Accutane
Isotretinoin · Capsule, Gelatin Coated · Oral
Uses
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, 2 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. In addition, Accutane is indicated only for those patients who are not pregnant, because Accutane can cause life-threatening 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 Accutane. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, Premature Epiphyseal Closure ).
Dosage and administration
Accutane should be administered with a meal (see PRECAUTIONS : Information for Patients ). The recommended dosage range for Accutane is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1 mg/kg/day, 8 it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects — some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Failure to take Accutane with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Accutane has not been established. Once daily dosing is not recommended. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Accutane, even in low doses, has not been studied, and is not recommended. It is important that Accutane be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Accutane on bone loss is unknown (see WARNINGS : Skeletal : Bone Mineral Density , Hyperostosis , and Premature Epiphyseal closure ). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS ). Table 4 Accutane Dosing by Body Weight (Based on Administration With Food) 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 *See DOSAGE AND ADMINISTRATION : the recommended dosage range is 0.5 to 1 mg/kg/day. INFORMATION FOR PHARMACISTS Access the iPLEDGE Program system via the internet ( www.ipledgeprogram.com ), or telephone (1-866-495-0654) or through electornic telecommunication verification (via submission of an isotretinoin prescription claim) to obtain an authorization and the “do not dispense to patient after” date. Accutane must only be dispensed in no more than a 30 day supply. REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM. An Accutane Medication Guide must be given to the patient each time Accutane is dispensed, as required by law. This Accutane Medication Guide is an important part of the risk management program for the patient.
Contraindications
Pregnancy: Category X. See Boxed CONTRAINDICATIONS AND WARNINGS . Allergic Reactions Accutane is contraindicated in patients who are hypersensitive to this medication or to any of its components ( see PRECAUTIONS: Hypersensitivity ).
Warnings
Special Patient Populations Pediatric Patients The pharmacokinetics of isotretinoin were evaluated after single and multiple doses in 38 pediatric patients (12 to 15 years) and 19 adult patients (≥18 years) who received Accutane for the treatment of severe recalcitrant nodular acne. In both age groups, 4- oxo -isotretinoin was the major metabolite; tretinoin and 4- oxo -tretinoin were also observed. The dose-normalized pharmacokinetic parameters for isotretinoin following single and multiple doses are summarized in Table 3 for pediatric patients. There were no statistically significant differences in the pharmacokinetics of isotretinoin between pediatric and adult patients. Table 3. Pharmacokinetic Parameters of Isotretinoin Following Single and Multiple Dose Administration in Pediatric Patients, 12 to 15 Years of Age Mean ( ± SD), N=38* Parameter Isotretinoin (Single Dose) Isotretinoin (Steady-State) C max (ng/mL) 573.25 (278.79) 731.98 (361.86) AUC (0-12) (ng⋅hr/mL) 3033.37 (1394.17) 5082 (2184.23) AUC (0-24) (ng⋅hr/mL) 6003.81 (2885.67) – T max (hr)† 6 (1 to 24.6) 4 (0 to12) C ss min (ng/mL) – 352.32 (184.44) T 1/2 (hr) – 15.69 (5.12) CL/F (L/hr) – 17.96 (6.27) *The single and multiple dose data in this table were obtained following a non-standardized meal that is not comparable to the high-fat meal that was used in the study in Table 2 . † Median (range) In pediatric patients (12 to 15 years), the mean ± SD elimination half-lives (t 1/2 ) of isotretinoin and 4- oxo -isotretinoin were 15.7 ± 5.1 hours and 23.1 ± 5.7 hours, respectively. The accumulation ratios of isotretinoin ranged from 0.46 to 3.65 for pediatric patients. WARNINGS Psychiatric Disorders Accutane may cause depression, psycho sis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these events (see ADVERSE REACTIONS: Psychiatric ). Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults : A Guide for Prescribers of Isotretinoin . 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 Accutane therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy 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, as described in the brochure (“Recognizing Psychiatric Disorders in Adolescents and Young Adults”), 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 Accutane 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 Accutane therapy 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 Accutane therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Accutane therapy. 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 (see ADVERSE REACTIONS: Neurological ). Serious Skin Reactions There have been post-marketing reports of erythema multiforme and severe skin reactions [e.g., Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with isotretinoin use. These events may be serious and result in death, life-threatening events, hospitalization, or disability. Patients should be monitored closely for severe skin reactions, and discontinuation of Accutane should be considered if warranted. 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 in excess of 800 mg/dL have been reported in patients treated with Accutane. Marked elevations of serum triglycerides 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.
