Terbutaline sulfate is a synthetic sympathomimetic amine that stimulates β-adrenergic receptors less selectively than relatively selective β2-agonists (e.g., albuterol).
Terbutaline sulfate is used as a relatively short-acting bronchodilator in the symptomatic treatment of bronchial asthma and of reversible bronchospasm that may occur in association with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Several clinical practice guidelines are available for asthma management including the Global Initiative for Asthma (GINA) guidelines, which are published annually.12 The GINA guidelines provide evidence-based recommendations for the management of asthma in adults, adolescents, and children ≥6 years of age.12 The guideline states that all patients with asthma should be evaluated for symptom control, risk of future exacerbations, treatment issues (e.g., inhaler technique and adherence), and comorbidities.12 A stepwise approach to treatment is recommended where specific drugs are added or adjusted up or down through a series of steps (1 through 5) to achieve symptom control while keeping the patient on the lowest effective treatment.12 Drugs used in the management of asthma include inhaled corticosteroids (ICS)-formoterol, long-acting beta agonists (LABA), short-acting β2-adrenergic agonists (SABA), long-acting muscarinic agonists (LAMA), leukotriene receptor antagonists, theophylline, oral corticosteroids, and biologic agents.12 The GINA guidelines state that IV terbutaline† (administered as an initial IV bolus dose followed by continuous IV infusion) may be used as an alternative to inhaled SABA for the initial emergency department management of asthma exacerbations in children ≤5 years of age†.12
Some experts have suggested use of oral β2-adrenergic agonist therapy principally in patients unable to use inhaled bronchodilators (e.g., young children).183 However, oral administration is associated with a slower onset of action and increased incidence of adverse effects.167, 183
Subcutaneous terbutaline is reserved for prehospital management of severe asthma exacerbations when inhaled β2-selective agents are not readily available.175, 209 Subcutaneous terbutaline is not used routinely for treatment of severe exacerbations of asthma in hospitalized patients.209
Chronic Obstructive Pulmonary Disease
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual guideline on the comprehensive management of COPD.25 Risk reduction strategies such as smoking cessation and vaccinations are a key component of COPD management.25, 26 Pharmacologic therapy is used to reduce symptoms, reduce the frequency and severity of exacerbations, and improve overall health status.25 Drugs that are commonly used for maintenance treatment of COPD include short-acting β2-adrenergic agonists (SABA), long-acting β2-adrenergic agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), methylxanthines, roflumilast, and mucolytic agents.25 Choice of therapy should be individualized based on availability, cost, adverse effects, and clinical benefits of the drugs in relation to the patient's severity of symptoms and risk for exacerbations.25 The GOLD guideline states that inhaled bronchodilators (e.g., LABAs and LAMAs) used on a regular basis are central to symptom management in COPD.25 Terbutaline is not mentioned in the most recent (2023) GOLD guidelines.25
Terbutaline sulfate has been used IV† or subcutaneously in selected patients to inhibit uterine contractions in preterm labor† (tocolysis) and thus prolong gestation when such prolongation of intrauterine life would be expected to benefit pregnancy outcome.108, 109, 110, 111, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 188, 197 The American College of Obstetricians and Gynecologists (ACOG) considers terbutaline to be one of several possible tocolytic agents.188 Because of conflicting results, there is no clear first-line tocolytic agent.188 Although the US Food and Drug Administration (FDA) states that it may be clinically appropriate based on the clinician's judgment to administer terbutaline by injection in urgent and individual obstetrical situations in a hospital setting, the manufacturers and FDA warn that terbutaline sulfate injection is not FDA labeled for and should not be used for prolonged tocolysis (beyond 48-72 hours), and is contraindicated for such use, because of the potential for serious maternal cardiac effects and death.198, 210 The manufacturers and FDA also warn that oral terbutaline sulfate is not FDA labeled for and should not be used for acute or maintenance tocolysis, and is contraindicated for such use, because it has not been shown to be effective and has similar safety concerns as terbutaline sulfate injection.199, 201, 210 Terbutaline sulfate (injection or oral tablets) should not be used for maintenance tocolysis, particularly in the outpatient or home setting.198, 199, 200, 201, 210 (See Cautions: Adverse Effects.)
