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Tocolytics (also called anti-contraction medications or labor repressants) are medications used to suppress premature labor (from the Greek tokos, childbirth, and lytic, capable of dissolving). They are given when delivery would result in premature birth. The therapy also buys time for the administration of betamethasone, a glucocorticoid drug which greatly accelerates fetal lung maturity, but takes one to two days to work.

The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for several days. Depending on the tocolytic used the mother or fetus may require monitoring, as for instance blood pressure monitoring when nifedipine is used as it reduces blood pressure. In any case the risk of preterm labor alone justifies hospitalization.

Types of agents

There is no clear first-line tocolytic agent.^[1]^[2]

Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the U.S. Food and Drug Administration (FDA) for use in stopping uterine contractions in preterm labor, instead being used off label.

Drug	Mechanism	Description	Possible contraindications	Maternal side effects	Fetal and neonatal side effects
Terbutaline (Brethine)	β2-agonist	Is often the drug given first, especially if there is only low risk of preterm birth.^[3]	Cardiac arrhythmias^[4] diabetes	Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypertension, tachycardia, death ^[4]	Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia ^[4]
Ritodrine (Yutopar)	β2-agonist	No longer FDA approved.^[5]	Poorly controlled thyroid disease and diabetes^[4]	Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations ^[4]	Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage ^[4]
Fenoterol	β2-agonist		diabetes
Salbutamol	β2-agonist		diabetes
Nifedipine (Procardia, Adalat)	CCBs	Is one of the most commonly used tocolytic agents.^[6]	Cardiac disease.^[4] It should not be used concomitantly with magnesium sulfate.^[4]	Flushing, headache, dizziness, nausea, 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.^[4]	None noted as yet^[4]
Atosiban	oxytocin antagonist	Less side effects than B2 recap agonist
Indomethacin	NSAIDs		late pregnancy (ductus arteriosus), significant renal or hepatic impairment ^[4]	Nausea, heartburn ^[4]	Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis ^[4]
Sulindac	NSAIDs		Coagulation disorders or thrombocytopenia, nonsteroidal anti-inflammatory drug (NSAID)-sensitive asthma, other sensitivity to NSAIDs^[4]
IV Magnesium sulfate^[7]	myosin light chain inhibitor	Shown to be ineffective. Has been recommended for women at high risk.^[3] However, meta-analyses have failed to support it as a tocolytic agent.^[8]^[9]	Absolute contraindication: Myasthenia gravis^[4]	Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest ^[4]	Lethargy, hypotonia, respiratory depression, demineralization with prolonged use ^[4]
Ethyl alcohol	?	Shown to be ineffective. Was frequently prescribed as a tocolytic in the mid-20th century, but later double-blind studies^[10] found it was not effective.

Calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days.^[11] Otherwise, tocolysis is rarely successful beyond 24–48 hours because current medication do not alter the fundamentals of labor activation.^[8] However, just gaining 48 hours is sufficient to allow the pregnant women to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids the possibility to reduce neonatal organ immaturity.

The efficacy of beta-agonists, atosiban and indomethacin is a decreased odds ratio (OR) of delivery within 24 hours of 0.54 (95 percent confidence interval (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95 percent CI 0.30-0.75).^[1]

Antibiotics may delay the onset of labor in women with premature rupture of membranes, but this is not usually characterized as tocolysis.

Contraindications to tocolysis

In addition to drug-specific contraindications,^[4] several general factors may contraindicate delaying birth with the use of tocolytic medications.

Fetus is older than 34 weeks gestation ^[12]
Fetus weighs less than 2500 grams or has intrauterine growth restriction (IUGR)^[12] or placental insufficiency^[4]
Lethal congenital or chromosomal abnormalities^[4]^[12]
Cervical dilation is greater than 4 centimeters^[12]
Chorioamnionitis or intrauterine infection is present^[4]^[12]
Mother has severe pregnancy-induced hypertension,^[12] eclampsia^[12]/preeclampsia,^[4] active vaginal bleeding,^[12] placental abruption,^[4] a cardiac disease,^[12] or another condition which indicates that the pregnancy should not continue.^[12]
Other cause of fetal distress or fetal death^[12]

