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Isotretinoin (Monograph)

Brand names: Amnesteem, Claravis, Sotret
Drug class: Keratolytic Agents

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for isotretinoin to ensure that the benefits outweigh the risks. (See Restricted Distribution under Dosage and Administration.) The REMS may apply to one or more preparations of isotretinoin and consists of the following: medication guide, elements to assure safe use, and implementation system. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Warning

  • Known human teratogen; extremely high risk of severe birth defects if administered during pregnancy; may be life-threatening.201 203 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • iPLEDGE restricted distribution program is in effect to help ensure that fetal exposure does not occur.201 203 The iPLEDGE program specifies monthly requirements for the prescribing clinician, patient, and pharmacist.201 (See Restricted Distribution under Dosage and Administration.)

  • Contraindicated in female patients who are or may become pregnant and in female patients of childbearing potential, unless they comply with all the special conditions required by the iPLEDGE restricted distribution program.201 202 203

  • Pregnancy must be excluded by monthly negative serum or urine pregnancy test results and prevented by simultaneous use of 2 forms of reliable contraception.201 203 (See Advice to Patients.)

  • If pregnancy occurs, immediately discontinue drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.201 202 203 (See Pregnancy under Cautions.)

Introduction

Synthetic retinoid; anti-acne drug.1 2 93 108

Uses for Isotretinoin

Severe Nodular Acne

Treatment of severe recalcitrant nodular (cystic) acne unresponsive to conventional acne therapies, including oral and/or topical anti-infectives.1 29 30 31 32 33 104 105

Safety and efficacy not established for less severe forms of acne.79 89 108

Disorders of Keratinization† [off-label]

Has been used for the treatment of cutaneous disorders of keratinization† [off-label] unresponsive to conventional therapies (e.g., corticosteroids, topical tretinoin).58 59 60 87 88 93 108 114

Psoriasis† [off-label]

Has been used alone and in combination with a psoralen and UVA light (PUVA therapy) in the treatment of psoriasis† [off-label].61 93 108 115 116 117

Neoplasms† [off-label]

Has been used in the prevention, treatment, and adjunctive treatment of various cutaneous and extracutaneous malignant neoplasms† (of epithelial origin); however, the specific role of isotretinoin, if any, not established.4 46 58 63 64 65 66 94 97 118 160 161

Isotretinoin Dosage and Administration

General

Severe Nodular Acne

Administration

Restricted Distribution

Distribution of isotretinoin is restricted because of known, severe teratogenic effects.201 203 (See Boxed Warning and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

A centralized risk management program, called iPLEDGE, for all isotretinoin preparations was approved by FDA; this program replaced previous restricted distribution programs sponsored by various manufacturers.201 202 203 204 The program requires registration of wholesalers, prescribers, pharmacies, and patients; all must agree to accept specific responsibilities designed to minimize pregnancy exposures in order to distribute, prescribe, dispense, or use isotretinoin.201 202 203

The iPLEDGE program strengthened processes to ensure appropriately timed and properly documented pregnancy testing and counseling of patients before, during, and following isotretinoin therapy; the program is computer based and uses verifiable, trackable links between prescriber, patient, pharmacy, and wholesaler in a single registry to control prescribing, distribution, dispensing, and patient use of isotretinoin.201 202 203

To obtain detailed information on all requirements for patients (e.g., contraception, pregnancy testing), prescribing clinicians (e.g., program enrollment, patient registration, patient education), and dispensing pharmacists (e.g., obtaining dispensing authorization, providing patient medication guides), see the iPLEDGE program website at [Web].201 202 203

To facilitate pregnancy testing and counseling in accordance with the iPLEDGE program, clinicians must not prescribe more than a 30-day supply of drug.201 203 Telephone, fax, and electronic transmission (e.g., e-mail) of prescriptions are permitted.202 Refills require a new prescription and another authorization from the iPLEDGE program; automatic refills are not allowed.201 203

Pharmacists must dispense prescriptions prior to the date specified by the iPLEDGE system (7 days from the office visit date) and record this date on the prescription bag sticker.201 203 Patients must pick up prescriptions no later than this date; if not picked up by that date, pharmacists must return the drug to stock.201

Oral Administration

Administer orally twice daily with meals;1 105 111 once-daily dosing not recommended.105 196 197

To decrease the risk of esophageal irritation, swallow capsules whole with a full glass of liquid; do not suck or chew the capsules.105

Dosage

Pediatric Patients

Severe Nodular Acne
Oral

Adolescents ≥12 years of age: usual initial dosage is 0.5–1 mg/kg daily given in 2 divided doses with food.105 Adjust subsequent dosage after ≥2 weeks of treatment according to individual tolerance and response, using the lowest possible effective dosage.105

Usual duration of therapy: 15–20 weeks; discontinue therapy sooner if the total number of cysts has been reduced by more than 70%.102

A second course of therapy may be initiated if severe nodular acne persists and it is thought that the patient could benefit from further treatment; optimum interval between initial and subsequent courses of isotretinoin therapy has not been defined for adolescents who have not completed skeletal growth.105

Adults

Severe Nodular Acne
Oral

Usual initial dosage: 0.5–1 mg/kg daily given in 2 divided doses with food.105 Adjust subsequent dosage after ≥2 weeks of treatment according to individual tolerance and response, using the lowest possible effective dosage.105 If disease is severe or is mainly evident on the chest and back, instead of the face, dosages up to 2 mg/kg daily may be required.105

Usual duration of therapy: 15–20 weeks; discontinue therapy sooner if the total number of cysts has been reduced by more than 70%.102

A second course of therapy may be initiated if severe nodular acne persists and it is thought that the patient could benefit from further treatment; however, at least 2 months should elapse between courses in adults to assess the degree of improvement and the need for further therapy.105

Prescribing Limits

Pediatric Patients

Severe Nodular Acne
Oral

Maximum 2 mg/kg daily.105

Adults

Severe Nodular Acne
Oral

Maximum 2 mg/kg daily.105

Detailed Isotretinoin dosage information

Cautions for Isotretinoin

Contraindications

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Extremely high risk of severe birth defects (possibly life-threatening) if pregnancy occurs while receiving isotretinoin in any amount even for short periods of time; teratogenicity generally characterized by malformations involving craniofacial, cardiovascular, thymus and parathyroid gland, and CNS structures.100 143 144 145 146 147 173 203 Cases of IQ scores <85 with or without obvious CNS abnormalities also have been reported.203 Spontaneous abortions and premature births also reported.203 Contraindicated in female patients who are or who may become pregnant.201 203 (See Boxed Warning and also see Advice to Patients.) Distribution is restricted.201 203 (See Restricted Distribution under Dosage and Administration.)