While use of terbutaline sulfate may effectively delay delivery for about 48 hours,108, 109, 110, 111, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 188, 197 the principal goal of prolongation of gestation is to potentially reduce the incidence of neonatal death, preterm delivery, low-birthweight infants, respiratory distress syndrome, and long-term morbidity and mortality associated with prematurity, and there currently is insufficient evidence substantiating the efficacy of β-adrenergic tocolytic agents in this regard.111, 117, 118, 124, 126, 127, 188, 197, 211, 212, 213 Therefore, the main benefit currently derived from tocolytic therapy appears to be short term to forestall labor and provide time for patients to receive corticosteroids to increase fetal lung maturation and/or to be transferred to other (e.g., tertiary-care) facilities; any other potential benefits of prolonging pregnancy are unclear.124, 125, 126, 188, 189, 197, 211, 213 (See Uses: Antenatal Uses in the Corticosteroids General Statement 68:04.)
Terbutaline sulfate is administered orally or subcutaneously (usually into the lateral deltoid area).198, 199 Terbutaline sulfate also has been used IV† in selected patients to inhibit uterine contractions in preterm labor† (tocolysis).108, 109, 110, 111, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 197 The drug also has been administered by IV infusion† for the emergency treatment of acute asthma exacerbations in young children.12 However, administration of parenteral terbutaline sulfate by routes or methods other than subcutaneous injection (e.g., IV) is not recommended by the manufacturer.198
Standardized concentrations for IV terbutaline have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 249Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249 For additional information on S4S (including updates that may be available), see [Web].249
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Pediatric patients (<50 kg) | 1 mg/mL | mcg/kg/mina |
The usual adult oral dosage of terbutaline sulfate is 5 mg 3 times daily administered at approximately 6-hour intervals while the patient is awake.199 The total dosage of terbutaline sulfate in adults should not exceed 15 mg within a 24-hour period.199 If disturbing adverse effects occur, dosage may be reduced to 2.5 mg 3 times daily.199
The recommended dosage of terbutaline sulfate in children 12-15 years of age is 2.5 mg orally 3 times daily; the total dosage of terbutaline sulfate should not exceed 7.5 mg within a 24-hour period.199
The usual subcutaneous dose of terbutaline sulfate in adults and adolescents 12 years of age and older is 0.25 mg injected into the lateral deltoid area.198 If substantial clinical improvement does not occur within 15-30 minutes, a second dose of 0.25 mg may be administered.198 If the patient fails to respond within another 15-30 minutes, other therapeutic measures should be considered.198 The manufacturer states that the total dosage of terbutaline sulfate should not exceed 0.5 mg subcutaneously within a 4-hour period.198
In hospitalized children or adolescents older than 12 years of age with an asthma exacerbation, 0.25 mg of terbutaline sulfate every 20 minutes for a total of 3 doses has been suggested by some clinicians.209 In hospitalized children 12 years of age or younger† with an acute asthma exacerbation, 0.01 mg/kg has been given every 20 minutes for a total of 3 doses, then every 2-6 hours as needed.209
For initial emergency department management of asthma exacerbations in children ≤5 years of age†, terbutaline has been given as an IV bolus dose of 2 mcg/kg over 5 minutes, followed by continuous IV infusion† of 5 mcg/kg/hour.12 Closely monitor the child and adjust dosage according to response.12
For use as a tocolytic agent in the management of preterm labor†, the rate and duration of IV† infusions of terbutaline sulfate should be carefully adjusted according to the patient's response as indicated by uterine response, maternal blood pressure, and maternal and fetal heart rates.108, 109, 110, 111, 114, 115, 117, 118, 124, 126 For acute tocolytic therapy, IV terbutaline sulfate has been initiated at a dosage of 2.5-20 mcg/minute.108, 110, 111, 114, 115, 117, 118, 126 Dosage may be increased gradually as tolerated at 10- to 20-minute intervals until the desired effects are achieved.108, 109, 110, 111, 114, 115, 117, 118, 126 Effective maximum dosages have ranged from 17.5-30 mcg/minute, although higher maximum dosages (e.g., 70-80 mcg/minute) have been used cautiously in some patients.108, 109, 110, 111, 114, 115, 117, 118, 126 Terbutaline sulfate injection should not be used for prolonged tocolysis (beyond 48-72 hours).198, 210 (See Uses: Preterm Labor and Cautions: Adverse Effects.)