References

^ ^a ^b Tan TC, Devendra K, Tan LK, Tan HK (May 2006). "Tocolytic treatment for the management of preterm labour: a systematic review". Singapore Med J 47 (5): 361–6. PMID 16645683.
^ de Heus R, Mol BW, Erwich JJ et al. (2009). "Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study". BMJ 338: b744. doi:10.1136/bmj.b744. PMC 2654772. PMID 19264820.
^ ^a ^b Healthline > Treatment of Preterm Labor: Tocolytics Health Article Retrieved on 6 January 2009
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w Management of preterm labor. American College of Obstetricians and Gynecologists (ACOG). Management of preterm labor. Washington (DC): 2003 May. 9 p. (ACOG practice bulletin; no. 43).
^ [<Drugs@fda:fda approved drug products. (n.d.). Retrieved from http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=RITODRINE HCL> "Drugs@FDA"].
^ Welcome to the Women's - The Royal Women's Hospital Victoria Australia
^ Crowther CA, Hiller JE, Doyle LW (2002). Crowther, Caroline A, ed. "Magnesium sulphate for preventing preterm birth in threatened preterm labour". Cochrane Database Syst Rev (4): CD001060. doi:10.1002/14651858.CD001060. PMID 12519550.
^ ^a ^b Simhan HN, Caritis SN (2007). "Prevention of Preterm Delivery". New England Journal of Medicine 357 (5): 477–487. doi:10.1056/NEJMra050435. PMID 17671256.
^ Nanda, K; Grimes, DA (2006). "Magnesium sulfate tocolysis: Time to quit". Obstetrics and Gynecology 108 (4): 986–989. doi:10.1097/01.AOG.0000236445.18265.93. PMID 17012463.
^ Castrén O, Gummerus M, Saarikoski S (1975). "Treatment of imminent premature labour". Acta Obstet Gynecol Scand 54 (2): 95–100. PMID 1094787.
^ Iams JD, Romero R, Culhane JF, Goldenberg RL (2008). "Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth". The Lancet 371 (9607): 164–175. doi:10.1016/S0140-6736(08)60108-7. PMID 18191687.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Wong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002

UpToDate Contents

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1. 切迫早産の予防 inhibition of acute preterm labor
2. 切迫早産予防後の妊婦のマネージメント management of pregnant women after inhibition of acute preterm labor
3. 自然早産の予防 prevention of spontaneous preterm birth
4. 硫酸マグネシウムへの子宮内曝露の神経保護効果 neuroprotective effects of in utero exposure to magnesium sulfate
5. 妊娠中および周産期における急性呼吸不全 acute respiratory failure during pregnancy and the peripartum period

English Journal

Tocolysis for Women With Early Spontaneous Preterm Labor and Advanced Cervical Dilation.

Manuck TA1, Herrera CA, Korgenski EK, Jackson M, Stoddard GJ, Porter TF, Varner MW.
Obstetrics and gynecology.Obstet Gynecol.2015 Oct 5. [Epub ahead of print]
OBJECTIVE: To characterize tocolytic use and examine perinatal outcomes among women presenting very preterm with spontaneous labor and cervical dilation 4 cm or greater.METHODS: This was a retrospective cohort study. Data from January 2000 to June 2011 in a single health care system were reviewed. W
PMID 26444115

Vaginal progesterone for maintenance tocolysis: a systematic review and metaanalysis of randomized trials.

Suhag A1, Saccone G2, Berghella V3.
American journal of obstetrics and gynecology.Am J Obstet Gynecol.2015 Oct;213(4):479-87. doi: 10.1016/j.ajog.2015.03.031. Epub 2015 Mar 19.
OBJECTIVE: We sought to evaluate the efficacy of maintenance tocolysis with vaginal progesterone compared to control (placebo or no treatment) in singleton gestations with arrested preterm labor (PTL) in a metaanalysis of randomized controlled trials.STUDY DESIGN: Searches were performed in MEDLINE,
PMID 25797233

[Prenatal management of the risk of maternofetal infection in cases of PPROM].

Kayem G1, Girard G2.
Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie.Arch Pediatr.2015 Oct;22(10):1056-63. doi: 10.1016/j.arcped.2015.03.025. Epub 2015 Aug 21.
Preterm premature rupture of membranes (PPROM) occurs in 3 % of pregnancies and is responsible for 30 % of premature births. The risks described in cases of PPROM are those of prematurity, acute maternal-fetal infection, cord prolapse, and abruptio placentae. The main objective of prenatal care is
PMID 26303021