What Is ASTAGRAF XL^® (tacrolimus extended-release capsules)?

IMPORTANT SAFETY INFORMATION

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

1. Increased risk of cancer. People who take PROGRAF have an increased risk of getting some kinds of cancer, including skin and lymph gland cancer (lymphoma).
2. Increased risk of infection. PROGRAF is a medicine that affects your immune system. PROGRAF can lower the ability of your immune system to fight infections. Serious infections can happen in people receiving PROGRAF that can cause death. Call your doctor right away if you have symptoms of an infection such as fever, sweats or chills, cough or flu-like symptoms, muscle aches, and/or warm, red, or painful areas on your skin.

Do not take PROGRAF if you are allergic to tacrolimus or any of the ingredients in PROGRAF.

What should I tell my doctor before taking PROGRAF?
Before you take PROGRAF, tell your doctor if you: plan to receive any live vaccines, have or have had liver, kidney or heart problems, are pregnant or plan to become pregnant. Talk to your doctor if you are pregnant or plan to become pregnant. Tell your doctor if you are breastfeeding or plan to breastfeed. PROGRAF can pass into your breast milk. You and your doctor should decide if you will take PROGRAF or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take: cyclosporine (Gengraf^®, Neoral^®, and Sandimmune^®), sirolimus (Rapamune^®), nelfinavir (Viracept^®), telaprevir (Incivek^®), boceprevir (Victrelis^®) or amiodarone (Cordarone^®, Nexterone^®, Pacerone^®). PROGRAF may affect the way other medicines work, and other medicines may affect how PROGRAF works. Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How Should I Take PROGRAF?
Do not eat grapefruit or drink grapefruit juice while taking PROGRAF. Take PROGRAF exactly as your doctor tells you to take it. Take PROGRAF with or without food and the same way and time every day. If you take too much PROGRAF, call your doctor or go to the nearest hospital emergency room right away.

PROGRAF may cause serious side effects, including:

• high blood sugar (diabetes). Your doctor may do certain tests to check for diabetes.
• kidney problems. Your doctor may do certain tests to check your kidney function.
• nervous system problems
• high levels of potassium in your blood. Your doctor may do certain tests to check your potassium level.
• high blood pressure. Your doctor will monitor your blood pressure.
• heart problems (myocardial hypertrophy)

Call your doctor right away if you have any of these symptoms: frequent urination, increased thirst or hunger, blurred vision, confusion, drowsiness, loss of appetite, fruity smell on your breath, nausea, vomiting, stomach pain, muscle tremors, numbness and tingling, headache, seizures, vision changes, shortness of breath, chest pain, feel lightheaded, or feel faint.

The most common side effects of PROGRAF are: tremors (shaking of the body); high blood pressure; kidney problems; diarrhea; headache; stomach pain; trouble sleeping; nausea; pain; weakness or low red blood cell count (anemia); infection; constipation; low levels of phosphate in your blood; swelling of the hands, ankles, or legs; high levels of fat or potassium in your blood; numbness or tingling in your hands or feet; fever; or low levels of magnesium in the blood.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of PROGRAF. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see the Patient Information and full Prescribing Information, including Boxed Warnings.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about ASTAGRAF XL?
ASTAGRAF XL can cause serious side effects, including:

• Increased risk of cancer. People who take ASTAGRAF XL have an increased risk of getting some kinds of cancer, including skin and lymph gland cancer (lymphoma).
• Increased risk of infection. ASTAGRAF XL is a medicine that affects your immune system. ASTAGRAF XL can lower the ability of your immune system to fight infections. Serious infections can happen in people receiving ASTAGRAF XL that can cause death. Call your doctor right away if you have symptoms of an infection such as: fever, sweats or chills, cough or flu-like symptoms, muscle aches, or warm, red or painful areas on your skin.
• Increased risk of death in females who have had a liver transplant. You should not take ASTAGRAF XL if you have had a liver transplant without talking to your doctor.

Who should not take ASTAGRAF XL?
Do not take ASTAGRAF XL if you are allergic to tacrolimus or any of the ingredients in ASTAGRAF XL.

Before you take ASTAGRAF XL tell your doctor if you:

• plan to receive any live vaccines
• have or have had liver, kidney or heart problems, or have any other medical conditions
• are pregnant or plan to become pregnant. ASTAGRAF XL may harm your unborn baby
• are breastfeeding or plan to breastfeed. ASTAGRAF XL can pass into your breast milk. You and your doctor should decide if you will take ASTAGRAF XL or breastfeed. You should not do both.

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

How should I take ASTAGRAF XL?

• Take ASTAGRAF XL exactly as your doctor tells you to take it.
• Your doctor may change your dose if needed. Do not stop taking or change your dose of ASTAGRAF XL without talking to your doctor.
• Take ASTAGRAF XL capsules whole. Do not break, crush, chew or dissolve ASTAGRAF XL capsules before swallowing. If you cannot swallow ASTAGRAF XL capsules whole, tell your doctor.
• Take ASTAGRAF XL at the same time each morning, preferably on an empty stomach at least one hour before, or at least two hours after, you have eaten a meal.
• If you miss your dose of ASTAGRAF XL, it should be taken as soon as possible, but no longer than 14 hours after your regularly scheduled time. If it is longer than 14 hours, the missed dose should be skipped and the next dose should be taken the following morning at your regularly scheduled time. Do not take two doses at the same time.
• If you take too much ASTAGRAF XL, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking ASTAGRAF XL?

• Live vaccines such as flu vaccine through your nose, measles, mumps, rubella, polio by mouth, TB vaccine, yellow fever, chicken pox or typhoid.
• Exposure to sunlight and UV light such as tanning machines. Wear protective clothing and use a sunscreen.
• You should not eat grapefruit or drink grapefruit juice while taking ASTAGRAF XL.
• You should not drink alcohol when taking ASTAGRAF XL.

What are the possible side effects of ASTAGRAF XL?
ASTAGRAF XL may cause serious side effects, including:

• See "What is the most important information I should know about ASTAGRAF XL?"
• Graft rejection and other serious reactions. People who take ASTAGRAF XL have sometimes been given the wrong medicine, because some medicines have the same ingredient (tacrolimus) as ASTAGRAF XL. Serious reactions have happened including graft rejection. Check your ASTAGRAF XL when you get a new prescription medicine to make sure you have received the right medicine.
  • Call your doctor right away if you think you were given the wrong medicine
  • Ask your doctor or pharmacist if you are not sure what ASTAGRAF XL should look like.
• high blood sugar (diabetes). Your doctor may do certain tests to check for diabetes. Call your doctor right away if you have:
  • frequent urination, increased thirst or hunger, blurred vision, confusion, drowsiness, loss of appetite, fruity smell on your breath, nausea, vomiting, or stomach pain.
• kidney problems. Your doctor may do certain tests to check your kidney function.
• nervous system problems. Call your doctor or go to the nearest hospital emergency room right away if you get any of these symptoms while taking ASTAGRAF XL. These could be signs of serious nervous system problems:
  • confusion, changes in alertness, muscle tremors, numbness and tingling, headache, seizures, or vision changes.
• high levels of potassium in your blood. Your doctor may do certain tests to check your potassium level.
• high blood pressure. Your doctor will monitor your blood pressure.
• changes in the electrical activity of your heart (QT prolongation).

The most common side effects of ASTAGRAF XL are diarrhea, constipation, nausea, swelling of the hands, ankles or legs, and tremors (shaking of the body).

These are not all the possible side effects of ASTAGRAF XL. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see the Medication Guide and full Prescribing Information, including Boxed Warnings.