Blood Donations

Potential risk to the developing fetus from exposure to transfused blood containing isotretinoin; blood donation not recommended for both male and female patients during isotretinoin therapy and for at least 1 month following discontinuance of the drug.203

Psychiatric Disorders

May cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors;185 186 187 188 189 203 etiology not known.203 Prescribing clinicians should be familiar with manifestations of psychiatric disorders in adolescents and young adults and alert to the warning signs of psychiatric disorders in order to guide patients to receive the help they need.203

Prior to initiating therapy, ask patients and family members about any history of psychiatric disorder.203 At each visit during therapy, assess patients for symptoms of depression, mood disturbance, psychosis, or aggression to determine whether further evaluation is necessary.203

Patients who experience symptoms of depression, mood disturbance, psychosis, or aggression after initiating isotretinoin therapy should discontinue the drug and the patient or family member should promptly contact their prescribing clinician without waiting for the next scheduled visit.203 Discontinuance of the drug may be insufficient and further evaluation of the patient may be needed.203

Such monitoring may not detect all patients at risk.203 If a patient reports mental health problems or a family history of psychiatric disorders, discuss with the patient and/or the patient’s family; may need to refer patient to a mental health professional in some cases.203 Consider whether isotretinoin therapy is appropriate; for some patients, potential risks may outweigh potential benefits.203

Pseudotumor Cerebri

Pseudotumor cerebri (benign intracranial hypertension), usually associated with headache, visual disturbances, and papilledema, reported; some patients with pseudotumor cerebri were receiving concomitant tetracycline therapy.105 107 141

Screen patients who develop manifestations of pseudotumor cerebri (e.g., headache, nausea and vomiting, visual disturbances) for the presence of papilledema and, if present, discontinue the drug immediately and refer to a neurologist for further evaluation and care.105

Pancreatitis

Possible acute, life-threatening pancreatitis (e.g., hemorrhagic pancreatitis) with either elevated or normal serum triglyceride concentrations;105 108 132 133 use with caution in patients with preexisting elevated fasting serum triglyceride concentrations and in patients with increased tendency to develop hypertriglyceridemia (e.g., patients with diabetes mellitus, obesity, increased alcohol intake).105 108

If serum triglyceride concentrations cannot be controlled at an acceptable level or if symptoms of pancreatitis occur, discontinue therapy.105

Hepatitis

Clinical hepatitis reported; mild to moderate elevations of hepatic enzymes reported, which resolved despite continued therapy in some patients.105 Perform pretreatment and follow-up liver function tests at weekly or biweekly intervals until response to isotretinoin is established.105

If hepatitis is suspected or abnormal liver function test results develop and persist during isotretinoin therapy, discontinue the drug and investigate the cause of the abnormality.105

Effects on Lipoproteins

Possible lipid abnormalities (e.g., hyperlipidemia, elevated fasting triglycerides and cholesterol, decreased HDL-cholesterol); usually reversible with cessation of therapy.105

Monitor fasting blood lipid levels prior to initiating therapy and at weekly or biweekly intervals until lipid response is established.1 105 If alcohol is consumed prior to testing, at least 36 hours should elapse before these determinations are made.105

Use with caution in patients with diabetes mellitus, obesity, increased alcohol intake, lipid metabolism disorder or familial history of lipid metabolism disorder.105 More frequent serum lipid and/or glucose monitoring recommended in such patients.105

Inflammatory Bowel Disease

Inflammatory bowel syndrome (including regional ileitis) has been reported in patients without a history of intestinal disorders.105 105

If abdominal pain, rectal bleeding, or severe diarrhea occurs, immediately discontinue therapy.105 Symptoms may persist even after discontinuance of isotretinoin therapy.105

Musculoskeletal Effects

Possible arthralgias, hyperostosis, premature epiphyseal closure, osteoporosis, osteopenia, bone loss or fractures, and delayed healing of bone fractures; do not exceed recommended dosage and/or duration of treatment.105

Participation in sports with repetitive impact, where the risks of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known, may increase the risk of developing such adverse effects.105 196 197

Use with caution in patients with a genetic predisposition for age-related osteoporosis; a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism; in patients diagnosed with anorexia nervosa; and in those receiving chronic drug therapy with agents that induce osteoporosis/osteomalacia and/or affect vitamin D metabolism (e.g., systemic corticosteroids, anticonvulsants).105 196 197

Otic Effects

Hearing impairment or tinnitus reported, sometimes persisting even after discontinuance of isotretinoin.105 If such otic effects occur during therapy, discontinue the drug and consult an appropriate specialist for further evaluation.105

Ocular Effects

Possible corneal opacities, cataracts, and decreased night vision.105 If visual difficulties occur during therapy, discontinue the drug and perform an ophthalmologic examination.105

Sensitivity Reactions

Hypersensitivity Reactions

Possible anaphylactic or allergic reactions; cutaneous allergic reactions and serious allergic vasculitis, often with purpura of extremities and extracutaneous involvement (e.g., renal).105

If such reactions occur, discontinue therapy and institute appropriate treatment.105

Paraben Sensitivity

Some formulations contain parabens; contraindicated in sensitive patients.203

Photosensitivity

Photosensitivity reactions reported;1 6 29 105 minimize exposure of treated areas to natural or artificial (e.g., sunlamps) sunlight.105

General Precautions

Hematologic Effects

Possible anemia, thrombocytopenia, neutropenia, and (rarely) agranulocytosis; discontinue the drug if clinically important decreases in leukocyte counts occur.203

Dermatologic Effects

Possible scarring; avoid wax epilation and skin resurfacing procedures (such as dermabrasion, laser) during therapy and for at least 6 months thereafter.105

Specific Populations

Pregnancy

Category X.203

Report all pregnancies during or up to 1 month following therapy to FDA Medwatch Program at 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or through the program’s website ([Web]).201 202 203 (See Fetal/Neonatal Morbidity and Mortality under Cautions and also see Boxed Warning.)

Lactation

Not known whether isotretinoin is distributed into milk; contraindicated in nursing women.105

Pediatric Use

Safety and efficacy not established in children <12 years of age.105 No substantial differences in efficacy of the drug in adolescents ≥12 years of age relative to adults.105

Possible increased risk for adverse musculoskeletal effects (e.g., arthralgias, back pain, premature closure of the epiphyses); use with caution in adolescents 12–17 years of age, particularly those with known metabolic or structural bone disease.105 (See Musculoskeletal Effects under Cautions.)

Perform appropriate evaluations of the musculoskeletal system if symptoms of such effects occur during or after a course of isotretinoin therapy.105 If any substantial abnormality is found, consider discontinuing therapy.105

Titrate dosage carefully; do not exceed recommended dosage and duration of treatment.105 196 197 Effects of long-term or multiple courses of isotretinoin therapy on the developing musculoskeletal system remain to be established.105

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.105

Common Adverse Effects

Cheilitis, conjunctivitis, hypertriglyceridemia, and adverse musculoskeletal effects (e.g., bone or joint pain, generalized muscle aches, arthralgia).105

Drug Interactions

Metabolized principally by CYP2C8, 2C9, 3A4, and 2B6.105 Does not inhibit CYP2C9.105

Specific Drugs

Drug

Interaction

Comment

Corticosteroids

Possible additive effects on bone loss196 197 203

Use with caution196 197 203

Hormonal contraceptives

Possible risk of contraceptive failure, particularly in female patients using a single contraceptive method or when used concomitantly with St. John’s wort203

Use 2 effective forms of contraception simultaneously, at least 1 of which must be a primary form 203

Phenytoin

Possible additive effects on bone loss196 197 203

Use with caution196 197 203

St. John’s wort (Hypericum perforatum)

Possible risk of hormonal contraceptive failure during concomitant use203

Avoid concomitant use203

Tetracyclines

Possible increased risk for pseudotumor cerebri (benign intracranial hypertension)105 196 197

Avoid concomitant use105 196 197

Vitamin A

Possible additive adverse effects105

Avoid concomitant use105
Isotretinoin drug interactions (more detail)

Isotretinoin Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract following an initial lag time of about 0.5–2 hours.53 110 111 112

