Effectiveness and Safety of Isoxsuprine Hydrochloride as Tocolytic Agent in Arresting Active/Threatened Preterm Labor and Its Role in Maintenance Tocolysis: A Prospective, Open-Label Study

Abstract

Objective The aim of the study is to obtain insights on the short and long-term safety and effectiveness of isoxsuprine hydrochloride as a tocolytic agent in the management of PTL.

Study Design In this prospective, single-center, noncomparative study, patients (with preterm labor at gestational age of 24–37 weeks) were administered intravenous (IV) infusion of 40-mg isoxsuprine hydrochloride until uterine quiescence, followed by intramuscular (IM) injection of isoxsuprine hydrochloride 10 mg/4-hourly for first 24 hours and maintained with retard 40-mg sustained release capsule (two times a day) till the time of delivery or 37 completed weeks of pregnancy.

Results All patients (n = 50) achieved successful tocolysis in 24 hours and 48 hours postadministration of isoxsuprine hydrochloride (IV/IM/oral). Mean (±SD) gestation age at the time of delivery was 39.8 ± 2.1 weeks, with latency period of 58.5 ± 18.7 days. Pregnancy outcomes were normal in all the patients and no congenital anomaly/fetal infection was reported. Mean (±SD) fetal birth weight was 2.7 ± 0.3 kg; mean (±SD) Apgar score at 1 and 5 minutes were 7.5 ± 0.6 and 9.2 ± 0.4, respectively. Maternal tachycardia and vomiting (8.0% each) were the commonly reported adverse drug reactions, which were resolved with dose adjustment.

Conclusion Isoxsuprine was found to be an effective and well-tolerated tocolytic agent in arresting PTL, in turn resulting in the overall improvement in maternal and perinatal outcomes.

Keywords

isoxsuprine - latency period - preterm labor - pregnancy prolongation - tocolytics

Note

This data was presented (oral presentation) at the 26th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), London, UK—November 23 to 25, 2018

