Tretinoin

IMPORTANT WARNING:

Tretinoin may cause severe side effects. Tretinoin should be given only under the supervision of a doctor who has experience in treating people who have leukemia (cancer of the white blood cells) and in a hospital where patients can be monitored for severe side effects and treated if these side effects occur.

Tretinoin may cause a serious or life-threatening group of symptoms called retinoic acid-APL(RA-APL) syndrome. Your doctor will monitor you carefully to see whether you are developing this syndrome. If you experience any of the following symptoms, call your doctor immediately: fever; weight gain; swelling of the arms, hands, feet, ankles, or lower legs; shortness of breath; labored breathing; wheezing; chest pain; or cough. At the first sign that you are developing RA-APL syndrome, your doctor will prescribe one or more medications to treat the syndrome.

Tretinoin may cause a rapid increase in the number of white blood cells in the body. This is associated with a higher risk of life-threatening side effects. If you have a very high number of white blood cells before you begin tretinoin treatment, or if you have an increase in the number of white blood cells during your treatment with tretinoin, expecially if you experience any of the symptoms of RA-APL syndrome, your doctor may prescribe one or more medications to treat or prevent the increase in white blood cells.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to tretinoin.

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

For female patients:

Tretinoin must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that tretinoin will cause the baby to be born with birth defects (physical problems that are present at birth).

If you can become pregnant, you will need to avoid pregnancy during your treatment with tretinoin. You must use two acceptable forms of birth control during your treatment and for 1 month after your treatment, even if you have infertility (difficulty becoming pregnant) or have experienced menopause ('change of life'; end of monthly menstrual periods). You must use these two forms of birth control at all times unless you can promise that you will not have any sexual contact with a male for 1 month after your treatment. Your doctor will tell you which forms of birth control are acceptable, and will give you full information about birth control.

If you plan to use oral contraceptives (birth control pills) while taking tretinoin, tell your doctor the name of the pill you will use. Microdosed progestin ('minipill') oral contraceptives (Ovrette, Micronor, Nor-D) may not be an effective form of birth control for people who are taking tretinoin.

You must have a negative pregnancy test within 1 week before you begin to take tretinoin. You will also need to be tested for pregnancy in a laboratory each month during your treatment. Tell your doctor immediately if you think you might be pregnant at any time during your treatment with tretinoin.

WHY is this medicine prescribed?

Tretinoin is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there are too many immature blood cells in the blood and bone marrow) in people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. Tretinoin is used to produce remission (a decrease or disappearance of signs and symptoms of cancer) of APL, but other medications must be used after treatment with tretinoin to prevent the cancer from returning. Tretinoin is in a class of medications called retinoids. It works by slowing or stopping the growth of cancer cells by causing immature blood cells to develop into normal blood cells.

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?

Tretinoin comes as a capsule to take by mouth. It is usually taken twice a day for up to 90 days. Take tretinoin at around the same times 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 tretinoin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take tretinoin even if you feel well. Do not stop taking tretinoin without talking to your doctor.

What SPECIAL PRECAUTIONS should I follow?

Before taking tretinoin,

• tell your doctor and pharmacist if you are allergic to tretinoin, other retinoids such as acitretin (Soriatane), etretinate (Tegison), bexarotene, or isotretinoin (Accutane, Claravis, Sotret), any other medications, parabens (a preservative), or any of the other ingredients in tretinoin capsules. Ask your doctor or pharmacist for a list of the ingredients.

• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: aminocaproic acid (Amicar); certain calcium channel blockers such as diltiazem (Cardizem, Dilacor, Tiazac, others) and verapamil (Calan, Covera, Isoptin, Verelan); cimetidine (Tagamet); cyclosporine (Sandimmune, Gengraf, Neoral); erythromycin (E.E.S., Erythrocin, E-Mycin); hydroxyurea (Droxia); ketoconazole (Nizoral); pentobarbital; phenobarbital; rifampin (Rifadin, Rimactane);oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Monodox, Vibramycin, others), minocycline (Minocin), oxytetracycline (Terramycin), and tetracycline (Sumycin, Tetrex, others); tranexamic acid (Cyklokapron); and vitamin A. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with tretinoin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• tell your doctor if you have or have ever had increased amounts of cholesterol (a fat-like substance) and other fatty substances in the blood, or liver or heart disease.

• tell your doctor if you are breast-feeding.

• you should know that tretinoin may cause dizziness or severe headache.Do not drive a car or operate machinery until you know how this medication affects you.

What SPECIAL DIETARY instructions should I follow?

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.

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 almost time for the next dose, 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?

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

• weakness
• extreme tiredness
• shivering
• pain
• earache
• feeling of fullness in the ears
• dry skin
• rash
• hair loss
• constipation
• diarrhea
• stomach pain
• heartburn
• loss of appetite
• weight loss
• bone pain
• dizziness
• numbness, burning, or tingling in the hands or feet
• nervousness
• depression
• difficulty falling asleep or staying asleep
• confusion
• agitation
• hallucinating (seeing things or hearing voices that do not exist)
• difficulty urinating
• flushing

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:

• headache
• nausea
• vomiting
• blurred or double vision, or other vision problems
• unusual bruising or bleeding
• vomit that is bloody or looks like coffee grounds
• bright red or black and tarry stools
• irregular heartbeat
• hearing loss
• bleeding
• infections

Tretinoin may increase the levels of cholesterol and other fats in your blood and may stop your liver from working normally. Your doctor will monitor you carefully to see whether you are experiencing either of these side effects.

Tretinoin 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 away from excess heat and moisture (not in the bathroom).

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.

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

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
• flushing
• red, cracked, and sore lips
• stomach pain
• dizziness
• loss of coordination

What OTHER INFORMATION should I know?

Do not let anyone else take your medication. Ask your pharmacist if you have any questions 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.