Editing Tocolytic

{{Short description|Drugs used to suppress premature births}}
{{Use dmy dates|date=March 2020}}
{{Infobox medical intervention
| name         = Tocolytic
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| specialty    =OB/GYN
| synonyms     = Labor suppressants
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'''Tocolytics''' (also called '''anti-contraction medications''' or '''labor suppressants''') are medications used to suppress [[premature labor]] (from Greek τόκος ''tókos'', "[[childbirth]]", and λύσις ''lúsis'', "loosening"). Preterm birth accounts for 70% of neonatal deaths.<ref name=":5">{{Cite journal|date=2016|title=Practice Bulletin No. 171: Management of Preterm Labor|url=https://dx.doi.org/10.1097/AOG.0000000000001711|journal=Obstetrics & Gynecology|language=en-US|volume=128|issue=4|pages=e155–e164|doi=10.1097/AOG.0000000000001711|pmid=27661654|issn=0029-7844|author1=American College of Obstetricians Gynecologists' Committee on Practice Bulletins—Obstetrics|s2cid=5537988|url-access=subscription}}</ref> Therefore, tocolytic therapy is provided when delivery would result in [[premature birth]], postponing delivery long enough for the administration of [[glucocorticoid]]s (which accelerate fetal lung maturity) to be effective, as they may require one to two days to take effect.

Commonly used tocolytic medications include [[Beta2-adrenergic agonist|β<sub>2</sub> agonists]], [[calcium channel blocker]]s, [[Nonsteroidal anti-inflammatory drug|NSAIDs]], and [[magnesium sulfate]]. These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal [[Disease|morbidity]] and [[Mortality rate|mortality]] associated with preterm birth.<ref>{{Citation|last1=Mayer|first1=Christopher|title=Tocolysis|date=2021|url=http://www.ncbi.nlm.nih.gov/books/NBK562212/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=32965883|access-date=2021-07-29|last2=Apodaca-Ramos|first2=Irasema}}</ref> The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for a matter of days. Depending on the tocolytic used, the pregnant woman or fetus may require monitoring (e.g., blood pressure monitoring when [[nifedipine]] is used as it reduces blood pressure; [[cardiotocography]] to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization.

== Indications ==
Tocolytics are used in preterm labor, which refers to when a baby is born too early before 37 weeks of pregnancy. As [[preterm birth]] represents one of the leading causes of neonatal morbidity and mortality, the goal is to prevent neonatal morbidity and mortality through delaying delivery and increasing [[Gestational age (obstetrics)|gestational age]] by gaining more time for other management strategies like [[corticosteroid]]s therapy that may help with fetus lung maturity.<ref>{{Cite book|last1=Ouzounian|first1=Joseph G|title=Management of Common Problems in Obstetrics and Gynecology.|last2=Goodwin|first2=T. Murphy|last3=Paulson|first3=Richard J|last4=Montoro|first4=Martin N|last5=Muderspach|first5=Laila I|last6=Roy|first6=Subir|publisher=Blackwell Publishing Ltd|year=2010|isbn=9781444323030|pages=9–11}}</ref><ref>{{Cite journal|last1=Harrison|first1=Margo S.|last2=Goldenberg|first2=Robert L.|date=2016|title=Global burden of prematurity|url=https://pubmed.ncbi.nlm.nih.gov/26740166/|journal=Seminars in Fetal & Neonatal Medicine|volume=21|issue=2|pages=74–79|doi=10.1016/j.siny.2015.12.007|issn=1878-0946|pmid=26740166}}</ref> Tocolytics are considered for women with confirmed preterm labor between 24 and 34 weeks of gestation age and used in conjunction with other therapies that may include corticosteroids administration, fetus [[neuroprotection]], and safe transfer to facilities.<ref name=":7">{{Cite journal|last1=Hanley|first1=Margaret|last2=Sayres|first2=Lauren|last3=Reiff|first3=Emily S.|last4=Wood|first4=Amber|last5=Grotegut|first5=Chad A.|last6=Kuller|first6=Jeffrey A.|date=2019|title=Tocolysis: A Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/30648727/|journal=Obstetrical & Gynecological Survey|volume=74|issue=1|pages=50–55|doi=10.1097/OGX.0000000000000635|issn=1533-9866|pmid=30648727|s2cid=58563849}}</ref>

