also:

Further information

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