Amnesteem

Amnesteem is a prescription medication used to treat the most severe form of acne called nodular acne. Amnesteem belongs to a group of drugs called retinoids. It is thought to work by preventing oil production in glands under the skin.

This medication comes in capsule form and is usually taken twice daily, with food. Amnesteem may be taken for four or five months. A longer period of use is not recommended.

Common side effects of Amnesteem include dry skin, chapped lips, dry eyes, or dry nose causing nosebleeds. Amnesteem can also cause birth defects, miscarriages, or premature births.

Because Amnesteem can cause birth defects, patients, doctors, and pharmacies must be registered with a special distribution program called the iPLEDGE program.

Amnesteem is a prescription medication used to treat severe from of acne (nodular acne) that has not responded to other treatments.

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

• Mylan Pharmaceuticals, Inc.

Serious side effects have been reported with Amnesteem. See “Amnesteem Precautions” section.

Common side effects of Amnesteem may include the following:

• dry skin
• chapped lips
• dry eyes
• dry nose that may lead to nosebleeds

Call your doctor if you get any side effect that bothers you or that does not go away.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Amnesteem and certain other medicines can interact with each other, sometimes causing serious side effects. Especially tell your doctor if you take:

• Vitamin A supplements. Vitamin A in high doses has many of the same side effects as Amnesteem. Taking both together may increase your chance of getting side effects.
• tetracycline antibiotics such as doxycycline, tetracycline, or minocycline (Minocin)
• progestin-only birth control pills (mini-pills) such as Camilla, and Norethindrone
• Dilantin (phenytoin)
• corticosteroids such as dexamethasone, hydrocortisone, or fludrocortisone (Florinef)
• St. John’s wort

These medicines should not be used with Amnesteem unless your doctor tells you it is okay.

Know the medicines you take. Keep a list of them to show to your doctor and pharmacist. Do not take any new medicine without talking with your doctor.

• Because Amnesteem can cause birth defects, Amnesteem is only for patients who can understand and agree to carry out all of the instructions in the iPLEDGE program.
• Amnesteem may cause serious mental health problems.

Amnesteem can cause serious side effects:

1) Birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby and early (premature) births. Female patients who are pregnant or who plan to become pregnant must not take Amnesteem. Female patients must not get pregnant:

• or 1 month before starting Amnesteem
• while taking Amnesteem
• for 1 month after stopping Amnesteem

If you get pregnant while taking Amnesteem, stop taking it right away and call your doctor. Doctors and patients should report all cases of pregnancy to:

• FDA MedWatch at 1-800-FDA-1088, and
• the iPLEDGE pregnancy registry at 1-866-495-0654

2) Serious mental health problems. Amnesteem may cause:

• depression
• psychosis (seeing or hearing things that are not real)
• suicide. Some patients taking Amnesteem have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives.

Stop Amnesteem and call your doctor right away if you or a family member notices that you have any of the following signs and symptoms of depression or psychosis:

• start to feel sad or have crying spells
• lose interest in activities you once enjoyed
• sleep too much or have trouble sleeping
• become more irritable, angry, or aggressive than usual (for example, temper outbursts, thoughts of violence)
• have a change in your appetite or body weight
• have trouble concentrating
• withdraw from your friends or family
• feel like you have no energy
• have feelings of worthlessness or guilt
• start having thoughts about hurting yourself or taking your own life (suicidal thoughts)
• start acting on dangerous impulses
• start seeing or hearing things that are not real

Other serious side effects:

• Serious brain problems: Amnesteem can increase the pressure in your brain. This can lead to permanent loss of eyesight and, in rare cases, death. Stop taking Amnesteem and call your doctor right away if you get any of these signs of increased brain pressure:
  • bad headache
  • blurred vision
  • dizziness
  • nausea or vomiting
  • seizures (convulsions)
  • stroke
• Skin problems: Skin rash can occur in patients taking Amnesteem. In some patients a rash can be serious. Stop using Amnesteem and call your doctor right away if you develop conjunctivitis (red or inflamed eyes, like “pink eye”), a rash with a fever, blisters on legs, arms or face and/or sores in your mouth, throat, nose, eyes, or if your skin begins to peel.
• Stomach area (abdomen) problems: Certain symptoms may mean that your internal organs are being damaged. These organs include the liver, pancreas, bowel (intestines) and esophagus (connection between mouth and stomach). If your organs are damaged, they may not get better even after you stop taking Amnesteem. Stop taking Amnesteem and call your doctor if you get:
  • severe stomach, chest or bowel pain.
  • trouble swallowing or painful swallowing.
  • new or worsening heartburn.
  • diarrhea.
  • rectal bleeding.
  • yellowing of your skin or eyes.
  • dark urine.
• Bone and muscle problems: Amnesteem may affect bones, muscles, and ligaments and cause pain in your joints or muscles. Tell your doctor if you plan hard physical activity during treatment with Amnesteem. Tell your doctor if you get:
  • back pain.
  • joint pain.
  • broken bone. Tell all healthcare providers that you take Amnesteem if you break a bone.