==Types of agents==
There is no clear [[First-line treatment|first-line]] tocolytic agent.<ref name="Tan">{{Cite journal|vauthors=Tan TC, Devendra K, Tan LK, Tan HK |title=Tocolytic treatment for the management of preterm labour: a systematic review |journal=Singapore Med J |volume=47 |issue=5 |pages=361–6 |date=May 2006 |pmid=16645683 }}</ref><ref name="pmid19264820">{{Cite journal |vauthors=de Heus R, Mol BW, Erwich JJ, etal |title=Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study |journal=BMJ |volume=338 |pages=b744 |year=2009 |pmid=19264820 |pmc=2654772 |doi= 10.1136/bmj.b744}}</ref> Current evidence suggests that first line treatment with β<sub>2</sub> agonists, calcium channel blockers, or NSAIDs to prolong pregnancy for up to 48 hours is the best course of action to allow time for glucocorticoid administration.<ref name=":5" />

Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) for use in stopping uterine contractions in preterm labor, instead being used [[off-label use|off-label]].{{cn|date=February 2022}}

According to a 2022 Cochrane review, the most effective tocolytics for delaying preterm birth by 48 hours, and 7 days were the nitric oxide donors, calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics.<ref name="cochrane2022">{{cite journal |last1=Wilson |first1=Amie |last2=Hodgetts-Morton |first2=Victoria A |last3=Marson |first3=Ella J |last4=Markland |first4=Alexandra D |last5=Larkai |first5=Eva |last6=Papadopoulou |first6=Argyro |last7=Coomarasamy |first7=Arri |last8=Tobias |first8=Aurelio |last9=Chou |first9=Doris |last10=Oladapo |first10=Olufemi T |last11=Price |first11=Malcolm J |last12=Morris |first12=Katie |last13=Gallos |first13=Ioannis D |title=Tocolytics for delaying preterm birth: a network meta-analysis (0924) |journal=Cochrane Database of Systematic Reviews |date=10 August 2022 |volume=2022 |issue=8 |pages=CD014978 |doi=10.1002/14651858.CD014978.pub2|pmid=35947046 |pmc=9364967 }}</ref>

