What Is the Best Approach to Reducing Birth Defects Associated with Isotretinoin?

Abroms, Lorien C.; Maibach, Edward; Lyon-Daniel, Katherine; Feldman, Steven R.

doi:10.1371/journal.pmed.0030483

Cited by 54 publications

(36 citation statements)

References 24 publications

(37 reference statements)

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“…In the UK, only consultant dermatologists are authorized to prescribe isotretinoin because of their good knowledge of the medication. In the US, the iPLEDGE program requires prescribers to be registered in a computerized database in order to prescribe isotretinoin (131). Currently, there is no system in place in…”

Section: Discussionmentioning

confidence: 99%

Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris

Azoulay¹,

Blais²,

Koren³

et al. 2008

J. Clin. Psychiatry

129

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Section: Discussionmentioning

confidence: 99%

Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris

Azoulay¹,

Blais²,

Koren³

et al. 2008

J. Clin. Psychiatry

129

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“…7 Repeat testing may lead to earlier detection of pregnancy and subsequent earlier cessation of treatment or pregnancy termination. 8 Variability in the pharmacokinetics of isotretinoin may also lead to exposure during pregnancy. Continued use of contraception for 1 month after the end of isotretinoin therapy has been advocated to provide an adequate safety margin to prevent fetal exposure, based on more than 5 elimination half-lives of the drug.…”

Section: Pregnancy and Isotretinoin Therapymentioning

confidence: 99%

“…Furthermore, all patients with prescriptions for isotretinoin and their pharmacists are registered in a single database. 8 Seven years after its introduction, this program does not appear to have solved the issue of fetal exposure to isotretinoin. Shin and colleagues recently reported 29 fetal exposures out of a total of 9912 courses of treatment with the drug.…”

Section: Preventing Fetal Exposure To Isotretinoinmentioning

confidence: 99%

Pregnancy and isotretinoin therapy

Choi

Koren

Nulman

2013

CMAJ

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A 29-year-old woman was given isotretinoin for severe, recalcitrant acne. During the first 3 months of treatment, she was taking an oral contraceptive agent that she had started at the same time as the isotretinoin. After deciding she wanted to become pregnant, the patient stopped taking the contraceptive agent but continued to take iso tretinoin for another 2 months.When the patient became pregnant, she sought advice from the Motherisk program regarding the fetal risks of exposure to iso tretinoin. With counselling, it became apparent that the patient had not understood the connection between isotretinoin and birth defects, and hence the need for continued effective contraception while taking the drug. After repeated counselling, the patient decided to terminate her pregnancy.

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“…The teratogenic consequences of retinoid supplementation during pregnancy depend on the stage of development, the nature of the retinoid metabolite, and the genetic and environmental factors (120). Caution must be exercised in prescribing retinoids to ensure that pregnancy is avoided during treatment (126). Additionally, the administration of retinoids to young animals and children results in delayed growth as a result of premature epiphyseal plate closure (127,128).…”

Section: Retinol Toxicity and The Side Effects Associated With Retinomentioning

confidence: 99%

Delivery of Retinoid-Based Therapies To Target Tissues

et al. 2007

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Through its various metabolites, vitamin A controls essential physiological functions. Both naturally occurring metabolites and novel retinoid analogues have shown effectiveness in many clinical settings that include skin diseases and cancer, and in animal models of human conditions affecting vision.In this review, we analyze several potential retinoid-based therapies from the point of view of drug metabolism and transport to target tissues. We focus on the endogenous factors that affect the absorption, transport, and metabolism of retinoids by taking into account data obtained from the analysis of animal models that lack the enzymes or proteins involved in the storage and absorption of retinoids. We also discuss findings of toxicity associated with retinoids in an effort to improve the outcome of retinoid-based therapies. In this context, we review evidence that esterification of retinol and retinol-based drugs within target tissues provides one of the most efficient means to improve the absorption and to reduce the toxicity associated with pharmacological doses of retinoids. Future retinoid-based therapeutic strategies could involve targeted delivery mechanisms leading to lower toxicity and improved effectiveness of retinoids.Vitamin A, retinol, plays essential roles in many biological processes including vision, immunity, growth, development, and cellular differentiation. The various functions of vitamin A are carried out by several known physiologically active metabolites including 11-cis-retinal, the visual chromophore (1), and all-trans-retinoic acid (RA 1 ), which controls gene expression through the RA receptor (RAR) (2,3). Other retinol metabolites that have shown biological activities in vitro are the 9-cis-isomer of RA, which activates both retinoid X receptors (RXRs) and RARs (4), and the retro-retinoids, anhydroretinol (AR), and 14-hydroxy-4,14-retro-retinol (14-HRR), which are involved in the regulation of lymphocyte proliferation (5-7). Alltrans-13,14-dihydroxy-retinol was shown to have activity comparable to that of 14-HRR in supporting the proliferation of promyelocytic HL-60 cells and in the activation of T cells (8). The conversion of all-trans-retinol to all-trans-13,14-dihydroretinol by the recently described † This research was supported in part by U.S. Public Health Service Grants EY01730, EY015399, and EY08061 from the National Eye Institute, National Institutes of Health, Bethesda, MD (to K.P.) and Grant DK068437 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (to W.S.B.). * To whom correspondence should be addressed. Phone: 216-368-1284. Fax: 216-368-1300. E-mail: ram50@case.edu. ‡ Case Western Reserve University. § Institute of Human Nutrition, Columbia University. || Department of Medicine, Columbia University.1 Abbreviations: A2E, pyridinium bis-retinoid; ADH, medium-chain alcohol dehydrogenases; ADRP, autosomal dominant retinitis pigmentosa; apoE, apolipoprotein E; AR, anhydroretinol; ARAT, acyl-CoA-retin...

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What Is the Best Approach to Reducing Birth Defects Associated with Isotretinoin?

Cited by 54 publications

References 24 publications

Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris

Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris

Pregnancy and isotretinoin therapy

Delivery of Retinoid-Based Therapies To Target Tissues

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