Publikationsverlauf

Eingereicht: 11. Juni 2019

Angenommen: 01. August 2019

Artikel online veröffentlicht:
24. September 2019

• References

• 1 Chmaj-Wierzchowska K, Olejniczak T, Tuzel J. et al. Threatened preterm labour—analysis of the cytokine profile and progesterone treatment efficiency. J Matern Fetal Neonatal Med 2017; 30 (07) 814-817
• 2 Georgiou HM, Di Quinzio MK, Permezel M, Brennecke SP. Predicting preterm labour: current status and future prospects. Dis Markers 2015; 2015: 435014
• 3 Singh N, Dubey P, Gupta N, Dwivedi S, Balyan R, Chandanan A. Comparative study of various tocolytics in preterm labor. Int J Reprod Contracept Obstet Gynecol 2015; 4: 334-337
• 4 Tambe SK, Alnure Y. Comparative study of transdermal nitroglycerin patch versus isoxsuprine hydrochloride in patients with preterm labor. Int J Sci Res (Ahmedabad) 2015; 6: 1238-1246
• 5 Singh U, Singh N, Seth S. A prospective analysis of etiology and outcome of preterm labor. J Obstet Gynaecol India 2007; 57: 48-52
• 6 ACOG Committee on Practice Bulletins. American College of Obstetricians and Gynecologist. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. Number 43, May 2003. Management of preterm labor. Obstet Gynecol 2003; 101 (5 Pt 1): 1039-1047
• 7 March of Dimes. Born Too Soon: The Global Action Report on Preterm Birth. Geneva, Switzerland: WHO; 2012 . Accessed January 3, 2019 at: https://www.who.int/pmnch/media/news/2012/201204_borntoosoon-report.pdf
• 8 Chatterjee J, Gullam J, Vatish M, Thornton S. The management of preterm labour. Arch Dis Child Fetal Neonatal Ed 2007; 92 (02) F88-F93
• 9 Sanu O, Lamont RF. Periodontal disease and bacterial vaginosis as genetic and environmental markers for the risk of spontaneous preterm labor and preterm birth. J Matern Fetal Neonatal Med 2011; 24 (12) 1476-1485
• 10 Denney JM, Culhane JF, Goldenberg RL. Prevention of preterm birth. Womens Health (Lond) 2008; 4 (06) 625-638
• 11 Sayres Jr WG. Preterm labor. Am Fam Physician 2010; 81 (04) 477-484
• 12 Mahajan A, Marwah P. Isoxsuprine as a tocolytic agent in preterm labor. Int J Basic Appl Med Sci 2015; 5: 86-91
• 13 Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ. Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ 2012; 345: e6226
• 14 Vogel JP, Nardin JM, Dowswell T, West HM, Oladapo OT. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst Rev 2014; (07) CD006169
• 15 National Formulary of India. Government of India. Ministry of Health & Family Welfare. 4th ed. 2011 . Accessed January 28, 2019 at: http://www.cdsco.nic.in/writereaddata/NFI_2011%20(1).pdf
• 16 Bishop EH, Wouterz TB. Isoxsuprine, a myometrial relaxant. J Obstet Gynaecol India 1961; 24: 266-269
• 17 Hendricks CH, Cibils LA, Pose SV, Eskes TK. The pharmacologic control of excessive uterine activity with isoxsuprine. Am J Obstet Gynecol 1961; 82: 1064-1078
• 18 Giorgino FL, Egan CG. Use of isoxsuprine hydrochloride as a tocolytic agent in the treatment of preterm labour: a systematic review of previous literature. Arzneimittelforschung 2010; 60 (07) 415-420
• 19 Nagendrappa SB, Hanumaiah I, Nandaagopal KM. et al. Suppression of preterm labor: a comparative study between isoxsuprine and nifedipine. Int J Biol Med Res 2012; 3: 2333-2336
• 20 Yogol NS, Shakya R, Thapa P. Ritodrine and isoxsuprine in management of preterm labor. JNMA J Nepal Med Assoc 2009; 48 (176) 265-268
• 21 Schenken RS, Hayashi RH, Valenzuela GV, Castillo MS. Treatment of premature labor with beta sympathomimetics: results with isoxsuprine. Am J Obstet Gynecol 1980; 137 (07) 773-780
• 22 Jaju PB, Sood A, Chavan V. et al. Practice patterns in the management of preterm labor in India: a multi-centric, retrospective study. Int J Reprod Contracept Obstet Gynecol 2017; 6: 5306-5312
• 23 Rohtagi P. A clinical evaluation of isoxsuprine Duvadilan in premature labour. J Obstet Gynaecol India 1971; 21: 339
• 24 Singh VK, Sharma M, Malhotra A. Isoxsuprine and premature labour. J Obstet Gynaecol India 1987; 37: 485-489
• 25 Lamont CD, Jørgensen JS, Lamont RF. The safety of tocolytics used for the inhibition of preterm labour. Expert Opin Drug Saf 2016; 15 (09) 1163-1173
• 26 Das RK. Isoxsuprine in premature labour. J Obstet Gynaecol India 1969; 19: 566-570
• 27 Manuck TA, Herrera CA, Korgenski EK. et al. Tocolysis for women with early spontaneous preterm labor and advanced cervical dilation. Obstet Gynecol 2015; 126 (05) 954-961
• 28 Roy V, Prasad GS, Latha K. Tocolysis with ritodrine: a comparative study in preterm labor. Pak J Med Sci 2006; 22: 64-69
• 29 Raymajhi R, Pratap K. A comparative study between nifedipine and isoxsuprine in the suppression of preterm labour. Kathmandu Univ Med J (KUMJ) 2003; 1 (02) 85-90
• 30 Sirohiwal D, Sachan A, Bano A, Gulati N. Tocolysis with ritodrine: a comparative study in preterm labour. J Obstet Gynaecol India 2001; 56: 66-67
• 31 Singh N, Singh U, Seth S. Comparative study of nifedipine and isoxsuprine as tocolytics for preterm labor. J Obstet Gynaecol India 2007; 61: 512-515