  Stop Amnesteem and call your doctor right away if you have muscle weakness. Muscle weakness with or without pain can be a sign of serious muscle damage.

  Amnesteem may stop long bone growth in teenagers who are still growing.

• Hearing problems: Stop using isotretinoin and call your doctor if your hearing gets worse or if you have ringing in your ears. Your hearing loss may be permanent.
• Vision problems: Amnesteem may affect your ability to see in the dark. This condition usually clears up after you stop taking Amnesteem, but it may be permanent. Other serious eye effects can occur. Stop taking Amnesteem and call your doctor right away if you have any problems with your vision or dryness of the eyes that is painful or constant. If you wear contact lenses, you may have trouble wearing them while taking Amnesteem and after treatment.
• Lipid (fats and cholesterol in blood) problems: Amnesteem can raise the level of fats and cholesterol in your blood. This can be a serious problem. Return to your doctor for blood tests to check your lipids and to get any needed treatment. These problems usually go away when Amnesteem treatment is finished.
• Serious allergic reactions: Stop taking Amnesteem and get emergency care right away if you develop hives, a swollen face or mouth or have trouble breathing. Stop taking Amnesteem and call your doctor if you get a fever, rash or red patches or bruises on your legs.
• Blood sugar problems: Amnesteem may cause blood sugar problems including diabetes. Tell your doctor if you are very thirsty or urinate a lot.
• Decreased red and white blood cells: Call your doctor if you have trouble breathing, faint or feel weak.

After stopping Amnesteem, you may also need follow-up mental health care if you had any of these symptoms.

• Do not take Amnesteem if you are pregnant, plan to become pregnant or become pregnant during Amnesteem treatment. Amnesteem causes severe birth defects.
• Do not take Amnesteem if you are allergic to anything in it.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Amnesteem there are no specific foods that you must exclude from your diet when receiving Amnesteem.

Tell your doctor if you have any of the following health conditions:

• mental problems
• asthma
• liver disease
• diabetes
• heart disease
• bone loss (osteoporosis) or weak bones
• an eating problem called anorexia nervosa (where people eat too little)
• food or medicine allergies

Tell your doctor if you are pregnant or breastfeeding. Amnesteem must not be used by women who are pregnant or breastfeeding.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Amnesteem and certain other medicines can interact with each other, sometimes causing serious side effects.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amnesteem falls into category X. Amnesteem must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that Amnesteem will cause birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby and early (premature) births. See "Drug Precautions" section.

A program called iPLEDGE has been set up to make sure that pregnant women do not take Amnesteem and that women do not become pregnant while taking Amnesteem. All patients, including women who cannot become pregnant and men, can get Amnesteem only if they are registered with iPLEDGE, have a prescription from a doctor who is registered with iPLEDGE and fill the prescription at a pharmacy that is registered with iPLEDGE. Before prescribing Amnesteem, your doctor will:

• explain the iPLEDGE program to you
• have you sign the Patient Information/Informed Consent form (for all patients). Female patients who can get pregnant must also sign another consent form.

You will not be prescribed Amnesteem if you cannot agree to or follow all the instructions of the iPLEDGE program. Female patients must not get pregnant:

• for 1 month before starting Amnesteem
• while taking Amnesteem
• for 1 month after stopping Amnesteem

• FDA MedWatch at 1-800-FDA-1088, and
• the iPLEDGE pregnancy registry at 1-866-495-0654

Do not breastfeed while taking Amnesteem and for one month after stopping Amnesteem. It is not known if Amnesteem is excreted in human breast milk or if it will harm your nursing baby. Tell your doctor if you are breastfeeding before you receive Amnesteem.