Precautions
Accutane must only be prescribed by prescribers who are enrolled and activated with the iPLEDGE REMS. Accutane must only be dispensed by a pharmacy enrolled and activated with iPLEDGE, and must only be dispensed to patients who are enrolled and meet all the requirements of iPLEDGE. Enrolled and activated pharmacies must receive Accutane only from wholesalers enrolled with iPLEDGE. iPLEDGE REMS requirements for wholesalers, prescribers, and pharmacists are described below: Wholesalers: For the purpose of the iPLEDGE REMS, the term wholesaler refers to wholesaler, distributor, and/or chain pharmacy distributor. To distribute Accutane, wholesalers must be enrolled with iPLEDGE, and agree to meet all iPLEDGE requirements for wholesale distribution of isotretinoin products. Wholesalers must enroll with iPLEDGE by signing and returning the iPLEDGE wholesaler agreement that affirms they will comply with all iPLEDGE requirements for distribution of isotretinoin. These include: Enrolling prior to distributing isotretinoin and re-enrolling annually thereafter Distributing only FDA approved isotretinoin product Only shipping isotretinoin to - wholesalers enrolled in the iPLEDGE REMS with prior written consent from the manufacturer or - pharmacies licensed in the US and enrolled and activated in the iPLEDGE REMS Notifying the isotretinoin manufacturer (or delegate) of any non-enrolled and/or non-activated pharmacy or unenrolled wholesaler that attempts to order isotretinoin Complying with inspection/audit of wholesaler records for verification of compliance with the iPLEDGE REMS by the isotretinoin manufacturer (or delegate) Returning to the manufacturer (or delegate) any undistributed product if the wholesaler is deactivated by the iPLEDGE REMS or if the wholesaler chooses to not re-enroll annually Prescribers: To prescribe isotretinoin, the prescriber must be enrolled and activated with the pregnancy risk management program iPLEDGE. Prescribers can enroll by signing and returning the completed enrollment form. Prescribers can only activate their enrollment by affirming that they meet requirements and will comply with all iPLEDGE requirements by attesting to the following points: I know the risk and severity of fetal injury/birth defects from isotretinoin. I know the risk factors for unplanned pregnancy and the effective measures for avoidance of unplanned pregnancy. I have the expertise to provide the patient with detailed pregnancy prevention counseling, or I will refer the patient to an expert for such counseling, reimbursed by the manufacturer. I will comply with the iPLEDGE REMS requirements described in the booklets entitled iPLEDGE REMS Prescriber Guide. Before beginning treatment of patients who can become pregnant with isotretinoin, and on a monthly basis, the patient will be counseled to avoid pregnancy by using two forms of contraception simultaneously and continuously for at least one month prior to initiation of isotretinoin treatment, during isotretinoin treatment and for one month after discontinuing isotretinoin treatment, unless the patient commits to continuous abstinence, not having any sexual contact with a partner that could result in pregnancy. I will not prescribe isotretinoin to any patient who can become pregnant until verifying the patient has a negative screening pregnancy test and monthly negative CLIA-certified (Clinical Laboratory Improvement Amendment) pregnancy tests. Patients should have a pregnancy test at the completion of the entire course of isotretinoin and another pregnancy test one month later. I will report any pregnancy case that I become aware of while the patient who can become pregnant is on isotretinoin or one month after the last dose to the pregnancy registry. To prescribe isotretinoin, the prescriber must access the iPLEDGE system via the internet ( www.ipledgeprogram.com ) or telephone (1-866-495-0654) to: 1) Enroll each patient in the iPLEDGE REMS. 2) Confirm monthly that each patient has received counseling and education. 3) For patients who can become pregnant : Enter patient’s two chosen forms of contraception each month. Enter monthly result from CLIA-certified laboratory conducted pregnancy test. Isotretinoin must only be prescribed to patients who are known not to be pregnant as confirmed by a negative CLIA-certified laboratory conducted pregnancy test. Isotretinoin must only be dispensed by a pharmacy enrolled and activated with the pregnancy risk management program iPLEDGE and only when the enrolled patient meets all the requirements of the iPLEDGE REMS. Meeting the requirements for a patient who can become pregnant signifies that the patient: Has been counseled and has signed a Patient Enrollment Form for Patients who can get Pregnant that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin. The patient must sign the informed consent form before starting treatment and patient counseling must also be done at that time and on a monthly basis thereafter. Has 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 should be at least 19 days. - For patients with regular menstrual cycles, the second pregnancy test should 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 forms of contraception for one month.
