Because it is a high-risk drug, Accutane should be reserved for cases of "severe recalcitrant nodular acne," according to the product's labeling. This type of acne is resistant to standard acne treatment, including oral antibiotics, and is characterized by many nodules or cysts--inflammatory lesions filled with pus and lodged deep within the skin. These lesions can cause pain, permanent scarring, and negative psychological effects.
This is about 10% of the possible adverse reactions one can have to Accutane. INDICATIONS AND USAGE: Severe Recalcitrant Nodular Acne: Accutane is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition, means "many" as opposed to "few or several" nodules. Because of significant adverse effects associated with its use, Accutane should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. Contraindications and Warnings Psychiatric Risk Management-Accutane WARNINGS Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events. Pseudotumor Cerebri: Accutane use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Concomitant treatment with tetracyclines should therefore be avoided. Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, they should be told to discontinue Accutane immediately and be referred to a neurologist for further diagnosis and care. ADVERSE REACTIONS Neurological: pseudotumor cerebri, dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke, syncope, weakness. Psychiatric: suicidal ideation, suicide attempts, suicide, depression, psychosis, emotional instability. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy. Accutane (isotretinoin) Accutane is a retinoid related to vitamin A. Patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects. Pancreatitis: Acute pancreatitis has been reported in patients with either elevated or normal serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has been reported. Accutane should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur. Lipids: Elevations of serum triglycerides have been reported in patients treated with Accutane. Marked elevations of serum triglycerides in excess of 800 mg/dL were reported in approximately 25% of patients receiving Accutane in clinical trials. In addition, approximately 15% developed a decrease in high-density lipoproteins and about 7% showed an increase in cholesterol levels. In clinical trials, the effects on triglycerides, HDL, and cholesterol were reversible upon cessation of Accutane therapy. Some patients have been able to reverse triglyceride elevation by reduction in weight, restriction of dietary fat and alcohol, and reduction in dose while continuing Accutane. Blood lipid determinations should be performed before Accutane is given and then at intervals until the lipid response to Accutane is established, which usually occurs within 4 weeks. Especially careful consideration must be given to risk/benefit for patients who may be at highrisk during Accutane therapy (patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or familial history of lipid metabolism disorder). If Accutane therapy is instituted, more frequent checks of serum values for lipids and/or blood sugar are recommended. Hearing Impairment: Impaired hearing has been reported in patients taking Accutane; in some cases, the hearing impairment has been reported to persist after therapy has been discontinued. Mechanism(s) and causality for this event have not been established. Patients who experience tinnitus or hearing impairment should discontinue Accutane treatment and be referred for specialized care for further evaluation. Hepatotoxicity: Clinical hepatitis considered to be possibly or probably related to Accutane therapy has been reported. Additionally, mild to moderate elevations of liver enzymes have been observed in approximately 15% of individuals treated during clinical trials, some of which normalized with dosage reduction or continued administration of the drug. If normalization does not readily occur or if hepatitis is suspected during treatment with Accutane, the drug should be discontinued and the etiology further investigated. Inflammatory Bowel Disease: Accutane has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. In some instances, symptoms have been reported to persist after Accutane treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue Accutane immediately. Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the Accutane population. While causality to Accutane has not been established, an effect cannot be ruled out. Longer term effects have not been studied. It is important that Accutane be given at the recommended doses for no longer than the recommended duration. Hyperostosis: A high prevalence of skeletal hyperostosis was noted in clinical trials for disorders of keratinization with a mean dose of 2.24 mg/kg/day. Additionally, skeletal hyperostosis was noted in 6 of 8 patients in a prospective study of disorders of keratinization. Minimal skeletal hyperostosis and calcification of ligaments and tendons have also been observed by x-ray in prospective studies of nodular acne patients treated with a single course of therapy at recommended doses. The skeletal effects of multiple Accutane treatment courses for acne are unknown. Premature Epiphyseal Closure: There are spontaneous reports of premature epiphyseal closure in acne patients receiving recommended doses of Accutane. The effect of multiple courses of Accutane on epiphyseal closure is unknown. Vision Impairment: Visual problems should be carefully monitored. All Accutane patients experiencing visual difficulties should discontinue Accutane treatment and have anophthalmological examination (see ADVERSE REACTIONS: Special Senses). Corneal Opacities: Corneal opacities have occurred in patients receiving Accutane for acne and more frequently when higher drug dosages were used in patients with disorders of keratinization. The corneal opacities that have been observed in clinical trial patients treated with Accutane have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuation of the drug (see ADVERSE REACTIONS: Special Senses). Decreased Night Vision: Decreased night vision has been reported during Accutane therapy and in some instances the event has persisted after therapy was discontinued. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. PRECAUTIONS: The Accutane Pregnancy Prevention and Risk Management Programs consist of the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.) and the Accutane Pregnancy Prevention Program (PPP). S.M.A.R.T. should be followed for prescribing Accutane with the goal of preventing fetal exposure to isotretinoin. It consists of: 1) reading the booklet entitled System to Manage Accutane Related Teratogenicity (S.M.A.R.T.) Guide to Best Practices, 2) signing and returning the completed S.M.A.R.T. Letter of Understanding containing the Prescriber Checklist, 3) a yellow self-adhesive Accutane Qualification Sticker tobe affixed to the prescription page. In addition, the patient educational material, Be Smart, Be Safe, Be Sure, should be used with each patient. 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 or not Accutane therapy is appropriate in this setting. Patients should be informed that they must not share Accutane with anyone else because of the risk of birth defects and other serious adverse events. Patients should not donate blood during therapy and for 1 month following discontinuance of the drug because the blood might be given to a pregnant woman whose fetus must not be exposed to Accutane. Patients should be reminded to take Accutane with a meal. 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 Accutane therapy and for at least 6 months thereafter due to the possibility of scarring. 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 Accutane 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 Accutane, but in some cases persisted. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity (Rhabdomyolysis is a life-threatening colapse of the skeletal muscle that allows toxins from cells to leak into the bloodstream). Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with Accutane developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female 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 Accutane. Hypersensitivity: Anaphylactic reactions and other allergic reactions have been reported.Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement (including renal) have been reported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical management. Glucose: Some patients receiving Accutane have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during Accutane therapy, although no causal relationship has been established. Carcinogenesis, Mutagenesis and Impairment of Fertility: In male and female Fischer 344 rats given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 to 5.3 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma (a cortisol-producing tumor that induces Cushing's Syndrome) relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to the human population is uncertain. Regards, Catherine -- The silver-list is a moderated forum for discussion of colloidal silver. Instructions for unsubscribing may be found at: http://silverlist.org To post, address your message to: [email protected] Silver-list archive: http://escribe.com/health/thesilverlist/index.html List maintainer: Mike Devour <[email protected]>
