Patient Information

Oral isotretinoin therapy for acne vulgaris

Oral isotretinoin ,therapy ,acne vulgaris
Oral isotretinoin ,therapy ,acne vulgaris
Oral isotretinoin therapy for acne vulgaris
Author
Cindy Owen, MD
Section Editors
Robert P Dellavalle, MD, PhD, MSPH
Moise L Levy, MD
Mark V Dahl, MD
Deputy Editor
Abena O Ofori, MD

INTRODUCTION — Oral isotretinoin (13-cis retinoic acid) is effective for the treatment of severe recalcitrant nodular acne. However, isotretinoin is associated with multiple adverse effects and is teratogenic. Thus, it must be used with appropriate caution in selected patients.

This topic will discuss clinical use of oral isotretinoin and related safety concerns. The pathogenesis, clinical manifestations, diagnosis, and conventional treatment of acne vulgaris are discussed separately. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris" and "Hormonal therapy for women with acne vulgaris" and "Treatment of acne vulgaris".)

MECHANISM OF ACTION — Oral isotretinoin counteracts the pathogenic factors that contribute to the development of acne vulgaris [1,2] . Therapy leads to shrinkage of sebaceous glands and a marked attenuation of sebum secretion. The decrease in sebum results in the inhibition of the sebum-dependent bacterium Propionibacterium acnes (P. acnes), which is a key promoter of inflammation in acne vulgaris. Oral isotretinoin also inhibits comedogenesis by fostering keratinocyte differentiation and by normalizing desquamation.

CLINICAL USE — Oral isotretinoin is effective for the treatment of acne vulgaris (picture 1) [3-10] . The first study to show the benefit of oral isotretinoin was a case series of 14 patients with treatment-resistant severe acne [3] . After four months of treatment, 13 out of 14 patients experienced complete clearance of their disease.

Indications — In the United States, the Food and Drug Administration (FDA) approved usage of oral isotretinoin only for severe, recalcitrant, nodular acne. "Severe, recalcitrant, nodular acne" is defined as acne with many (greater than 5 mm) inflammatory nodules that is unresponsive to conventional therapy, including systemic antibiotics.

Clinicians also prescribe oral isotretinoin for selected patients without severe nodular recalcitrant acne. Patients for whom isotretinoin may be considered include those with the following [11]  (see "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris"):

  • Treatment-resistant acne [12-14]
  • Scarring acne [12-14]
  • Acne causing significant psychological distress [12-14]
  • Acne fulminans [15,16]
  • Antibiotic-induced gram-negative folliculitis in patients with acne vulgaris [17,18]

Administration — Treatment is initiated at a dose of 0.5 mg/kg/day for the first month of therapy, and is subsequently increased to 1 mg/kg/day. Dosing can be once or twice daily. The total treatment goal is 120 to 150 mg/kg, and is typically reached over four to six months (usual duration of treatment 20 weeks) [11,19] . The drug is discontinued without tapering. There is some evidence that lower doses may also be effective [20] . Absorption of isotretinoin is improved when taken with food.

Other acne medications are typically discontinued during isotretinoin therapy. Isotretinoin causes temporary xerosis, cutaneous atrophy, and skin fragility [2] , and topical acne medications may be poorly tolerated. Isotretinoin should not be given with tetracycline antibiotics due to the risk of idiopathic intracranial hypertension (pseudotumor cerebri) associated with both of these drugs.

Acne may initially worsen with isotretinoin therapy; initiating therapy at 0.5 mg/kg/day during the first month may decrease this risk. The early flare typically resolves with further treatment [2] . More severe flares may occur in patients presenting with severe inflammatory acne (eg, acne conglobata, acne fulminans). In some of these cases, the inflammatory nodules may ulcerate or form exuberant granulation tissue. If this happens, isotretinoin is temporarily stopped. Systemic glucocorticoids (0.5 to 1 mg/kg/day) are sometimes given before isotretinoin therapy or concurrently for the first two to four weeks of treatment in an attempt to prevent severe flares. Rarely, isotretinoin may induce acne fulminans [21,22] . (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Acne variants'.)

