Pralsetinib Dosage

Medically reviewed by Drugs.com. Last updated on Oct 9, 2023.

Applies to the following strengths: 100 mg

Usual Adult Dose for Non-Small Cell Lung Cancer

400 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity.

Comments:

Select patients based on the presence of a RET (rearranged during transfection) gene fusion.
Information on FDA-approved tests for RET gene fusion is available at http://www.fda.gov/CompanionDiagnostics.

Use: For the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test

Usual Adult Dose for Thyroid Cancer

400 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity.

Comments:

Select patients based on the presence of a RET (rearranged during transfection) gene fusion (thyroid cancer).
However, FDA-approved gene fusion tests for RET gene fusion (thyroid cancer) and are currently not available.

Use:

For the treatment of advanced or metastatic RET fusion-positive thyroid cancer patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

Usual Pediatric Dose for Thyroid Cancer

12 years or older: 400 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity.

Comments:

Select patients based on the presence of a RET (rearranged during transfection) gene fusion (thyroid cancer).
However, FDA-approved gene fusion tests for RET gene fusion (thyroid cancer) are currently not available.

Use:

For the treatment of advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

Renal Dose Adjustments

Mild to moderate renal impairment (CrCl 30 to less than 90 mL/min): No adjustment recommended
Severe renal impairment (CrCl 15 to less than 30 mL/min): Data not available
ESRD: Data not available

Liver Dose Adjustments

Mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] and AST greater than ULN, or total bilirubin greater than 1 to 1.5 x ULN and any AST): No adjustment recommended
Moderate and Severe hepatic impairment (total bilirubin greater than 1.5 x ULN and any AST): Data not available

Dose Adjustments

DOSE REDUCTIONS FOR ADVERSE REACTIONS:

First dose reduction: 300 mg orally once a day
Second dose reduction: 200 mg orally once a day
Third dose reduction: 100 mg orally once a day
Discontinue therapy in patients unable to tolerate 100 mg/day.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
ILD/PNEUMONITIS:

Grade 1 or 2: Withhold therapy until resolution, resume at reduced dose.
Grade 3 or 4 or recurrent: Permanently discontinue for recurrent or confirmed ILD/pneumonitis.

HYPERTENSION:

Grade 3: Withhold therapy for Grade 3 hypertension that persists despite optimal antihypertensives and resume at reduced dose when hypertension is controlled.
Grade 4: Permanently discontinue therapy.

HEPATOTOXICITY:

Grade 3 or 4: Withhold therapy, monitor transaminases weekly until recovery to Grade 1 or baseline and resume at reduced dose. If hepatotoxicity recurs at Grade 3 or higher, discontinue.

HEMORRHAGIC EVENTS:

Grade 3 or 4: Withhold therapy until recovery to baseline, Grade 0, or 1.
Severe or life-threatening hemorrhagic events: Discontinue therapy.

OTHER ADVERSE REACTIONS:

Grade 3 or 4: Withhold therapy until improvement to Grade 2 or less, resume at reduced dose.
Recurrent Grade 4: Permanently discontinue the therapy.

COADMINISTRATION WITH COMBINED P-GLYCOPROTEIN (P-gp) AND STRONG CYP450 3A INHIBITORS:

Avoid coadministration with combined P-gp and strong CYP450 3A inhibitors.
If coadministration cannot be avoided, reduce dose of this drug (if current dose is 300 mg/day or 400 mg/day reduce dose to 200 mg/day. If current dose is 200 mg/day reduce dose to 100 mg/day).
After combined P-gp and strong CYP450 3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume this drug at dose taken prior to initiating combined P-gp and strong CYP450 3A inhibitor.

COADMINISTRATION WITH STRONG CYP450 3A INDUCERS:

Avoid coadministration with strong CYP450 3A inducers.
If coadministration with a strong CYP450 3A inducer cannot be avoided, increase the starting dose of this drug to double the current dose starting on Day 7 of coadministration.
After CYP450 3A inducer has been discontinued for at least 14 days, resume this drug at dose taken prior to initiating CYP450 3A inducer.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 12 years for thyroid cancer.
Safety and efficacy have not been established in patients younger than 18 years for NSCLC.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Take orally on an empty stomach, no food should be consumed for at least 2 hours before and at least 1 hour after dosing.

MISSED DOSE: If a dose is missed, take as soon as possible on the same day. Resume regular daily dose schedule on the next day.

Do not take an additional dose if vomiting occurs but continue with next dose as scheduled.

Storage requirements:

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

General:

The use of this drug is under accelerated approval based on overall response rate and duration of response. Continued approval for use in thyroid cancer may be contingent upon verification and description of clinical benefit in confirmatory trials.

Monitoring:

Monitor for pulmonary symptoms.
Monitor blood pressure after 1 week, and monthly thereafter, and as clinically indicated.
Obtain AST and ALT at baseline, every 2 weeks during first 3 months, then monthly thereafter, and as clinically indicated.
Monitor at-risk patients for tumor lysis syndrome.
Monitor growth plates in adolescent patients with open growth plates.

Patient advice:

Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
Advise patients to take this drug on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after dosing).
Patients should be instructed to report new or worsening respiratory symptoms, bleeding, impaired wound healing, and/or signs of hepatotoxicity.
Patients should understand they may need to stop therapy prior to surgery.
Women of childbearing potential and males with female partners of reproductive potential should be advised on effective contraception.
Patients should seek advice on effective fertility preservation prior to starting therapy.