(6) Fetal Exposure to Isotretinoin in Saudi Arabia: Real-World Data Analysis from 2015-2020

Publication Number: 337

Background: Isotretinoin is a potent acne treatment but with severe teratogenic effects. Although the Saudi Food and Drug Authority approved and updated risk minimization measures to prevent fetal exposure over the years, the extent of fetal exposure to isotretinoin in Saudi Arabia is unknown.

Objectives: To quantify fetal exposure to isotretinoin in Saudi Arabia using real-world data.

Methods: We included 5888 women of childbearing age (WCBAs) who initiated isotretinoin between 2015 and 2020 using electronic health records from three healthcare institutions. Isotretinoin users were followed from 1st day of dispensing to 30 days post discontinuation, during which WCBAs must avoid pregnancy (risk period). WCBAs’ characteristics were collected within 6 months before initiation of isotretinoin therapy including indications, comorbidities and medication use. We defined pregnancy as any positive pregnancy test (urine or serum) or any diagnosis or procedure related to pregnancy. The fetal exposure was quantified as the total number of pregnancies during the risk period divided by total number of WCBA’s included in the study. Moreover, to quantify adherence to risk minimization measures, we estimated contraceptive use (oral or intrauterine contraceptives) and pregnancy test (serum or urine) in the study cohort from the period prior to isotretinoin initiation until one month after therapy ended.

Results: Adolescents comprised 28% of the sample and 80% were younger than 30 years old. Asthma (4%), hypothyroidism (3%) and polycystic ovary syndrome (6%) were the most prevalent medical diagnosis identified. Previous acne treatments included antibiotics and tretinoins; however, the majority (60%) were not treated with any acne treatment before isotretinoin initiation. Only 5% of WCBAs received at least one prescription of contraceptives. Most WCBA isotretinoin users (90%) were not tested for pregnancy before initiating isotretinoin. We identified 22 confirmed pregnancies (4.5 per 1000 WCBAs isotretinoin users). After adding suspected cases, the pregnancy risk was 9.5 per 1000.

Conclusions: Although risk minimization measures exist in Saudi Arabia, considerable fetal exposure to isotretinoin occurred. Continuous evaluation of risk minimization measures is imperative to identify potential improvements to the system to prevent fetal exposure. Our study sets a baseline to examine the effectiveness of future updates of precautionary measures concerning isotretinoin use.