Isotretinoin is associated with a number of adverse effects that can be severe and limit its use. Isotretinoin should only be prescribed by clinicians who are completely familiar with the medication. In the US, the FDA has imposed restrictions on who may prescribe and distribute isotretinoin. (See 'Isotretinoin safety' below.)

RESPONSE TO THERAPY — Oral isotretinoin is the only acne medication that can permanently alter the natural course of the disorder. The majority of patients experience long-term improvement in acne severity after one course of treatment (picture 1) [23] . Continued improvement may occur for several months after cessation of therapy; at least five months should elapse before considering retreatment with isotretinoin. The vast majority of relapses (96 percent) occur within the first three years of stopping therapy; the highest relapse rates occur in patients with predominantly truncal acne or in those receiving a total cumulative dose of less than 120 mg/kg [23] . In one study of 88 patients, 82 percent of patients who received cumulative doses <120 mg/kg relapsed, compared with only 20 percent of patients given >120 mg/kg [23] . Patients who receive isotretinoin as young teenagers (under age 16) may also have an increased risk for relapse [24] .

Despite the high response rate after a single course of isotretinoin, only a minority of patients are truly cured. In one series, 39 percent were cured but 61 percent still required the use of topical therapy (16.9 percent), topical therapy plus an oral antibiotic (25.3 percent), or another course of isotretinoin (18.8 percent) [25] . Following isotretinoin treatment, acne is more likely to be responsive to conventional therapies [26] . Response rates after a second course of isotretinoin are similar to those following the initial course of treatment [26] .

Low dose isotretinoin — Doses of isotretinoin lower than 0.5 mg/kg/day may be effective for the treatment of some patients with acne [20,27] . In a 24-week single-blind randomized trial, 60 patients with moderate acne were treated with one of three regimens of isotretinoin: 0.5 to 0.7 mg/kg/day (higher dose regimen), 0.25 to 0.4 mg/kg/day (lower dose regimen), or 0.5 to 0.7 mg/kg daily for one week every four weeks (intermittent regimen) [27] . All three treatment courses resulted in clinically significant improvement. The lower dose and higher dose regimens were similarly effective and had equivalent rates of relapse after one year; however, more adverse effects were reported in the higher dose group during treatment. A lesser degree of improvement and a lower duration of effect were detected in the patients who received intermittent therapy.

The results of this trial suggest that treatment with less than 0.5 mg/kg/day of isotretinoin is as effective as a slightly higher dose regimen in patients with moderate acne and is associated with fewer adverse effects. Of note, the study excluded individuals with severe acne, a group of patients for which isotretinoin therapy is frequently indicated.

ISOTRETINOIN SAFETY — Isotretinoin is associated with a number of adverse effects that can be severe and limit its use.

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Teratogenicity and the iPLEDGE program — Isotretinoin is teratogenic; it causes both spontaneous abortions and severe life-threatening congenital malformations [28] . Embryopathy associated with exposure in the first trimester of pregnancy includes craniofacial, cardiac, thymic, and central nervous system malformations [29] . Fetal abnormalities have not been attributed to the use of isotretinoin in men [2] .

Among pregnant women exposed to isotretinoin, the risk of spontaneous abortion is approximately 20 percent; among pregnancies that progress, approximately 20 to 30 percent of neonates have evidence of embryopathy [30] . Although data are limited, children who appear physically normal may have a higher rate of mental retardation and impaired neuropsychological function.

Despite stringent rules in the United States intended to prevent women who are pregnant from beginning isotretinoin, and to prevent pregnancy while taking the drug [31] , some women taking isotretinoin still become pregnant. In 2006, the US FDA established a computer-based Risk Evaluation and Mitigation Strategy (REMS) risk management program with the goal of eliminating fetal exposure to isotretinoin (iPLEDGE). Prescribers, pharmacies dispensing isotretinoin, wholesalers distributing isotretinoin, and all patients receiving isotretinoin are required to comply with the registry requirements.