{| class="wikitable" border="1"
|-
! Drug
! Mechanism of action
! Description
! Possible<br />contraindications
! Maternal side effects
! Fetal and neonatal side effects
|-
| [[Terbutaline]] (Brethine)
| [[Beta2-adrenergic agonist|β<sub>2</sub> agonist]]
| Off-label use, FDA has advised that injectable terbutaline should only be used in urgent situations, and that the oral form of the drug should never be used<ref name="healthline">[https://www.nwhn.org/doctors-still-use-terbutaline-delay-preterm-labor-despite-major-health-risks Why do doctors still use terbutaline to delay preterm labor despite its major health risks?] Retrieved on October 20th, 2020</ref>
| Cardiac tachyarrhythmias, poorly controlled [[diabetes mellitus]], hyperthyroidism, prolonged tocolysis(>48 to 72 hours)<ref name=":5" />
| [[Tachycardia]], [[palpitations]], [[hypotension]], [[Shortness of breath|dyspnea]], chest pain, [[hypokalemia]], [[hyperglycemia]], [[lipolysis]], [[pulmonary edema]], [[Coronary artery disease|myocardial ischemia]]<ref>{{Cite journal|pmid = 10546776|year = 1999|last1 = Gyetvai|first1 = K.|last2 = Hannah|first2 = M. E.|last3 = Hodnett|first3 = E. D.|last4 = Ohlsson|first4 = A.|title = Tocolytics for preterm labor: A systematic review|journal = Obstetrics and Gynecology|volume = 94|issue = 5 Pt 2|pages = 869–877|doi = 10.1016/s0029-7844(99)00329-4}}</ref>
| Fetal [[tachycardia]], [[hyperinsulinemia]], [[hypoglycemia]], myocardial and septal [[hypertrophy]], [[Coronary artery disease|myocardial ischemia]]<ref>{{Cite journal|last1=Gaudet|first1=Laura M.|last2=Singh|first2=Kavita|last3=Weeks|first3=Laura|last4=Skidmore|first4=Becky|last5=Tsertsvadze|first5=Alexander|last6=Ansari|first6=Mohammed T.|date=2012|title=Effectiveness of Terbutaline Pump for the Prevention of Preterm Birth. A Systematic Review and Meta-Analysis|journal=PLOS ONE|volume=7|issue=2|pages=e31679|doi=10.1371/journal.pone.0031679|issn=1932-6203|pmc=3283660|pmid=22363704|bibcode=2012PLoSO...731679G|doi-access=free}}</ref>
|-
| [[Ritodrine]] (Yutopar)
| [[Beta2-adrenergic agonist|β<sub>2</sub> agonist]]
| No longer FDA approved<ref>{{Cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/|archive-url=https://web.archive.org/web/20161104020628/http://www.accessdata.fda.gov/scripts/cder/daf/|url-status=dead|archive-date=4 November 2016|title=Drugs@FDA: FDA-Approved Drugs|website=www.accessdata.fda.gov}}</ref>
| Poorly controlled thyroid disease, hypertension, and diabetes<ref>{{Cite journal|last=Pool|first=Beverly A. Von Der|date=1998|title=Preterm Labor: Diagnosis and Treatment|url=https://www.aafp.org/afp/1998/0515/p2457.html|journal=American Family Physician|volume=57|issue=10|pages=2457–2464|pmid=9614414|issn=0002-838X}}</ref>
| Metabolic hyperglycemia, [[hyperinsulinemia]], [[hypokalemia]], antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations<ref name=":0">{{Cite book|last=Modak|first=Raj K.|url=https://books.google.com/books?id=39brbet5mmEC|title=Anesthesiology Keywords Review|date=2013|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-7782-4|language=en}}</ref>
| Neonatal [[tachycardia]], [[hypoglycemia]], [[hypocalcemia]], [[Jaundice|hyperbilirubinemia]], [[hypotension]], [[intraventricular hemorrhage]]<ref name=":0" />
|-
| [[Fenoterol]]
| [[Beta2-adrenergic agonist|β<sub>2</sub> agonist]]
|Not approved for tocolysis by FDA
| [[Diabetes]], tachyarrhythmia, hypertrophic obstructive cardiomyopathy, hypersensitivity to fenoterol<ref>{{Cite web|title=Fenoterol drug information {{!}} DrugsUpdate India|url=https://www.drugsupdate.com/generic/view/1181|access-date=2021-08-02|website=www.drugsupdate.com}}</ref>
|Palpitations, [[tachycardia]], and chest pain<ref>{{Cite journal|last1=Neilson|first1=James P.|last2=West|first2=Helen M.|last3=Dowswell|first3=Therese|date=2014-02-05|title=Betamimetics for inhibiting preterm labour|url=https://pubmed.ncbi.nlm.nih.gov/24500892/|journal=The Cochrane Database of Systematic Reviews|issue=2|pages=CD004352|doi=10.1002/14651858.CD004352.pub3|issn=1469-493X|pmid=24500892|pmc=10603219}}</ref>
|[[Tachycardia]],<ref>{{Cite journal|last1=Verdurmen|first1=Kim M. J.|last2=Hulsenboom|first2=Alexandra D. J.|last3=van Laar|first3=Judith O. E. H.|last4=Oei|first4=S. Guid|date=2017|title=Effect of tocolytic drugs on fetal heart rate variability: a systematic review|url=https://pubmed.ncbi.nlm.nih.gov/27756155/|journal=The Journal of Maternal-Fetal & Neonatal Medicine |volume=30|issue=20|pages=2387–2394|doi=10.1080/14767058.2016.1249844|issn=1476-4954|pmid=27756155|s2cid=6900277}}</ref> impaired carbohydrate tolerance, [[Hyperinsulinemia|hyperinsulinaemia]]<ref>{{Cite book|url=https://www.worldcat.org/oclc/892869035|title=Drugs during pregnancy and lactation : treatment options and risk assessment|date=2015|others=Christof Schaefer, P. W. J. Peters, Richard K. Miller|isbn=978-0-12-407901-4|edition=Third|location=London, UK|oclc=892869035}}</ref>
|-
| [[Salbutamol]] <small>([[International nonproprietary name|INN]])</small> or albuterol <small>([[United States Adopted Name|USAN]])</small>
| [[Beta2-adrenergic agonist|β<sub>2</sub> agonist]]
|Shown to be less effective than nifedipine for tocolysis regarding neonatal outcome<ref>{{Cite journal|last=Tsatsaris|first=V|date=2001|title=Tocolysis with nifedipine or beta-adrenergic agonists: a meta-analysis1|url=http://linkinghub.elsevier.com/retrieve/pii/S0029784400012126|journal=Obstetrics & Gynecology|language=en|volume=97|issue=5|pages=840–847|doi=10.1016/S0029-7844(00)01212-6|pmid=11336775|url-access=subscription}}</ref>
| [[Diabetes]], ischemic cardiopathy, cardiac arrhythmia, [[placenta praevia]], hyperthyroidism, hypersensitivity to salbutamol (albuterol) <ref>{{Citation|last1=Johnson|first1=Donavon B.|title=Albuterol|date=2021|url=http://www.ncbi.nlm.nih.gov/books/NBK482272/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29489143|access-date=2021-08-02|last2=Merrell|first2=Brigham J.|last3=Bounds|first3=Connor G.}}</ref><ref>{{Cite book|last1=Spirlet|first1=Marina de|title=Fundamental & Clinical Pharmacology|last2=Treluyer|first2=Jean-Marc|last3=Chevret|first3=Sylvie|last4=Rey|first4=Elisabeth|last5=Tournaire|first5=Michel|last6=Cabrol|first6=Dominique|last7=Pons|first7=Gérard|publisher=Blackwell Science Ltd|year=2004|location=Oxford, UK|pages=207–217}}</ref>