Actual oral bioavailability not yet determined in humans; in animals, oral bioavailability is about 25%, possibly because of biodegradation of the drug in the GI lumen and/or metabolism of the drug during absorption (in the GI mucosa) and first pass through the liver.53

Food

Food appears to increase the bioavailability of isotretinoin without altering its disposition.105

Distribution

Extent

Following oral administration in animals, the drug is distributed into many tissues including liver, ureters, adrenals, ovaries, and lacrimal glands.1 Distributed into bile in humans.53 54 113 Unlike vitamin A, isotretinoin is not stored in the liver.7

Crosses the placenta in animals.1 55

It is not known if isotretinoin is distributed into milk.1

Distributes into semen of male patients taking the drug; however, the amount delivered to a female partner in semen would be about 1 million times lower than an oral dose of 40 mg.105 191

Plasma Protein Binding

>99%, principally albumin.105

Elimination

Metabolism

Metabolized in the liver by CYP microsomal enzyme system, principally by CYP2C8, CYP2C9, CYP3A4, and CYP2B6 isoenzymes, to several active metabolites (e.g., 4-oxo-isotretinoin, retinoic acid [tretinoin], and 4-oxo-retinoic acid [4-oxo-tretinoin]).105

Elimination Route

Excreted in urine and feces in relatively equal amounts as conjugates of isotretinoin and its metabolites.105

Half-life

Biphasic; initial phase half-life (t½α) averages 0.5 hours53 and the half-life in the terminal phase (t½β) averages 10–20 hours (range: 7–39 hours).53 108 110 112

Stability

Storage

Oral

Capsules

15–30°C in tight, light-resistant containers.2 105

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Isotretinoin is available only through a restricted distribution program.201 (See Restricted Distribution under Dosage and Administration.)

ISOtretinoin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

10 mg

Amnesteem

Mylan

Claravis

Barr

Sotret (with parabens)

Ranbaxy

20 mg

Amnesteem

Mylan

Claravis

Barr

Sotret (with parabens)

Ranbaxy

30 mg

Sotret (with parabens)

Ranbaxy

40 mg

Amnesteem

Mylan

Claravis

Barr

Sotret (with parabens)

Ranbaxy

AHFS DI Essentials™. © Copyright 2025, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

1. Roche Laboratories. Accutane (isotretinoin) capsules package insert. Nutley, NJ; 1982 May.

2. Roche Laboratories. Accutane (isotretinoin/Roche) comprehensive product information. Nutley, NJ; 1982.

3. Mayer H, Bollag W, Hanni R et al. Retinoids: a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology. Experientia. 1978; 34:1105-19. https://pubmed.ncbi.nlm.nih.gov/363444

4. Sporn MB, Newton DL, Smith JM et al. Retinoids and cancer prevention: the importance of the terminal group of the retinoid molecule in modifying activity and toxicity. In: Griffin AC, Shaw CR, eds. Carcinogens: identification and mechanisms of action. New York: Raven Press; 1979:441-53.

5. Sporn MB, Dunlop NM, Newton DL et al. Relationships between structure and activity of retinoids. Nature. 1976; 263:110-3. https://pubmed.ncbi.nlm.nih.gov/987541

6. Windhorst DB, Nigra T. General clinical toxicology of oral retinoids. J Am Acad Dermatol. 1982(4 Part 2); 6:675-82.

7. Elias PM, Williams ML. Retinoids, cancer, and the skin. Arch Dermatol. 1981; 117:160-80. https://pubmed.ncbi.nlm.nih.gov/7011212

8. Voorhees JJ, Orfanos CE. Oral retinoids: broad-spectrum dermatologic therapy for the 1980’s. Arch Dermatol. 1981; 117:418-21. https://pubmed.ncbi.nlm.nih.gov/6455092

9. Orfanos CE. Oral retinoids—present status. Br J Dermatol. 1980; 103:473-81. https://pubmed.ncbi.nlm.nih.gov/6449212

10. Zil JS. Vitamin A acid effects on epidermal mitotic activity, thickness, and cellularity in the hairless mouse. J Invest Dermatol. 1972; 59:228-32. https://pubmed.ncbi.nlm.nih.gov/5055185

11. Yuspa SH, Eigjo K, Morse MA et al. Retinyl acetate modulation of cell growth kinetics and carcinogen-cellular interaction in mouse epidermal cell cultures. Chem Biol Interact. 1977; 16:251-64. https://pubmed.ncbi.nlm.nih.gov/862128

12. Zachman RD. The stimulation of RNA synthesis in vivo and in vitro by retinol in the intestine of vitamin A deficient rats. Life Sci. 1967; 6:2207-13. https://pubmed.ncbi.nlm.nih.gov/6061006

13. Johnson BC, Kennedy M, Chiba N. Vitamin A and nuclear RNA synthesis. Am J Clin Nutr. 1969; 22:1048-58. https://pubmed.ncbi.nlm.nih.gov/5805213

14. Sporn MB, Dunlop NM, Yuspa SH. Retinyl acetate: effect on cellular content of RNA in epidermis in cell culture in chemically defined medium. Science. 1973; 182:722-3. https://pubmed.ncbi.nlm.nih.gov/4752212

15. Tsai CH, Chytil F. Effect of vitamin A deficiency on RNA synthesis in isolated cat liver nuclei. Life Sci. 1978; 23:1466-72.

16. Smith KB. Early effects of vitamin A on protein synthesis in the epidermis of embryonic chick skin cultured in serum-containing medium. Dev Biol. 1973; 30:241-8. https://pubmed.ncbi.nlm.nih.gov/4703676

17. De Luca LM. The direct involvement of vitamin A in glycol transfer reactions of mammalian membranes. Vitam Horm. 1977; 34:1-57.

18. Hassell JR, Silverman-Jones CS, De Luca LM. Stimulation of mannose incorporation into specific glycolipids and glycopeptides of rat liver by high doses of retinyl palmitate. J Biol Chem. 1978; 253:1627-31. https://pubmed.ncbi.nlm.nih.gov/627560

19. Wolf G, Kiorpes TC, Masushige S et al. Recent evidence for the participation of vitamin A in glycoprotein synthesis. Fed Proc. 1979; 38:2540-3. https://pubmed.ncbi.nlm.nih.gov/90625

20. Pochi PE. Oral retinoids in dermatology. Arch Dermatol. 1982; 118:57-61.

21. Ziboh VA, Price B, Fulton J. Effects of retinoic acid on prostaglandin biosynthesis in guinea-pig skin. J Invest Dermatol. 1975; 65:370-4. https://pubmed.ncbi.nlm.nih.gov/1176787

22. Aso K, Rabinowitz I, Farber EM. The role of prostaglandin E, cyclic AMP, and cyclic GMP in the proliferation of guinea-pig ear skin stimulated by topical application of vitamin A acid. J Invest Dermatol. 1976; 67:231-4. https://pubmed.ncbi.nlm.nih.gov/181494

23. Ziboh VA. Regulation of prostaglandin E2 biosynthesis in guinea pig skin by retinoic acid. Acta Derm Venereol. 1975; 55(Suppl 74):56-60.