Access to the iPLEDGE program is available online (www.ipledgeprogram.com). The iPLEDGE program requires the following [32] :

  • All female patients of childbearing potential must select and commit to the use of two forms of birth control for at least one month prior to starting isotretinoin therapy, during therapy, and for one month after therapy. The forms of contraception that meet these requirements are specified by the iPLEDGE program.
  • All female patients who can become pregnant must have two negative urine or blood pregnancy tests (with a sensitivity of at least 25 mIU/mL) before receiving the initial prescription. The second pregnancy test must be conducted in a CLIA-certified laboratory. For each month of therapy and one month after completing therapy, female patients must return to their physicians for evaluation, counseling, education, and a pregnancy test conducted by a CLIA-certified laboratory.
  • For female patients who can become pregnant, prescribing physicians must, on a monthly basis, document in the iPLEDGE system the results of the pregnancy test as well as report the two forms of birth control being used by the patient. The clinician must also confirm that the patient has received counseling and education. For all other patients, prescribers must document that the patient was counseled on the iPLEDGE program requirements, which include knowledge of the birth defects that may result from the use of isotretinoin by females of child-bearing potential.
  • As part of this system, physicians must certify expertise in the diagnosis and treatment of acne, and knowledge of the risk and severity of birth defects with isotretinoin.

Mucocutaneous side effects — Mucocutaneous side effects of isotretinoin, including cheilitis, dry skin and mucous membranes, epistaxis, desquamation, photosensitivity, and pruritus, are predictable and dose-dependent. The cheilitis can be significant and often requires the liberal use of topical emollients. Patients also have an increased risk of cutaneous staphylococcal infections [33] . Pyogenic granulomas, temporary diffuse alopecia, or nail brittleness may occasionally appear [34] . Skin fragility and cutaneous atrophy can occur during therapy, and dermabrasion and waxing should be avoided during treatment [2] . Avoidance of chemical peels and laser treatments has also been proposed.

Inflammatory bowel disease — It is unclear whether treatment with isotretinoin increases the risk for inflammatory bowel disease (ulcerative colitis or Crohn’s disease) [35] . Although one case-control study of 2,008 patients with inflammatory bowel disease and 19,814 controls found no evidence supporting a relationship between isotretinoin and inflammatory bowel disease [36] , a subsequent case-control study (8,189 subjects with IBD, 21,832 controls) reported an increased risk for ulcerative colitis among patients who had been treated with isotretinoin (OR 4.36, 95% CI 1.97-9.66) [37] . The absolute risk for the disease was small, estimated at 14 excess cases within a population of 4,428 patients with ulcerative colitis. In concordance with the preceding study, the authors did not find an association between isotretinoin and Crohn’s disease. (See "Epidemiology and environmental factors in inflammatory bowel disease in adults", section on 'Isotretinoin'.)

More studies are necessary to determine whether isotretinoin therapy is a risk factor for inflammatory bowel disease. Until additional information is available, it is advisable to mention the risk of inflammatory bowel disease when discussing the potential adverse effects of isotretinoin with patients.

Other side effects — Isotretinoin has been associated with a number of other side effects [2] :

  • Myalgias may occur in patients taking oral isotretinoin, particularly those who engage in vigorous physical activity.
  • Decreased night vision, corneal opacities, hepatotoxicity, and bone marrow suppression may occur infrequently.
  • Hypertriglyceridemia occurs in up to 45 percent of patients on isotretinoin therapy and elevations of total cholesterol and low-density lipoprotein are seen in approximately 30 percent [38] . These elevations are transient in about 80 percent of subjects and are rarely severe enough to require termination of therapy. (See 'Monitoring and discontinuation' below.)
  • Isotretinoin may cause idiopathic intracranial hypertension (pseudotumor cerebri). The use of medications that share this side effect (eg, tetracycline antibiotics) should be avoided during therapy. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Epidemiology and pathogenesis", section on 'Medications'.)
  • Diffuse skeletal hyperostosis and calcifications in ligaments and tendons may rarely occur, especially among patients being treated with high doses for longer than usual periods.

Psychiatric effects — Concerns have been raised about a possible association of isotretinoin with depression and suicide. Isotretinoin has been in the top 10 drugs reported to the FDA's Adverse Event Reporting System for depression and suicide attempts [39] . Between the time isotretinoin was marketed in 1982 and January 2005, the FDA received reports of 190 patients in the United States treated with isotretinoin who committed suicide [40] .

