Prevention of Preterm Labor with 17α-Hydroxyprogesterone (17OHP) Caproate: A Comparison of Adverse Drug Reaction Rates between Compounded and Commercial Formulations

Abstract

Objective A commercial formulation of injectable 17α-hydroxyprogesterone (17OHP) for prevention of preterm birth was introduced in 2011; however, use of compounded formulations remains widespread. This study compared the frequency of adverse drug reactions (ADRs) associated with compounded versus commercial 17OHP formulations, aiding in provider assessment of 17OHP tolerability.

Study Design A retrospective cohort evaluation of data obtained from the electronic medical record (EMR) of patients prescribed weekly 17OHP injections at an obstetric clinic between 2009 and 2015 was performed. A descriptive analysis characterized the frequency and proportion of ADRs associated with 17OHP administration. Patient differences between 17OHP formulations were identified with t-test, chi-square, or Fischer's exact tests.

Results Of 175 patients included, 56% received commercial formulation and 44% received compounded formulation. ADRs occurred in 16 patients, all of whom received the compounded formulation (p < 0.001). The most common ADRs were injection site reaction (n = 7) and acute coughing following 17OHP administration (n = 6). Of patients with an ADR, 63% discontinued all medication therapy for prevention of preterm birth or changed to an alternative therapy.

Conclusion Comparison of ADR rates between compounded and commercial formulation differed significantly. In addition to food and drug administration (FDA) compliance, providers may consider preferential use of the commercial formulation, since 21% of women receiving compounded product experienced an ADR.

Keywords

preterm labor - preterm birth - compounding - 17OHP - Makena - hydroxyprogesterone

• References

• 1 Martin JA, Hamilton BE, Osterman MJ. Births in the United States, 2014. NCHS Data Brief 2015; 216 (216) 1-8
• 2 Schoen CN, Tabbah S, Iams JD, Caughey AB, Berghella V. Why the United States preterm birth rate is declining. Am J Obstet Gynecol 2015; 213 (02) 175-180
• 3 Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol 2012; 206 (05) 376-386
• 4 How HY, Sibai BM. Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety. Ther Clin Risk Manag 2009; 5 (01) 55-64
• 5 Patel Y, Rumore MM. Hydroxyprogesterone caproate injection (makena) one year later: to compound or not to compound that is the question. PT 2012; 37 (07) 405-411
• 6 Meis PJ, Klebanoff M, Thom E. , et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348 (24) 2379-2385
• 7 Society for Maternal Fetal Medicine Publications Committee. ACOG Committee Opinion number 419 October 2008 (replaces no. 291, November 2003). Use of progesterone to reduce preterm birth. Obstet Gynecol 2008; 112 (04) 963-965
• 8 Food and Drug Adminstration. FDA Statement on Makena. Rockville, MD: National Press Office; 2011
• 9 Food and Drug Administration. Federal Food, Drug, and Cosmetic Act: Section 503A, Pharmacy Compounding. Available at: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm376733.htm Updated December 2, 2013 . Accessed February 22, 2017
• 10 Makena® [packag insert]. Waltham, MA: AMAG Pharmaceuticals Inc; 2016. Available at: makenahcp.com/pdf/makena_pi.pdf
• 11 Chollet JL, Jozwiakowski MJ. Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection. Drug Dev Ind Pharm 2012; 38 (05) 540-549
• 12 Chang J, Zhao Y, Zhao W, Venkataramanan R, Caritis SN. ; Obstetrical-Fetal Pharmacology Research Units Network. Quality assessment of compounded 17-hydroxyprogesterone caproate. Am J Obstet Gynecol 2014; 210 (01) 47.e1-47.e7
• 13 Food and Drug Administration. Updated FDA Statement on Compounded Versions of hydroxyprogesterone caproate (the active ingredient in Makena). Rockville, MD: National Press Office; 2012
• 14 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (02) 377-381
• 15 Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R D 2013; 13 (01) 1-8
• 16 Multistate Outbreak of Fungal Meningitis and Other Infections. Centers for Disease Control and Prevention Website. Available at: https://www.cdc.gov/hai/outbreaks/meningitis.html . Updated February 18, 2016 . Accessed February 22, 2017
• 17 Pharmaceuticals AMAG. Inc. Makena Care Connection & Support Programs Website. Available at: http://www.makenahcp.com/makena-care-connection . Accessed February 22, 2017
• 18 Morra D, Nicholson S, Levinson W, Gans DN, Hammons T, Casalino LP. US physician practices versus Canadians: spending nearly four times as much money interacting with payers. Health Aff (Millwood) 2011; 30 (08) 1443-1450
• 19 Maher MA, Abdelaziz A, Ellaithy M, Bazeed MF. Prevention of preterm birth: a randomized trial of vaginal compared with intramuscular progesterone. Acta Obstet Gynecol Scand 2013; 92 (02) 215-222
• 20 Herman-Kideckel SM, Cadesky SM, Sussman SMD, Maclachlan SM, Sussman SM. Association of dermographic urticaria with the use of progesterone in cottonseed oil. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology. 2011; 106 (05) 439-440
• 21 Sánchez-Guerrero IM, Huertas AJ, López MP, Carreño A, Ramírez M, Pajarón M. Angioedema-like allergic contact dermatitis to castor oil. Contact Dermat 2010; 62 (05) 318-319
• 22 Shaw DW. Allergic contact dermatitis from 12-hydroxystearic acid and hydrogenated castor oil. Dermatitis 2009; 20 (06) E16-E20
• 23 Taghipour K, Tatnall F, Orton D. Allergic axillary dermatitis due to hydrogenated castor oil in a deodorant. Contact Dermat 2008; 58 (03) 168-169
• 24 Bernstein IL, Bernstein DI, Lummus ZL, Bernstein JA. A case of progesterone-induced anaphylaxis, cyclic urticaria/angioedema, and autoimmune dermatitis. J Womens Health (Larchmt) 2011; 20 (04) 643-648