Rozlytrek^®

entrectinib

Indications & Important Safety Information

What is 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 1 month of age 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 in children with ROS1 NSCLC or in children under 1 month of age with NTRK solid tumors.

The approval of ROZLYTREK was based on a study that measured response to treatment and duration of response. Continued approval for this use may depend on the results of an ongoing study to confirm the benefit of ROZLYTREK for this use.

Important Safety Information

What is the most important information I should know about ROZLYTREK?
ROZLYTREK may cause serious side effects, including:

• Congestive heart failure. ROZLYTREK may cause congestive heart failure or make the congestive heart failure that you already have worse. Your healthcare provider will do tests before your treatment and may do tests during your treatment with ROZLYTREK to check your heart function. Tell your healthcare provider right away if you have any of the following signs and symptoms of congestive heart failure:
  • persistent coughing or wheezing
  • trouble breathing when lying down
  • sudden weight gain
  • increasing shortness of breath
  • tiredness, weakness, or fatigue
  • swelling in ankles, feet, or legs
• Central nervous system (CNS) effects. ROZLYTREK may cause dizziness, changes in your mood, or may affect how you think and cause confusion, hallucinations, and problems with concentration, attention, memory, speaking, understanding what you hear or read, and sleep. Tell your healthcare provider right away if you develop any of these symptoms.
• Bone fractures. ROZLYTREK may increase your risk for bone fractures. Bone fractures may happen with or without a fall or other injury. Tell your healthcare provider if you develop pain, changes in movement, or bone abnormalities.
• Liver problems (hepatotoxicity). Your healthcare provider will do blood tests to check your liver function during treatment with ROZLYTREK. Tell your healthcare provider right away if you develop any of the following sympptoms of liver problems:
  • loss of appetite
  • nausea or vomiting
  • pain in the upper right stomach area
  • yellowing of your skin or the white part of your eyes
  • dark urine
• Increased uric acid level in your blood (hyperuricemia). ROZLYTREK may cause too much of uric acid in your blood. Your healthcare provider will do tests before and during your treatment with ROZLYTREK to check the uric acid level in your blood. Your healthcare provider may prescribe medications if you have high blood uric acid levels. Tell your healthcare provider if you develop any of the following symptoms of hyperuricemia:
  • red, hot, tender, or swollen joints, especially in your big toe
  • pain in your stomach-area or sides
  • nausea or vomiting
  • pink or brown urine
• Changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. Your healthcare provider will do tests before and during your treatment with ROZLYTREK to check the electrical activity of your heart and your body salts (electrolytes). Tell your healthcare provider right away if you feel faint, lightheaded, dizzy, or feel your heart beating irregularly or fast during your treatment with ROZLYTREK. These may be symptoms related to QT prolongation.
• Vision problems. ROZLYTREK may cause vision problems. Your healthcare provider may stop ROZLYTREK and refer you to an eye specialist if you develop severe vision problems during treatment with ROZLYTREK. Tell your healthcare provider right away if you develop any loss of vision or any change in vision, including:
  • double vision
  • blurry vision
  • new or increased floaters
  • seeing flashes of light
  • light hurting your eyes

Your healthcare provider may temporarily stop treatment, decrease your dose, or permanently stop ROZLYTREK if you develop certain side effects during treatment with ROZLYTREK.

Before taking ROZLYTREK, tell your healthcare provider about all your medical conditions, including if you:

• have liver or kidney problems
• have any heart problems, including a condition called long QT syndrome
• have nervous system (neurological) problems
• have or have had eye or vision problems
• are pregnant or plan to become pregnant. ROZLYTREK can cause harm to your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with ROZLYTREK.

  Females who can become pregnant:

  • Your healthcare provider will do a pregnancy test before you start treatment with ROZLYTREK.
  • Use effective birth control (contraception) during treatment with ROZLYTREK and for at least 5 weeks after the last dose.

  Males with female partners that can become pregnant:

  • Use effective birth control (contraception) during treatment with ROZLYTREK and for 3 months after the last dose.
• are breastfeeding or plan to breastfeed. It is not known if ROZLYTREK passes into your breast milk. Do not breastfeed during treatment with ROZLYTREK and for 7 days (1 week) after the last dose of ROZLYTREK. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, or herbal supplements.

Taking ROZLYTREK with certain other medicines may affect the amount of ROZLYTREK or other medicine in your blood and may cause side effects or affect the way that ROZLYTREK or the other medicine work. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

What should I avoid while taking ROZLYTREK?

• You should not drink grapefruit juice or eat grapefruit during your treatment with ROZLYTREK. It may increase the amount of entrectinib in your blood to a harmful level and increase your chance of getting side effects.
• Do not drive or operate heavy machinery until you know how ROZLYTREK affects you. If you experience dizziness, fainting, tiredness, blurred vision, memory loss, changes in mental status, confusion, or hallucinations, do not drive or operate heavy machines until your symptoms resolve.

What are some possible side effects of ROZLYTREK?

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.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see the ROZLYTREK full Prescribing Information for additional Important Safety Information.