This information is not for clinical use. These highlights do not include all the information needed to use Isotretinoin safely and effectively. Before taking Isotretinoin please consult with your doctor. See full prescribing information for Isotretinoin.

Warning

CONTRAINDICATIONS AND WARNINGS Isotretinoin 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 isotretinoin 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 isotretinoin 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 isotretinoin, isotretinoin 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 isotretinoin's teratogenicity and to minimize fetal exposure, isotretinoin is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE ® . Isotretinoin must only be prescribed by prescribers who are registered and activated with the iPLEDGE Program. Isotretinoin 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 (see PRECAUTIONS ).

Indications And Usage

Severe Recalcitrant Nodular Acne Isotretinoin capsules are 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,2 means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, isotretinoin capsules should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, isotretinoin capsules are indicated only for those female patients who are not pregnant, because isotretinoin capsules can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS ). A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients.1,3,4 If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off isotretinoin capsules. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS, Skeletal, Bone Mineral Density, Hyperostosis and Premature Epiphyseal Closure ).

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Dosage And Administration

Body Weight Total mg/day
kilograms pounds 0.5 mg/kg 1 mg/kg 2 mg/kg*
40 88 20 40 80
50 110 25 50 100
60 132 30 60 120
70 154 35 70 140
80 176 40 80 160
90 198 45 90 180
100 220 50 100 200

Contraindications

Pregnancy Teratogenic Effects Category X See BoxedAND WARNINGS . Allergic Reactions Isotretinoin capsules are contraindicated in patients who are hypersensitive to this medication or to any of its components (see PRECAUTIONS, Hypersensitivity ).

Adverse Reactions

Clinical Trials and Postmarketing Surveillance The adverse reactions listed below reflect the experience from investigational studies of isotretinoin, and the postmarketing experience. The relationship of some of these events to isotretinoin therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving isotretinoin are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, e.g., of the lips, nasal passage and eyes). Dose Relationship Cheilitis and hypertriglyceridemia are usually dose related. Most adverse reactions reported in clinical trials were reversible when therapy was discontinued; however, some persisted after cessation of therapy (see WARNINGS and). Body as a Whole Allergic reactions, including vasculitis, systemic hypersensitivity (see PRECAUTIONS, Hypersensitivity ), edema, fatigue, lymphadenopathy, weight loss. Cardiovascular Palpitation, tachycardia, vascular thrombotic disease, stroke. Endocrine/Metabolic Hypertriglyceridemia (see WARNINGS, Lipids ), alterations in blood sugar levels (see PRECAUTIONS, Laboratory Tests ). Gastrointestinal Inflammatory bowel disease (see WARNINGS, Inflammatory Bowel Disease ), hepatitis (see WARNINGS, Hepatotoxicity ), pancreatitis (see WARNINGS, Lipids ), bleeding and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, nausea, other nonspecific gastrointestinal symptoms. Hematologic Allergic reactions (see PRECAUTIONS, Hypersensitivity ), anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PRECAUTIONS, Information for Patients ). See PRECAUTIONS, Laboratory Tests for other hematological parameters. Musculoskeletal Skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density (see WARNINGS, Skeletal ), musculoskeletal symptoms (sometimes severe) including back pain, myalgia and arthralgia (see PRECAUTIONS, Information for Patients ), transient pain in the chest (see PRECAUTIONS, Information for Patients ), arthritis, tendonitis, other types of bone abnormalities, elevations of CPK/rare reports of rhabdomyolysis (see PRECAUTIONS, Laboratory Tests ). Neurological Pseudotumor cerebri (see WARNINGS, Pseudotumor Cerebri ), dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke, syncope, weakness. Psychiatric Suicidal ideation, suicide attempts, suicide, depression, psychosis, aggression, violent behaviors (see WARNINGS, Psychiatric Disorders ), emotional instability. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy. Reproductive System Abnormal menses. Respiratory Bronchospasms (with or without a history of asthma), respiratory infection, voice alteration. Skin and Appendages Acne fulminans, alopecia (which in some cases persists), bruising, cheilitis (dry lips), dry mouth, dry nose, dry skin, epistaxis, eruptive xanthomas,7 erythema multiforme, flushing, fragility of skin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, infections (including disseminated herpes simplex), nail dystrophy, paronychia, peeling of palms and soles, photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial erythema, seborrhea and eczema), Stevens-Johnson syndrome, sunburn susceptibility increased, sweating, toxic epidermal necrolysis, urticaria, vasculitis (including Wegener's granulomatosis; see PRECAUTIONS, Hypersensitivity ), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see PRECAUTIONS, Information for Patients ). Special Senses: Hearing: hearing impairment (see WARNINGS, Hearing Impairment ), tinnitus. Vision: corneal opacities (see WARNINGS, Corneal Opacities ), decreased night vision which may persist (see WARNINGS, Decreased Night Vision ), cataracts, color vision disorder, conjunctivitis, dry eyes, eyelid inflammation, keratitis, optic neuritis, photophobia, visual disturbances. Urinary System: glomerulonephritis (see PRECAUTIONS, Hypersensitivity ), nonspecific urogenital findings (see PRECAUTIONS, Laboratory Tests for other urological parameters). Laboratory Elevation of plasma triglycerides (see WARNINGS, Lipids ), decrease in serum high-density lipoprotein (HDL) levels, elevations of serum cholesterol during treatment. Increased alkaline phosphatase, SGOT (AST), SGPT (ALT), GGTP or LDH (see WARNINGS, Hepatotoxicity ). Elevation of fasting blood sugar, elevations of CPK (see PRECAUTIONS, Laboratory Tests ), hyperuricemia. Decreases in red blood cell parameters, decreases in white blood cell counts (including severe neutropenia and rare reports of agranulocytosis; (see PRECAUTIONS, Information for Patients ), elevated sedimentation rates, elevated platelet counts, thrombocytopenia. White cells in the urine, proteinuria, microscopic or gross hematuria.

