Yeni Kardiyovasküler İlaçların Gebe Hastalarda Kullanımı: Teratojenik Riskler

Yıl 2018, Cilt: 27 Sayı: 3, 287 - 298, 30.09.2018

Duygun Altıntaş Aykan

https://doi.org/10.17827/aktd.389836

Öz

Yeni oral antikoagülan ilaçlar dabigatran, rivaroksaban, apiksaban, edoksaban; antitrombositer ajanlar prasugrel, tikagrelor; antilipidemik ajanlar alirocumab ve evolocumab kardiyovasküler tedavilere alternatif yeni ajanlar olarak geliştirilmiş olup günümüzde sıklıkla reçetelendirilmektedir. Bu ajanlara maruz kalacak olan gebe hastaların veya gebeliğinin farkında olmadan ilacı kullanan kadınların sayısının yakın gelecekte hızla artması muhtemeldir. Bu çalışmada, farmakokinetik parametrelerin ışığı altında bu ilaçların gebelikte maruziyeti ile ilgili literatürdeki hayvan çalışmaları ve insan gebelik raporları incelenmiş ve bu ilaçların gebelikte kullanımı sonucunda oluşabilecek potansiyel teratojenik etkiler derlenmiştir. 

Anahtar Kelimeler

Teratojenite, İlaca Bağlı Anomaliler, Kardiyovasküler İlaçlar

Use of Novel Cardiovascular Drugs in Pregnant Patients: Teratogenic Risks

Öz

New oral anticoagulant drugs dabigatran, rivaroxaban, apixaban, edoxaban; antithrombotic agents prasugrel, ticagrelor; antilipidemic agents alirocumab and evolocumab have been developed as alternative agents to cardiovascular treatments and are frequently prescribed. It is likely that the number of pregnant patients who will be exposed to these agents or the number of women who are unaware of their pregnancy will increase rapidly in the near future. In this study, under the light of pharmacokinetic parameters, animal studies and human pregnancy reports in the literature about exposure to these new drugs during pregnancy were reviewed and the potential teratogenic effects of these drugs were summarized.