|Headache, palpitations, [[tachycardia]], tremor, sweating, and shortness of breath<ref name=":2">{{Cite journal|last1=Lamont|first1=Ronald F.|last2=Jørgensen|first2=Jan S.|date=2019|title=Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour|url=https://pubmed.ncbi.nlm.nih.gov/30931850/|journal=Current Pharmaceutical Design|volume=25|issue=5|pages=577–592|doi=10.2174/1381612825666190329124214|issn=1873-4286|pmid=30931850|s2cid=89620227}}</ref>
|Fetal [[tachycardia]], [[hypoglycemia]], [[Hyperinsulinemia|hyperinsulinaemia]]<ref name=":2" />
|-
| [[Hexoprenaline]] (Gynipral)
| [[Beta2-adrenergic agonist|β<sub>2</sub> agonist]]
| Not FDA approved
| [[Hyperthyroidism]], [[cardiovascular disease]]s, [[glaucoma]], [[placental abruption]], [[vaginal bleeding]], inflammatory diseases of internal genitalia, 1st trimester of pregnancy, [[breastfeeding]]<ref name="PI">{{cite web|title=Gynipral (hexoprenaline) Full Prescribing Information|url=http://grls.rosminzdrav.ru/Grls_View_v2.aspx?idReg=143837&t=|website=Russian State Register of Medicinal Products|publisher=Nycomed Austria GmbH. St. Peter-Straße 25, A-4020, Linz, Austria|access-date=19 March 2016|language=Russian}}</ref><ref name="RLS">{{cite web|title=Gynipral (hexoprenaline) Tablets 0.5 mg, Solution for Intravenous Infusion 5 ''μ''g/mL (0.0005%)|url=http://www.rlsnet.ru/tn_index_id_1005.htm|website="RLS" (РЛС): Russian Register of Medical Products|language=Russian|access-date=19 March 2016}}</ref>
| Vertigo, anxiety, tremor, [[hyperhidrosis]], [[tachycardia]], [[hypotension]], [[hyperglycemia]], edema
| [[Hypoglycemia]], [[bronchospasm]], [[Anaphylaxis|anaphylactic shock]]<ref name = "RLS" />
|-
| [[Nifedipine]] (Procardia, Adalat)
| [[Calcium channel blocker|Ca<sup>2+</sup> channel blocker]]
| Is one of the most commonly used tocolytic agents.<ref>[http://www.rwh.org.au/rwhcpg/maternity.cfm?doc_id=1821 Welcome to the Women's – The Royal Women's Hospital Victoria Australia<!-- Bot generated title -->]</ref>
| Hypotension, preload-dependent cardiac disease.<ref name="AHFS2015">{{Cite web|date=2015|title=Nifedipine Monograph for Professionals - Drugs.com|url=http://www.drugs.com/monograph/nifedipine.html|url-status=live|access-date=|archive-url=https://web.archive.org/web/20151225224837/http://www.drugs.com/monograph/nifedipine.html|archive-date=25 December 2015}}</ref> It should not be used concomitantly with [[magnesium sulfate]]<ref>{{Cite journal|last1=Koontz|first1=Stephanie L.|last2=Friedman|first2=Steven A.|last3=Schwartz|first3=Martin L.|date=2004|title=Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine|url=https://pubmed.ncbi.nlm.nih.gov/15284796/|journal=American Journal of Obstetrics and Gynecology|volume=190|issue=6|pages=1773–1776|doi=10.1016/j.ajog.2004.02.050|issn=0002-9378|pmid=15284796}}</ref>
| [[Flushing (physiology)|Flushing]], headache, dizziness, nausea, [[hypotension|transient hypotension]]. Administration of calcium channel blockers should be used with care in patients with renal disease and hypotension. Concomitant use of calcium channel blockers and magnesium sulfate may result in [[cardiovascular collapse]]<ref>{{Cite journal|last1=Davis|first1=W. B.|last2=Wells|first2=S. R.|last3=Kuller|first3=J. A.|last4=Thorp|first4=J. M.|date=March 1997|title=Analysis of the risks associated with calcium channel blockade: implications for the obstetrician-gynecologist|url=https://pubmed.ncbi.nlm.nih.gov/9061722/|journal=Obstetrical & Gynecological Survey|volume=52|issue=3|pages=198–201|doi=10.1097/00006254-199703000-00023|issn=0029-7828|pmid=9061722}}</ref>
| Calcium channel blockers have the fewest neonatal adverse effects<ref name=":7" />
|-
| [[Atosiban]]
| [[Oxytocin receptor]] antagonist
| Safer than both nifedipine and beta agonists; As effective as nifedipine and more effective than beta agonists.<ref>{{Cite journal|last1=Lyndrup|first1=Jens|last2=Lamont|first2=Ronald F|date=2007|title=The choice of a tocolytic for the treatment of preterm labor: a critical evaluation of nifedipine versus atosiban|url=http://www.tandfonline.com/doi/full/10.1517/13543784.16.6.843|journal=Expert Opinion on Investigational Drugs|language=en|volume=16|issue=6|pages=843–853|doi=10.1517/13543784.16.6.843|pmid=17501696|s2cid=1012738|issn=1354-3784|url-access=subscription}}</ref> Fewer side effects than β<sub>2</sub> agonists.<ref>{{Cite journal|last1=Flenady|first1=Vicki|last2=Reinebrant|first2=Hanna E|last3=Liley|first3=Helen G|last4=Tambimuttu|first4=Eashan G|last5=Papatsonis|first5=Dimitri NM|date=2014|editor-last=Cochrane Pregnancy and Childbirth Group|title=Oxytocin receptor antagonists for inhibiting preterm labour|url=https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004452.pub3|journal=Cochrane Database of Systematic Reviews|issue=6|pages=CD004452|language=en|doi=10.1002/14651858.CD004452.pub3|pmid=24903678|pmc=11086629}}</ref> Although not FDA approved in the US, atosiban was developed specifically to delay preterm labor.<ref>{{Cite journal|date=2007|title=Oxytocin Receptor Antagonists for Inhibiting Preterm Labour|url=https://dx.doi.org/10.1097/01.AOG.0000269669.34758.4e|journal=Obstetrics & Gynecology|language=en|volume=110|issue=1|pages=180–181|doi=10.1097/01.AOG.0000269669.34758.4e|pmid=17601917|issn=0029-7844|last1=Neilson|first1=J. P.|s2cid=35984198|url-access=subscription}}</ref>
|No current contraindications
|No maternal adverse effects<ref name=":6">{{Cite journal|last1=Tsatsaris|first1=Vassilis|last2=Carbonne|first2=Bruno|last3=Cabrol|first3=Dominique|date=2004|title=Atosiban for Preterm Labour|url=http://link.springer.com/10.2165/00003495-200464040-00003|journal=Drugs|language=en|volume=64|issue=4|pages=375–382|doi=10.2165/00003495-200464040-00003|pmid=14969573|s2cid=946463|issn=0012-6667|url-access=subscription}}</ref>
|No adverse effects to the baseline fetal heart rate. No significant difference in neonatal side effect compared to other treatments<ref name=":6" />
|-
