Rozlytrek

Rozlytrek (entrectinib) is an oral kinase inhibitor that may be used to treat:

• Adults with confirmed ROS1-positive non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastasized)
• Adults and children 1 month and older with solid tumors that have spread or cannot be safely removed with surgery, or when other treatments have failed or are not safe options. The tumor must have a confirmed neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation. This indication is authorized under the accelerated approval criteria.

Rozlytrek works by targeting ROS1 fusion proteins. Normally, the ROS1 gene makes a protein that can send signals to your cells, telling them to grow. When a normal ROS1 gene breaks apart and attaches to another part of a gene, it can create a ROS1 gene fusion which results in a ROS1 fusion protein. ROS1 fusion proteins continuously send signals that can cause cancer cells to develop, grow, and spread. When Rozlytrek finds ROS1 fusion proteins, it binds to them inside cancer cells, blocking their action and slowing or stopping the cancer from growing. About 2% of people with metastatic NSCLC have abnormal ROS1 genes. Roxlytrek also has activity against NTRK and ALK fusion genes.

Available as oral capsules and oral pellets, and the capsules can be made into an oral suspension.

Rozlytrek was FDA-approved on August 15, 2019.

Use Rozlytrek exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

• You may take Rozlytrek with or without food.
• Taken orally (by mouth).
• Take Rozlytrek once a day.
• Your healthcare provider will prescribe: capsules which are to be swallowed whole or prepared and taken or given as a suspension or oral pellets to be sprinkled on 1 or more spoonfuls of soft food before taking.

If you vomit shortly after taking Rozlytrek, take another dose. Do not change your dose or stop taking Rozlytrek without your doctor's advice.

Rozlytrek capsules

• Swallow whole with drinking water. Do not crush or chew the capsule.

Rozlytrek capsules prepared as a suspension

Carefully open the prescribed number of capsules and pour the contents into room-temperature drinking water or milk. Your healthcare provider will tell you how much water or milk to use, how much suspension to take or give, and provide you with a measuring device like an oral syringe or measuring cup.

• Let the suspension sit for 15 minutes before taking it.
• You may need to take less suspension than you prepared depending on your prescribed dose.
• Drink water after taking the suspension to make sure you have swallowed all the medicine.
• If you do not take the suspension right away, you can store it for up to 2 hours at room temperature below 86°F (30°C). Throw away (discard) the unused suspension if it is not used within 2 hours of preparation.
• If you cannot swallow and have a gastric or nasogastric tube, the suspension can be given through the feeding tube.

Rozlytrek oral pellets

Sprinkle the prescribed number of packets of pellets on 1 or more spoonfuls of soft food like applesauce, yogurt, or pudding, and take within 20 minutes of sprinkling the pellets on the soft food.

• Do not crush or chew the pellets to avoid a bitter taste.
• Drink water after taking the prescribed dose to make sure you have swallowed all the medicine.
• Use the whole packet of pellets. Do not use part of the packet to try to prepare a dose.
• Do not use the pellets to make a suspension.
• Do not give the pellets through a gastric or nasogastric tube because the pellets may clog the feeding tube

Rozlytrek may cause new or worsened symptoms of congestive heart failure. Your healthcare provider will do tests before your treatment and may do tests during your treatment to check your heart function. Call your doctor at once if you have swelling in your lower legs, rapid weight gain, cough, wheezing, shortness of breath, or trouble breathing while lying down.

May cause Central Nervous System (CNS) side effects, such as cognitive impairment, mood disorders, dizziness, and sleep disturbances. Your healthcare provider may withhold treatment temporarily or discontinue it permanently.

May cause liver toxicity. Your healthcare provider will monitor your liver function every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated.

May also cause high levels of uric acid, QRS or QTc interval prolongation, and increase your risk for fractures (broken bones).

Rozlytrek may affect your vision. Report any changes in vision to your healthcare provider and they may conduct an ophthalmological evaluation as appropriate.

Can harm an unborn baby. Do not use it if you are pregnant. Your doctor may conduct a pregnancy test before you start treatment if you are a woman of childbearing age. Use a non-hormonal form of birth control to prevent pregnancy while using Rozlytrek and for at least 2 weeks after your last dose.

