Gavreto (pralsetinib)

Gavreto is a prescription medicine for adults with non-small cell lung cancer (NSCLC) that has metastasized and is caused by RET gene rearrangement. Your healthcare provider will test to determine if Gavreto is suitable for you.

Gavreto’s safety and effectiveness in children are unknown.

Side Effects of Gavreto

Gavreto may cause serious side effects, including:

• Lung problems. Gavreto may cause severe or life-threatening lung inflammation, potentially leading to death. Contact your healthcare provider immediately if you experience new or worsening symptoms, such as:
• Shortness of breath
• Cough
• Fever
• Confusion
• Headaches
• Shortness of breath
• Dizziness
• Chest pain
• Yellowing of skin or eyes (jaundice)
• Dark “tea-colored” urine
• Sleepiness
• Bleeding or bruising
• Loss of appetite
• Nausea or vomiting
• Pain on upper right side of stomach
• Vomiting blood or coffee-ground-like substance
• Pink or brown urine
• Red or black stools
• Coughing up blood or blood clots
• Unusual bleeding or bruising
• Heavier-than-normal menstrual bleeding
• Unusual vaginal bleeding
• Frequent nose bleeds
• Drowsiness or difficulty being awakened
• Confusion
• Headache
• Change in speech

The most common side effects of Gavreto include:

• Tiredness
• Constipation
• Muscle and joint pain
• High blood pressure
• Decreased white and red blood cell counts
• Decreased phosphate levels in the blood
• Decreased sodium levels in the blood
• Decreased calcium levels in the blood
• Abnormal liver function blood tests

Gavreto may affect fertility in males and females, potentially impacting the ability to have children. Discuss your concerns with your healthcare provider.

These are not all the possible side effects of Gavreto. Consult your doctor for medical advice about side effects. Report side effects to the FDA at 1-800-FDA-1088.

Dosage for Gavreto

Patient Selection

Select patients for Gavreto treatment based on the presence of a RET gene fusion. Visit http://www.fda.gov/CompanionDiagnostics for information on FDA-approved tests.

Recommended Dosage

The recommended dosage of Gavreto is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking Gavreto). Continue treatment until disease progression or unacceptable toxicity occurs.

If you miss a dose of Gavreto, take it as soon as possible on the same day. Resume the regular daily dose schedule for Gavreto the next day. Do not take an additional dose if vomiting occurs after Gavreto but continue with the next scheduled dose.

Dosage Modifications For Adverse Reactions

Refer to Table 1 and Table 2 for recommended dose reductions and modifications in response to adverse reactions.

Table 1: Recommended Dose Reductions for Gavreto for Adverse Reactions

Permanently discontinue Gavreto if unable to tolerate 100 mg taken orally once daily.

Consult Table 2 for recommended dosage modifications in response to adverse reactions.

Table 2: Recommended Dosage Modifications for Gavreto for Adverse Reactions

Permanently discontinue Gavreto in case of recurrent ILD/pneumonitis or for severe or life-threatening hemorrhagic events. Resume at reduced dose (Table 1). Permanently discontinue for recurrent Grade 4 adverse reactions.

Dose Modification For Use With Combined P-Glycoprotein (P-gp) And Strong CYP3A Inhibitors

Avoid coadministration of Gavreto with combined P-gp and strong CYP3A inhibitors. If unavoidable, reduce Gavreto dosage as indicated in Table 3. After discontinuing the inhibitor for 3 to 5 elimination half-lives, resume Gavreto at the previous dose.

Table 3: Recommended Dosage Modifications for Gavreto for Coadministration with Combined P-gp and Strong CYP3A Inhibitors

Dose Modification For Use With Strong CYP3A Inducers

Avoid coadministration of Gavreto with strong CYP3A inducers. If unavoidable, double the initial Gavreto dosage starting on Day 7 of coadministration. After discontinuing the inducer for at least 14 days, resume Gavreto at the previous dose.

Drug Interactions with Gavreto

Effects Of Other Drugs On Gavreto

Strong CYP3A Inhibitors

Avoid coadministration with strong CYP3A inhibitors as it increases pralsetinib exposure, potentially leading to more severe adverse reactions. If coadministration with combined P-gp and strong CYP3A inhibitors is unavoidable, reduce Gavreto dosage.

Strong CYP3A Inducers

Coadministration of Gavreto with strong CYP3A inducers decreases pralsetinib exposure, potentially reducing Gavreto’s efficacy. Avoid coadministration if possible; if not, increase Gavreto dosage.

Is it safe to take Gavreto during pregnancy or while breastfeeding?

Gavreto can cause fetal harm in pregnant women based on results from animal studies and its mechanism of action. No data is available on Gavreto use in pregnant women to determine associated risks.

No data exists regarding the presence of pralsetinib or its metabolites in human milk, or the effects on breastfed infants or milk production. To avoid serious adverse reactions in breastfed infants, women should not breastfeed during Gavreto treatment and for 1 week after the final dose.

Summary

Gavreto is a prescription medicine for adults with metastatic non-small cell lung cancer (NSCLC) caused by RET gene rearrangement.