24. Ong DE, Chytil F. Specificity of cellular retinol-binding protein for compounds with vitamin A activity. Nature. 1975; 255:74-5. https://pubmed.ncbi.nlm.nih.gov/1128671

25. Sani BP, Donovan MK. Localization of retinoic acid-binding protein in nuclei and the uptake of retinoic acid. Cancer Res. 1979; 39:2492-6. https://pubmed.ncbi.nlm.nih.gov/221105

26. Van Der Wateren AR, Cormane RH. Oral retinoic acid as therapy for erythrokeratoderma variabilis. Br J Dermatol. 1977; 97:83-5. https://pubmed.ncbi.nlm.nih.gov/142506

27. Roels OA, Anderson OR, Lui NST et al. Vitamin A and membranes. Am J Clin Nutr. 1969; 22:1020-32. https://pubmed.ncbi.nlm.nih.gov/5805210

28. Wang CC, Straight S, Hill DL. Destabilization of mouse liver lysosomes by vitamin A compounds and analogues. Biochem Pharmacol. 1976; 25:471-5. https://pubmed.ncbi.nlm.nih.gov/938574

29. Peck GL, Olsen TG, Yoder FW et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med. 1979; 300:329-33. https://pubmed.ncbi.nlm.nih.gov/153472

30. Goldstein JA, Socha-Szott A, Thomsen RJ et al. Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion. J Am Acad Dermatol. 1982; 6(4 Part 2):760-5. https://pubmed.ncbi.nlm.nih.gov/6461679

31. Strauss JS, Stranieri AM, Farrell LN et al. The effect of marked sebum production with 13cis-retinoic acid on skin surface lipid composition. J Invest Dermatol. 1980; 74:66-7. https://pubmed.ncbi.nlm.nih.gov/6444323

32. Jones H, Blanc D, Cunliffe WJ. 13-cis-retinoic acid and acne. Lancet. 1980; 2:1048-9. https://pubmed.ncbi.nlm.nih.gov/6107678

33. Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13-cis-retinoic acid: evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol. 1980; 3:602-11. https://pubmed.ncbi.nlm.nih.gov/6451637

34. Pochi PE, Strauss JS, Downing DT. Skin surface lipid composition, acne, pubertal development, and urinary excretion of testosterone and 17-ketosteroids in children. J Invest Dermatol. 1977; 69:485-9. https://pubmed.ncbi.nlm.nih.gov/143498

35. Strauss JS, Peck GL, Olsen TG et al. Sebum composition during oral 13-cis-retinoic acid administration. J Invest Dermatol. 1978; 70:228.

36. Smith JG Jr. Dermatology—acne, retinoids, and other skin diseases. JAMA. 1979; 241:1376-7. https://pubmed.ncbi.nlm.nih.gov/155165

37. Heel RC, Brogden RN, Speight TM et al. Vitamin A acid: a review of its pharmacological properties and therapeutic use in the topical treatment of acne vulgaris. Drugs. 1977; 14:401-19. https://pubmed.ncbi.nlm.nih.gov/145940

38. Esterly NB, Furey NL. Acne: current concepts. Pediatrics. 1978; 62:1044-55. https://pubmed.ncbi.nlm.nih.gov/153517

39. Entwisle B. Oral 13-cis-retinoic acid in severe acne. Med J Aust. 1979; 2:119-20.

40. Jones DH, Blanc D, Cunliffe WJ. The effect of 13-cis-retinoic acid in acne. Paper presented at International Dermatology Symposium on Retinoids. Berlin: 1980.

41. Gomez EC. Effects of 13-cis-retinoic acid on the hamster flank organ. J Invest Dermatol. 1980; 74:392-7. https://pubmed.ncbi.nlm.nih.gov/7381230

42. Chytil F, Ong DE. Mediation of retinoic acid-induced growth and anti-tumor activity. Nature. 1976; 260:49-51. https://pubmed.ncbi.nlm.nih.gov/944375

43. Prutkin L. Mucous metaplasia and gap junctions in the vitamin A acid-treated skin tumor, keratoacanthoma. Cancer Res. 1975; 35:364-9. https://pubmed.ncbi.nlm.nih.gov/1109802

44. Elias PM, Friend DS. Vitamin A-induced mucous metaplasia: an in vitro system for modulating tight and gap junction differentiations. J Cell Biol. 1976; 68:173-88. https://pubmed.ncbi.nlm.nih.gov/1245547 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2109636/

45. McNutt NS. Freeze-fracture techniques and applications to the structural analysis of the mammalian plasma membrane. In: Poste G, Nicolson GL, eds. Cell surface reviews. Amsterdam: North-Holland Publishing Co; 1977:75-126.

46. Peck GL, Olsen TG, Butkus D et al. Treatment of basal cell carcinomas with 13-cis-retinoic acid. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1979; 20:56.

47. Elias PM, Grayson S, Gross EG et al. Influence of topical and systemic retinoids on basal cell carcinoma cell membranes. Cancer. 1981; 48:932-8. https://pubmed.ncbi.nlm.nih.gov/7272935

48. Boutwell RK, Verma AK. Effects of vitamin A and retinoids on the biochemical processes linked to carcinogenesis. Pure Appl Chem. 1979; 51:857-66.

49. O’Brien TG, Simsiman REC, Boutwell RK. Induction of the polyamine-biosynthetic enzymes in mouse epidermis and their specificity for tumor promotion. Cancer Res. 1975; 34:2426-33.

50. O’Brien TG. The induction of ornithine decarboxylase as an early, possibly obligatory, event in mouse skin carcinogenesis. Cancer Res. 1976; 36(7 Part 2):2644-53. https://pubmed.ncbi.nlm.nih.gov/1277170

51. Verma AK, Boutwell RK. Vitamin A acid (retinoic acid): a potent inhibitor of 12-o-tetradecanoyl-phorrbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis. Cancer Res. 1977; 37:2196-201. https://pubmed.ncbi.nlm.nih.gov/861945

52. Verma AK, Shapas BG, Rice HM et al. Correlation of the inhibition by retinoids of tumor promotorinduced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion. Cancer Res. 1979; 39:419-25. https://pubmed.ncbi.nlm.nih.gov/761215

53. Brazzell RK, Colburn WA. Pharmacokinetics of the retinoids isotretinoin and etretinate. J Am Acad Dermatol. 1982; 6(4 Part 2):643-51. https://pubmed.ncbi.nlm.nih.gov/6461675

54. Hoffmann-La Roche Inc. Data on file. Nutley, NJ.

55. Kochar DM. Transplacental passage of label after administration of [3H] retinoic acid (vitamin A acid) to pregnant mice. Teratology. 1976; 14:53-63. https://pubmed.ncbi.nlm.nih.gov/960011

56. Vane FM, Bugge CJL. Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood. Drug Metab Dispos. 1981; 6:515-20.

57. Peck GL, Olsen TG, Butkus D et al. Isotretinoin versus placebo in the treatment of cystic acne: a randomized double-blind study. J Am Acad Dermatol. 1982; 6(4 Part 2):735-45. https://pubmed.ncbi.nlm.nih.gov/6461677

58. Peck GL, Yoder FW, Olsen TG et al. Treatment of Darier’s disease, lamellar ichthyosis, PRP, cystic acne and basal cell carcinoma with oral 13-cis-retinoic acid. Dermatologica. 1978; 157(Suppl 1):11-3. https://pubmed.ncbi.nlm.nih.gov/150981

59. Dicken CH, Bauer EA, Hazen PG et al. Isotretinoin treatment of Darier’s disease. J Am Acad Dermatol. 1982; 6(4 Part 2):721-6. https://pubmed.ncbi.nlm.nih.gov/7040515

