Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy

Henry, David; Dormuth, Colin R.; Winquist, Brandace; Carney, Greg; Bugden, Shawn; Teare, Gary; Lévesque, Linda E.; Bérard, Anick; Paterson, J. Michael; Platt, Robert W.

doi:10.1503/cmaj.151243

Cited by 54 publications

(62 citation statements)

References 18 publications

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“…We showed that isotretinoin‐exposed pregnancy rates were lower than an internally matched population, indicating that efforts to reduce exposed pregnancies have been effective, though not infallible. Prior estimates of isotretinoin‐exposed pregnancy rates between 1989 and 2011 ranged from 9 to 37 per 1000 PYs and from 4 to 6 per 1000 users . Our estimate of 3 per 1000 PYs in 2011 to 2015 might be lower because of REMS improvements over time; our study population excluded women covered by Medicaid where pregnancy rates may be higher, or due to an underestimation of terminations.…”

Section: Discussionmentioning

confidence: 80%

“…Since its introduction, a variety of risk evaluation and mitigation strategies (REMS) have been implemented to prevent exposed pregnancies . Despite low overall pregnancy rates, exposed pregnancies still occur and continued surveillance is needed . On the other hand, a topical version of isotretinoin, tretinoin, is presumed safe for fetal development because of low systemic bioavailability .…”

Section: Introductionmentioning

confidence: 99%

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Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance

MacDonald

Cohen

Panchaud

et al. 2019

Pharmacoepidemiology and Drug

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Purpose The purpose of the study is to develop an algorithm to identify pregnancies in administrative databases and apply it to assess pregnancy rates and outcomes in women prescribed isotretinoin or tretinoin. Methods Using the 2011 to 2015 Truven Health MarketScan Database, we identified pregnancies, including losses and terminations. In a cohort design, nonpregnant women filling a prescription for isotretinoin or tretinoin were matched to five women without either prescription. Women were followed for 365 days or until conception, medication discontinuation, or enrollment discontinuation (“prescription episode”). Rates of pregnancy, risks of pregnancy losses, and prevalence of infant malformations at birth were assessed by exposure. Results We identified 2 179 192 livebirths, 8434 stillbirths, 2521 mixed births, 415 110 spontaneous abortions, 124 556 elective terminations, and 8974 unspecified abortions. There were 86 834 isotretinoin and 973 587 tretinoin episodes, matched to 5 302 105 unexposed women. Pregnancy rates were 3 (isotretinoin), 19 (tretinoin), and 34 (unexposed) per 1000 person‐years. Risk of spontaneous pregnancy losses were similar; however, terminations were more common in the isotretinoin‐exposed (28% [95% CI: 21%‐36%]) than the tretinoin‐exposed (10% [95% CI: 9%‐11%]) or unexposed pregnancies (6%). Malformations occurred in 4.5% (95% CI: 3.5%‐5.6%) of the tretinoin‐exposed pregnancies and 4.2% of the unexposed pregnancies (adjusted odds ratio: 1.16 [95% CI: 0.85‐1.58]); isotretinoin‐exposed births were too few to assess malformations. Conclusions Administrative databases can complement risk evaluation and mitigation strategies (REMS) for known teratogens and contribute to safety surveillance for other medications. Here, isotretinoin‐exposed pregnancy rates were low, but existent, and many pregnancies were terminated. Tretinoin exposure was not associated with a meaningfully elevated risk of losses or malformations as compared with unexposed pregnancies.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance

MacDonald

Cohen

Panchaud

et al. 2019

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

show abstract

“…Claims data do not allow us to assess whether a woman was sexually active and thus in need of contraception while on mycophenolate. In addition, studies have reported pregnancies among women taking mycophenolate and low contraception provision among females of child‐bearing age taking teratogenic medications, including isotretinoin and contraception . The assessment of contraception use in claims data has important specific limitations.…”

Section: Discussionmentioning

confidence: 99%

A new analytic tool developed to assess safe use recommendations

Cocoros

Wagner

Haynes

et al. 2019

Pharmacoepidemiology and Drug

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Purpose Develop a flexible analytic tool for the Food and Drug Administration's (FDA's) Sentinel System to assess adherence to safe use recommendations with two capabilities: characterize adherence to patient monitoring recommendations for a drug, and characterize concomitant medication use before, during, and/or after drug therapy. Methods We applied the tool in the Sentinel Distributed Database to assess adherence to the labeled recommendation that patients treated with dronedarone undergo electrocardiogram (ECG) testing no less often than every 3 months. Measures of length of treatment, time to first ECG, number of ECGs, and time between ECGs were assessed. We also assessed concomitant use of contraception among female users of mycophenolate per label recommendations (concomitancy 4 weeks before through 6 weeks after discontinuation of mycophenolate). Unadjusted results were stratified by age, month‐year, and sex. Results We identified 21 457 new episodes of dronedarone use of greater than or equal to 90 days (July 2009 to September 2015); 86% had greater than or equal to one ECG, and 22% met the recommendation of an ECG no less often than every 3 months. We identified 21 942 new episodes of mycophenolate use among females 12 to 55 years (January 2016 to September 2015); 16% had greater than or equal to 1 day of concomitant contraception dispensed, 12% had concomitant contraception use for greater than or equal to 50% of the 4 weeks before initiation through 6 weeks after mycophenolate; younger females had more concomitancy. These results may be underestimates as the analyses are limited to claims data. Conclusions We developed a tool for use in databases formatted to the Sentinel Common Data Model that can assess adherence to safe use recommendations involving patient monitoring and concomitant drug use over time.

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“…The first teratogenic effects of high doses of vitamin A during pregnancy was reported in rats by Cohlan in 1954, involving exencephaly, eye malformations, cleft palate, shortening of the mandible and maxilla, spina bifida with meningocele, and hydrocephalus (Cohlan, 1954). Indeed, relevant data showed that average age of isotretinoin users is estimated to be 24 years (Henry et al, 2016). Indeed, relevant data showed that average age of isotretinoin users is estimated to be 24 years (Henry et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Isotretinoin: Still the cause of anxiety for teratogenicity

Aykan

Ergün

2019

Dermatologic Therapy

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Isotretinoin is known as a potent teratogenic agent. Pregnancy should be ruled out before isotretinoin is prescribed. In this study, we evaluated the fetal outcomes of pregnant women who had inadvertently been exposed to isotretinoin during or before pregnancy. We collected data of pregnant women who had admitted to the Teratology Information Service due to isotretinoin exposure. Data regarding medications and comorbidities were documented. Outcomes were grouped as: live births, stillbirths, live births with congenital malformations, induced abortions (due to fetal abnormalities), spontaneous abortions, and elective abortions. We found that three women had gone to elective abortions. Three babies were live born without birth defects, of which, maternal exposure periods were between 0 and 3 weeks, 9 and 10 weeks before last menstrual period. One woman, exposed to isotretinoin up to the fourth week of gestation, decided ongoing her pregnancy with no current drugrelated complications. Although many risk management programs worldwide have been used to prevent isotretinoin-related teratogenicity, the results of the present study showed that women became pregnant during isotretinoin intake and opted for pregnancy termination. Attention should be paid to the risk management programs mandating effective contraceptions, in order to lessen the drug-related terminations.

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Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy

Cited by 54 publications

References 18 publications

Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance

Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance

A new analytic tool developed to assess safe use recommendations

Isotretinoin: Still the cause of anxiety for teratogenicity

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