| [[Indomethacin]]
| [[Nonsteroidal anti-inflammatory drug|NSAID]]
|Shown to effectively delay premature birth, studies show that it is safer and more effective for pregnant women that are <= 32 weeks of gestation <ref>{{Cite journal|last1=Macones|first1=George A.|last2=Robinson|first2=Charlah A.|date=1997|title=Is there justification for using indomethacin in preterm labor? An analysis of neonatal risks and benefits|url=https://linkinghub.elsevier.com/retrieve/pii/S0002937897702758|journal=American Journal of Obstetrics and Gynecology|language=en|volume=177|issue=4|pages=819–824|doi=10.1016/S0002-9378(97)70275-8|pmid=9369826|url-access=subscription}}</ref>
| Late pregnancy ([[ductus arteriosus]]), significant renal or hepatic impairment<ref name=":8">{{Cite journal|last1=Loudon|first1=Jenifer A. Z.|last2=Groom|first2=Kate M.|last3=Bennett|first3=Philip R.|date=2003|title=Prostaglandin inhibitors in preterm labour|url=https://pubmed.ncbi.nlm.nih.gov/12972011/|journal=Best Practice & Research. Clinical Obstetrics & Gynaecology|volume=17|issue=5|pages=731–744|doi=10.1016/s1521-6934(03)00047-6|issn=1521-6934|pmid=12972011}}</ref>
| Nausea, heartburn<ref>{{Cite web|title=Indomethacin Side Effects: Common, Severe, Long Term|url=https://www.drugs.com/sfx/indomethacin-side-effects.html|access-date=2021-07-30|website=Drugs.com|language=en}}</ref>
| Constriction of [[ductus arteriosus]], [[pulmonary hypertension]], reversible decrease in renal function with [[oligohydramnios]], [[intraventricular hemorrhage]], [[Jaundice|hyperbilirubinemia]], [[necrotizing enterocolitis]]<ref>{{Cite book|url=https://www.worldcat.org/oclc/946116669|title=Management of high-risk pregnancy : a practical approach.|date=2016|others=S. S. Trivedi, Manju, MD Puri, Swati Agrawal|isbn=978-93-5250-046-8|edition=Second|location=New Delhi|oclc=946116669}}</ref>
|-
| [[Sulindac]]
| [[Nonsteroidal anti-inflammatory drug|NSAID]]
|Studies show that it has similar efficacy to that of indomethacin and has a milder effect on the fetal ductus arteriousus <ref>{{Cite journal|last1=Räsänen|first1=Juha|last2=Jouppila|first2=Pentti|date=1995|title=Fetal cardiac function and ductus arteriosus during indomethacin and sulindac therapy for threatened preterm labor: A randomized study|url=https://doi.org/10.1016/0002-9378(95)90163-9|journal=American Journal of Obstetrics and Gynecology|volume=173|issue=1|pages=20–25|doi=10.1016/0002-9378(95)90163-9|pmid=7631682|issn=0002-9378|url-access=subscription}}</ref>
| Coagulation disorders or thrombocytopenia, NSAID-sensitive asthma, other sensitivity to NSAID<ref>{{Cite journal|last=Stevenson|first=Donald D.|date=2004|title=Aspirin and NSAID sensitivity|url=https://pubmed.ncbi.nlm.nih.gov/15242723/|journal=Immunology and Allergy Clinics of North America|volume=24|issue=3|pages=491–505, vii|doi=10.1016/j.iac.2004.03.001|issn=0889-8561|pmid=15242723}}</ref>
|GI complications such as nausea, vomiting and stomach pain due to COX inhibition<ref>{{Cite journal|last1=Castellsague|first1=Jordi|last2=Riera-Guardia|first2=Nuria|last3=Calingaert|first3=Brian|last4=Varas-Lorenzo|first4=Cristina|last5=Fourrier-Reglat|first5=Annie|last6=Nicotra|first6=Federica|last7=Sturkenboom|first7=Miriam|last8=Perez-Gutthann|first8=Susana|last9=Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project|date=2012-12-01|title=Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project)|journal=Drug Safety|volume=35|issue=12|pages=1127–1146|doi=10.2165/11633470-000000000-00000|issn=1179-1942|pmc=3714137|pmid=23137151}}</ref>
|NSAIDs have been shown to be associated with constriction of the [[Ductus arteriosus|ductus arteriousus]] and [[oligohydramnios]]<ref name=":8" />
|-
| [[Magnesium sulfate]]<ref name="Crowther2014">{{cite journal|last1=Crowther|first1=CA|last2=Brown|first2=J|last3=McKinlay|first3=CJ|last4=Middleton|first4=P|date=2014|title=Magnesium sulphate for preventing preterm birth in threatened preterm labour.|journal=The Cochrane Database of Systematic Reviews|issue=8|pages=CD001060|doi=10.1002/14651858.CD001060.pub2|pmid=25126773|doi-access=free|pmc=10838393}}</ref>
| [[Myosin]] light chain inhibitor
| Probably effective in delaying preterm birth by 48 hours.<ref name="cochrane2022" /> It is used for its neuro-protective effects since it is shown to decrease the risk of [[cerebral palsy]] in infants.<ref name=":4" />
| '''Absolute contraindication''': [[myasthenia gravis]].<ref name=":1">{{Cite journal|last=William G. Sayres|first=Jr|date=2010|title=Preterm Labor|url=https://www.aafp.org/afp/2010/0215/p477.html|journal=American Family Physician|volume=81|issue=4|pages=477–484|pmid=20148502|issn=0002-838X}}</ref> Use as a tocolytic agent may result in death of the fetus or infant.<ref name=Crowther2014 />
| Flushing, lethargy, headache, muscle weakness, [[diplopia]], dry mouth, [[pulmonary edema]], [[cardiac arrest]]<ref name=":1" />
| Lethargy, [[hypotonia]], respiratory depression, demineralization with prolonged use<ref name=":1" />
|-
| [[Ethanol]]
| [[GABAA receptor|GABA<sub>A</sub> receptor]] [[Allosteric modulator|PAM]]
| Shown to be ineffective: no better than placebo.<ref name=":2" />[[Source revision needed]] Was a frequently used tocolytic in the mid-20th century, but later [[double-blind]] studies<ref>{{Cite journal|vauthors=Castrén O, Gummerus M, Saarikoski S |title=Treatment of imminent premature labour |journal=Acta Obstet Gynecol Scand |volume=54 |issue=2 |pages=95–100 |year=1975 |pmid=1094787 |doi= 10.3109/00016347509156739|s2cid=22685586 }}</ref> found it was not effective.
|Pregnancy: no amount of ethanol is safe to the fetus<ref name=":3">{{Cite journal|date=2011|title=Committee opinion no. 496: At-risk drinking and alcohol dependence: obstetric and gynecologic implications|url=https://pubmed.ncbi.nlm.nih.gov/21775870/|journal=Obstetrics and Gynecology|volume=118|issue=2 Pt 1|pages=383–388|doi=10.1097/AOG.0b013e31822c9906|issn=1873-233X|pmid=21775870|s2cid=205474115 }}</ref>
|Intoxication, withdrawal<ref name=":2" />
|[[Fetal alcohol spectrum disorder|Fetal alcohol syndrome]]: ethanol is a teratogen and can harm fetus<ref name=":3" />
|}