If there were no association between isotretinoin and suicide, 220 suicides would have been expected in users of isotretinoin in the US between 1982 and 2002, while there were actually only 165 suicides reported to the FDA in that time frame [40] . However, not all such suicides would have been reported to the FDA so the interpretation of these numbers is uncertain.

Reviews, including a systematic review, have concluded that data on suicidal behavior and depression during treatment with isotretinoin are inadequate to establish a causal relationship [41-44] . Some authors have proposed that psychological distress over severe acne, rather than isotretinoin, could be a contributing factor to suicide or depression in patients treated with the drug. In a study of 3775 patients (ages 18 to 19 years), suicidal ideation was significantly more common among patients with severe acne, compared with patients with little or no acne [45] . In addition, a retrospective cohort study (n=5756) that found an increased rate of suicide attempts in patients treated with isotretinoin compared with the general population also identified a nonsignificant trend towards elevated rates of suicide attempts prior to treatment with isotretinoin [46] .

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In sum, the relationship between isotretinoin and depression and suicide is uncertain. Patients should be advised of a possible link and should be followed closely for the development of depression or suicidal ideation [40] . (See "Suicidal ideation and behavior in adults" and "Evaluation and management of suicidal behavior in children and adolescents".)

Monitoring and discontinuation — Fasting serum triglycerides and cholesterol, liver function tests, and a complete blood count (CBC) should be obtained prior to initiating therapy [2,26] . Product information for isotretinoin recommends checking fasting lipids weekly or biweekly until the lipid response has been established; however, in otherwise healthy, asymptomatic, young individuals without a personal or family history of diabetes or dyslipidemia, many practitioners perform laboratory testing on a less frequent basis. In patients receiving isotretinoin for acne, a CBC, fasting lipid profile, and liver function tests should be performed at baseline and repeated after four and eight weeks of therapy. If these test results are normal and the dose of isotretinoin remains stable, monitoring can be discontinued.

Women of childbearing potential must have a monthly serum or urine pregnancy test throughout the duration of therapy. A pregnancy test also should be performed one month after the last dose of isotretinoin.

Most of the adverse effects associated with isotretinoin can be managed without discontinuing the drug (eg, emollients for dry skin, nonsteroidal antiinflammatory drugs for myalgias or arthralgias, dietary manipulation for lipid abnormalities).

Creatinine kinase (CK) levels are elevated in approximately 15 to 50 percent of patients with isotretinoin-induced myalgias; however, checking CK levels is not indicated in the absence of severe muscular pain [2] . Mild, transient elevations in hepatic transaminases occur early in the course of therapy in approximately 15 to 20 percent of patients; levels typically normalize within a few weeks [2] .

Indications for stopping therapy include severe hypertriglyceridemia (eg, above 800 mg/dL or 9 mmol/L) because of the risk of acute pancreatitis [47] , and other marked abnormalities on laboratory testing. Discontinuation of isotretinoin is recommended if hepatic transaminase levels reach more than three times greater than normal values [2,26] .

Although hypertriglyceridemia usually resolves with cessation of isotretinoin, patients may need ongoing monitoring since one report suggests that they may be at increased risk for future hyperlipidemia and the metabolic syndrome [48] . In a cross-sectional study, 102 patients in whom the serum triglyceride concentration increased at least 89 mg/dL (1.0 mmol/L) during isotretinoin therapy (hyperresponders) were compared with 100 patients in whom the serum triglyceride concentration changed ≤9 mg/dL (0.1 mmol/L, nonresponders). Four years after completion of isotretinoin therapy, hyperresponders were significantly more likely to have hypertriglyceridemia (odds ratio [OR] 4.8, 95% CI 1.6-13.8), hypercholesterolemia (OR 9.1, 95% CI 1.9-43), truncal obesity (OR 11.0, 95% CI 2.0-59), and hyperinsulinemia (OR 3.0, 95% CI 1.6-5.7).

