GAVRETO Dosing

GAVRETO offers patients a once-daily dosing schedule

Start your patients at the recommended 400-mg dose1

Four 100-mg capsules, 1x daily Four 100-mg capsules, 1x daily
  • Continue treatment until disease progression or until unacceptable toxicity 
  • If a dose of GAVRETO is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for GAVRETO the next day
  • Advise patients not to take an additional dose if vomiting occurs after taking GAVRETO but to continue with the next dose as scheduled
  • Select patients for treatment with GAVRETO based on the presence of a RET gene fusion (NSCLC or thyroid cancer)

NSCLC=non–small cell lung cancer; RET=rearranged during transfection.

Recommended dosage reductions for adverse reactions1

GAVRETO's single dosage strength allows for convenient dose reductions.

dose modifcations infographic

Capsules are not actual size.

Permanently discontinue GAVRETO in patients who are unable to tolerate 100 mg taken orally once daily.

In exposure-response analyses, clinically improved outcomes were associated with starting at the recommended 400 mg dose of GAVRETO compared to starting at lower doses (≤300 mg QD)1,2

Exposure-response analyses were conducted on data obtained from patients in the phase 1/2 ARROW study, including patients with RET fusion-positive NSCLC. This consisted of dose escalation (phase 1, doses from 30-600 mg QD or BID) and dose expansion (phase 2, dose of 400 mg QD) phases. The exposure-response analyses were designed to evaluate the relationships between exposure and efficacy/safety outcomes, and to assess and adjust for covariate effects.2

Recommended dosage modifications for GAVRETO for adverse reactions1

Adverse ReactionSeverity*Dosage Modification
ILD/PneumonitisGrade 1 or 2Withhold GAVRETO until resolution. Resume by reducing the dose (see dose reduction table).
Permanently discontinue GAVRETO for recurrent ILD/pneumonitis.
Grade 3 or 4Permanently discontinue for confirmed ILD/pneumonitis.
HypertensionGrade 3Withhold GAVRETO for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled.
Grade 4Discontinue GAVRETO.
HepatotoxicityGrade 3 or Grade 4Withhold GAVRETO and monitor AST/ALT once weekly until resolution to Grade 1 or baseline. Resume at reduced dose. For recurrent events at Grade 3 or higher, discontinue GAVRETO.
Hemorrhagic EventsGrade 3 or Grade 4Withhold GAVRETO until recovery to baseline or Grade 0 or 1.
Discontinue GAVRETO for severe or life-threatening hemorrhagic events.
Other Adverse ReactionsGrade 3 or 4Withhold GAVRETO until improvement to ≤Grade 2.
Resume at reduced dose.
Permanently discontinue for recurrent Grade 4 adverse reactions.

*Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
ILD=interstitial lung disease.

Adverse event monitoring and coadministration

Monitor patients for the following adverse events1:

  • ILD/pneumonitis: Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (such as dyspnea, cough, and fever)
  • Hypertension: Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate
  • Hepatotoxicity: Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated

Avoid coadministration of GAVRETO with any of the following1,3:

  • Strong CYP3A inhibitors, such as ritonavir
  • Moderate CYP3A inhibitors, such as amlodipine
  • P-gp inhibitors, such as clarithromycin
  • Combined P-gp and strong CYP3A inhibitors, such as verapamil
  • Combined P-gp and moderate CYP3A inhibitors, such as amiodarone

If coadministration with any of the above inhibitors cannot be avoided, reduce the current dose of GAVRETO as recommended in the Prescribing Information. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume GAVRETO at the dose taken prior to initiating the inhibitor.1

Avoid coadministration of GAVRETO with any of the following1,3:

  • Strong CYP3A inducers, such as rifampin
  • Moderate CYP3A inducers, such as St. John's wort

If coadministration with any of the above inducers cannot be avoided, increase the current dose of GAVRETO as recommended in the Prescribing Information, starting on Day 7 of coadministration of GAVRETO with the inducer. After the inducer has been discontinued for at least 14 days, resume GAVRETO at the dose taken prior to initiating the inducer.1

CYP3A=cytochrome P450 3A; P-gp=P-glycoprotein.

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References:

 

1. GAVRETO® [Package insert], South San Francisco, CA: Rigel Pharmaceuticals, Inc.

 

2. GAVRETO: Data on file, Rigel Pharmaceuticals, Inc. June 2024.

 

3. Kassir N, McDougall D, Kuruvilla D, et al. Exposure-response relationships for pralsetinib in patients with RET-altered thyroid cancer or RET fusion-positive nonsmall cell lung cancer. J Clin Pharmacol. 2024;64(6):685-696. doi:10.1002/jcph.2409

 

4. Wu S, Hoang HB, Yang JZ, et al. Drug-drug interactions in pulmonary arterial hypertension. Chest. 2022;162(6):1360-1372.

Indications & Important Safety Information

INDICATIONS

GAVRETO (pralsetinib) is indicated for the treatment of:

  • Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)*

*This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal ILD/pneumonitis can occur in patients treated with GAVRETO. Pneumonitis occurred in 12% of patients who received GAVRETO, including 3.3% with Grade 3-4, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD.

Hypertension: Occurred in 35% of patients, including Grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.

Hepatotoxicity: Serious hepatic adverse reactions occurred in 1.5% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 49% of patients, including Grade 3 or 4 in 7% and increased alanine aminotransferase (ALT) occurred in 37% of patients, including Grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range: 5 days to 2.5 years) and increased ALT was 24 days (range: 7 days to 3.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.

Hemorrhagic Events: Serious, including fatal, hemorrhagic events can occur with GAVRETO. Grade ≥3 events occurred in 4.1% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.

Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Risk of Impaired Wound Healing: Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the last dose.

Common adverse reactions (≥25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased leukocytes, decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium, and increased bilirubin.

Avoid coadministration of GAVRETO with strong or moderate CYP3A inhibitors, P-gp inhibitors, or combined P-gp and strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong or moderate CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.

Lactation: Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose.

Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here to see the full Prescribing Information and Patient Information for GAVRETO.