Side effects
Clinical Trials and Postmarketing Surveillance The adverse reactions listed below reflect the experience from investigational studies of Accutane, and the postmarketing experience. The relationship of some of these events to Accutane therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane 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 ADVERSE REACTIONS ). 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 Drug Interactions Vitamin A: Because of the relationship of Accutane to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects. Tetracyclines: Concomitant treatment with Accutane and tetracyclines should be avoided because Accutane 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 Accutane therapy. Although other hormonal contraceptives are highly effective, there have been reports of pregnancy from patients who can become pregnant 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 patients who can become pregnant who use only a single form of contraception. It is not known if hormonal contraceptives differ in their effectiveness when used with Accutane. Therefore, it is critically important for patients who can become pregnant to select and commit to use two forms of effective contraception simultaneously, at least one of which must be a primary form (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, Accutane 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: Accu tane 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: Accutane 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 Accutane. 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 Accutane. Therefore, caution should be exercised when using these drugs together.
Pregnancy
Pregnancy: Category X. See Boxed CONTRAINDICATIONS AND WARNINGS.
Pediatric use
Pediatric Use The use of Accutane in pediatric patients less than 12 years of age has not been studied. The use of Accutane for the treatment of severe recalcitrant nodular acne in pediatric patients ages 12 to 17 years should be given careful consideration, especially for those patients where a known metabolic or structural bone disease exists (see PRECAUTIONS : General ). Use of Accutane in this age group for severe recalcitrant nodular acne is supported by evidence from a clinical study comparing 103 pediatric patients (13 to 17 years) to 197 adult patients (≥18 years). Results from this study demonstrated that Accutane, at a dose of 1 mg/kg/day given in two divided doses, was equally effective in treating severe recalcitrant nodular acne in both pediatric and adult patients. In studies with Accutane, adverse reactions reported in pediatric patients were similar to those described in adults except for the increased incidence of back pain and arthralgia (both of which were sometimes severe) and myalgia in pediatric patients (see ADVERSE REACTIONS ). In an open-label clinical trial (N=217) of a single course of therapy with Accutane for severe recalcitrant nodular acne, bone density measurements at several skeletal sites were not significantly decreased (lumbar spine change >-4% and total hip change >-5%) or were increased in the majority of patients. One patient had a decrease in lumbar spine bone mineral density >4% based on unadjusted data. Sixteen (7.9%) patients had decreases in lumbar spine bone mineral density >4%, and all the other patients (92%) did not have significant decreases or had increases (adjusted for body mass index). Nine patients (4.5%) had a decrease in total hip bone mineral density >5% based on unadjusted data. Twenty-one (10.6%) patients had decreases in total hip bone mineral density >5%, and all the other patients (89%) did not have significant decreases or had increases (adjusted for body mass index). Follow-up studies performed in eight of the patients with decreased bone mineral density for up to 11 months thereafter demonstrated increasing bone density in five patients at the lumbar spine, while the other three patients had lumbar spine bone density measurements below baseline values. Total hip bone mineral densities remained below baseline (range −1.6% to −7.6%) in five of eight patients (62.5%). In a separate open-label extension study of ten patients, ages 13 to 18 years, who started a second course of Accutane 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25% (see WARNINGS : Skeletal : Bone Mineral Density ).
Geriatric use
Geriatric Use Clinical studies of isotretinoin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with isotretinoin therapy (see WARNINGS and PRECAUTIONS ).