[[Calcium channel blocker|Calcium-channel blockers]] (such as [[nifedipine]]) and [[Oxytocin receptor#antagonist|oxytocin antagonists]] (such as [[atosiban]]) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered.<ref name="Iams2008">
{{Cite journal
 |vauthors=Iams JD, Romero R, Culhane JF, Goldenberg RL |year=2008
 |title=Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth
 |journal=[[The Lancet]]
 |volume=371 |issue=9607 |pages=164–175
 |pmid=18191687
 |doi=10.1016/S0140-6736(08)60108-7
|s2cid=8204299
 }}</ref> [[Nonsteroidal anti-inflammatory drug|NSAIDs]] (such as [[Indometacin|indomethacin]]) and [[calcium channel blocker]]s (such as [[nifedipine]]) are the most likely to delay delivery for 48 hours, with the least amount of maternal and neonatal side effects.<ref name="Haas 2012">{{Cite journal|last1=Haas|first1=David M|last2=Caldwell|first2=Deborah M|last3=Kirkpatrick|first3=Page|last4=McIntosh|first4=Jennifer J|last5=Welton|first5=Nicky J|date=2012|title=Tocolytic therapy for preterm delivery: systematic review and network meta-analysis|journal=The BMJ|volume=345|pages=e6226|doi=10.1136/bmj.e6226|issn=0959-8138|pmc=4688428|pmid=23048010}}</ref> Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation.<ref name="Simham2007">
{{Cite journal
 |vauthors=Simhan HN, Caritis SN |year=2007
 |title=Prevention of Preterm Delivery
 |journal=[[New England Journal of Medicine]]
 |volume=357 |pages=477–487
 |pmid=17671256
 |doi=10.1056/NEJMra050435
 |issue=5
}}</ref> However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus administer corticosteroids for the possibility to reduce neonatal organ immaturity.<ref name="Haas 2012"/>