60. Bergfeld WF, Derbes VJ, Elias PM et al. The treatment of keratosis palmaris et plantaris with isotretinoin: a multicenter study. J Am Acad Dermatol. 1982; 6(4 Part 2):727-31. https://pubmed.ncbi.nlm.nih.gov/6461676

61. Goerz G, Orfanos CE. Systemic treatment of psoriasis with a new aromatic retinoid. Dermatologica. 1978; 157(Suppl 1):38-44. https://pubmed.ncbi.nlm.nih.gov/357217

62. Katz RA. Treatment of acanthosis nigricans with oral isotretinoin. Arch Dermatol. 1980; 116:110-1. https://pubmed.ncbi.nlm.nih.gov/7352756

63. Sporn MB, Dunlop NM, Newton DL et al. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc. 1976; 35:1332-8. https://pubmed.ncbi.nlm.nih.gov/770206

64. Sporn MB, Newton DL. Chemoprevention of cancer with retinoids. Fed Proc. 1979; 38:2528-34. https://pubmed.ncbi.nlm.nih.gov/488376

65. Lotan R. Effects of vitamin A and its analogues (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980; 605:33-91. https://pubmed.ncbi.nlm.nih.gov/6989400

66. Michscke M, Cermi C, Kokron O et al. Stimulation of immune response in lung cancer patients by vitamin A therapy. Oncology. 1977; 34:234-8. https://pubmed.ncbi.nlm.nih.gov/917457

67. Peck GL. Retinoids in dermatology—an interim report. Arch Dermatol. 1980; 116:283-4. https://pubmed.ncbi.nlm.nih.gov/7369742

68. Haydey RP, Reed ML, Dzubow LM et al. Treatment of keratoacanthomas with oral 13-cis-retinoic acid. N Engl J Med. 1980; 303:560-2. https://pubmed.ncbi.nlm.nih.gov/6931285

69. Kamm JJ. Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids. J Am Acad Dermatol. 1982; 6(4 Part 2):652-9. https://pubmed.ncbi.nlm.nih.gov/7040511

70. Blackman HF, Peck GL, Olsen TG et al. Blepharoconjunctivitis: a side effect of oral 13-cis-retinoic acid therapy for dermatologic diseases. Ophthalmology (Rochester). 1979; 86:753-9.

71. Bring SV, Ricard CA, Zaehringer MV. Relationship between cholesterol and vitamin A metabolism in rats fed at different levels of vitamin A. J Nutr. 1965; 85:400-6. https://pubmed.ncbi.nlm.nih.gov/14273741

72. Gerber LE, Erdman JW. Hypertriglyceridemia in rats administered all-trans or 13-cis retinoic acid. Fed Proc. 1979; 38:761.

73. Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization. Arch Dermatol. 1980; 116:1369-72. https://pubmed.ncbi.nlm.nih.gov/6161583

74. Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid). Arch Dermatol. 1980; 116:951-2. https://pubmed.ncbi.nlm.nih.gov/6931550

75. Weiss J, Degnan M, Leupold R et al. Bilateral corneal opacities: occurrence in a patient treated with oral isotretinoin. Arch Dermatol. 1981; 117:182-3. https://pubmed.ncbi.nlm.nih.gov/6938168

76. Wagner A, Plewig G. 13-cis-Retinsaure: Pharmakologische und toxikologische Untersuchungen bei der Behandlung schwerster Akneformen. (German; with English abstract.) Muench Med Wochenschr. 1980; 122:1294-1300.

77. Farb RM, Lazarus GM, Chiaramonti A et al. The effect of 13-cis-retinoic acid on epidermal lysosomal hydrolase activity in Darier’s disease and pityriasis rubra pilaris. J Invest Dermatol. 1980; 75:133-5. https://pubmed.ncbi.nlm.nih.gov/6997395

78. Lotan R, Dennert G. Stimulatory effects of vitamin A analogs on induction of cell-mediated cytotoxicity in vivo. Cancer Res. 1979; 39:55-8. https://pubmed.ncbi.nlm.nih.gov/761198

79. Anon. Isotretinoin (Accutane) for acne. Med Lett Drugs Ther. 1982; 24:79-81. https://pubmed.ncbi.nlm.nih.gov/6213842

80. Elias PM, Fritsch P, Lampe MA et al. Effects of systemic retinoids on epidermal barrier function, proliferation, structure, and glycosylation. Clin Res. 1980; 28:248.

81. Strauss JS, Stranieri AM. Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol. 1982; 6(4 Part 2):751-5. https://pubmed.ncbi.nlm.nih.gov/6461678

82. Plewig G, Nikolowski J, Wolff HH. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. 1982; 6(4 Part 2):766-85. https://pubmed.ncbi.nlm.nih.gov/6461680

83. Brinckerhoff CE, Nagase H, Nagel JE et al. Effects of all-trans-retinoic acid (retinoic acid) and 4-hydroxyphenylretinamide on synovial cells and articular cartilage. J Am Acad Dermatol. 1982; 6(4 Part 2):591-602. https://pubmed.ncbi.nlm.nih.gov/6279710

84. Bauer EA, Seltzer JL, Eisen AZ. Inhibition of collagen degradative enzymes by retinoic acid in vitro. J Am Acad Dermatol. 1982; 6(4 Part 2):603-7. https://pubmed.ncbi.nlm.nih.gov/6279711

85. Colburn WA (Roche Laboratories, Nutley, NJ): Personal communication; 1982 Oct.

86. Roche Laboratories. Roche Scientific Summary. Accutane (isotretinoin/Roche) in the treatment of severe, recalcitrant cystic acne. Nutley, NJ; 1982.

87. Baden HP, Buxman MM, Weinstein GD et al. Treatment of ichthyosis with isotretinoin. J Am Acad Dermatol. 1982; 6(4 Part 2):716-20. https://pubmed.ncbi.nlm.nih.gov/7040514

88. Goldsmith LA, Weinrich AE, Shupack J. Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol. 1982; 6(4 Part 2):710-5. https://pubmed.ncbi.nlm.nih.gov/7040513

89. Boyland JI (Roche Laboratories, Nutley, NJ): Personal communication; 1982 Nov.

90. Meyskens FL Jr, Gilmartin E, Alberts DS et al. Activity of isotretinoin against squamous cell cancers and preneoplastic lesions. Cancer Treat Rep. 1982; 66:1315-9. https://pubmed.ncbi.nlm.nih.gov/6211233

91. Weissmann A, Wagner A, Plewig G. Reduction of bacterial skin flora during treatment with 13-cis-retinoic acid. Arch Dermatol Res. 1981; 270:179-83. https://pubmed.ncbi.nlm.nih.gov/6454395

92. Reviewers’ comments (personal observations); 1982.

93. Peck GL, Yoder FW. Treatment of lamellar ichthyosis and other keratinising dermatoses with an oral synthetic retinoid. Lancet. 1976; 2:1172-4. https://pubmed.ncbi.nlm.nih.gov/62999

94. Peck GL, Gross EG, Butkus D et al. Chemoprevention of basal cell carcinoma with isotretinoin. J Am Acad Dermatol. 1982; 6(4 Part 2):815-23. https://pubmed.ncbi.nlm.nih.gov/6950957

95. Moon RC, McCormick DL. Inhibition of chemical carcinogenesis by retinoids. J Am Acad Dermatol. 1982; 6(4 Part 2):809-14. https://pubmed.ncbi.nlm.nih.gov/7068981

96. Camisa C, Eisenstat B, Ragaz A et al. The effects of retinoids on neutrophil functions in vitro. J Am Acad Dermatol. 1982; 6(4 Part 2):620-9. https://pubmed.ncbi.nlm.nih.gov/6279712

97. Yoder FW. Isotretinoin: a word of caution. JAMA. 1983; 249:350-1. https://pubmed.ncbi.nlm.nih.gov/6217354

98. Roche Laboratories. Important information concerning your treatment with Accutane. Nutley, NJ; 1985 Jun.

99. Meyskens FL Jr, Goodman GE, Alberts DS. 13-cis-Retinoic acid: pharmacology, toxicology, and clinical applications for the prevention and treatment of human cancer. CRC Crit Rev Oncol Hematol. 1985; 3:75-101.

