Rozlytrek (entrectinib)

Rozlytrek is a prescription medicine used to treat:

• Adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by an abnormal ROS1 gene.
• Adults and children 12 years and older with solid tumors (cancer) that:
  • are caused by certain abnormal NTRK genes and
  • have spread or if surgery to remove their cancer is likely to cause severe complications, and
  • there is no satisfactory alternative treatment option or the cancer grew or spread on other treatment.
• It is not known if Rozlytrek is safe and effective for use in children less than 12 years of age.

The most common side effects of Rozlytrek include:

• tiredness
• constipation
• change in taste
• swelling
• dizziness
• diarrhea
• nausea
• abnormal touch sensation
• shortness of breath
• muscle pain
• confusion, mental status changes, memory problems, and hallucinations
• weight gain
• cough
• vomiting
• fever
• joint pain
• vision changes

These are not all the possible side effects of Rozlytrek. For more information, ask your healthcare provider or pharmacist.

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 the treatment of metastatic NSCLC with Rozlytrek based on the presence of ROS1 rearrangement(s) in tumor specimens. An FDA-approved test for detection of ROS1 rearrangement(s) in NSCLC for selecting patients for treatment with Rozlytrek is not available.
• Select patients for treatment of locally advanced or metastatic solid tumors with Rozlytrek based on the presence of a NTRK gene fusion. An FDA-approved test for the detection of NTRK gene fusion in solid tumors is not available.

Recommended Dosage For ROS1-Positive Non-Small Cell Lung Cancer

• The recommended dosage of Rozlytrek is 600 mg orally once daily with or without food until disease progression or unacceptable toxicity.

Recommended Dosage For NTRK Gene Fusion-Positive Solid Tumors

Adults

• The recommended dosage of Rozlytrek in adults is 600 mg orally once daily with or without food until disease progression or unacceptable toxicity.

Pediatric Patients 12 Years And Older (Adolescents)

• The recommended dosage of Rozlytrek is based on body surface area (BSA) as shown in Table 1 below.
• Take Rozlytrek orally once daily with or without food until disease progression or unacceptable toxicity.

Table 1: Dosing in Pediatric Patients 12 Years and Older (Adolescents)

Dosage Modifications For Adverse Reactions

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

Table 2: Recommended Dose Reductions for Rozlytrek Adverse Reactions

Table 3 describes dosage modifications for specific adverse reactions.

Table 3: Recommended Dosage Modifications for Rozlytrek for Adverse Reactions

Dosage Modifications For Drug Interactions

Moderate And Strong CYP3A Inhibitors

Adults And Pediatric Patients 12 Years And Older With BSA Greater Than 1.50 m²

Avoid coadministration of Rozlytrek with moderate or strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the Rozlytrek dose as follows:

• Moderate CYP3A Inhibitors: 200 mg orally once daily
• Strong CYP3A Inhibitors: 100 mg orally once daily

After discontinuation of a strong or moderate CYP3A inhibitor for 3 to 5 elimination half-lives, resume the Rozlytrek dose that was taken prior to initiating the CYP3A inhibitor.

Administration

• Swallow capsules whole. Do not open, crush, chew, or dissolve the contents of the capsule.
• If a patient misses a dose, patients should make up that dose unless the next dose is due within 12 hours.
• If a patient vomits immediately after taking a dose, they should repeat that dose.

Effect Of Other Drugs On Rozlytrek

Moderate And Strong CYP3A Inhibitors

Adults And Pediatric Patients 12 Years And Older With BSA Greater Than 1.50 m²

• Coadministration of Rozlytrek with a strong or moderate CYP3A inhibitor increases entrectinib plasma concentrations, which could increase the frequency or severity of adverse reactions. Avoid coadministration of strong or moderate CYP3A inhibitors with Rozlytrek.
• If coadministration is unavoidable, reduce the Rozlytrek dose.

Pediatric Patients 12 Years And Older With BSA Less Than Or Equal To 1.50 m²

• Avoid coadministration of Rozlytrek with moderate or strong CYP3A inhibitors.
• Avoid grapefruit products during treatment with Rozlytrek, as they contain inhibitors of CYP3A.

Moderate And Strong CYP3A Inducers

• Coadministration of Rozlytrek with a strong or moderate CYP3A inducer decreases entrectinib plasma concentrations, which may reduce Rozlytrek efficacy. Avoid coadministration of strong and moderate CYP3A inducers with Rozlytrek.

Drugs That Prolong QT Interval

• QTc interval prolongation can occur with Rozlytrek. Avoid coadministration of Rozlytrek with other products with a known potential to prolong QT/QTc interval.

• Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action, Rozlytrek can cause fetal harm when administered to a pregnant woman.
• There are no available data on Rozlytrek use in pregnant women.
• There are no data on the presence of entrectinib or its metabolites in human milk or their effects on either the breastfed child or on milk production.
• Because of the potential adverse reactions in breastfed children from Rozlytrek, advise a lactating woman to discontinue breastfeeding during treatment with Rozlytrek and for 7 days after the final dose.