The efficacy of [[Beta-adrenergic agonist|β-adrenergic agonists]], atosiban, and [[Indometacin|indomethacin]] is a decreased [[odds ratio]] (OR) of delivery within 24 hours of 0.54 (95% [[confidence interval]] (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75).<ref name=Tan/>

Antibiotics were thought to delay delivery, but no studies have shown any evidence that using antibiotics during preterm labor effectively delays delivery or reduces neonatal morbidity.<ref name=":4" /> Antibiotics are used in people with [[premature rupture of membranes]], but this is not characterized as tocolysis.<ref>{{Cite journal|last1=Kenyon|first1=Sara|last2=Boulvain|first2=Michel|last3=Neilson|first3=James P.|date=2013-12-02|title=Antibiotics for preterm rupture of membranes|url=https://pubmed.ncbi.nlm.nih.gov/24297389/|journal=The Cochrane Database of Systematic Reviews|issue=12|pages=CD001058|doi=10.1002/14651858.CD001058.pub3|issn=1469-493X|pmid=24297389|pmc=11297390}}</ref>

==Contraindications to tocolytics==
In addition to drug-specific contraindications,<ref name=":4">{{Cite journal|last1=Rundell|first1=Kristen|last2=Panchal|first2=Bethany|date=2017|title=Preterm Labor: Prevention and Management|url=https://www.aafp.org/afp/2017/0315/p366.html|journal=American Family Physician|volume=95|issue=6|pages=366–372|pmid=28318214|issn=0002-838X}}</ref> several general factors may contraindicate delaying childbirth with the use of tocolytic medications.
* Fetus is older than 34 weeks gestation<ref name="wong">{{cite book | last1=Wong | first1=D. L. | last2=Perry | first2=S. E. | last3=Hockenberry | first3=M. J. | last4=Lowdermilk | first4=D. L. | title=Maternal Child Nursing Care | publisher=Mosby | year=2002 | isbn=978-0-323-01399-4 | url=https://books.google.com/books?id=n_qBQgAACAAJ}}</ref>
* Fetus weighs less than 2.5&nbsp;kg, or has [[intrauterine growth restriction]] (IUGR)<ref name=wong/> or [[placental insufficiency]]<ref name="wong" />
* Lethal congenital or chromosomal abnormalities<ref name=wong/>
* [[Cervical dilation]] is greater than 4 centimeters<ref name=wong/>
* [[Chorioamnionitis]] or intrauterine infection is present<ref name=wong/>
* Pregnant woman has severe [[pregnancy-induced hypertension]],<ref name=wong/> severe [[eclampsia]]<ref name=wong/>/[[preeclampsia]],<ref name=":4" /> active [[vaginal bleeding]],<ref name=wong/> [[placental abruption]], a [[cardiac disease]],<ref name=wong/> or another condition which indicates that the pregnancy should not continue.<ref name=wong/>
* Maternal hemodynamic instability with bleeding<ref name=":4" />
* [[Intrauterine fetal demise]], lethal fetal anomaly, or non-reassuring fetal status<ref name=":4" />

