Gavreto (pralsetinib)

Gavreto is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that:

• has spread to other parts of the body (metastatic), and
• is caused by abnormal rearranged during transfection (RET) genes. Your healthcare provider will perform a test to make sure that Gavreto is right for you.

It is not known if Gavreto is safe and effective in children.

Gavreto may cause serious side effects, including:

• Lung problems. Gavreto may cause severe or life-threatening inflammation of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you have any new or worsening symptoms, including:
  • shortness of breath
  • cough
  • fever
• High blood pressure (hypertension). High blood pressure is common with Gavreto and may sometimes be severe. You should check your blood pressure regularly during treatment with Gavreto. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including:
  • confusion
  • headaches
  • shortness of breath
  • dizziness
  • chest pain
• Liver problems. Liver problems (increased liver function blood test results) can happen during treatment with Gavreto and may sometimes be serious. Your healthcare provider will do blood tests before and duringtreatment with Gavreto to check you for liver problems. Tell your healthcare provider right away if you get any signs or symptoms of liver problem during treatment, including:
  • yellowing of your skin or the white part of your eyes (jaundice)
  • dark “tea-colored” urine
  • sleepiness
  • bleeding or bruising
  • loss of appetite
  • nausea or vomiting
  • pain on the upper right side of your stomach area
• Bleeding problems. Gavreto can cause bleeding which can be serious and cause death. Tell your healthcare provider if you have any signs or symptoms of bleeding during treatment, including:
  • vomiting blood or if your vomit looks like coffee-grounds
  • pink or brown urine
  • red or black (looks like tar) stools
  • coughing up blood or blood clots
  • unusual bleeding or bruising of your skin
  • menstrual bleeding that is heavier than normal
  • unusual vaginal bleeding
  • nose bleeds that happen often
  • drowsiness or difficulty being awakened
  • confusion
  • headache
  • change in speech
• Risk of wound healing problems. Wounds may not heal properly during treatment with Gavreto. Tell your healthcare provider if you plan to have any surgery before or during treatment with Gavreto. You should not take Gavreto for at least 5 days before surgery. Your healthcare provider should tell you when you may start taking Gavreto again after surgery.

The most common side effects of Gavreto include:

• tiredness
• constipation
• muscle and joint painhigh blood pressure
• decreased white blood cell and red blood cell counts
• decreased levels of phosphate in the blood
• decreased levels of body salt (sodium) in the blood
• decreased levels of calcium in the blood
• abnormal liver function blood tests

Gavreto may affect fertility in males and females, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of Gavreto.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Patient Selection

Select patients for treatment with Gavreto based on the presence of a RET gene fusion. Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics.

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 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.

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

Dosage Modifications For Adverse Reactions

The recommended dose reductions and dosage modifications for adverse reactions are provided in Table 1 and Table 2.

Table 1: Recommended Dose Reductions for Gavreto for Adverse Reactions

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

The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended Dosage Modifications for Gavreto for Adverse Reactions

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

Avoid coadministration of Gavreto with known combined P-gp and strong CYP3A inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor cannot be avoided, reduce the current dose of Gavreto as recommended in Table 3. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume Gavreto at the dose taken prior to initiating the combined P-gp and strong CYP3A inhibitor.

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 coadministration with a strong CYP3A inducer cannot be avoided, increase the starting dose of Gavreto to double the current Gavreto dosage starting on Day 7 of coadministration of Gavreto with the strong CYP3A inducer. After the inducer has been discontinued for at least 14 days, resume Gavreto at the dose taken prior to initiating the strong CYP3A inducer.

Effects Of Other Drugs On Gavreto

Strong CYP3A Inhibitors

Avoid coadministration with strong CYP3A inhibitors. Coadministration of Gavreto with a strong CYP3A inhibitor increases pralsetinib exposure, which may increase the incidence and severity of adverse reactions of Gavreto.

Avoid coadministration of Gavreto with combined P-gp and strong CYP3A inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor cannot be avoided, reduce the Gavreto dose.

Strong CYP3A Inducers

Coadministration of Gavreto with a strong CYP3A inducer decreases pralsetinib exposure, which may decrease efficacy of Gavreto. Avoid coadministration of Gavreto with strong CYP3A inducers. If coadministration cannot be avoided, increase the Gavreto dose.

Based on findings from animal studies and its mechanism of action, Gavreto can cause fetal harm when administered to a pregnant woman. There are no available data on Gavreto use in pregnant women to inform drug-associated risk.

There are no data on the presence of pralsetinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, women should be advised not to breastfeed during treatment with Gavreto and for 1 week after the final dose.