Overdosage
The oral LD 50 of isotretinoin is greater than 4000 mg/kg in rats and mice (>600 times the recommended clinical dose of 1 mg/kg/day after normalization of the rat dose for total body surface area and >300 times the recommended clinical dose of 1 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolve without apparent residual effects. Accutane causes life-threatening birth defects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS ). Patients who can become pregnant who present with isotretinoin overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the Boxed CONTRAINDICATIONS AND WARNINGS . Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in PRECAUTIONS . Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a patient who is or might become pregnant, for one month after the overdose. All patients with isotretinoin overdose should not donate blood for at least one month.
Description
Isotretinoin USP, a retinoid, is available as Accutane (isotretinoin capsules, USP) in 10 mg, 20 mg, 30 mg and 40 mg soft gelatin capsules for oral administration. Each capsule contains butylatedhydroxyanisole, edetate disodium, hydrogenated vegetable oil (Type-I and Type-II), medium chain triglyceride, refined soybean oil and white wax. Gelatin capsules contain ferric oxide red, ferricoxide yellow (for 30 mg), gelatin, glycerin, methyl paraben, propyl paraben, lake blend blue(LB-332) containing D&C Yellow No.10, FD&C Blue No.1 (for 10 mg), lake blend red (LB-1574) containing D&C Red No.27, D&C Red No.30 (for 20 mg), lake blend green (LB-333) containing D&C Yellow No.10, FD&C Blue No.1 (for 40 mg), lake blend white (TLB-1774) containing FD&C Blue No.2, titanium dioxide, and opacode black S-1-17823 containing iron oxide black, N-butyl alcohol, propylene glycol, ammonium hydroxide and shellac. Chemically, isotretinoin is 13-cis-retinoic acid and is related to both retinoic acid and retinol (vitamin A). It is a yellow to slightly orange crystalline powder with a molecular weight of 300.44. The structural formula is: Meets USP Dissolution Test 5. chemical structure
How supplied
Accutane (isotretinoin capsules USP) 10 mg are opaque blue elliptical soft gelatin capsules imprinted with black ink, “J1” on one side and are supplied in boxes of 30 containing 3 prescription packs of 10 capsules as unit dose blisters Boxes of 30 (3 Prescription Packs of 10 capsules) NDC 72143-251-30 Accutane (isotretinoin capsules USP) 20 mg are opaque pink elliptical soft gelatin capsules imprinted with black ink, “J2” on one side and are supplied in boxes of 30 containing 3 prescription packs of 10 capsules as unit dose blisters Boxes of 30 (3 Prescription Packs of 10 capsules) NDC 72143-252-30 Accutane (isotretinoin capsules USP) 30 mg are reddish brown colored opaque, elliptical shaped soft gelatin capsule imprinted with “J3” in black colored ink along the length of body on one side and are supplied in boxes of 30 containing 3 prescription packs of 10 capsules as unit dose blisters Boxes of 30 (3 Prescription Packs of 10 capsules) NDC 72143-253-30 Accutane (isotretinoin capsules USP) 40 mg are opaque green elliptical soft gelatin capsules imprinted with black ink, “J4” on one side and are supplied in boxes of 30 containing 3 prescription packs of 10 capsules as unit dose blisters Boxes of 30 (3 Prescription Packs of 10 capsules) NDC 72143-254-30
Label text from the FDA structured product label by JG Pharma Inc. (revised Jan 30, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Isotretinoin in 4 products
Accutane NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 72143-251 | Isotretinoin 10 mg/1 Capsule, Gelatin Coated | JG Pharma Inc. | ANDA |
| 72143-252 | Isotretinoin 20 mg/1 Capsule, Gelatin Coated | JG Pharma Inc. | ANDA |
| 72143-253 | Isotretinoin 30 mg/1 Capsule, Gelatin Coated | JG Pharma Inc. | ANDA |
| 72143-254 | Isotretinoin 40 mg/1 Capsule, Gelatin Coated | JG Pharma Inc. | ANDA |
Frequently asked questions
What is Accutane used for?
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, 2 means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Accutane should be…
What are the side effects of Accutane?
Clinical Trials and Postmarketing Surveillance The adverse reactions listed below reflect the experience from investigational studies of Accutane, and the postmarketing experience. The relationship of some of these events to Accutane therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane are similar to those described in patients taking very high… See the full label for the complete list.
Who makes Accutane?
Accutane is listed by 1 labeler in the FDA NDC directory, including JG Pharma Inc..