Anahtar Kelimeler

Teratogenesis, abnormalities, drug-ınduced, cardiovascular drugs, pregnancy

Kaynakça

• 28.https://www.uptodate.com/contents/edoxaban-drug-information?source=search_result&search=edoxaban&selectedTitle=1~67
• 10. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, et al, “Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest 2012;141(2 Suppl):7-47.
• 29. Product information. Effient. Eli Lilly, 2009.
• 30. Product information. Effient. Daiichi Sankyo, 2009.
• 2. Zhang H, Zhang P, Dong P, Yang X, Wang Y, Zhang H, et al. Effect of ticagrelor versus prasugrel on platelet reactivity: a meta-analysis. Coron Artery Dis 2017;28(7):597-604.
• 31. Pragrel Pharmacology review, parts 5 and 6. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022307s00
• 32. Tello-Montoliu A, Seecheran NA, Angiolillo DJ. Successful pregnancy and delivery on prasugrel treatment: Considerations for the use of dual antiplatelet therapy during pregnancy in clinical practice. J Thromb Thrombolysis 2013;36(3);348-51.
• 33. Product information. Brilinta. AstraZeneca, 2011.
• 34.https://www.uptodate.com/contents/ticagrelor-drug-information?source=search_result&search=ticagrelor&selectedTitle=1~69
• 35. Product information. Praluent. Sanofi-Aventis U.S., 2015.
• 20. Konigsbrugge O, Langer M, Hayde M, Ay C, Pabinger I. Oral anticoagulation with rivaroxaban during pregnancy: a case report. Thromb Haemost 2014; 112(6):1323-4.
• 36.https://www.uptodate.com/contents/alirocumab-drug-information?source=preview&search=alirocumab&anchor=F28895637#F28895637 37. Product information. Repatha. Amgen, 2016.
• 38.https://www.uptodate.com/contents/evolocumab-drug-information?source=preview&search=evolocumab&anchor=F29871556#F29871556
• 11. Cutts BA, Dasgupta D, Hunt BJ. New directions in the diagnosis and treatment of pulmonary embolism in pregnancy. Am J Obstet Gynecol 2013;208(2):102-8.
• 3. Yang J, Zeng P, Cai WY. Comparison of treatment outcomes of ticagrelor and clopidogrel among patients undergoing percutaneous coronary intervention: A meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2017 Oct;37(5):675-680.
• 4. Hoeltzenbein M, Beck E, Meixner K, Schaefer C, Kreutz R. Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in women at suspected risk for thromboembolic events: a case series from the German Embryotox Pharmacovigilance Centre. Clin Res Cardiol 2016;105(2):117-26.
• 5. Briggs GG, Freeman RK, Towers CV, Forinash AB. Drugs in Pregnancy and Lactation. 11th ed. Alphen aan den Rijn, The Netherlands. 2017.
• 6. Product information. Pradaxa. Boehringer Ingelheim Pharmaceuticals, 2011.
• 7.U.S.FDA.2010. Dabigatran summary review https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Or
• 8. Huisman MV. Further issues with new oral anticoagulants. Curr Pharm Des 2010;16:3487–9.
• 9. Bapat P, Kedar R, Lubetsky A, Matlow JN, Aleksa K, Berger H, et al. Transfer of dabigatran and dabigatran etexilate mesylate across the dually perfused human placenta. Obstet Gynecol 2014;123(6):1256-61.
• 1. McDonagh M, Peterson K, Holzhammer B, Fazio S. A Systematic Review of PCSK9 Inhibitors Alirocumab and Evolocumab. J Manag Care Spec Pharm 2016;22(6):641-53.
• 12. http://www.micromedexsolutions.com/reprotox 13. Product information. Xarelto. Janssen Pharmaceuticals, 2011
• 14. U.S. FDA. Drug Approval Package. Xarelto (rivaroxaban) pharmacology review. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/02
• 15. Huisman MV. Further issues with new oral anticoagulants. Curr Pharm Des 2010;16:3487–9.
• 16. Bapat P, Pinto LS, Lubetsky A, Berger H, Koren G. Rivaroxaban transfer across the dually perfused isolated human placental cotyledon. Am J Obstet Gynecol 2015;213:710.e1–6.
• 17. Xarelto 20mg film-coated tablets. Summary of Product Characteristics last updated on the eMC: May 2016.http://www.medicines.org.uk/emc/medicine/25586/SPC#PRECLINI
• 18. Cutts BA, Dasgupta D, Hunt BJ. New directions in the diagnosis and treatment of pulmonary embolism in pregnancy. Am J Obstet Gynecol. 2013;208(2):102-8.
• 19. Myers B, Neal R, Myers O, Ruparelia M. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning. Obstet Med 2015; 9(1): 40-42.
• 21.https://www.uptodate.com/contents/dabigatran-drug-information?source=search_result&search=dabigatran&selectedTitle=1~132#references
• 22. Product information. Eliquis. Bristol-Myers Squibb, 2012.
• 23. Eliquis (apixaban) 2.5 and 5 mg Tablets. Pharmacology review: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202155Ori
• 24. Wang L, He K, Maxwell B, Grossman SJ, Tremaine LM, Humphreys WG, et al. Tissue distribution and elimination of [14C]apixaban in rats. Drug Metab Dispos 2011;39(2):256-64.
• 25. Bapat P, Pinto LSR, Lubetsky A, Aleska K, Berger H, Koren G, et al. Examining the transplacental passage of apixaban using the dually perfused human placenta. J Thromb Haemost 2016;14(7):1436–41.
• 26. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2Suppl):e691S-e736S.
• 27. Product information. Savaysa. Daiichi Sankyo, 2015.