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

  • Basics topics (see "Patient information: Acne (The Basics)")
  • Beyond the Basics topics (see "Patient information: Acne")

SUMMARY AND RECOMMENDATIONS

  • Isotretinoin is an effective treatment for acne vulgaris that diminishes sebum production, inhibits the growth of Propionibacterium acnes (P. acnes), and inhibits comedogenesis. However, multiple adverse effects limit its widespread use. (See 'Introduction' above.)
  • Isotretinoin is teratogenic. Women of childbearing potential must use two forms of contraception during treatment and for one month thereafter. For patients with severe, recalcitrant, nodular acne who have not responded to other topical and oral therapies, we recommend use of oral isotretinoin (Grade 1A). For patients with less severe but treatment-resistant acne that is scarring or psychologically disabling, we also suggest use of oral isotretinoin (Grade 2A). Isotretinoin should NOT be administered in pregnancy. (See 'Clinical use' above.)
  • In order to diminish treatment-induced flares, isotretinoin is typically started at a low dose (0.5 mg/kd/day) during the first month of therapy, and then increased to 1 mg/kg/day. A total treatment dose of 120 to 150 mg/kg of isotretinoin given over four to six months may decrease the risk of relapse. (See 'Clinical use' above.)
  • Patients with severe inflammatory acne (eg, acne conglobata, acne fulminans) may require concomitant treatment with systemic glucocorticoids starting before or at the initiation of oral isotretinoin therapy. (See 'Clinical use' above.)
  • Other systemic acne medications are typically discontinued during isotretinoin therapy. In particular, the use of isotretinoin with tetracyline-class antibiotics should be avoided due to the risk of idiopathic intracranial hypertension (pseudotumor cerebri). (See 'Clinical use' above.)
  • Most patients improve after isotretinoin therapy, although the majority of patients will continue to require the use of other acne therapies. Subsequent courses of isotretinoin should not be initiated until at least five months after completion of the previous treatment period. A second course of isotretinoin is needed in approximately 20 percent of patients. (See 'Response to therapy' above.)
  • In the United States, all prescribing clinicians and patients are required to participate in the iPLEDGE program, an online registry initiated by the FDA to minimize the risk of fetal exposure to isotretinoin. (See 'Teratogenicity and the iPLEDGE program' above.)
  • Isotretinoin has multiple side effects, including teratogenicity, mucocutaneous disorders, myalgias, visual changes, idiopathic intracranial hypertension, hepatotoxicity, and hyperlipidemia. Patients should be screened for these and other complaints via questioning and laboratory studies at regular follow-up visits during treatment. In women of childbearing potential, a monthly serum or urine HCG is required during the duration of therapy. HCG should be repeated one month following therapy. (See 'Isotretinoin safety' above.)
  • An association of isotretinoin with depression and suicide has been proposed. Although studies have concluded that a causal relationship cannot be definitively established, patients should be advised of these risks, and should be asked to report any symptoms of depression. (See 'Psychiatric effects' above.)
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REFERENCES

