Tocolytics are medications used to suppress premature labor (from the Greek tokos, childbirth

Childbirth

Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

, and lytic, capable of dissolving). They are given when delivery would result in premature birth

Premature birth

In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...

. The therapy also buys time for the administration of betamethasone

Betamethasone

Betamethasone is a potent glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. Unlike other drugs with these effects, betamethasone does not cause water retention. It is applied as a topical cream, ointment, foam, lotion or gel to treat itching...

, a glucocorticoid

Glucocorticoid

Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

 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

Nifedipine

Nifedipine is a dihydropyridine calcium channel blocker...

 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.

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

Off-label use

Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...

.

Drug	Mechanism	Description	Possible contraindications	Maternal side effects	Fetal and neonatal side effects
Terbutaline Terbutaline Terbutaline is a β2-adrenergic receptor agonist.Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption has been obtained in advance.Terbutaline is currently used to delay...  (Brethine)	β2-agonist Beta2-adrenergic receptor agonist β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...	Is often the drug given first, especially if there is only low risk of preterm birth.	Cardiac arrhythmias	Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypotension, tachycardia, death	Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia
Ritodrine Ritodrine Ritodrine is a tocolytic drug, was used to stop premature labor. It is available in oral tablets or as an injection, and is typically used as the hydrochloride salt, ritodrine hydrochloride...  (Yutopar)	β2-agonist	The only FDA approved tocolytic	Poorly controlled thyroid disease and diabetes	Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations	Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage
Fenoterol Fenoterol Fenoterol is an asthma medication designed to open up the airways to the lungs. It is classed as sympathomimetic beta2 agonist.Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as Berodual N....	β2-agonist		diabetes
Salbutamol Salbutamol Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....	β2-agonist		diabetes
Nifedipine Nifedipine Nifedipine is a dihydropyridine calcium channel blocker...  (Procardia, Adalat)	CCB Calcium channel blocker A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with... s	Is one of the most commonly used tocolytic agents.	Cardiac disease. It should not be used concomitantly with magnesium sulfate.	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.	None noted as yet
Atosiban Atosiban Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form...	oxytocin Oxytocin Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...  antagonist
Indomethacin	NSAIDs Non-steroidal anti-inflammatory drug Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...		late pregnancy (ductus arteriosus Ductus arteriosus In the developing fetus, the ductus arteriosus , also called the ductus Botalli, is a shunt connecting the pulmonary artery to the aortic arch. It allows most of the blood from the right ventricle to bypass the fetus's fluid-filled lungs. Upon closure at birth, it becomes the ligamentum arteriosum... ), significant renal or hepatic impairment	Nausea, heartburn	Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis
Sulindac Sulindac Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck as Clinoril.-Uses:...	NSAIDs Non-steroidal anti-inflammatory drug Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...		Coagulation disorders or thrombocytopenia, nonsteroidal anti-inflammatory drug (NSAID)-sensitive asthma, other sensitivity to NSAIDs
IV Magnesium sulfate Magnesium sulfate Magnesium sulfate is a chemical compound containing magnesium, sulfur and oxygen, with the formula MgSO4. It is often encountered as the heptahydrate epsomite , commonly called Epsom salt, from the town of Epsom in Surrey, England, where the salt was distilled from the springs that arise where the...	myosin Myosin Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...  light chain inhibitor	Shown to be ineffective. Has been recommended for women at high risk. However, meta-analyses have failed to support it as a tocolytic agent.	myasthenia gravis Myasthenia gravis Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...	Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest	Lethargy, hypotonia, respiratory depression, demineralization with prolonged use
Ethyl alcohol	?	Shown to be ineffective. Was frequently prescribed as a tocolytic in the mid-20th century, but later double-blind Double-blind A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....  studies found it was not effective.

Calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days. Otherwise, tocolysis is rarely successful beyond 24–48 hours because current medication do not alter the fundamentals of labor activation. 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

Odds ratio

The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...

 (OR) of delivery within 24 hours of 0.54 (95 percent confidence interval

Confidence interval

In statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...

 (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95 percent CI 0.30-0.75).

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, several general factors may contraindicate delaying birth with the use of tocolytic medications.

• Fetus is older than 34 weeks gestation
• Fetus weighs less than 2500 grams or has intrauterine growth restriction
  Intrauterine growth restriction
  Intrauterine growth restriction refers to poor growth of a baby while in the mother's womb during pregnancy. The causes can be many, but most often involve poor maternal nutrition or lack of adequate oxygen supply to the fetus....
  
   (IUGR) or placental insufficiency
• Lethal congenital or chromosomal abnormalities
• Cervical dilation
  Cervical dilation
  Cervical dilation is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery...
  
   is greater than 4 centimeters
• Chorioamnionitis
  Chorioamnionitis
  Chorioamnionitis is an inflammation of the fetal membranes due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labour...
  
   or intrauterine infection is present
• Mother has severe pregnancy-induced hypertension
  Pregnancy-induced hypertension
  Gestational hypertension or pregnancy-induced hypertension is defined as the development of new arterial hypertension in a pregnant woman after 20 weeks gestation without the presence of protein in the urine.-Conditions:...
  
  , eclampsia
  Eclampsia
  Eclampsia , an acute and life-threatening complication of pregnancy, is characterized by the appearance of tonic-clonic seizures, usually in a patient who had developed pre-eclampsia...
  
  /preeclampsia, active vaginal bleeding
  Vaginal bleeding
  Vaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional menstrual cycle or caused by hormonal or organic problems of the reproductive system. Vaginal bleeding may occur at any age, but always needs investigation when encountered in female...
  
  , placental abruption
  Placental abruption
  Placental abruption is a complication of pregnancy, wherein the placental lining has separated from the uterus of the mother. It is the most common pathological cause of late pregnancy bleeding. In humans, it refers to the abnormal separation after 20 weeks of gestation and prior to birth...
  
  , a cardiac disease, or another condition which indicates that the pregnancy should not continue.
• Other cause of fetal distress
  Fetal distress
  In medicine , the term fetal distress refers to the presence of signs in a pregnant woman—before or during childbirth—that suggest that the fetus may not be well...
  
  or fetal death