Take Amnesteem exactly as prescribed. You must also follow all the instructions of the iPLEDGE program. Before prescribing Amnesteem, your doctor will:

• explain the iPLEDGE program to you
• have you sign the Patient Information/Informed Consent form (for all patients). Female patients who can get pregnant must also sign another consent form.

You will not be prescribed Amnesteem if you cannot agree to or follow all the instructions of the iPLEDGE program.

• You will get no more than a 30 day supply of Amnesteem at a time. This is to make sure you are following the iPLEDGE program. You should talk with your doctor each month about side effects.
• The amount of Amnesteem you take has been specially chosen for you. It is based on your body weight, and may change during treatment.
• Take Amnesteem 2 times a day with a meal, unless your doctor tells you otherwise. Swallow your Amnesteem capsules whole with a full glass of liquid. Do not chew or suck on the capsule. Amnesteem can hurt the tube that connects your mouth to your stomach (esophagus) if it is not swallowed whole.
• If you miss a dose, just skip that dose. Do not take two doses at the same time.
• If you take too much Amnesteem or overdose, call your doctor or poison control center right away.
• Your acne may get worse when you first start taking Amnesteem. This should last only a short while. Talk with your doctor if this is a problem for you.
• You must return to your doctor as directed to make sure you don’t have signs of serious side effects. Your doctor may do blood tests to check for serious side effects from Amnesteem. Female patients who can get pregnant will get a pregnancy test each month.
• Female patients who can get pregnant must agree to use two separate forms of effective birth control at the same time one month before, while taking and for one month after taking Amnesteem. You must access the iPLEDGE system to answer questions about the program requirements and to enter your two chosen forms of birth control. To access the iPLEDGE system, go to www.ipledgeprogram.com or call 1-866-495-0654.

You must talk about effective birth control methods with your doctor or go for a free visit to talk about birth control with another doctor or family planning expert. Your doctor can arrange this free visit, which will be paid for by the company that makes Amnesteem.

If you have sex at any time without using two forms of effective birth control, get pregnant or miss your expected period, stop using Amnesteem and call your doctor right away.

What you should avoid while taking Amnesteem:

• Do not get pregnant while taking Amnesteem and for one month after stopping Amnesteem. See “Amnesteem Precautions" section.
• Do not breastfeed while taking Amnesteem and for one month after stopping Amnesteem. It is not known if Amnesteem can pass through your milk and harm the baby.
• Do not give blood while you take Amnesteem and for one month after stopping Amnesteem. If someone who is pregnant gets your donated blood, her baby may be exposed to Amnesteem and may be born with birth defects.
• Do not take other medicines or herbal products with Amnesteem unless you talk to your doctor.
• Do not drive at night until you know if Amnesteem has affected your vision. Amnesteem may decrease your ability to see in the dark.
• Do not have cosmetic procedures to smooth your skin, including waxing, dermabrasion, or laser procedures, while you are using Amnesteem and for at least 6 months after you stop. Amnesteem can increase your chance of scarring from these procedures. Check with your doctor for advice about when you can have cosmetic procedures.
• Avoid sunlight and ultraviolet lights as much as possible. Tanning machines use ultraviolet lights. Amnesteem may make your skin more sensitive to light.
• Do not share Amnesteem with other people. It can cause birth defects and other serious health problems.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on your weight.

The recommended dosage range for Amnesteem (isotretinoin) is 0.5 to 1 mg/kg/day given in two divided doses.

Some patients may require dose adjustments up to 2 mg/kg/day.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if an overdose is suspected, seek emergency medical attention.

• Store at 68° to 77°F (20° to 25°C).
• Protect from light.
• Keep Amnesteem and all medicines out of the reach of children.

CONTRAINDICATIONS AND WARNINGS

Amnesteem must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking Amnesteem in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected.

Birth defects which have been documented following Amnesteem exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion and premature births have been reported.

Documented external abnormalities include: skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include: CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases death has occurred with certain of the abnormalities previously noted.

If pregnancy does occur during treatment of a female patient who is taking Amnesteem, Amnesteem must be discontinued immediately and she should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Special Prescribing Requirements

Because of Amnesteem’s teratogenicity and to minimize fetal exposure, Amnesteem is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE™. Amnesteem must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Amnesteem must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE