Amnesteem isotretinoin 10 mg Capsule, 30-count — NDC 0378-6611-93 (Billing 00378-6611-93)
This is a package of 30 capsules of Amnesteem isotretinoin 10 mg Capsule from Mylan Pharmaceuticals Inc., marketed since Nov 2002 and currently FDA-listed; retail pharmacies pay about $1.96 per capsule (NADAC). It is this product's only package size.
Other active recalls for Isotretinoin (different manufacturers) — 4 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 036045
- GCN: 59841
- HICL (First Databank): 002476
- AHFS class code: 84:28.00.00
- RxCUI (RxNorm): 197843
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Retinoid class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Isotretinoin is used to treat severe recalcitrant nodular acne (a certain type of severe acne) that has not been helped by other treatments, such as antibiotics. Isotretinoin is in a class of medications called retinoids. It works by slowing the production of certain natural substances that can cause acne.
Read the full MedlinePlus article ↗- Isotretinoin causes extremely serious birth defects — even one dose during pregnancy can cause devastating harm to a developing baby. Because of that risk, the FDA requires everyon...
- Why is there so much paperwork and testing before I can even get this prescription filled?
- For most brands — including Accutane, Amnesteem, Claravis, and generic isotretinoin — yes, taking it with food is essential. Studies show that a fatty meal more than doubles the am...
- Do I really need to take this with food every time?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Isotretinoin — tap one for details:
Isotretinoin may be associated with lower levels of 4 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.963 | $58.89 / 30 capsules |
| Medicaid paysCMS SDUD · 12 mo | $2.77 | $83.15 / 30 capsules |
| Medicare drug plans payPart D · Q2 2026 | $3.51 | $105.32 / 30 capsules |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00378-6611-93 You're viewing this Main listing | 3 BLISTER PACK in 1 CARTON / 10 CAPSULE in 1 BLISTER PACK | 2002-11-11 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Amnesteem 10 mgthis 00378-6611-93 | Mylan | 30 capsules | $1.963 | AB1 | Availability likely | — |
| Claravis 10 mg 00555-1054-56 | Teva | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Isotretinoin 10 mg 00832-8301-30 | Upsher-Smith | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Zenatane 10 mg 55111-0135-81 | Dr. | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Zenatane 10 mg 68001-0652-17 | BluePoint | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Isotretinoin 10 mg 68308-0781-30 | Mayne | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Isotretinoin 10 mg 69238-1174-03 | Amneal | 10 capsules | $1.963 | AB1 | Availability likely | — |
| Isotretinoin 10 mg 00245-0570-01 | Upsher-Smith | 10 capsules | $11.936 | AB2 | Availability likely | +508% |
| Isotretinoin 10 mg 00591-2433-15 | Actavis | 30 capsules | $11.936 | AB2 | Availability likely | +508% |
| Isotretinoin 10 mg 57664-0020-97 | Sun | 30 capsules | $11.936 | AB2 | Availability likely | +508% |
| Isotretinoin 10 mg 59651-0631-03 | Aurobindo | 30 capsules | $11.936 | AB2 | Availability likely | +508% |
| Isotretinoin 10 mg 68308-0570-30 | Mayne | 10 capsules | $11.936 | AB2 | Availability likely | +508% |
| Isotretinoin 10 mg 70710-1574-08 | Zydus | 30 capsules | $11.936 | AB2 | Availability likely | +508% |
| Absorica 10 mg 10631-0115-31 | Sun | 30 capsules | — | AB2 | FDA listed | — |
| Isotretinoin 10 mg 69238-1254-03 | Amneal | 30 capsules | — | — | FDA listed | — |
| Isotretinoin 10 mg 70710-1022-04 | Zydus | 100 capsules | — | AB1 | FDA listed | — |
| Isotretinoin 10 mg 70771-1557-04 | Zydus | 100 capsules | — | AB1 | FDA listed | — |
| Isotretinoin 10 mg 70771-1662-08 | Zydus | 30 capsules | — | AB2 | FDA listed | — |
| Accutane 10 mg 72143-0251-30 | JG | 10 capsules | — | AB1 | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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15 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: EMBRYO-FETAL TOXICITY - CONTRAINDICATED IN PREGNANCY Amnesteem can cause life-threatening birth defects and is contraindicated in pregnancy . 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 . If pregnancy occurs, discontinue Amnesteem immediately and refer the patient to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ] . Because of the risk of embryo-fetal toxicity, Amnesteem is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the iPLEDGE REMS [see Warnings and Precautions (5.2) ].
WARNING: EMBRYO-FETAL TOXICITY – CONTRAINDICATED IN PREGNANCY See full prescribing information for complete boxed warning. • Amnesteem can cause life-threatening birth defects and is contraindicated in pregnancy. There is an extremely high risk that life-threatening birth defects will result if pregnancy occurs while taking Amnesteem 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. ( 4 , 5.1 , 8.1 ) • Amnesteem is available only through a restricted program called the iPLEDGE REMS. ( 5.2 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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 ▾
2 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 )
2.1Evaluations 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) ] .
2.2Recommended 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.
2.3Recommended 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 bee… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 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 ▾
4 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 Cautions ▾
5 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 )
5.1Embryo-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. •… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 va… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Vitamin A : Avoid concomitant use ( 7.1 ) Tetracyclines : Avoid concomitant use ( 7.2 )
7.1Vitamin 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.
7.2Tetracyclines 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) ].
7.3Oral 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 ▾
8 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 ).
8.1Pregnancy 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.
8.2Lactation 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.
8.3Females 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 th… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric 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 ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics Decreased sebum secretion is related to the dose and duration of treatment with Amnesteem.
12.3Pharmacokinetics The following parameters are presented as mean [coefficient of variation (CV%)] following a single oral dose of 80 mg of Amnesteem in healthy adult subjects unless otherwise stated. Isotretinoin C max is 862 (22%) ng/mL and AUC 0-inf is 10,004 (22%) ng*h/mL when Amnesteem was administered with food in healthy adults. Isotretinoin accumulation ratio ranged from 0.90 to 5.43 in patients with cystic acne after multiple doses.
No clinically significant differences in the pharmacokinetics of isotretinoin were observed between patients with nodular acne and healthy subjects without acne. Absorption Isotretinoin time to maximum concentration (T max ) is 5.3 hours (77%) when administered with food. Effect on Food Isotretinoin AUC 0-inf increased 2.7-fold and C max increased 2.9-fold relative to the fasted state following a high-fat meal.
In addition, the extent of formation of all metabolites was higher, T max increased to 5.3 hours (77%), and the elimination half-life was unchanged under fed conditions [see Dosage and Administration (2.1) ] . Distribution Isotretinoin is more than 99.9% bound to plasma proteins, primarily to albumin. Elimination The mean ± SD elimination half-life of isotretinoin is 21± 8.2 hours and 24 ± 5.3 hours for its 4-oxo-isotretinoin metabolite.
Metabolism Isotretinoin is primarily metabolized by CYP2C8, 2C9, 3A4, and 2B6 in vitro. Isotretinoin and its metabolites are further metabolized into conjugates. Isotretinoin is metabolized into at least three metabolites (4-oxo-isotretinoin, retinoic acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin)) which are detected in human plasma.
Retinoic acid and 13-cis-retinoic acid are geometric isomers and show reversible interconversion. The administration of one isomer will give rise to the other. Isotretinoin is also irreversibly oxidized to 4-oxo-isotretinoin, which forms its geometric isomer 4-oxo-tretinoin.
The exposure of adult cystic acne patients to 4-oxo-isotretinoin at steady state under fasted and fed conditions was approximately 3.4 times higher than that of isotretinoin. All of these metabolites possess retinoid activity in vitro, however the clinical significance is unknown. Excretion Following administration of 80 mg of radiolabeled isotretinoin as a liquid suspension, the metabolites of isotretinoin were excreted in feces and urine in relatively equal amounts (total of 65% to 83%).
Specific Populations Pediatric Patients No clinically statistically significant differences in isotretinoin pharmacokinetics were observed based on age (12 to 15 years, and ≥ 18 years) in patients who received single and multiple doses of Amnesteem. In both age groups, 4- oxo -isotretinoin was the major metabolite compared to tretinoin and 4- oxo -tretinoin . Drug Interaction Studies Clinical Studies • Norethindrone and Ethinyl Estradiol : There were no clinically significant differences in the pharmacokinetics of norethindrone and ethinyl estradiol after the concomitant use of Amnesteem (dosage of 1 mg/kg/day) with an oral contraceptive agent in premenopausal female patients with severe recalcitrant nodular acne.
Additionally, there were no clinically significa… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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.
📋 Description ▾
11 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
💬 Information for Patients ▾
17 PATIENT COUNSELING 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 isotretinoi… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Amnesteem ® [am-nes-team] (Isotretinoin Capsules) for oral use Read the Medication Guide that comes with Amnesteem before you start taking it and each time you get a prescription. There may be new information. This information does not take the place of talking with your health care provider about your medical condition or your treatment.
What is the most important information I should know about Amnesteem? • Amnesteem can harm your unborn baby, including birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby, and early (premature) births. Patients who are pregnant or who plan to become pregnant must not take Amnesteem. o Because of the risk of birth defects , Amnesteem is only available through a special program called the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). o Your healthcare provider must be enrolled in the iPLEDGE REMS for you to be prescribed Amnesteem. o Before you start treatment with Amnesteem, you must enroll in the iPLEDGE REMS. o You must understand and agree to do everything required in the iPLEDGE REMS.
Patients must not get pregnant: o for 1 month before starting Amnesteem o during treatment with Amnesteem o for 1 month after stopping Amnesteem If you get pregnant during treatment with Amnesteem, stop taking it right away and tell your health care provider. Health care providers and patients should report all cases of pregnancy that happen during treatment or 1 month after stopping treatment to: o FDA MedWatch at 1-800-FDA-1088, and o the iPLEDGE Pregnancy Registry at 1-866-495-0654 or www.ipledgeprogram.com If you have any questions about the iPLEDGE REMS, ask your healthcare provider, or go to www.ipledgeprogram.com or call 1-866-495-0654. • Serious mental health problems , including: o depression o psychosis (seeing or hearing things that are not real) o suicide.
Some patients taking Amnesteem have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. Some people have ended their own lives.
Stop taking Amnesteem and tell your health care provider right away if you or a family member notices that you get any of the following signs and symptoms of depression or psychosis: o start to feel sad or have crying spells o lose interest in activities you once enjoyed o sleep too much or have trouble sleeping o become more irritable, angry, or aggressive than usual (for example, temper outbursts, thoughts of violence) o have a change in your appetite or body weight o suicide attempts o have trouble concentrating o withdraw from your friends or family o feel like you have no energy o have feelings of worthlessness or guilt o start having thoughts about hurting yourself or taking your own life (suicidal thoughts) o start acting on dangerous impulses o start seeing or hearing things that are not real Your health care provider may tell you to see a mental health care professional if you have any of these symptoms.
See “ What are the possible side effects of Amnesteem? ” for more information about side effects. What is Amnesteem? Amnesteem is a prescription medicine used in patients 12 years of age and older, who are not pregnant, for the treatment of severe acne (nodular acne) that cannot be cleared up by any other acne treatments, including antibiotics.
Amnesteem can cause serious side effects (see “What is the most important information I should know about Amnesteem?” ). Amnesteem can only be: • prescribed by health care providers that are enrolled in the iPLEDGE REMS • dispensed by a pharmacy that is enrolled in the iPLEDGE REMS • given to patients who are enrolled in the iPLEDGE REMS and agree to do everything required in the program. It is not known if Amnesteem is safe and effective in children less than 12 years of age.
Do not take Amnesteem if you: • are pregnant, plan to become pregnant, or become pregnant during Amnesteem treatment. Amnesteem can cause life-t… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics The following parameters are presented as mean [coefficient of variation (CV%)] following a single oral dose of 80 mg of Amnesteem in healthy adult subjects unless otherwise stated. Isotretinoin C max is 862 (22%) ng/mL and AUC 0-inf is 10,004 (22%) ng*h/mL when Amnesteem was administered with food in healthy adults. Isotretinoin accumulation ratio ranged from 0.90 to 5.43 in patients with cystic acne after multiple doses.
No clinically significant differences in the pharmacokinetics of isotretinoin were observed between patients with nodular acne and healthy subjects without acne. Absorption Isotretinoin time to maximum concentration (T max ) is 5.3 hours (77%) when administered with food. Effect on Food Isotretinoin AUC 0-inf increased 2.7-fold and C max increased 2.9-fold relative to the fasted state following a high-fat meal.
In addition, the extent of formation of all metabolites was higher, T max increased to 5.3 hours (77%), and the elimination half-life was unchanged under fed conditions [see Dosage and Administration (2.1) ] . Distribution Isotretinoin is more than 99.9% bound to plasma proteins, primarily to albumin. Elimination The mean ± SD elimination half-life of isotretinoin is 21± 8.2 hours and 24 ± 5.3 hours for its 4-oxo-isotretinoin metabolite.
Metabolism Isotretinoin is primarily metabolized by CYP2C8, 2C9, 3A4, and 2B6 in vitro. Isotretinoin and its metabolites are further metabolized into conjugates. Isotretinoin is metabolized into at least three metabolites (4-oxo-isotretinoin, retinoic acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin)) which are detected in human plasma.
Retinoic acid and 13-cis-retinoic acid are geometric isomers and show reversible interconversion. The administration of one isomer will give rise to the other. Isotretinoin is also irreversibly oxidized to 4-oxo-isotretinoin, which forms its geometric isomer 4-oxo-tretinoin.
The exposure of adult cystic acne patients to 4-oxo-isotretinoin at steady state under fasted and fed conditions was approximately 3.4 times higher than that of isotretinoin. All of these metabolites possess retinoid activity in vitro, however the clinical significance is unknown. Excretion Following administration of 80 mg of radiolabeled isotretinoin as a liquid suspension, the metabolites of isotretinoin were excreted in feces and urine in relatively equal amounts (total of 65% to 83%).
Specific Populations Pediatric Patients No clinically statistically significant differences in isotretinoin pharmacokinetics were observed based on age (12 to 15 years, and ≥ 18 years) in patients who received single and multiple doses of Amnesteem. In both age groups, 4- oxo -isotretinoin was the major metabolite compared to tretinoin and 4- oxo -tretinoin . Drug Interaction Studies Clinical Studies • Norethindrone and Ethinyl Estradiol : There were no clinically significant differences in the pharmacokinetics of norethindrone and ethinyl estradiol after the concomitant use of Amnesteem (dosage of 1 mg/kg/day) with an oral contraceptive agent in premenopausal female patients with severe recalcitrant nodular acne.
Additionally, there were no clinically significant differences in the serum levels of progesterone, follicle-stimulating hormone, and luteinizing hormone in in these patients. • Phenytoin : There were no clinically significant differences in the pharmacokinetics of phenytoin when used concomitantly with isotretinoin.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Decreased sebum secretion is related to the dose and duration of treatment with Amnesteem.
🔬 Clinical Studies ▾
Clinical Studies • Norethindrone and Ethinyl Estradiol : There were no clinically significant differences in the pharmacokinetics of norethindrone and ethinyl estradiol after the concomitant use of Amnesteem (dosage of 1 mg/kg/day) with an oral contraceptive agent in premenopausal female patients with severe recalcitrant nodular acne. Additionally, there were no clinically significant differences in the serum levels of progesterone, follicle-stimulating hormone, and luteinizing hormone in in these patients. • Phenytoin : There were no clinically significant differences in the pharmacokinetics of phenytoin when used concomitantly with isotretinoin.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In male and female Fischer 344 rats given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 or 5.3 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to humans is uncertain.
Mutagenesis The Ames test was conducted with isotretinoin in two laboratories. The results of the tests in one laboratory were negative, while in the second laboratory, a weakly positive response (less than 1.6 times background) was noted in S. typhimurium TA100 when the assay was conducted with metabolic activation. No dose response effect was seen, and all other strains were negative.
Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse micronucleus test, S. cerevisiae D7 assay, in vitro clastogenesis assay with human-derived lymphocytes, and unscheduled DNA synthesis assay) were all negative. Impairment of Fertility In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of isotretinoin of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area).
In dogs, testicular atrophy was noted after treatment with oral isotretinoin for approximately 30 weeks at dosages of 20 or 60 mg/kg/day (10 or 30 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of spermatogenesis, but some sperm were observed in all testes examined, and in no instance were completely atrophic tubules seen.
13.2Animal Toxicology and/or Pharmacology In rats given 8 or 32 mg/kg/day of isotretinoin (1.3 or 5.3 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, respectively, after normalization for total body surface area) for 18 months or longer, the incidences of focal calcification, fibrosis and inflammation of the myocardium, calcification of coronary, pulmonary and mesenteric arteries, and metastatic calcification of the gastric mucosa were greater than in control rats of similar age. Focal endocardial and myocardial calcifications associated with calcification of the coronary arteries were observed in two dogs after approximately 6 to 7 months of treatment with isotretinoin at a dosage of 60 to 120 mg/kg/day (30 to 60 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area).
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In male and female Fischer 344 rats given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 or 5.3 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to humans is uncertain.
Mutagenesis The Ames test was conducted with isotretinoin in two laboratories. The results of the tests in one laboratory were negative, while in the second laboratory, a weakly positive response (less than 1.6 times background) was noted in S. typhimurium TA100 when the assay was conducted with metabolic activation. No dose response effect was seen, and all other strains were negative.
Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse micronucleus test, S. cerevisiae D7 assay, in vitro clastogenesis assay with human-derived lymphocytes, and unscheduled DNA synthesis assay) were all negative. Impairment of Fertility In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of isotretinoin of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area).