100. Anon. Update on birth defects with isotretinoin. FDA Drug Bull. 1984; 14:15-6. https://pubmed.ncbi.nlm.nih.gov/6592122

101. Colburn WA, Gibson DM. Isotretinoin kinetics after 80 to 320 mg oral doses. Clin Pharmacol Ther. 1985; 37:411-4. https://pubmed.ncbi.nlm.nih.gov/3856501

102. Roche Laboratories. Accutane prescribing information. Nutley, NJ; 1985 May.

103. Stamatos MN. Accutane: New Clinical Information/Revised Package Insert (isotretinoin/Roche). Letter to pharmacists. Roche Laboratories. Nutley, NJ; 1985 Jun.

104. Strauss JS, Rapini RP, Shalita AR et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol. 1984; 10:490-6. https://pubmed.ncbi.nlm.nih.gov/6233335

105. Roche Laboratories. Accutane (isotretinoin) capsules prescribing information. Nutley, NJ; 2004 Aug.

106. Rofsky HE. Accutane: New Safety Information. Letter to physicians. Roche Laboratories. Nutley, NJ; 1986 Sep.

107. Anon. Adverse effects with isotretinoin. FDA Drug Bull. 1983; 13:21-3. https://pubmed.ncbi.nlm.nih.gov/6581108

108. Ward A, Brogden RN, Heel RC et al. Isotretinoin: a review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders. Drugs. 1984; 28:6-37. https://pubmed.ncbi.nlm.nih.gov/6235105

109. Harms M, Philippe I, Ceyrac D et al. Isotretinoin ineffective topically. Lancet. 1985; 1:398. https://pubmed.ncbi.nlm.nih.gov/2857449

110. Khoo KC, Reik D, Colburn WA. Pharmacokinetics of isotretinoin following a single oral dose. J Clin Pharmacol. 1982; 22:395-402. https://pubmed.ncbi.nlm.nih.gov/6957421

111. Colburn WA, Gibson DM, Wiens RE et al. Food increases the bioavailability of isotretinoin. J Clin Pharmacol. 1983; 23:534-9. https://pubmed.ncbi.nlm.nih.gov/6582073

112. Brazzell RK, Vane FM, Ehmann CW et al. Pharmacokinetics of isotretinoin during repetitive dosing to patients. Eur J Clin Pharmacol. 1983; 24:695-702. https://pubmed.ncbi.nlm.nih.gov/6575917

113. Colburn WA, Vane FM, Bugge CJL et al. Pharmacokinetics of14C-isotretinoin in healthy volunteers and volunteers with biliary T-tube drainage. Drug Metab Dispos. 1985; 13:327-32. https://pubmed.ncbi.nlm.nih.gov/2861992

114. Gilgor RS, Chiaramonti A, Goldsmith LA et al. Evaluation of 13-cis-retinoic acid in lamellar ichthyosis, pityriasis rubra pilaris and Darier’s disease. Cutis. 1980; 25:380-1,385. https://pubmed.ncbi.nlm.nih.gov/6928816

115. Sofen HL, Moy RL, Lowe NJ. Treatment of generalized pustular psoriasis with isotretinoin. Lancet. 1984; 1:40. https://pubmed.ncbi.nlm.nih.gov/6140356

116. Moy RL, Kingston TP, Lowe NJ. Isotretinoin vs etretinate therapy in generalized pustular and chronic psoriasis. Arch Dermatol. 1985; 121:1297-1301. https://pubmed.ncbi.nlm.nih.gov/3862363

117. Hönigsmann H, Wolff K. Isotretinoin-PUVA for psoriasis. Lancet. 1983; 1:236. https://pubmed.ncbi.nlm.nih.gov/6130263

118. Levine N, Miller RC, Meyskens FL Jr. Oral isotretinoin therapy: use in a patient with multiple cutaneous squamous cell carcinomas and keratoacanthomas. Arch Dermatol. 1984; 120:1215-7. https://pubmed.ncbi.nlm.nih.gov/6591861

119. Kessler JF, Meyskens FL Jr, Levine N et al. Treatment of cutaneous T-cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid. Lancet. 1983; 1:1345-7. https://pubmed.ncbi.nlm.nih.gov/6134133

120. Warrell RP Jr, Coonley CJ, Kempin SJ et al. Isotretinoin in cutaneous T-cell lymphoma. Lancet. 1983; 2:629. https://pubmed.ncbi.nlm.nih.gov/6136780

121. Kessler JF, Jones SE, Levine N et al. Isotretinoin and cutaneous helper T-cell lymphoma (mycosis fungoides). Arch Dermatol. 1987; 123:201-4. https://pubmed.ncbi.nlm.nih.gov/2949706

122. Neely SM, Mehlmauer M, Feinstein DI. The effect of isotretinoin in six patients with cutaneous T-cell lymphoma. Arch Intern Med. 1987; 147:529-31. https://pubmed.ncbi.nlm.nih.gov/3493744

123. Gold EJ, Mertelsmann RH, Itri LM et al. Phase I clinical trial of 13-cis-retinoic acid in myelodysplastic syndromes. Cancer Treat Rep. 1983; 67:981-6. https://pubmed.ncbi.nlm.nih.gov/6580071

124. Greenberg BR, Durie BGM, Barnett TC et al. Phase I-II study of 13-cis-retinoic acid in myelodysplastic syndrome. Cancer Treat Rep. 1985; 69:1369-74. https://pubmed.ncbi.nlm.nih.gov/3865701

125. Picozzi VJ Jr, Swanson GF, Morgan R et al. 13-cis Retinoic acid treatment for myelodysplastic syndromes. J Clin Oncol. 1986; 4:589-95. https://pubmed.ncbi.nlm.nih.gov/3514807

126. Clark RE, Jacobs A, Lush CJ et al. Effect of 13-cis-retinoic acid on survival of patients with myelodysplastic syndrome. Lancet. 1987; 1:763-5. https://pubmed.ncbi.nlm.nih.gov/2882180

127. Buzaid AC, Garewal HS, Greenberg BR. Management of myelodysplastic syndromes. Am J Med. 1986; 80:1149-57. https://pubmed.ncbi.nlm.nih.gov/3524212

128. Koch HF. Biochemical treatment of precancerous oral lesions: the effectiveness of various analogues of retinoic acid. J Maxillofac Surg. 1978; 6:59-63. https://pubmed.ncbi.nlm.nih.gov/274508

