Palovarotene

IMPORTANT WARNING:

Palovarotene may cause harm to the fetus if taken during pregnancy. Females who are pregnant or plan to become pregnant should not take palovarotene. If you have the potential to become pregnant, your doctor will ask you to take a pregnancy test 1 week before starting palovarotene, periodically during treatment and for 1 month after. Your doctor will recommend starting an effective birth control at least 1 month before, during and for 1 month after treatment with palovarotene. If pregnancy occurs during treatment with palovarotene, discontinue treatment immediately and call your provider right away.

Palovarotene can cause bone growth changes. Your child may stop growing while receiving palovarotene, or early closure of the growth plate may occur. Your doctor or nurse will closely monitor your child's bone growth and height during treatment with palovarotene.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with palovarotene and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risk(s) of taking palovarotene.

WHY is this medicine prescribed?

Palovarotene is used to reduce the number of new heterotrophic ossification (bony formations in muscle and soft tissue) in patients with fibrodysplasia ossificans progressive (FOP) in females aged 8 years or older or females aged 10 years or older. Palovarotene is in a class of medications called retinoids. It works by stopping the signaling responsible for heterotophic ossification.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Palovarotene comes as a capsule to take by mouth. It is usually taken with food once daily. Take palovarotene at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take palovarotene exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole. If not able to swallow palovarotene whole, the capsule may be opened and contents emptied onto one teaspoonful of soft food (e.g. applesauce, low-fat yogurt, warm oatmeal) and taken within 1 hour (as long as it has not been exposed to direct sunlight).

Your doctor will place you on a dose of palovarotene to take daily when not experiencing a flare-up. When experiencing a flare-up of symptoms, your doctor will prescribe you a higher dose of palovarotene to take.

Palovarotene controls FOP but does not cure it. Continue to take palovarotene even if you feel well. Do not stop taking palovarotene without talking to your doctor.

What SPECIAL PRECAUTIONS should I follow?

Before taking palovarotene,

• tell your doctor and pharmacist if you are allergic to palovarotene, other retinoids such as tretinoin, isotretinoin, or alitretinoin any other medications, or any of the ingredients in palovarotene capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.

• some medications should not be taken with palovarotene. Other medications may cause dosing changes or extra monitoring when taken with palovarotene. Make sure you have discussed any medications you are currently taking or plan to take before starting palovarotene with your doctor and pharmacist. Before starting, stopping, or changing any medications while taking palovarotene, please get the advice of your doctor or pharmacist.

• the following nonprescription or herbal products may interact with palovarotene: St. John's wort, vitamin A. Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking palovarotene. Do not start any of these medications while taking palovarotene without discussing with your healthcare provider.

• tell your doctor if you have or have ever had depression, anxiety, bipolar disorder, schizophrenia, or other mood disorders, or current or past thoughts of harm to self or others. Palovarotene may cause or worsen pre-existing mood disorders.

• tell your doctor if you have or have ever had kidney or liver disease, bone loss, weak or brittle bones, or any other bone problems.

• you should know that palovarotene may make cause night blindness (making it difficult to see at night). Do not drive a car or operate machinery at night until you know how this medication affects you. If night blindness does occur, know that it usually goes away after you stop the medication.

• plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Palovarotene may make your skin sensitive to sunlight.

• plan to use skin emollients, lotion, lip moisturizer and artificial tears while taking palovarotene. Palovarotene can cause dryness and peeling of skin as well dryness of lips and eyes.

• do not donate blood while receiving palovarotene or for one week after taking the last dose.

What SPECIAL DIETARY instructions should I follow?

Do not take this medication with grapefruit or pomelo or any juice containing these fruits.

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it. However, if it is has been almost 6 hours since the scheduled dosing time, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

Palovarotene may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dry, red or itchy skin; peeling skin
• joint pain; pain in arms or legs; or pain in muscle; back pain
• red skin or rash
• baldness
• headache
• dry lips
• nausea
• dry eyes
• swelling in extremities
• tiredness

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• ulcers or sores on skin that grow or are slow to heal
• fracture of the bone or severe bone pain
• feelings of sadness or anxiety, sleepiness, changes in appetite, thoughts of self harm
• lower abdominal pain, yellowing of skin or whites of the eyes, dark urine
• ringing in the ear, temporary blindness, double vision, blind spots, peripheral vision loss

Palovarotene may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• headache
• nausea or vomiting
• drowsiness
• irritability
• itchy skin

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory.

Your doctor will order bone density tests periodically during treatment to monitor the effects palovarotene has on your bones. Make sure you keep these appointments.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.