See PRECAUTIONS and Boxed CONTRAINDICATIONS AND WARNINGS.

  * Patients must be instructed to read the Medication Guide supplied as required by law when Amnesteem is dispensed. The complete text of the Medication Guide is reprinted at the end of this document. For additional information, patients must also be instructed to read the iPLEDGE program patient educational materials. All patients must sign the Patient Information/Informed Consent (for all patients) form.
  * Female patients of childbearing potential must be instructed that they must not be pregnant when Amnesteem therapy is initiated, and that they should use two forms of effective contraception simultaneously for one month before starting Amnesteem, while taking Amnesteem, and for one month after Amnesteem has been stopped, unless they commit to continuous abstinence from heterosexual intercourse. They should also sign a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form prior to beginning Amnesteem therapy. They should be given an opportunity to view the patient DVD provided by the manufacturer to the prescriber. The DVD includes information about contraception, the most common reasons that contraception fails, and the importance of using two forms of effective contraception when taking teratogenic drugs and comprehensive information about types of potential birth defects which could occur if a female patient who is pregnant takes Amnesteem at any time during pregnancy. Female patients should be seen by their prescribers monthly and have a urine or serum pregnancy test, in a CLIA-certified laboratory, performed each month during treatment to confirm negative pregnancy status before another Amnesteem prescription is written (see Boxed CONTRAINDICATIONS AND WARNINGS and PRECAUTIONS).
  * Amnesteem is found in the semen of male patients taking Amnesteem, but the amount delivered to a female partner would be about one million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin induced embryopathy is unknown, 20 years of post-marketing reports include four with isolated defects compatible with features of retinoid exposed fetuses; however two of these reports were incomplete and two had other possible explanations for the defects observed.
  * Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of Amnesteem treatment, patients and family members should be asked about any history of psychiatric disorder, and at each visit during treatment patients should be assessed for symptoms of depression, mood disturbance, psychosis or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses and persistent physical symptoms unresponsive to treatment. Patients should stop Amnesteem and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis or aggression, without waiting until the next visit. Discontinuation of Amnesteem treatment may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient’s family. A referral to a mental health professional may be necessary. The physician should consider whether Amnesteem therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Amnesteem therapy. 
  * Patients must be informed that some patients, while taking Amnesteem or soon after stopping Amnesteem, have become depressed or developed other serious mental problems. Symptoms of depression include sad, “anxious” or empty mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down or trouble concentrating. 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. There were reports that some of these people did not appear depressed. There have been reports of patients on Amnesteem becoming aggressive or violent. No one knows if Amnesteem caused these behaviors or if they would have happened even if the person did not take Amnesteem. Some people have had other signs of depression while taking Amnesteem. 
  * Patients must be informed that they must not share Amnesteem with anyone else because of the risk of birth defects and other serious adverse events. 
  * Patients must be informed not to donate blood during therapy and for one month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to Amnesteem.
  * Patients should be reminded to take Amnesteem with a meal (see DOSAGE AND ADMINISTRATION). To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid.
  * Patients should be informed that transient exacerbation (flare) of acne has been seen, generally during the initial period of therapy.
  * Wax epilation and skin resurfacing procedures (such as dermabrasion, laser) should be avoided during Amnesteem therapy and for at least 6 months thereafter due to the possibility of scarring (see ADVERSE REACTIONS: Skin and Appendages).
  * Patients should be advised to avoid prolonged exposure to UV rays or sunlight.
  * Patients should be informed that they may experience decreased tolerance to contact lenses during and after therapy.
  * Patients should be informed that approximately 16% of patients treated with Amnesteem in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug. Transient pain in the chest has been reported less frequently. In the clinical trial, these symptoms generally cleared rapidly after discontinuation of Amnesteem, but in some cases persisted (see ADVERSE REACTIONS: Musculoskeletal). There have been rare post-marketing reports of rhabdomyolysis, some associated with strenuous physical activity (see Laboratory Tests: CPK).
  * Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with Amnesteem developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of Amnesteem. Consideration should be given to discontinuation of Amnesteem if any significant abnormality is found.
  * Neutropenia and rare cases of agranulocytosis have been reported. Amnesteem should be discontinued if clinically significant decreases in white cell counts occur.
  * Patients should be advised that severe skin reactions (Steven-Johnson Syndrome and toxic epidermal necrolysis) have been reported in post-marketing data. Amnesteem should be discontinued if clinically significant skin reactions occur.