Drug Interactions

Drug Interactions Vitamin A: Because of the relationship of isotretinoin to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects. Tetracyclines: Concomitant treatment with isotretinoin and tetracyclines should be avoided because isotretinoin use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Micro-dosed Progesterone Preparations: Micro-dosed progesterone preparations (“minipills” that do not contain an estrogen) may be an inadequate method of contraception during isotretinoin therapy. Although other hormonal contraceptives are highly effective, there have been reports of pregnancy from female patients who have used combined oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products. These reports are more frequent for female patients who use only a single method of contraception. It is not known if hormonal contraceptives differ in their effectiveness when used with isotretinoin. Therefore, it is critically important for females of reproductive potential (FRP) to select and commit to use two methods of effective contraception simultaneously, at least one of which must be a primary method (see PRECAUTIONS ). Norethindrone/ethinyl estradiol: In a study of 31 premenopausal female patients with severe recalcitrant nodular acne receiving Ortho-Novum® 7/7/7 Tablets as an oral contraceptive agent, isotretinoin at the recommended dose of 1 mg/kg/day, did not induce clinically relevant changes in the pharmacokinetics of ethinyl estradiol and norethindrone and in the serum levels of progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prescribers are advised to consult the package insert of medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. St. John’s Wort: Isotretinoin use is associated with depression in some patients (see WARNINGS, Psychiatric Disorders and ADVERSE REACTIONS, Psychiatric ). Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John’s Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John’s Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John’s Wort. Phenytoin: Isotretinoin has not been shown to alter the pharmacokinetics of phenytoin in a study in seven healthy volunteers. These results are consistent with the in vitro finding that neither isotretinoin nor its metabolites induce or inhibit the activity of the CYP 2C9 human hepatic P450 enzyme. Phenytoin is known to cause osteomalacia. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between phenytoin and isotretinoin. Therefore, caution should be exercised when using these drugs together. Systemic Corticosteroids: Systemic corticosteroids are known to cause osteoporosis. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between systemic corticosteroids and isotretinoin. Therefore, caution should be exercised when using these drugs together. Laboratory Tests Pregnancy Test - Females of reproductive potential (FRP) must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial isotretinoin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for isotretinoin. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests must be at least 19 days. - For patients with regular menstrual cycles, the second pregnancy test must be done during the first 5 days of the menstrual period immediately preceding the beginning of isotretinoin therapy and after the patient has used two methods of contraception for 1 month. - For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, the second pregnancy test must be done immediately preceding the beginning of isotretinoin therapy and after the patient has used two methods of contraception for 1 month. - Each month of therapy, patients must have a negative result from a urine or serum pregnancy test. A pregnancy test must be repeated each month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription. Lipids Pretreatment and follow-up blood lipids should be obtained under fasting conditions. After consumption of alcohol, at least 36 hours should elapse before these determinations are made. It is recommended that these tests be performed at weekly or biweekly intervals until the lipid response to isotretinoin is established. The incidence of hypertriglyceridemia is one patient in four on isotretinoin therapy (see WARNINGS, Lipids ). Liver Function Tests Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to isotretinoin has been established (see WARNINGS, Hepatotoxicity ). Glucose Some patients receiving isotretinoin have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during isotretinoin therapy, although no causal relationship has been established. CPK Some patients undergoing vigorous physical activity while on isotretinoin therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. In a clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, transient elevations in CPK were observed in 12% of patients, including those undergoing strenuous physical activity in association with reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these patients, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal within 4 weeks. No cases of rhabdomyolysis were reported in this trial.