Amnesteem
Isotretinoin · Capsule · Oral
Uses
Amnesteem is indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with its use, Amnesteem is reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. Limitations of Use : If a second course of Amnesteem treatment is needed, it is not recommended before a two-month waiting period because the patient's acne may continue to improve following a 15 to 20-week course of treatment [see Dosage and Administration (2.2) ]. Amnesteem is a retinoid indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with its use, Amnesteem is reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. ( 1 ) Limitations of Use : If a second course of Amnesteem treatment is needed, it is not recommended before a two-month waiting period because the patient's acne may continue to improve following a 15 to 20-week course of treatment. ( 1 )
Dosage and administration
• Evaluations Prior to Prescribing and Use of Amnesteem: o In patients who can get pregnant, only prescribe Amnesteem after verification and documentation that they are not pregnant. See the Full Prescribing Information for the detailed requirements prior to prescribing Amnesteem ( 2.1 , 8.3 ) o Complete the following laboratory tests in all patients: fasting lipid profile and liver function tests. ( 2.1 )
• Recommended dosage is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks ( 2.2 )
• Adult patients with very severe disease (scarring, trunk involvement) may increase dosage to 2 mg/kg/day in two divided doses with food. ( 2.1 )
• Once daily dosing is not recommended. ( 2.2 )
• If a dose is missed, just skip that dose. Do not take two doses at the same time. ( 2.2 )
• See the Full Prescribing Information for the recommended duration of use ( 2.3 ) 2.1 Evaluations Prior to Prescribing and Use of Amnesteem In patients who can get pregnant, only prescribe Amnesteem after verification and documentation that they are not pregnant [see Contraindications (4) and Warnings and Precautions (5.1 , 5.2) ] . For the detailed requirements prior to prescribing Amnesteem, see Use in Specific Populations (8.3) . Prior to Amnesteem use in all patients, complete the following laboratory testing:
• A fasting lipid profile including triglycerides [see Warnings and Precautions (5.7 , 5.14) ] .
• Liver function tests [see Warnings and Precautions (5.9 , 5.14) ] . 2.2 Recommended Dosage The recommended dosage range for Amnesteem is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks (see Tables 1 and 2, respectively) [see Clinical Pharmacology (12.3) ] . Table 1: Amnesteem: Recommended Divided Doses (0.5 mg/kg/day dosage) Body Weight First Dose Second Dose 40 kg 10 mg 10 mg 50 kg 12.5 mg 12.5 mg 60 kg 15 mg 15 mg 70 kg 17.5 mg 17.5 mg 80 kg 20 mg 20 mg 90 kg 22.5 mg 22.5 mg 100 kg 25 mg 25 mg Table 2: Amnesteem: Recommended Divided Doses (1 mg/kg/day dosage) Body Weight First Dose Second Dose 40 kg 20 mg 20 mg 50 kg 25 mg 25 mg 60 kg 30 mg 30 mg 70 kg 35 mg 35 mg 80 kg 40 mg 40 mg 90 kg 45 mg 45 mg 100 kg 50 mg 50 mg To decrease the risk of esophageal irritation, instruct patients to swallow the capsules with a full glass of liquid. Swallow capsules whole. Do not split, crush, chew, or suck on the capsules. During treatment, the dosage may be adjusted according to response of the disease and/or adverse reactions, 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 dosage adjustments up to 2 mg/kg/day for Amnesteem in divided doses with food, as tolerated (see Table 3). Table 3: Amnesteem: Recommended Divided Doses (2 mg/kg/day dosage) Body Weight First Dose Second Dose 40 kg 40 mg 40 mg 50 kg 50 mg 50 mg 60 kg 60 mg 60 mg 70 kg 70 mg 70 mg 80 kg 80 mg 80 mg 90 kg 90 mg 90 mg 100 kg 100 mg 100 mg The safety and effectiveness of once daily dosing with Amnesteem has not been established and is not recommended. If a dose of Amnesteem is missed, just skip that dose. Do not take two doses of Amnesteem at the same time. 2.3 Recommended Duration of Use A course of treatment is 15 to 20 weeks. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, may discontinue Amnesteem. After a period of 2 months or more off treatment, and if warranted by persistent or recurring severe nodular acne, may initiate a second course of Amnesteem in patients who have completed skeletal growth. The use of another course of Amnesteem treatment is not recommended before a two-month waiting period because the patient's acne may continue to improve after a 15 to 20-week course of treatment. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Amnesteem, even in low dosages, has not been studied, and is not recommended. The effect of long-term use of Amnesteem on bone loss is unknown [see Warnings and Precautions (5.11) ] .
Dosage forms and strengths
Amnesteem (Isotretinoin Capsules, USP) contains 10 mg, 20 mg, 30 mg or 40 mg of isotretinoin, USP.
• The 10 mg capsules are reddish brown and imprinted with I10.
• The 20 mg capsules are reddish brown and cream and imprinted with I20.
• The 30 mg capsules are cream opaque and imprinted with I30.
• The 40 mg capsules are orange-brown and imprinted with I40. Capsules: 10 mg, 20 mg, 30 mg and 40 mg ( 3 )
Contraindications
Amnesteem is contraindicated in:
• Pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] .
• Patients with hypersensitivity to isotretinoin (or Vitamin A, given the chemical similarity to isotretinoin) or to any of its components (anaphylaxis and other allergic reactions have occurred) [see Warnings and Precautions (5.14) ] . Amnesteem is contraindicated in:
• Pregnancy ( 4 , 8.1 )
• Patients with hypersensitivity to isotretinoin (or Vitamin A) or any of its components (4.2, 5.13 )
Warnings and precautions
• Psychiatric Disorders (depression, psychosis, suicidal thoughts and behavior, and aggressive and/or violent behaviors): Prior to and during treatment assess for these conditions; stop if these conditions occur on treatment ( 5.3 )
• Intracranial Hypertension (Pseudotumor Cerebri): Avoid concomitant use with tetracyclines ( 5.4 , 7.2 )
• Serious Skin Reactions : Monitor for Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other serious skin reactions and discontinue treatment if they occur ( 5.5 )
• Acute Pancreatitis : If pancreatitis symptoms occur, discontinue treatment ( 5.6 )
• Lipid Abnormalities (hypertriglyceridemia, low HDL, and elevation of cholesterol): Monitor lipid levels at regular intervals; stop if hypertriglyceridemia cannot be controlled ( 5.7 )
• Hearing Impairment : Discontinue and refer to specialized care ( 5.8 )
• Hepatotoxicity : Monitor liver function tests prior to and during treatment ( 5.9 , 5.14 )
• Inflammatory Bowel Disease : Discontinue for abdominal pain, rectal bleeding, or severe diarrhea ( 5.10 )
• Musculoskeletal Abnormalities : Arthralgias, back pain, decreases in bone mineral density and premature epiphyseal closure ( 5.11 )
• Ocular Abnormalities e.g., corneal opacities, decreased night vision: If visual symptoms occur, discontinue, and refer for an ophthalmological exam ( 5.12 ) 5.1 Embryo-Fetal Toxicity Amnesteem is contraindicated in pregnancy [see Contraindications (4) ] . Based on human data, Amnesteem can cause fetal harm when administered to a pregnant patient. There is an extremely high risk that life-threatening birth defects will result if pregnancy occurs while taking any amount of Amnesteem even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining prenatally whether an exposed fetus has been affected. Major congenital malformations, spontaneous abortions, and premature births have been documented following exposure to isotretinoin during pregnancy [see Use in Specific Populations (8.1) ]. If a pregnancy occurs during Amnesteem treatment, immediately discontinue Amnesteem and refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Immediately report any suspected fetal exposure during or 1 month after Amnesteem treatment to the FDA via the MedWatch telephone number 1-800-FDA-1088, and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). Inform patients not to donate blood during Amnesteem treatment and for 1 month following discontinuation because the blood might be given to a pregnant patient whose fetus must not be exposed to isotretinoin. Amnesteem is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.2) ]. 5.2 iPLEDGE REMS Because of the risk of embryo-fetal toxicity, Amnesteem is available only through a restricted program under a REMS called the iPLEDGE REMS [see Warnings and Precautions (5.1) ] . Notable requirements of the iPLEDGE REMS include the following:
• Prescribers must be certified with the REMS and comply with the REMS requirements, including the following: o Assess the reproductive status of all patients prior to initiating and during treatment. o Counsel patients who cannot get pregnant on the risk and REMS requirements prior to initiating treatment. o Counsel patients who can get pregnant on:
• The risk and REMS requirements prior to and during treatment.
• Pregnancy prevention requirements prior to and during treatment, or refer patients who can get pregnant to an expert for such counseling. o Comply with the pregnancy testing requirements. o Assess the pregnancy status for patients who can get pregnant by reviewing pregnancy tests and documenting a negative result prior to each prescription. o Report all pregnancies to the REMS.
• Patients who can become pregnant must be enrolled in the REMS and must comply with REMS requirements, including the following: o Comply with the pregnancy testing and pregnancy prevention requirements [see Use in Specific Populations (8.3) ]. o Demonstrate comprehension of the risk and REMS requirements before each prescription is dispensed. o Obtain the prescription within the 7-day prescription window (i.e., within 7 days of the pregnancy test collection).
• Patients who cannot become pregnant must be enrolled in the REMS and must comply with the REMS requirements, including to not share Amnesteem and not donate blood.
• Pharmacies that dispense Amnesteem must be certified in the REMS and must comply with the REMS requirements, including the following: o Obtain authorization to dispense and only dispense to patients who are authorized to receive Amnesteem. o Dispense a maximum of a 30-day supply with a Medication Guide. o Do not dispense refills.
• Wholesalers and distributors must be registered in the REMS and must only distribute to certified pharmacies. Further information, including a list of qualified pharmacies and distributors, is available at www.ipledgeprogram.com or 1-866-495-0654. 5.3 Psychiatric Disorders Amnesteem may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors [see Adverse Reactions (6) ] . Be alert to the warning signs of psychiatric disorders to help ensure patients receive the help they need (Prescribers should read the REMS educational material on recognizing psychiatric disorders). Prior to initiation of Amnesteem treatment, ask patients and family members about any history of psychiatric disorder, and at each visit during treatment assess patients for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation is necessary.
Side effects
The following adverse reactions with Amnesteem are described in more detail in other sections of the labeling:
• Embryo-Fetal Toxicity [see Warnings and Precautions (5.1) ]
• Psychiatric Disorders [see Warnings and Precautions (5.3) ]
• Intracranial Hypertension (Pseudotumor Cerebri) [see Warnings and Precautions (5.4) ]
• Serious Skin Reactions [see Warnings and Precautions (5.5) ]
• Pancreatitis [see Warnings and Precautions (5.6) ]
• Lipid Abnormalities [see Warnings and Precautions (5.7) ]
• Hearing Impairment [see Warnings and Precautions (5.8) ]
• Hepatotoxicity [see Warnings and Precautions (5.9) ]
• Inflammatory Bowel Disease [see Warnings and Precautions (5.10) ]
• Musculoskeletal Abnormalities [see Warnings and Precautions (5.11) ]
• Ocular Abnormalities [see Warnings and Precautions (5.12) ]
• Hypersensitivity Reactions [see Warnings and Precautions (5.13) ] The following adverse reactions, presented alphabetically by body system, associated with the use of Amnesteem were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse Reactions with a Dose Relationship Cheilitis and hypertriglyceridemia were dose related. Body as a Whole Allergic reactions, dry mouth, edema, fatigue, irritability, lymphadenopathy, pain, systemic hypersensitivity, vasculitis, weight loss. Cardiovascular Palpitation, stroke, tachycardia, vascular thrombotic disease Endocrine/Metabolism and Nutritional Alterations in blood sugar levels, decreased appetite, hypertriglyceridemia, weight fluctuation. Gastrointestinal Abdominal pain, bleeding and inflammation of the gums, colitis, constipation, diarrhea, esophageal ulceration, esophagitis, ileitis, nausea, hepatitis, inflammatory bowel disease, other nonspecific gastrointestinal symptoms, pancreatitis, vomiting. Hematologic Anemia, neutropenia including severe neutropenia, rare reports of agranulocytosis, thrombocytopenia. Infections and Infestations Infections (including disseminated herpes simplex, hordeolum, nasopharyngitis, upper respiratory tract infections). Laboratory Abnormalities
• The following lab test values were increased: alkaline phosphatase, ALT, AST, bilirubin, cholesterol, CPK, fasting blood glucose, gamma-glutamyltransferase, LDH, LDL, platelet counts, sedimentation rate, triglycerides, and uric acid (hyperuricemia).
• The following lab test values were decreased: high density lipoprotein (HDL), RBC parameters, and WBC counts.
• Urine findings included increased microscopic or gross hematuria, proteinuria, white cells. Musculoskeletal and Connective Tissue Arthritis, calcification of tendons and ligaments; decreases in bone mineral density; elevations of CPK/rare reports of rhabdomyolysis musculoskeletal symptoms (sometimes severe) including arthralgia, back pain, extremity pain, musculoskeletal pain or stiffness, myalgia, neck pain [see Warnings and Precautions (5.11) ] ; other types of bone abnormalities; premature epiphyseal closure; skeletal hyperostosis; tendonitis; and transient chest pain. Neurological Dizziness, drowsiness, intracranial hypertension (pseudotumor cerebri), headache, insomnia, lethargy, malaise, nervousness, paresthesia, seizures, syncope, stroke, and weakness. Psychiatric Aggression, auditory hallucinations, anger, depression, emotional instability, insomnia, irritability, panic attack, psychosis, suicidal ideation, suicide, suicide attempts, violent behaviors. In some patients who reported depression, their depression subsided with discontinuation of Amnesteem treatment but recurred with reinstitution of Amnesteem treatment. Reproductive System Abnormal menses, sexual dysfunction that may continue after discontinuation of treatment (including erectile dysfunction, decreased libido, decreased vaginal lubrication, and vaginal dryness). Respiratory Bronchospasm (with or without a history of asthma), epistaxis, nasal dryness, respiratory infection, voice alteration. Skin and Subcutaneous Tissue Abnormal wound healing (delayed healing or exuberant granulation tissue with crusting), acne fulminans, alopecia (which in some cases persists), bruising, cheilitis (dry lips), contact dermatitis, dermatitis, dry mouth, dry nose, dry skin, epistaxis, erythema, eruptive xanthomas, erythema multiforme, flushing, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, nail dystrophy, paronychia, peeling of palms and soles, photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial erythema, seborrhea, and eczema), skin fragility, Stevens-Johnson syndrome, sunburn, sweating, toxic epidermal necrolysis, urticaria, vasculitis (including granulomatosis with polyangiitis), wound healing abnormal (delayed healing or exuberant granulation tissue with crusting). Senses Hearing: hearing impairment, tinnitus. Ocular: asthenopia, blurred vision, cataracts, color vision disorder, conjunctivitis, corneal opacities, decreased night vision which may persist, dry eyes, eye irritation, eye pruritis, eyelid inflammation, increased lacrimation, keratitis, ocular hyperemia, optic neuritis, photophobia, reduced visual acuity, visual disturbances. Renal and Urinary Glomerulonephritis, nonspecific urogenital findings. Most common adverse reactions are (incidence ≥ 5%): dry lips, dry skin, back pain, dry eye, arthralgia, epistaxis, headache, nasopharyngitis, chapped lips, dermatitis, increased creatine kinase, cheilitis, musculoskeletal discomfort, upper respiratory tract infection, reduced visual acuity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug interactions
Vitamin A : Avoid concomitant use ( 7.1 ) Tetracyclines : Avoid concomitant use ( 7.2 ) 7.1 Vitamin A Avoid concomitant use of Amnesteem with supplements containing vitamin A. Amnesteem is closely related to vitamin A. Therefore, concomitant use of Amnesteem with vitamin A may lead to Amnesteem-related adverse reactions. 7.2 Tetracyclines Avoid concomitant use of Amnesteem with tetracyclines. Amnesteem use has been associated with a number of cases of intracranial hypertension (pseudotumor cerebri), some of which involved concomitant use with tetracyclines [see Warnings and Precautions (5.4) ]. 7.3 Oral Contraceptives It is not known if there is an interaction between Amnesteem with oral contraceptives that do not contain norethindrone and ethinyl estradiol. Amnesteem did not result in clinically significant changes in the pharmacokinetics of norethindrone and ethinyl estradiol when used concomitantly with norethindrone and ethinyl estradiol oral contraceptive [see Clinical Pharmacology (12.3) ] .
Use in specific populations
Lactation : Breastfeeding not recommended ( 8.2 ). In Patients Who Can Get Pregnant : Pregnancy testing is required prior to, during, and after Amnesteem treatment. See the Full Prescribing Information for the detailed pregnancy test and contraception requirements. ( 8.3 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that documents pregnancies in patients exposed to isotretinoin during pregnancy. Report any suspected fetal exposure during or 1 month after Amnesteem treatment immediately to the FDA via the MedWatch telephone number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). Risk Summary Amnesteem is contraindicated during pregnancy because isotretinoin can cause fetal harm when administered to a pregnant patient. There is an increased risk of major congenital malformations, spontaneous abortions, and premature births following isotretinoin exposure during pregnancy in humans [see Warnings and Precautions (5.1) ]. If Amnesteem is used during pregnancy, or if the patient becomes pregnant while taking Amnesteem, apprise the patient of the potential hazard to a fetus. If pregnancy occurs during treatment of a patient who is taking Amnesteem, immediately discontinue Amnesteem and refer the patient to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling. Data Human Data Major congenital malformations that have been documented following Amnesteem exposure include malformations of the face, eyes, ears, skull, central nervous system (CNS), cardiovascular system, and thymus and parathyroid glands. External malformations include: skull; ear (including anotia, micropinna, small or absent external auditory canals); eye (including microphthalmia); facial dysmorphia and cleft palate. Internal abnormalities include: CNS (including cerebral and cerebellar malformations, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular; thymus gland; parathyroid hormone deficiency. In some cases, death has occurred as a result of the malformations. Cases of IQ scores less than 85 with or without other abnormalities have been reported in children exposed in utero to isotretinoin. An increased risk of spontaneous abortion and premature births have been reported with isotretinoin exposure during pregnancy. 8.2 Lactation Risk Summary There are no data on the presence of isotretinoin in either animal or human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in nursing infants from isotretinoin, advise patients that breastfeeding is not recommended during treatment with Amnesteem, and for at least 8 days after the last dose of Amnesteem. 8.3 Females and Males of Reproductive Potential All patients who can become pregnant must comply with the iPLEDGE REMS requirements [see Warnings and Precautions (5.2) ] . Pregnancy Testing In patients who can get pregnant, pregnancy testing is required prior to, during, and after Amnesteem treatment. Pregnancy Testing Prior to Prescribing Amnesteem In patients who can get pregnant, only prescribe Amnesteem after verification and documentation that they are not pregnant: (1) Complete the first urine or serum pregnancy test (screening test) in a medical setting (e.g., prescriber’s office, clinic, laboratory) and verify and document that the test is negative, AND (2) For patients with:
• Regular menstrual cycles, complete the second urine or serum pregnancy test (confirmatory test) in a medical setting (1) at least 30 days after the screening test and during the first five days of their menstrual period immediately preceding the beginning of Amnesteem treatment, AND (2) after the patient has used their chosen pregnancy prevention methods (i.e., two forms of contraception or committed to abstinence) for at least 30 days. Verify and document that the confirmatory test is negative, OR
• Amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding , complete the second urine or serum pregnancy test (confirmatory test) in a medical setting (1) at least 30 days after the screening test and immediately preceding the beginning of Amnesteem treatment, AND (2) after the patient has used their chosen pregnancy prevention methods (i.e., two forms of contraception or committed to abstinence) for at least 30 days. Verify and document that the confirmatory test is negative. If a patient who can get pregnant has had negative screening and confirmatory pregnancy tests but they missed the 7-day prescription window (the patient has not obtained their Amnesteem prescription starting from the day of the pregnancy test through six days after the day of the pregnancy test) and have not started Amnesteem treatment, repeat a urine or serum pregnancy test in a medical setting and verify and document that this repeat test is negative prior to prescribing Amnesteem. The confirmatory pregnancy test must be repeated, as needed, until the patient receives Amnesteem. Pregnancy Testing During Treatment with Amnesteem In patients who can get pregnant who are being treated with Amnesteem, within 7-days before each prescription obtain a urine or serum pregnancy test in a medical setting (e.g., prescriber’s office, laboratory, clinic) or instruct patients to use a home pregnancy test. If the patient who can get pregnant missed the 7-day prescription window (the patient has not obtained their Amnesteem prescription starting from the day of the pregnancy test through six days after the day of the pregnancy test), repeat the urine or serum pregnancy test within seven days before the next prescription in a medical setting or instruct patients to use a home pregnancy test. Verify and document the negative pregnancy test result prior to prescribing additional Amnesteem treatment.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that documents pregnancies in patients exposed to isotretinoin during pregnancy. Report any suspected fetal exposure during or 1 month after Amnesteem treatment immediately to the FDA via the MedWatch telephone number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). Risk Summary Amnesteem is contraindicated during pregnancy because isotretinoin can cause fetal harm when administered to a pregnant patient. There is an increased risk of major congenital malformations, spontaneous abortions, and premature births following isotretinoin exposure during pregnancy in humans [see Warnings and Precautions (5.1) ]. If Amnesteem is used during pregnancy, or if the patient becomes pregnant while taking Amnesteem, apprise the patient of the potential hazard to a fetus. If pregnancy occurs during treatment of a patient who is taking Amnesteem, immediately discontinue Amnesteem and refer the patient to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling. Data Human Data Major congenital malformations that have been documented following Amnesteem exposure include malformations of the face, eyes, ears, skull, central nervous system (CNS), cardiovascular system, and thymus and parathyroid glands. External malformations include: skull; ear (including anotia, micropinna, small or absent external auditory canals); eye (including microphthalmia); facial dysmorphia and cleft palate. Internal abnormalities include: CNS (including cerebral and cerebellar malformations, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular; thymus gland; parathyroid hormone deficiency. In some cases, death has occurred as a result of the malformations. Cases of IQ scores less than 85 with or without other abnormalities have been reported in children exposed in utero to isotretinoin. An increased risk of spontaneous abortion and premature births have been reported with isotretinoin exposure during pregnancy.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Amnesteem for the treatment of severe recalcitrant nodular acne have been established in non-pregnant pediatric patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater who are unresponsive to conventional treatment, including systemic antibiotics. Use of Amnesteem in this age group for this indication is supported by evidence from a clinical trial comparing 103 pediatric patients (13 to 17 years) to 197 adults (both with severe recalcitrant nodular acne). Results from this study demonstrated that Amnesteem, at a dosage of 1 mg/kg/day given in two divided doses, was similarly effective in treating severe recalcitrant nodular acne in both pediatric and adult patients. The safety and effectiveness of Amnesteem in pediatric patients less than 12 years of age have not been established. Adverse Reactions in Pediatric Patients In trials with Amnesteem, adverse reactions reported in pediatric patients aged 12 to 17 years old 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. In a trial of pediatric patients aged 12 to 17 years old treated with Amnesteem, approximately 29% (104/358) developed back pain. Back pain was severe in 14% (14/104) of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias occurred in 22% (79/358) of pediatric patients including severe arthralgias in 8% (6/79) of patients. Evaluate the musculoskeletal system in pediatric patients 12 years of age and older who present with these symptoms during or after a course of Amnesteem. Consider discontinuing Amnesteem if any significant abnormality is found. Effects on Bone Mineral Density in Pediatric Patients In an open-label clinical trial (N = 217) of a single course of treatment with Amnesteem for adolescents with severe recalcitrant nodular acne, BMD at several skeletal sites were assessed:
• One patient had a decrease in lumbar spine BMD > 4% based on unadjusted data; 16 (8%) patients had decreases in lumbar spine BMD > 4%, and all the other patients (92%) did not have significant decreases or had increases (adjusted for body mass index).
• Nine patients (5%) had a decrease in total hip BMD > 5% based on unadjusted data. Twenty-one (11%) patients had decreases in total hip BMD > 5%, and all the other patients (89%) did not have significant decreases or had increases (adjusted for body mass index). Follow-up trials performed in 8 of the patients with decreased BMD for up to 11 months thereafter demonstrated increasing BMD in 5 patients at the lumbar spine, while the other 3 patients had lumbar spine BMD measurements below baseline values. Total hip BMD remained below baseline (range -1.6% to -7.6%) in 5 of 8 patients (63%). In a separate open-label extension trial of 10 patients including those ages 13 to 17 years, who started a second course of Amnesteem 4 months after the first course, two patients showed a decrease in mean lumbar spine BMD up to 3.3%. Epiphyseal Closure There have been spontaneous literature reports of premature epiphyseal closure in acne patients who received the recommended dosage of Amnesteem. The effect of multiple courses of Amnesteem on epiphyseal closure is unknown [see Warnings and Precautions (5.11) ] .
Geriatric use
8.5 Geriatric Use Clinical studies of Amnesteem did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. The effects of aging may increase some risks associated with Amnesteem treatment.
Overdosage
Isotretinoin overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. Evaluate patients who can become pregnant who present with an isotretinoin overdosage for pregnancy. Because an overdosage would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, instruct male patients treated with Amnesteem to use a condom, or avoid reproductive sexual activity with a patient who is or might become pregnant, for 1 month after the overdose. Instruct all patients with Amnesteem overdose not donate blood for at least 1 month. If an overdose occurs, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
Chemically, isotretinoin is 13- cis -retinoic acid and is related to both retinoic acid and retinol (vitamin A). It is a yellow to orange crystalline powder with a molecular weight of 300.44. Isotretinoin has high lipophilicity. The structural formula is: Amnesteem contains 10 mg, 20 mg, 30 mg or 40 mg of isotretinoin (a retinoid) for oral administration. In addition to the active ingredient, isotretinoin, each 10 mg, 20 mg, 30 mg and 40 mg soft gelatin capsule contains the following inactive ingredients: butylhydroxyanisole, gelatin, glycerol, hydrogenated partially vegetable oil, medium chain triglycerides, sodium edetate, soy lecithin, soybean oil and yellow beeswax. The 10 mg, 20 mg, and 40 mg capsules also contain red iron oxide in glycerin, and the 20 mg, 30 mg and 40 mg capsules also contain titanium dioxide in glycerin and yellow iron oxide in glycerin. The black imprinting ink contains ammonium hydroxide, black iron oxide, polyethylene glycol, propylene glycol and polyvinyl acetate phthalate. Meets USP Dissolution Test 4. Isotretinoin Structural Formula
Mechanism of action
12.1 Mechanism of Action The exact mechanism of action of Amnesteem in the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater who are unresponsive to conventional therapy, including systemic antibiotics is unknown. Isotretinoin, a retinoid, inhibits sebaceous gland function and keratinization. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.
How supplied
Amnesteem (Isotretinoin Capsules, USP) contains 10 mg, 20 mg, 30 mg or 40 mg of isotretinoin, USP. The 10 mg capsules are reddish brown and imprinted with I10. They are available as follows: NDC 0378-6611-93 cartons of 30 containing 3 prescription packs of 10 capsules The 20 mg capsules are reddish brown and cream and imprinted with I20. They are available as follows: NDC 0378-6612-93 cartons of 30 containing 3 prescription packs of 10 capsules The 30 mg capsules are cream opaque and imprinted with I30. They are available as follows: NDC 0378-6613-93 cartons of 30 containing 3 prescription packs of 10 capsules The 40 mg capsules are orange-brown and imprinted with I40. They are available as follows: NDC 0378-6614-93 cartons of 30 containing 3 prescription packs of 10 capsules Store at 68° to 77°F (20° to 25°C). [See USP Controlled Room Temperature.] Protect from light.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity There is an extremely high risk of life-threatening birth defects when Amnesteem is used in pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Instruct patients who can become pregnant that they must not be pregnant during or up to one month after Amnesteem treatment. Instruct patients to not donate blood during Amnesteem treatment and for 1 month following discontinuation to avoid blood donation to a pregnant patient. iPLEDGE REMS Amnesteem is available only through a restricted program called the iPLEDGE REMS [see Warnings and Precautions (5.2) ]. Inform patients who can get pregnant of the following notable requirements. These patients must:
• Enroll in the REMS
• Comply with REMS requirements, including: o Comply with the pregnancy testing and pregnancy prevention requirements [see Use in Specific Populations (8.3) ] o Demonstrate comprehension of the risk and REMS requirements prior to each prescription o Obtain the prescription within the 7-day prescription window (i.e., within 7 days of the pregnancy test collection) o Inform their health care provider if they become pregnant and stop treatment. Inform patients who cannot get pregnant of the following notable requirements. These patients must enroll in the REMS and comply with the REMS requirements. Amnesteem is available only from certified pharmacies participating in the REMS. Therefore, provide patients with the telephone number and website for information on how to obtain Amnesteem [see Warnings and Precautions (5.2) ] . Lactation Because of the potential for serious adverse reactions in nursing infants from isotretinoin, advise patients that breastfeeding is not recommended during treatment with Amnesteem, and for at least 8 days after the last dose of Amnesteem [see Use in Specific Populations (8.2) ]. Psychiatric Disorders Instruct patients and/or their caregivers/families that Amnesteem may cause depression, psychosis, suicidal ideation, suicide attempts, and aggressive or violent behavior. Instruct patients to stop Amnesteem and to contact a health care provider if they develop any of these signs or symptoms [see Warnings and Precautions (5.3) ]. Important Administration Instructions To decrease the risk of esophageal irritation, instruct patients to swallow the capsules with a full glass of liquid. Instruct patients to administer this Amnesteem product with food [see Dosage and Administration (2.1) ]. Intracranial Hypertension (Pseudotumor Cerebri) Advise patients that intracranial hypertension (pseudotumor cerebri) has occurred with Amnesteem use including concomitant use with tetracyclines. Thus, advise patients to avoid concomitant use with tetracyclines and to discontinue Amnesteem immediately if they have symptoms of intracranial hypertension [see Warnings and Precautions (5.4) ]. Serious Skin Reactions Advise patients that severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported in patients treated with isotretinoin and to discontinue Amnesteem if clinically significant skin reactions occur [see Warnings and Precautions (5.5) ]. Inflammatory Bowel Disease Advise patients that inflammatory bowel disease (including regional ileitis) have occurred with isotretinoin use including those without a prior history of IBD and if they experience IBD symptoms, to discontinue Amnesteem immediately [see Warnings and Precautions (5.10) ]. Musculoskeletal Abnormalities Inform patients that :
• There have been reports of osteoporosis and fractures and that isotretinoin may have a negative effect on bone mineral density [see Warnings and Precautions (5.11) ].
