Tocolytic - Types of Agents

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.

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. Cardiac arrhythmias Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypotension, tachycardia, death Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia
Ritodrine (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 β2-agonist diabetes
Salbutamol β2-agonist diabetes
Nifedipine (Procardia, Adalat) CCBs 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 oxytocin antagonist
Indomethacin NSAIDs late pregnancy (ductus arteriosus), 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 NSAIDs Coagulation disorders or thrombocytopenia, nonsteroidal anti-inflammatory drug (NSAID)-sensitive asthma, other sensitivity to NSAIDs
IV Magnesium sulfate myosin 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 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 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 (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).

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

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