For acute tocolytic therapy in the management of preterm labor†, subcutaneous terbutaline sulfate at a dosage of 0.25 mg every 0.3-3 hours has been recommended.188 If pulse rate exceeds 120 beats/minute, terbutaline sulfate therapy should be temporarily discontinued.188 (See Cautions: Adverse Effects.) Terbutaline sulfate injection should not be used for prolonged tocolysis (beyond 48-72 hours).198, 210 (See Uses: Preterm Labor and Cautions: Adverse Effects.)
The most common adverse effects of terbutaline sulfate are dose related and characteristic of sympathomimetic agents. Adverse effects of terbutaline include tachycardia, nervousness, tremor, palpitation, dizziness, headache, nausea, vomiting, anxiety, restlessness, lethargy, drowsiness, weakness, flushes, sweating, chest discomfort, muscle cramps, and tinnitus.130, 198, 199 Seizures, hypersensitivity vasculitis, and elevations in liver enzymes have been reported rarely in patients receiving terbutaline sulfate.198, 199 Seizures did not recur following discontinuance of the drug.198, 199 Immediate hypersensitivity reactions and exacerbations of bronchospasm have been reported in patients receiving terbutaline.198, 199 Pain at the injection site may occur in some patients receiving terbutaline subcutaneously. Adverse effects with usual oral or subcutaneous doses are generally transient and usually do not require treatment; however, the increase in heart rate may persist for a relatively long time.
ECG changes, including flattening of the T wave, prolongation of the corrected QT (QTc) interval, and ST-segment depression, have been reported with β-agonist therapy;198, 199 the clinical importance of these findings is unknown.198, 199
Serious adverse effects, including death, have been reported after administration of terbutaline sulfate in pregnant women.161, 198, 199, 210 Such adverse effects in pregnant women include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia.124, 130, 197, 198, 199, 201, 210 In addition, increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration of terbutaline.130, 197, 198, 199 In February 2011, the US Food and Drug Administration (FDA) reported the results of an analysis of postmarketing reports of maternal death and serious cardiovascular events submitted to the FDA Adverse Event Reporting System (AERS) associated with obstetric use of terbutaline.210 Between 1976 and 2009, 16 maternal deaths were reported to AERS.161, 210 Of the 16 reports of maternal death, 3 involved outpatient use of terbutaline administered by a subcutaneous infusion pump, 9 involved use of oral terbutaline (2 cases of outpatient use and 7 cases of inpatient use) alone or in addition to subcutaneous or IV† terbutaline, and 4 involved subcutaneous, IV, or unknown routes of administration.161, 210 Between January 1, 1998 and July 2009, 12 maternal cases of serious cardiovascular events, including cardiac arrhythmias, myocardial infarction, pulmonary edema, hypertension, and tachycardia, associated with use of terbutaline were reported to AERS.210 Among the 12 maternal cases of serious cardiovascular events were 3 cases involving use of terbutaline administered by a subcutaneous infusion pump and 5 cases involving use of oral terbutaline (3 cases of outpatient use and 2 cases of inpatient use) alone or in addition to subcutaneous terbutaline.210
Based on these results and a review of the medical literature, the FDA has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged tocolysis with terbutaline injection (beyond 48-72 hours) or acute or prolonged tocolysis with oral terbutaline.198, 199, 210 Because of the potential for serious maternal cardiac effects and death, the manufacturers and FDA warn that terbutaline sulfate injection is not FDA labeled for and should not be used for prolonged tocolysis (beyond 48-72 hours) and is contraindicated for such use.198, 210 The manufacturers and FDA also warn that oral terbutaline sulfate is not FDA labeled for and should not be used for acute or maintenance tocolysis, and is contraindicated for such use.199, 201, 210 Terbutaline sulfate (injection or oral tablets) should not be used for maintenance tocolysis, particularly in the outpatient or home setting.198, 199, 200, 201, 210 Clinicians are encouraged to report adverse events involving terbutaline to the FDA MedWatch program.210 (See Uses: Preterm Labor.)