• Isotretinoin use has been associated with musculoskeletal abnormalities (e.g., arthralgia, back pain) [see Warnings and Precautions (5.11) ]. Inform pediatric patients and their families that isotretinoin use in pediatric patients who participated in sports with repetitive impact increased their risk of spondylolisthesis or hip growth plate injuries [see Warnings and Precautions (5.11) ] . Inform pediatric patients and their caregivers that pediatric patients treated with Amnesteem developed back pain including severe back pain, and arthralgias including severe arthralgias [see Use in Specific Populations (8.4) ]. Ocular Abnormalities Inform patients that they may experience dry eyes, corneal opacities, and decreased night vision and contact lens wearers may experience decreased tolerance to contact lenses during and after treatment [see Warnings and Precautions (5.12) ]. Rhabdomyolysis Inform patients there have been rare postmarketing reports of rhabdomyolysis in patients treated with Amnesteem, some associated with strenuous physical activity [see Warnings and Precautions (5.14) ]. Hypersensitivity Reactions Given that anaphylactic reactions and other allergic reactions have been reported in patients treated with Amnesteem, instruct the patient to discontinue Amnesteem and contact their health care provider if they have a severe allergic reaction [see Warnings and Precautions (5.13) ]. Lipid Abnormalities Instruct patients that hypertriglyceridemia, decreased HDL, and increased cholesterol levels were reported in patients treated with Amnesteem [see Warnings and Precautions (5.7) ]. Additional Instructions Inform patients:
• To not share Amnesteem with anyone else because of the risk of birth defects and other serious adverse reactions.
• That transient exacerbation (flare) of acne has been seen, generally during the initial period of treatment.
• To avoid wax epilation and skin resurfacing procedures (such as dermabrasion, laser) during Amnesteem treatment and for at least 6 months thereafter due to the possibility of scarring.
• To avoid prolonged exposure to UV rays or sunlight.
Label text from the FDA structured product label by Mylan Pharmaceuticals Inc. (revised Aug 15, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Isotretinoin in 4 products
Amnesteem NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0378-6611 | Isotretinoin 10 mg/1 Capsule | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-6612 | Isotretinoin 20 mg/1 Capsule | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-6613 | Isotretinoin 30 mg/1 Capsule | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-6614 | Isotretinoin 40 mg/1 Capsule | Mylan Pharmaceuticals Inc. | ANDA |
Amnesteem recalls
- D-0399-2026 Mar 11, 2026 · Class II · Ongoing
Failed Dissolution Specifications
Frequently asked questions
What is Amnesteem used for?
Amnesteem is indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with its use, Amnesteem is reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic…
What are the side effects of Amnesteem?
The following adverse reactions with Amnesteem are described in more detail in other sections of the labeling: • Embryo-Fetal Toxicity [see Warnings and Precautions (5.1) ] • Psychiatric Disorders [see Warnings and Precautions (5.3) ] • Intracranial Hypertension (Pseudotumor Cerebri) [see Warnings and Precautions (5.4) ] • Serious Skin Reactions [see Warnings and Precautions (5.5) ] •… See the full label for the complete list.
Who makes Amnesteem?
Amnesteem is listed by 1 labeler in the FDA NDC directory, including Mylan Pharmaceuticals Inc..
Has Amnesteem been recalled?
The FDA enforcement database lists 1 recall for Amnesteem, most recently D-0399-2026 (class ii): Failed Dissolution Specifications