GAVRETO Dosing

The only once-daily RET inhibitor1

Recommended starting dose: 400 mg once daily

Four 100-mg capsules, 1x daily Four 100-mg capsules, 1x daily

GAVRETO offers patients a clear, once-daily dosing schedule

  • 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)
  • An FDA-approved test for the detection of RET gene fusions (thyroid cancer) is not currently available

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

Recommended dosage reductions and modifications for adverse reactions

GAVRETO is available in a single-dosage strength that allows for dose reductions within an existing bottle

dose modifcations infographic

Capsules are not actual size.

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

Recommended Dose Reductions for GAVRETO for Adverse Reactions

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.

Coadministration with CYP3A and/or P-gp inhibitors

Avoid coadministration of GAVRETO with strong or moderate CYP3A inhibitors, P-gp inhibitors, combined P-gp and moderate CYP3A inhibitors, and combined P-gp and strong CYP3A inhibitors.

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

Current GAVRETO DosageRecommended GAVRETO Dosage When Coadministered With:
 Combined P-gp and strong CYP3A inhibitors
  • Strong CYP3A inhibitors
  • Moderate CYP3A inhibitors
  • P-gp inhibitors
  • Combined P-gp and moderate CYP3A inhibitors
400 mg orally once daily200 mg orally once daily300 mg orally once daily
300 mg orally once daily200 mg orally once daily200 mg orally once daily
200 mg orally once daily100 mg orally once daily100 mg orally once daily

CYP=cytochrome P450; P-gp=P-glycoprotein.

Coadministration with CYP3A inducers

Avoid coadministration of GAVRETO with strong or moderate CYP3A inducers.

If coadministration with any of the above inducers cannot be avoided, increase the starting dose of GAVRETO as recommended below, 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.

Current GAVRETO DosageRecommended GAVRETO Dosage When Coadministered With:
 Strong CYP3A inducers
Moderate CYP3A inducers
400 mg orally once daily800 mg orally once daily600 mg orally once daily
300 mg orally once daily600 mg orally once daily500 mg orally once daily
200 mg orally once daily400 mg orally once daily300 mg orally once daily
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GAV_PAN-24054 0924

Reference:

 

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

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.