==Future direction of tocolytics==
Most tocolytics are currently being used off-label. The future direction of the development of tocolytics agents should be directed toward better efficacy in intentionally prolonging pregnancy. This will potentially result in less maternal, fetal, and neonatal adverse effects when delaying preterm childbirth. A few tocolytic alternatives worth pursuing include [[Barusiban]], a last generation of oxytocin receptor antagonists, as well as [[COX-2 inhibitor]]s.<ref>{{Cite journal|last1=Hubinont|first1=C.|last2=Debieve|first2=F.|date=2011|title=Prevention of Preterm Labour: 2011 Update on Tocolysis|journal=Journal of Pregnancy|language=en|volume=2011|page=941057|doi=10.1155/2011/941057|pmid=22175022|pmc=3228310|issn=2090-2727|doi-access=free}}</ref> More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation.<ref>{{Cite journal|last1=Cole|first1=Stephen|last2=Smith|first2=Roger|last3=Giles|first3=Warwick|date=2004|title=Tocolysis: current controversies, future directions|url=https://pubmed.ncbi.nlm.nih.gov/15134284|journal=Current Opinion in Investigational Drugs |volume=5|issue=4|pages=424–429|issn=1472-4472|pmid=15134284}}</ref>

==See also==
* [[Labor induction]]

==References==
{{Reflist}}

{{Other gynecologicals}}

[[Category:Chemical substances for emergency medicine]]
[[Category:Tocolytics| ]]
[[Category:Obstetric drugs]]
[[Category:Obstetrics]]
[[Category:Obstetrical procedures]]
[[Category:Childbirth]]