129. Hong WK, Endicott J, Itri LM et al. 13-cis-Retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986; 315:1501-5. https://pubmed.ncbi.nlm.nih.gov/3537787

130. Shah JP, Strong EW, DeCosse JJ et al. Effect of retinoids on oral leukoplakia. Am J Surg. 1983; 146:466-70. https://pubmed.ncbi.nlm.nih.gov/6578687

131. Lyons F, Laker MF, Marsden JR et al. Effect of oral 13-cis-retinoic acid on serum lipids. Br J Dermatol. 1982; 107:591-5. https://pubmed.ncbi.nlm.nih.gov/6215057

132. Zech LA, Gross EG, Peck GL et al. Changes in plasma cholesterol and triglyceride levels after treatment with oral isotretinoin: a prospective study. Arch Dermatol. 1983; 119:987-93. https://pubmed.ncbi.nlm.nih.gov/6228196

133. Bershad S, Rubinstein A, Paterniti JR Jr et al. Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne. N Engl J Med. 1985; 313:981-5. https://pubmed.ncbi.nlm.nih.gov/2931603

134. Matsuoka LY, Wortsman J, Pepper JJ. Acute arthritis during isotretinoin treatment for acne. Arch Intern Med. 1984; 144:1870-1. https://pubmed.ncbi.nlm.nih.gov/6236765

135. Pennes DR, Ellis CN, Madison KC et al. Early skeletal hyperostoses secondary to 13-cis-retinoic acid. AJR. 1984; 142:979-83. https://pubmed.ncbi.nlm.nih.gov/6609585

136. Ellis CN, Madison KC, Pennes DR et al. Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol. 1984; 10:1024-9. https://pubmed.ncbi.nlm.nih.gov/6588057

137. Pittsley RA, Yoder FW. Retinoid hyperostosis: skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis. N Engl J Med. 1983; 308:1012-4. https://pubmed.ncbi.nlm.nih.gov/6403861

138. Milstone LM, McGuire J, Ablow RC. Premature epiphyseal closure in a child receiving oral 13-cis-retinoic acid. J Am Acad Dermatol. 1982; 7:663-6. https://pubmed.ncbi.nlm.nih.gov/6958690

139. Novick NL, Lawson W, Schwartz IS. Bilateral nasal bone osteophytosis associated with short-term oral isotretinoin therapy for cystic acne vulgaris. Am J Med. 1984; 77:736-9. https://pubmed.ncbi.nlm.nih.gov/6237578

140. Hodak E, Gadoth N, David M et al. Muscle damage induced by isotretinoin. BMJ. 1986; 293:425-6. https://pubmed.ncbi.nlm.nih.gov/3091143 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341241/

141. Fraunfelder FT, LaBraico JM, Meyer SM. Adverse ocular reactions possibly associated with isotretinoin. Am J Ophthalmol. 1985; 100:534-7. https://pubmed.ncbi.nlm.nih.gov/2931989

142. Weleber RG, Denman ST, Hanifin JM et al. Abnormal retinal function associated with isotretinoin therapy for acne. Arch Dermatol. 1986; 104:831-7.

143. Benke PJ. The isotretinoin teratogen syndrome. JAMA. 1984; 251:3267-9. https://pubmed.ncbi.nlm.nih.gov/6587131

144. de la Cruz E, Sun S, Vangvanichyakorn K et al. Multiple congenital malformations associated with maternal isotretinoin therapy. Pediatrics. 1984; 74:428-30. https://pubmed.ncbi.nlm.nih.gov/6591112

145. Lammer EJ, Chen DT, Hoar RM et al. Retinoic acid embryopathy. N Engl J Med. 1985; 313:837-41. https://pubmed.ncbi.nlm.nih.gov/3162101

146. Rosa FW, Wilk AL, Kelsey FO. Teratogen update: vitamin A congeners. Teratology. 1986; 33:355-64. https://pubmed.ncbi.nlm.nih.gov/3461576

147. Cohen M, Rubinstein A, Li JK et al. Thymic hypoplasia associated with isotretinoin embryopathy. Am J Dis Child. 1987; 141:263-6. https://pubmed.ncbi.nlm.nih.gov/3492909

148. Chalker DK, Lesher JL, Smith JG et al. Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: results of a multicenter, double-blind investigation. J Am Acad Dermatol. 1987; 17:251-4. https://pubmed.ncbi.nlm.nih.gov/2957398

149. American Academy of Dermatology. Guidelines for prescribing isotretinoin (Accutane) in the treatment of female acne patients of childbearing potential. Evanston, IL; 1988 Jul.

150. Young FE. Letter sent to Oddis JA (ASHP) regarding isotretinoin. Rockville, MD: Food and Drug Administration; 1988 Jul.

151. McLearn D. Isotretinoin (Accutane) restrictions. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1988 May 27.

152. Peterson F. Isotretinoin (Accutane) birth defects. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1988 Mar 30.

153. Anon. Birth defects caused by isotretinoin—New Jersey. MMWR Morb Mortal Wkly Rep. 1988; 37:171-72,177. https://pubmed.ncbi.nlm.nih.gov/3126387

154. Ayme S, Julian C, Gambarelli D et al. Isotretinoin dose and teratogenicity. Lancet. 1988; 1:655. https://pubmed.ncbi.nlm.nih.gov/2894594

155. Rosa F. Isotretinoin dose and teratogenicity. Lancet. 1987; 2:1154. https://pubmed.ncbi.nlm.nih.gov/2890055

156. Torok L, Kadar L, Kasa M. Spermatological investigations in patients treated with etretinate and isotretinoin. Andrologia. 1987; 19:629-33. https://pubmed.ncbi.nlm.nih.gov/3481225

157. Vogt HJ, Ewers R. [13-cis-Retinoic acid and spermatogenesis: spermatological and impulse cytophotometric studies.] (German; with English abstract.) Hautarzt. 1985; 36:281-6.

158. Zachariae H. Delayed wound healing and keloid formation following argon laser treatment or dermabrasion during isotretinoin treatment. Br J Dermatol. 1988; 118:703-6. https://pubmed.ncbi.nlm.nih.gov/2969261

159. Roenigk HH Jr. Dermabrasion and isotretinoin. JAMA. 1988; 259:3479.

160. Lippman SM, Meyskens FL Jr. Treatment of advanced squamous cell carcinoma of the skin with isotretinoin. Ann Intern Med. 1987; 107:499-501. https://pubmed.ncbi.nlm.nih.gov/3477106

161. Kraemer KH, DiGiovanna JJ, Moshell AN et al. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. 1988; 318:1633-7. https://pubmed.ncbi.nlm.nih.gov/3287161

162. Rubenstein R, Roenigk HH Jr, Stegman SJ et al. Atypical keloids after dermabrasion of patients taking isotretinoin. J Am Acad Dermatol. 1986; 15:280-95. https://pubmed.ncbi.nlm.nih.gov/3018052

163. Anon. Accutane risks evaluated: strong precautions needed. FDA Drug Bull. 1990; 20:5-6.

164. Crawford SY. Meeting of joint FDA advisory committees on Accutane (meeting report). Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 1990 Jun 15.

165. Crawford SY. Meeting with Roche Dermatologics to discuss Accutane (meeting report). Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 1990 Oct 10.