Precautions and Contraindications
Oral inhalation therapy with short-acting β2-agonists is intended for the acute symptomatic relief of bronchospasm in reversible, obstructive airway disease, and should not be used regularly (e.g., 4 times daily) in asthmatic patients formaintenance therapy.168, 180, 183 If control of mild asthma deteriorates and requires regular use of a short-acting β2-agonist (i.e., 4 times daily), long-term maintenance therapy (e.g., inhaled corticosteroids) should be instituted.168, 180, 183 Patients with deteriorating asthma should be instructed to contact a clinician for reevaluation and possible institution of maintenance therapy.168, 180, 183 Patients should be instructed on the importance of adherence to dosing schedules, including not exceeding the recommended dose or frequency of use.199 Patients should use inhaled or other antiasthma agents only as directed by a clinician.199
Failure to respond to a previously effective dosage of terbutaline may indicate seriously worsening asthma that requires reevaluation and possible institution of alternative regimens or therapy.183, 198, 199 Patients should be instructed to contact their clinician if decreased effectiveness of terbutaline occurs rather than increasing the dose or frequency of administration.199
Terbutaline sulfate should be used with caution in patients with diabetes mellitus, hypertension, hyperthyroidism, a history of seizures, or cardiac disease, including those with ischemic heart disease, coronary insufficiency, or associated arrhythmias.130, 198, 199 Adverse cardiovascular effects may require discontinuance of the drug.198, 199 Large IV† doses of terbutaline reportedly have aggravated preexisting diabetes and ketoacidosis;198, 199 however, the clinical relevance of this finding to other dosage forms of the drug is unknown.
Therapy with β-adrenergic agonists may produce clinically important hypokalemia in some patients, possibly via intracellular shunting, which has the potential to produce adverse cardiovascular effects; the decrease usually is transient and usually does not require supplementation.198, 199
Use of terbutaline sulfate injection for prolonged tocolysis (beyond 48-72 hours) and use of oral terbutaline sulfate for acute or maintenance tocolysis are contraindicated. 198, 199, 210 Terbutaline sulfate (injection or oral tablets) should not be used for maintenance tocolysis, particularly in the outpatient or home setting.198, 199, 210 (See Cautions: Adverse Effects and also Uses: Preterm Labor.)
Terbutaline sulfate also is contraindicated in patients who are known to be hypersensitive to sympathomimetic agents or any ingredient in the formulations.198, 199
Some studies on the use of terbutaline sulfate in asthmatic children indicate that the drug may be a useful alternative to epinephrine in acute asthmatic attacks; however, pending accumulation of further data on the use of terbutaline in children, the drug is not recommended by the manufacturer for use in children younger than 12 years of age.