To make sure Rozlytrek is safe for you, tell your doctor if you have ever had:

• gout
• heart problems
• long QT syndrome, QRS or QTc prolongation, or Brugada syndrome (in you or a family member)
• liver or kidney disease
• a nervous system disorder or
• problems with your eyes or vision.

You may need to have a negative pregnancy test before starting this treatment.

Pregnancy

Rozlytrek can harm an unborn baby or cause birth defects if the mother or the father is using this medicine. If you are a woman, do not use it if you are pregnant. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 5 weeks after your last dose.

If you are a man, use effective birth control if your sex partner can get pregnant. Keep using birth control for at least 3 months after your last dose.

Tell your doctor right away if a pregnancy inadvertently occurs while either the mother or the father is using Rozlytrek.

Breastfeeding

Do not breastfeed while using this medicine, and for at least 7 days after your last dose.

Get emergency medical help if you have signs of an allergic reaction to Rozlytrek: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Rozlytrek may cause serious side effects, including:

• Congestive heart failure. Tell your healthcare provider right away if you develop: persistent coughing or wheezing increasing shortness of breath trouble breathing when lying down tiredness, weakness, or fatigue sudden weight gain swelling in the ankles, feet, or legs.
• Central nervous system (CNS) effects. Tell your doctor if you experience dizziness, or 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.
• Bone fractures. 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. Tell your healthcare provider right away if you develop any of these symptoms: loss of appetite nausea or vomiting pain in your upper right stomach area yellowing of your skin or the white part of your eyes dark urine.
• Increased uric acid levels in your blood (hyperuricemia). Tell your healthcare provider if you develop any of the following symptoms: 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 (QRS or QTc prolongation). Tell your healthcare provider right away if you get severe dizziness, lightheadedness, feel faint, or feel your heart beating irregularly or fast during your treatment
• Vision problems. Tell your healthcare provider right away if you have any loss of vision or any vision change, including: double vision o seeing flashes of light blurry vision or light hurting your eyes new or increased floaters.

The most common side effects occurring in 20% or more people are:

• tiredness
• constipation
• change in taste
• swelling and water retention
• 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.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Your doctor should select the appropriate dosage form for your age and ability to swallow: oral capsules, capsules prepared as an oral suspension, or oral pellets.

• Use capsules prepared as suspension for enteral tube administration. Do not use pellets for enteral tube administration.
• Administer the dose once daily, with or without food.

Adult Dosage for ROS1-Positive Non-Small Cell Lung Cancer

• 600 mg orally once daily.

Adult and Pediatric Dosage for NTRK Gene Fusion-Positive Solid Tumors

• Adults: 600 mg orally once daily.
• Pediatric Patients: Recommended dosage is based on age and body surface area (BSA) as described in the prescribing information.

Use the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 12 hours. Do not use two doses at one time. the missed dose and take your next dose at your regular time.

If you vomit shortly after taking Rozlytrek, take another dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Grapefruit may interact with Rozlytrek and lead to unwanted side effects. Avoid the use of grapefruit products.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements, including:

• Strong or moderate CYP3A4 inhibitors, such as clarithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir. Avoid coadministration, but if unavoidable, reduce the dosage of Rozlytrek. For children under 2 years of age, avoid taking these medicines with Rozlytrek.
• Strong or moderate CYP3A4 inducers, such as phenobarbital, phenytoin, rifampicin, St. John's Wort, or glucocorticoids. Avoid coadministration.
• Drugs that prolong the QTc interval, such as haloperidol, ondansetron, or clarithromycin.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. See the prescribing information for a full list of interactions.

Store capsules and pellets below 86°F (30°C).

Store capsules in the original container and keep the bottle tightly closed to protect it from moisture.

Keep all medicines out of the reach of children.

Active: entrectinib

Inactive ingredients

Capsules: tartaric acid, lactose anhydrous, hypromellose, crospovidone, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

• Yellow opaque capsule shell: hypromellose, titanium dioxide, and yellow iron oxide
• Orange opaque capsule shell: hypromellose, titanium dioxide, and FD&C Yellow No. 6
• Printing ink: shellac, propylene glycol, strong ammonia solution, and FD&C Blue No. 2 aluminum lake

Pellets: tartaric acid, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate. Film-coating: polyvinyl alcohol (partially hydrolyzed), titanium dioxide, polyethylene glycol 3350, talc, yellow iron oxide, red iron oxide, and ferrosoferric oxide.

Genentech, Inc.