In dogs, testicular atrophy was noted after treatment with oral isotretinoin for approximately 30 weeks at dosages of 20 or 60 mg/kg/day (10 or 30 times the recommended clinical Amnesteem dosage of 1 mg/kg/day, after normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of spermatogenesis, but some sperm were observed in all testes examined, and in no instance were completely atrophic tubules seen.
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL – 10 mg NDC 0378-6611-93 Amnesteem ® (Isotretinoin Capsules, USP) Each capsule contains 10 mg isotretinoin WARNING TO PATIENTS: AVOID PREGNANCY Rx only 3 x 10-Count Prescription Packs Special Instructions to Pharmacists: • Only fill Amnesteem after authorization from the iPLEDGE REMS program by calling 1-866-495-0654 or visiting www.ipledgeprogram.com. • Dispense no more than a 30-day supply. • An Amnesteem Medication Guide is included in each Prescription Pack. • Dispense Prescription Packs intact. • Do not remove Prescription Packs from carton until dispensed.
Reminders for Pharmacists: • Dispense isotretinoin only for registered patients after obtaining authorization from the iPLEDGE REMS program by calling 1-866-495-0654 or visiting www.ipledgeprogram.com. • Write Risk Management Authorization number on the prescription. • Dispense no more than a 30-day supply. No refills. • Dispense Prescription Packs intact. • Do not dispense after the "Do not dispense to Patient After" date. • A Medication Guide is included in each Prescription Pack. Contraindicated in Pregnancy.
Each capsule contains 10 mg isotretinoin. Usual Dosage: For dosage recommendations and other important prescribing information, read accompanying insert. Store at 68° to 77°F (20° to 25°C). [See USP Controlled Room Temperature.] Protect from light.
Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in France AMNESTEEM is a registered trademark of Mylan Bertek Pharmaceuticals, Inc., a Viatris Company. © 2021 Viatris Inc.
Mylan.com MCAT:6611:93:30C:R4 Carton Image Amnesteem Capsules 10 mg Carton Label
PRINCIPAL DISPLAY PANEL – 20 mg N DC 0378-6612-93 Amnesteem ® (Isotretinoin Capsules, USP) 20 mg Each capsule contains 20 mg isotretinoin WARNING TO PATIENTS: AVOID PREGNANCY Rx only 3 x 10-Count Prescription Packs Special Instructions to Pharmacists: • Only fill Amnesteem after authorization from the iPLEDGE REMS program by calling 1-866-495-0654 or visiting www.ipledgeprogram.com. • Dispense no more than a 30-day supply. • An Amnesteem Medication Guide is included in each Prescription Pack. • Dispense Prescription Packs intact. • Do not remove Prescription Packs from carton until dispensed.
Reminders for Pharmacists: • Dispense isotretinoin only for registered patients after obtaining authorization from the iPLEDGE REMS program by calling 1-866-495-0654 or visiting www.ipledgeprogram.com. • Write Risk Management Authorization number on the prescription. • Dispense no more than a 30-day supply. No refills. • Dispense Prescription Packs intact. • Do not dispense after the "Do not dispense to Patient After" date. • A Medication Guide is included in each Prescription Pack. Contraindicated in Pregnancy.
Each capsule contains 20 mg isotretinoin. Usual Dosage: For dosage recommendations and other important prescribing information, read accompanying insert. Store at 68° to 77°F (20° to 25°C). [See USP Controlled Room Temperature.] Protect from light.
Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in France AMNESTEEM is a registered trademark of Mylan Bertek Pharmaceuticals, Inc., a Viatris Company. © 2021 Viatris Inc.
Mylan.com MCAT:6612:93:30C:R4 Carton Image Amnesteem Capsules 20 mg Carton Label
PRINCIPAL DISPLAY PANEL – 30 mg N DC 0378-6613-93 Amnesteem ® (Isotretinoin Capsules, USP) 30 mg Each capsule contains 30 mg isotretinoin WARNING TO PATIENTS: AVOID PREGNANCY Rx only 3 x 10-Count Prescription Packs Special Instructions to Pharmacists: • Only fill Amnesteem after authorization from the iPLEDGE REMS program by calling 1-866-495-0654 or visiting www.ipledgeprogram.com. • Dispense no more than a 30-day supply. • An Amnesteem Medication Guide is included in each Prescription Pack. • Dispense Prescription Packs intact. • Do not remove Prescription Packs from carton until dispensed.
Reminders for Pharmacists: • Dispense isotretinoin only for registered patients after obtaining authoriza… [Excerpted — this section continues on DailyMed.]