Clinical studies of terbutaline did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients.198 While other clinical experience has not revealed age-related differences in response, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range.198 The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.198
Although there are no adequate and controlled studies to date in humans, terbutaline sulfate has been associated with alterations in behavior and brain development, including decreased cellular proliferation and differentiation, in rat offspring when terbutaline was administered subcutaneously to dams during the late stage of the pregnancy and lactation period.198, 199 Terbutaline exposures in rat dams were approximately 6.5 times the human exposure of an oral adult dosage of terbutaline sulfate 15 mg daily (on a mg/m2 basis) and approximately 24-48 times the human exposure of a subcutaneous adult dosage of terbutaline sulfate 2-4 mg daily (on a mg/m2 basis). 198, 199 In embryofetal developmental studies, teratogenic effects were not observed in offspring when pregnant rats and rabbits received terbutaline sulfate at oral dosages up to 50 mg/kg daily (approximately 32 and 65 times, respectively, the maximum recommended oral dosage for adults on a mg/m2 basis; approximately 810 and 1600 times, respectively, the maximum recommended subcutaneous dosage for adults on a mg/m2 basis).198, 199
Terbutaline sulfate injection is not FDA labeled for and should not be used for prolonged tocolysis (beyond 48-72 hours), and is contraindicated for such use.198, 210 Oral terbutaline sulfate is not FDA labeled for and should not be used for acute or maintenance tocolysis, and is contraindicated for such use.199, 210 Terbutaline sulfate (injection or oral tablets) should not be used for maintenance tocolysis, particularly in the outpatient or home setting.198, 199, 210 Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate in pregnant women.161, 198, 199, 210 Such adverse reactions in pregnant women include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia.198, 199, 210 In addition, increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration of terbutaline.198, 199 The manufacturers state that terbutaline should be used with caution in pregnant women when needed for relief of bronchospasm during labor and only when the potential benefits are expected to clearly outweigh the possible risks.198, 199 The manufacturers also state that terbutaline should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.198, 199 (See Cautions: Adverse Effects and Uses: Preterm Labor.)
Patients should be advised that serious adverse effects, including maternal cardiac effects and death, have been reported after prolonged use of terbutaline to manage preterm labor.210 Patients should be advised that there are serious situations where a clinician may decide that short-term use of terbutaline injection in the hospital setting may benefit a pregnant woman.210 Patients should be advised that oral terbutaline should not be used either to treat preterm labor or prevent recurrent preterm labor.210 (See Cautions: Adverse Effects and Uses: Preterm Labor.) Patients receiving terbutaline for another condition (e.g., asthma) should be advised to contact their clinician if they are or plan to become pregnant.210
Terbutaline is distributed into milk, but in amounts generally considered insufficient to affect nursing infants; however, the drug should be used with caution in nursing women and only if the potential benefits justify the possible risks to the infant.
Terbutaline sulfate should not be administered concurrently with other sympathomimetic agents because of the possibility of additive adverse cardiovascular effects;198, 199 however, an aerosol bronchodilator of the adrenergic stimulant type may be used to relieve acute bronchospasm in patients receiving chronic oral terbutaline therapy.130, 199
There is some evidence from animal studies that concomitant administration of a sympathomimetic agent (e.g., terbutaline) and a theophylline derivative (e.g., aminophylline) may produce increased cardiotoxic effects.100, 101, 102, 103, 104 Although such an interaction has not been established in humans, a few reports have suggested that such a combination may have the potential for producing cardiac arrhythmias.100, 101, 102, 103, 104 Further accumulation of clinical data is needed to determine whether this potential interaction occurs in humans.102
The effects of terbutaline on the vascular system may be potentiated in patients receiving monoamine oxidase inhibitors or tricyclic antidepressants;198, 199 therefore, terbutaline should be administered with extreme caution to patients receiving these drugs or having recently received (i.e., within 2 weeks) such agents.198, 199
