Study of Safety of Medicinal Products in Pregnant Women in Crimea

According to international epidemiological studies, about 80% of women have to use medicinal products during pregnancy, mainly during the first weeks of organogenesis in the case of an unplanned pregnancy, and for the treatment of chronic diseases or acute conditions developing during pregnancy. Specificity of pharmacokinetics and pharmacodynamics in pregnant women contributes to the development of adverse drug reactions (ADRs), many of which are serious and pose a threat to the life of the patient. The aim of the study was to retrospectively assess the frequency and development of ADRs in pregnant women living in the Republic of Crimea, based on the data in the regional safety database ARCADe (Adverse Reactions in Crimea, Autonomic Database). Materials and methods: the authors analysed spontaneous ADR reports registered in the ARCADe database from 1 January 2009 until 31 December 2018 for the category of patients described as “Pregnant women/childbirth”. Results: during the specified period, 268 ADR cases in pregnant women were added to the database. The most common reasons of ADRs in this category of patients were antibacterials for systemic use (130 cases, 48.5%), agents that have an effect on haematopoiesis and blood (54 cases, 20.15%), and agents that have an effect on the functions of the gastrointestinal tract (29 cases, 10.82%). The study of ADR clinical manifestations revealed a high incidence of local allergic reactions (140 cases, 52.2%), inhibition of haematopoiesis (60 cases, 22.4%), and dyspepsia (36 cases, 13.4%). The analysis of the severity of the registered ADRs demonstrated that in 15 cases (5.6%) the use of the prescribed medicinal product posed a threat to the patient’s life and required urgent pharmacotherapy and discontinuation of the suspected medicine, in 8 cases (3%) it resulted in hospitalisation or prolongation of hospital treatment, and in 3 cases (1.12%) it resulted in the temporary inability to work. Conclusions: the results of the study indicate the need for further retrospective and prospective studies aimed at analysing the safety of medicine use in pregnant women and assessing the risks of toxic effects on the foetus.

1. Dathe K, Schaefer C. The use of medication in pregnancy. Dtsch Arztebl Int. 2019;116(46):783–90. https://doi.org/10.3238/arztebl.2019.0783

2. Ayad M, Costantine MM. Epidemiology of medications use in pregnancy. Semin Perinatol. 2015;39(7):508–11. https://doi.org/10.1053/j.semperi.2015.08.002

3. Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Semin Perinatol. 2015;39(7):512–9. https://doi.org/10.1053/j.semperi.2015.08.003

4. Chambers CD, Polifka JE, Friedman JM. Drug safety in pregnant women and their babies: ignorance not bliss. Clin Pharmacol Ther. 2008;83(1):181–3. https://doi.org/10.1038/sj.clpt.6100448

5. Macklin R. Enrolling pregnant women in biomedical research. Lancet. 2010;375(9715):632–3. https://doi.org/10.1016/s0140-6736(10)60257-7

6. Bérard A, Abbas-Chorfa F, Kassai B, Vial T, Nguyen KA, Sheehy O, Schott AM. The french pregnancy cohort: medication use during pregnancy in the french population. PLoS One. 2019;14(7):e0219095. https://doi.org/10.1371/journal.pone.0219095

7. Zhuravleva EO, Velts NYu, Zatolochina KE, Glagolev SV, Polivanov VA, Darmostukova MA, et al. Analysis of spontaneous reports of adverse reactions, developed in the use of drugs during pregnancy. Bezopasnost’ i risk farmakoterapii = Safety and Risk of Pharmacotherapy. 2017;5(2):61–9 (In Russ.)

8. Jain S, Anand S, Aherwar R. High risk scoring for prediction of pregnancy outcome: a prospective study. Int J Reprod Contracept Obstet Gynecol. 2014;3(3):516–22. https://doi.org/10.5455/2320-1770.ijrcog20140910

9. da Silva KDL, Fernandes FEM, de Lima Pessoa T, Lima SIVC, Oliveira AG, Martins RR. Prevalence and profile of adverse drug reactions in high-risk pregnancy: a cohort study. BMC Pregnancy Childbirth. 2019;19(1):199. https://doi.org/10.1186/s12884-019-2321-8

10. Smedberg J, Bråthen M, Waka MS, Jacobsen AF, Gjerdalen G, Nordeng H. Medication use and drug-related problems among women at maternity wards — a cross-sectional study from two Norwegian hospitals. Eur J Clin Pharmacol. 2016;72(7):849–57. https://doi.org/10.1007/s00228-016-2042-0

11. de Oliveira-Filho AD, Vieira AES, da Silva RC, Neves SJF, Gama TAB, Lima RV, et al. Adverse drug reactions in high-risk pregnant women: a prospective study. Saudi Pharm J. 2017;25(7):1073–7. https://doi.org/10.1016/j.jsps.2017.01.005

12. Daw JR, Hanley GE, Greyson DL, Morgan SG. Prescription drug use during pregnancy in developed countries: a systematic review. Pharmacoepidemiol Drug Saf. 2011;20(9):895–902. https://doi.org/10.1002/pds.2184

13. Tarasova LV, Markova TN, Zhuchkova SM, Busalaeva EI, Anisimova MYu. Reports on adverse reactions after drugs administration during pregnancy in the Chuvash Republic. Meditsinskiy al’manakh = Medical Almanac. 2018;(2):95–8 (In Russ.)

14. Bartlett J, Redfield R, Fam P, Mazus AI. Clinical aspects of HIV infection. Moscow: GRANAT; 2013 (In Russ.)

15. Radzinsky VE, Totchiev GF. Polypragmasy in the treatment of pregnant women. Farmateka = Pharmateka. 2011;(13):10–1 (In Russ.)

16. Matveev AV, Krasheninnikov AE, Egorova EA. Investigation of the safety of radiopaque compounds based on notification cards on adverse reactions registered in the Republic of Crimea. Vestnik rentgenologii i radiologii = Journal of radiology and nuclear medicine. 2020;101(6):344–53 (In Russ.)] https://doi.org/10.20862/0042-4676-2020-101-6-344-353

17. Velts NYu, Zhuravleva EO, Darmostukova MA, Zatolochina KE, Alyautdina OS. Drug-induced liver injuries in pregnancy in the context of polypragmasy. Bezopasnost’ i risk farmakoterapii = Safety and Risk of Pharmacotherapy. 2017;5(3):104–11 (In Russ.)

18.