166. David M, Hodak E, Lowe NJ. Adverse effects of retinoids. Med Toxicol Adverse Drug Exp. 1988; 3:273-88. https://pubmed.ncbi.nlm.nih.gov/3054426

167. Besa EG, Abraham JL, Bartholomew MJ et al. Treatment with 13-cis-retinoic acid in transfusion-dependent patients with myelodysplastic syndrome and decreased toxicity with addition of alpha-tocopherol. Am J Med. 1990; 89:739-47. https://pubmed.ncbi.nlm.nih.gov/2252043

168. McElwee NE, Schumacher MC, Johnson SC et al. An observational study of isotretinoin recipients treated for acne in a health maintenance organization. Arch Dermatol. 1991; 127:341-6. https://pubmed.ncbi.nlm.nih.gov/1825596

169. Hesdorffer CS, Weltman MD, Raftopoulos H et al. Thrombocytopenia caused by isotretinoin. S Afr Med J. 1986; 70:705. https://pubmed.ncbi.nlm.nih.gov/3466373

170. Johnson TM, Rapini RP. Isotretinoin-induced thrombocytopenia. J Am Acad Dermatol. 1987; 17:838-9. https://pubmed.ncbi.nlm.nih.gov/2960702

171. Rees JL, Cox NH. Effect of isotretinoin on eccrine gland function. Br J Dermatol. 1988; 119:79-82. https://pubmed.ncbi.nlm.nih.gov/3165666

172. Orfanos CE, Ehlert R, Gollnick H. The retinoids: a review of their clinical pharmacology and therapeutic use. Drugs. 1987; 34:459-503. https://pubmed.ncbi.nlm.nih.gov/3315625

173. Braun JT, Franciosi RA, Mastri AR et al. Isotretinoin dysmorphic syndrome. Lancet. 1984; 1:506-7. https://pubmed.ncbi.nlm.nih.gov/6142222

174. Hill RM. Isotretinoin teratogenicity. Lancet. 1984; 1:1465. https://pubmed.ncbi.nlm.nih.gov/6145899

175. Hersh JH, Danhauer DE, Hand ME et al. Retinoic acid embryopathy: timing of exposure and effects on fetal development. JAMA. 1985; 254:909-10. https://pubmed.ncbi.nlm.nih.gov/4021019

176. Anon. The teratogenicity of retinoids. Reprod Toxicol. 1986; 5:5-8.

177. Rappaport EB, Knapp M. Isotretinoin embryopathy: a continuing problem. J Clin Pharmacol. 1989; 29:463-5. https://pubmed.ncbi.nlm.nih.gov/2738179

178. Kizer KW, Fan AM, Bankowska J et al. Vitamin A: a pregnancy hazard alert. West J Med. 1990; 152:78-81. https://pubmed.ncbi.nlm.nih.gov/2309485 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002277/

179. Stern RS. When a uniquely effective drug is teratogenic: the case of isotretinoin. N Engl J Med. 1989; 320:1007-9. https://pubmed.ncbi.nlm.nih.gov/2522591

180. Faich G, Rosa F. When a uniquely effective drug is teratogenic: the case of isotretinoin. N Engl J Med. 1989; 321:756-7. https://pubmed.ncbi.nlm.nih.gov/2770803

181. Swensen RE. Avoiding pregnancy in isotretinoin users. West J Med. 1990; 152:406. https://pubmed.ncbi.nlm.nih.gov/18750719 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002360/

182. Cogenital Abnormalities Subcommittee of the Australian Drug Evaluation Committee. Isotretinoin: birth defects. Aust Prescriber. 1989; 12:26-7.

184. Anon. Continued reports of birth defects with isotretinoin engender labeling, packaging changes. FDA Drug Bull. 1988; 18:27-8.

185. Anon. Roche relabels Accutane after independent review of MedWatch reports. F-D-C Rep. 1998; Mar 2.

186. Anon. Isotretinoin (Accutane) safety information. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1998 Feb 25.

187. Ellison RH. Dear doctor letter regarding reports of psychiatric disorders with use of Accutane. Nutley, NJ: Roche Laboratories; 1998 Feb.

188. Ault A. Isotretinoin use may be linked with depression. Lancet. 1998; 351:730.

189. Anon. Side effects prompt stronger warning on acne drug. FDA Consumer. 1998; 32:3.

190. Hong J. Dear healthcare provider and pharmacist letter: Important prescribing information: new medication guide and informed consent documents for Accutane (isotretinoin). Nutley, NJ: Roche Laboratories; 2001 Jan.

191. Roche Laboratories Inc. Accutane (isotretinoin) System to Manage Accutane Related Teratogenicity (SMART) guide to best practices. Nutley, NJ; updated. From the FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18662s44lbl.pdf

192. Food and Drug Administration. Dermatologic and Ophthalmic Drugs Advisory Committee. Sept. 18-19, 2000 [accessed November 8, 2001]. Appendix II (Overview of Accutane and Pregnancy Exposure Performance of the Current Pregnancy Prevention Program) From the FDA website. http://www.fda.gov/ohrms/dockets/ac/accutane.htm

193. Food and Drug Administration. Division of dermatologic and dental Drug Products Center for Drug Evaluation and Research letter to the boards of pharmacy regarding Accutane prescriptions under the S.M.A.R.T. (System to Manage Accutane Related Teratogenicity) program. Rockville, MD; October 30, 2001. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18662s44lbl.pdf

194. DiGiovanna JJ. Isotretinoin effects on bone. J Am Acad Dermatol. 2001 (Suppl); 45:S176-82.

195. Castrow FF. Isotretinoin update. Washington, DC; 2002 Dec 9. Press release from the American Academy of Dermatology Association (AAD) government affairs website. http://www.aad.org

196. Bertek Pharmaceuticals, Inc. Amnesteem (isotretinoin) capsules prescribing information. Research Triangle Park, NC; 2002 Sep.

197. Ranbaxy Pharmaceuticals, Inc. Sotret (isotretinoin) capsules prescribing information. Princeton, NJ; 2002 Dec.

198. Barr Laboratories, Inc. Claravis (isotretinoin) capsules prescribing information Pomona, NY; 2003 Feb.

199. Food and Drug Administration. FDA announces enhancement to isotretinoin risk management program. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2004 Nov 23. From FDA website. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/printer.cfm?id=292

200. Food and Drug Administration. Accutane (isotretinoin) questions and answers. Rockville, MD: Food and Drug Administration; 2004 Nov 23. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm094308.htm

201. The iPLEDGE Program Guide to Best Practices for Isotretinoin. 2005. From the iPLEDGE website. http://www.ipledgeprogram.com

202. Food and Drug Administration. Public Health Advisory. Strengthened risk management program for isotretinoin. Rockville, MD; revised October 28, 2005. From the FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm164132.htm

203. Roche Laboratories. Accutane (isotretinoin) capsules prescribing information. Nutley, NJ; 2005 Aug.

204. Houn, F. Letter sent to Carey E (Hoffmann-La Roche) concerning implementation dates for the iPLEDGE RiskMAP program. Rockville, MD: Food and Drug Administration; 2005 Oct 27.

205. Food and Drug Administration. Public Health Advisory. Isotretinoin (marketed as Accutane) capsule information: iPLEGDE update. Rockville, MD; October 6, 2006. From the FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm094305.htm

206. Bottini PB, Mundkur C, Birgerson L et al. Dear healthcare provider letter: Effective immediately: elimination of the 23 day lock-out period for males and females of nonchildbearing potential. October 6, 2006. From the iPLEDGE website. http://www.ipledgeprogram.com

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