β-Adrenergic blocking agents such as propranolol not only block the pulmonary effects of β-agonists, but may produce severe bronchospasm in patients with asthma; therefore, these patients should not generally be treated with β-adrenergic blocking agents.198, 199 However, under certain circumstances (e.g., prophylaxis after myocardial infarction), there may be no acceptable alternatives to the use of β-adrenergic blocking agents in patients with asthma; cardioselective β-adrenergic blocking agents without intrinsic sympathomimetic activity (e.g., metoprolol, atenolol, esmolol) should be used with caution in these patients.198, 199, 202 Low dosages of a cardioselective β-adrenergic blocker should be used initially.202
Since terbutaline may lower serum potassium concentrations,198, 199 care should be taken in patients also receiving other drugs that can lower serum potassium concentration, such as non-potassium-sparing diuretics (such as loop or thiazide diuretics).198, 199 The electrocardiographic changes and/or hypokalemia that may result from the administration of non-potassium-sparing diuretics may be aggravated by concomitant β-agonists, especially when the recommended dosage of the β-agonist is exceeded.198, 199 Although the clinical importance of these effects is not known, caution is advised when administering β-agonists with non-potassium-sparing diuretics.198, 199
Terbutaline sulfate stimulates β-adrenergic receptors of the sympathetic nervous system and has little or no effect on α-adrenergic receptors. Data from in vitro and in vivo pharmacologic studies have demonstrated that terbutaline exerts a preferential effect on β2-adrenergic receptors.198 Terbutaline stimulates β-adrenergic receptors less selectively than relatively selective β2-agonists (e.g., albuterol). However, following subcutaneous administration of terbutaline in controlled clinical studies, no apparent preferential β2-adrenergic effect was noted.198 It is believed that β-adrenergic agonists stimulate the production of cyclic adenosine-3',5'-monophosphate (AMP) by activation of the enzyme adenyl cyclase, which appears to mediate numerous cellular responses, including bronchial smooth muscle relaxation and inhibition of the release of mediators from mast cells in the airways.198, 199 The main effect of terbutaline is relaxation of smooth muscles of the bronchial tree and the peripheral vasculature. The drug significantly increases pulmonary flow rates as measured by pulmonary function tests such as the forced expiratory volume in 1 second (FEV1).198, 199 Terbutaline does not appear to cause changes in arterial oxygen tension.
Like metaproterenol and albuterol, terbutaline appears to have a greater stimulating effect on β-receptors of the bronchial, vascular, and uterine smooth muscles (β2 receptors) than on the β-receptors of the heart (β1 receptors). Terbutaline relaxes uterine smooth muscle and inhibits uterine contractions.108, 109, 110, 111, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 188, 198, 201 (See Uses: Preterm Labor.) However, terbutaline may cause some cardiostimulatory effects and CNS stimulation. It is unclear whether the tachycardia that sometimes occurs with terbutaline is caused by β1 stimulation or by a reflex response to blood pressure changes secondary to peripheral vasodilation.
About 30-50% of an oral dose of terbutaline sulfate is absorbed from the GI tract. The drug is well absorbed following subcutaneous administration. Following subcutaneous administration, clinically important increases in FEV1 occur within 15 minutes, and maximum effects usually occur within 30-60 minutes.198 Clinically important bronchodilator activity may continue for 1.5-4 hours.198 Following oral administration, a change in flow rate usually occurs within 30 minutes; substantial clinical improvement in pulmonary function occurs within 1-2 hours and is maximal within 2-3 hours.130, 199 Clinically important decreases in airway and pulmonary resistance may persist for 4 hours or longer following oral administration.199
Terbutaline is apparently distributed into milk in concentrations at least as high as concurrent plasma concentrations; however, the amount distributed into milk is estimated to be less than 1% of a dose given to a nursing woman.
Terbutaline is partially metabolized in the liver, mainly to the inactive sulfate conjugate. Following parenteral administration, about 60% of a dose is excreted in urine unchanged, up to 3% of a dose is excreted in feces via the bile, and the remainder is excreted in urine as the conjugate. After oral administration, a larger proportion of a dose is excreted as the conjugate, indicating that metabolism of the drug may occur in the GI tract or during first pass through the liver. Excretion of the drug and its metabolites is essentially complete within 72-96 hours after a single parenteral or oral dose.