  1. 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.
  2. Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg 2008; 27:197.
  3. 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.
  4. Jones H, Blanc D, Cunliffe WJ. 13-cis retinoic acid and acne. Lancet 1980; 2:1048.
  5. 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.
  6. 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; 6:735.
  7. Lehucher-Ceyrac D, Weber-Buisset MJ. Isotretinoin and acne in practice: a prospective analysis of 188 cases over 9 years. Dermatology 1993; 186:123.
  8. 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.
  9. Jones DH, King K, Miller AJ, Cunliffe WJ. A dose-response study of I3-cis-retinoic acid in acne vulgaris. Br J Dermatol 1983; 108:333.
  10. 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.
  11. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007; 56:651.
  12. Cunliffe WJ, van de Kerkhof PC, Caputo R, et al. Roaccutane treatment guidelines: results of an international survey. Dermatology 1997; 194:351.
  13. Layton AM, Cunliffe WJ. Guidelines for optimal use of isotretinoin in acne. J Am Acad Dermatol 1992; 27:S2.
  14. Cooper AJ, Australian Roaccutane Advisory Board. Treatment of acne with isotretinoin: recommendations based on Australian experience. Australas J Dermatol 2003; 44:97.
  15. Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: a review of 25 cases. Br J Dermatol 1999; 141:307.
  16. Karvonen SL. Acne fulminans: report of clinical findings and treatment of twenty-four patients. J Am Acad Dermatol 1993; 28:572.
  17. Böni R, Nehrhoff B. Treatment of gram-negative folliculitis in patients with acne. Am J Clin Dermatol 2003; 4:273.
  18. Neubert U, Plewig G, Ruhfus A. Treatment of gram-negative folliculitis with isotretinoin. Arch Dermatol Res 1986; 278:307.
  19. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003; 49:S1.
  20. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol 2006; 54:644.
  21. López-Vílchez MA, Vicente Villa MA, García-Fructuoso MT, et al. [Acne fulminans after the treatment with isotretinoin] . An Esp Pediatr 1999; 51:200.
  22. Tan BB, Lear JT, Smith AG. Acne fulminans and erythema nodosum during isotretinoin therapy responding to dapsone. Clin Exp Dermatol 1997; 22:26.
  23. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris--10 years later: a safe and successful treatment. Br J Dermatol 1993; 129:292.
  24. Azoulay L, Oraichi D, Bérard A. Isotretinoin therapy and the incidence of acne relapse: a nested case-control study. Br J Dermatol 2007; 157:1240.
  25. White GM, Chen W, Yao J, Wolde-Tsadik G. Recurrence rates after the first course of isotretinoin. Arch Dermatol 1998; 134:376.
  26. Patton, TJ, Zirwas, MJ, Wolverton, SE. Systemic retinoids. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton, SE (Ed), Elsevier 2007, p.275.
  27. Lee JW, Yoo KH, Park KY, et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol 2011; 164:1369.
  28. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med 1985; 313:837.
  29. Centers for Disease Control and Prevention (CDC). Accutane-exposed pregnancies--California, 1999. MMWR Morb Mortal Wkly Rep 2000; 49:28.
  30. Sladden MJ, Harman KE. What is the chance of a normal pregnancy in a woman whose fetus has been exposed to isotretinoin? Arch Dermatol 2007; 143:1187.
  31. Vastag, B. More stringent rules on accutane. JAMA 2002; 287:832.
  32. www.ipledgeprogram.com (Accessed April 23, 2009).
  33. Leyden JJ, James WD. Staphylococcus aureus infection as a complication of isotretinoin therapy. Arch Dermatol 1987; 123:606.
  34. Ellis CN, Krach KJ. Uses and complications of isotretinoin therapy. J Am Acad Dermatol 2001; 45:S150.
  35. Crockett SD, Gulati A, Sandler RS, Kappelman MD. A causal association between isotretinoin and inflammatory bowel disease has yet to be established. Am J Gastroenterol 2009; 104:2387.
  36. Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol 2009; 104:2774.
  37. Crockett SD, Porter CQ, Martin CF, et al. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol 2010; 105:1986.
  38. Zane LT, Leyden WA, Marqueling AL, Manos MM. A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris. Arch Dermatol 2006; 142:1016.
  39. Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001; 45:515.
  40. www.fda.gov/cder/drug/InfoSheets/HCP/IsotretinoinHCP.htm (Accessed 8/12/05).
  41. Marqueling AL, Zane LT. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg 2005; 24:92.
  42. Magin P, Pond D, Smith W. Isotretinoin, depression and suicide: a review of the evidence. Br J Gen Pract 2005; 55:134.
  43. Hull PR, D'Arcy C. Acne, depression, and suicide. Dermatol Clin 2005; 23:665.
  44. Bigby M. Does isotretinoin increase the risk of depression? Arch Dermatol 2008; 144:1197.
  45. Halvorsen JA, Stern RS, Dalgard F, et al. Suicidal ideation, mental health problems, and social impairment are increased in adolescents with acne: a population-based study. J Invest Dermatol 2011; 131:363.
  46. Sundström A, Alfredsson L, Sjölin-Forsberg G, et al. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study. BMJ 2010; 341:c5812.
  47. McCarter TL, Chen YK. Marked hyperlipidemia and pancreatitis associated with isotretinoin therapy. Am J Gastroenterol 1992; 87:1855.
  48. Rodondi N, Darioli R, Ramelet AA, et al. High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study. Ann Intern Med 2002; 136:582.

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