Following subcutaneous administration of terbutaline, mean terminal half-life is 5.7 hours.198 Following administration of a single oral dose in patients with asthma, the elimination half-life of terbutaline is approximately 3.4 hours.199
Terbutaline sulfate is a synthetic sympathomimetic amine that is similar to isoproterenol and metaproterenol in chemical structure and in pharmacologic action. The drug occurs as a white to gray-white crystalline powder that is odorless or has a faint odor of acetic acid and is soluble in water and 0.1 N hydrochloric acid, slightly soluble in methanol, and insoluble in chloroform.100, 107, 130 The commercially available terbutaline sulfate injection is a sterile, nonpyrogenic, aqueous solution; sodium chloride has been added to adjust tonicity. Hydrochloric acid also may be added to adjust pH of the injection to 4 (tonicity range: 3-5).
Terbutaline sulfate is stable in solutions with a pH of 1-7 and is sensitive to excessive heat and light. Solutions of the drug should not be used if they are discolored. Terbutaline sulfate injection should be stored at 20-25°C and protected from light by storing in original carton until use.198 Terbutaline sulfate tablets should be stored at controlled room temperature (15-30°C); the tablets should be stored in tight, light-resistant containers.199
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 2.5 mg* | ||
5 mg* | Terbutaline Sulfate Tablets | |||
Parenteral | Injection, for subcutaneous use only | 1 mg/mL* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
12. Global Initiative for Asthma (GINA). GINA Report, Global Strategy for Asthma Management and Prevention. GINA. Updated 2022. Accessed Jan 23, 2023. [Web]
25. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2023 report. Accessed Feb 2, 2023. [Web]
26. Drugs for COPD. Med Lett Drugs Ther. 2020 Sep 7;62(1606):137-144. PMID: 32960872. [PubMed 32960872]
100. Geigy. Brethaire® (terbutaline sulfate) inhalation aerosol prescribing information. Summit, NJ; 1995 Nov.
101. Joseph X, Whitehurst VE, Bloom S et al. Enhancement of cardiotoxic effects of beta-adrenergic bronchodilators by aminophylline in experimental animals. Fundam Appl Toxicol . 1981; 1:443-7. [PubMed 6136445]
102. Anon. Interactions between methyl xanthines and beta adrenergic agonists. FDA Drug Bull . 1981; 11:19-20. [PubMed 6119269]
103. Kelly HW. Controversies in asthma therapy with theophylline and the β2-adrenergic agonists. Clin Pharm . 1984; 3:386-95. [PubMed 6147224]
104. Walker SB, Kradjan WA, Bierman CW. Bitolterol mesylate. A beta-adrenergic agent: chemistry, pharmacokinetics, pharmacodynamics, adverse effects and clinical efficacy in asthma. Pharmacotherapy . 1985; 5:127-37. [PubMed 3895171]
105. Hampson NB, Mueller MP. Cooling of metered-dose inhalers decreases pressure output from canisters. N Engl J Med . 1989; 320:321. [PubMed 2563147]
106. Lourenco RV, Cotromones E. Clinical aerosols: I. Characterization of aerosols and their diagnostic uses. Arch Intern Med . 1982; 142:2163-92. [PubMed 6753780]
107. Geigy. Brethine® (terbutaline sulfate) injection prescribing information. Summit, NJ; 1995 Dec.
108. Beall MH, Edgar BW, Paul RH et al. A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor. Am J Obstet Gynecol . 1985; 153:854-9. [PubMed 4073155]
109. Kosasa TS, Busse R, Wahl N et al. Long-term tocolysis with combined intravenous terbutaline and magnesium sulfate: a 10-year study of 1000 patients. Obstet Gynecol . 1994; 84:369-73. [PubMed 8058233]
110. Caritis SN, Toig G, Heddinger LA et al. A double-blind study comparing ritodrine and terbutaline in the treatment of preterm labor. Am J Obstet Gynecol . 1984; 150:7-14. [PubMed 6383045]
111. Travis BE, McCullough JM. Pharmacotherapy of preterm labor. Pharmacotherapy . 1993; 13:28-36. [PubMed 8437965]
112. Angel JL, O'Brien WF, Knuppel RA et al. Carbohydrate intolerance in patients receiving oral tocolytics. Am J Obstet Gynecol . 1988; 159:726-6.
113. Schreyer P, Caspi E, Snir E et al. Metabolic effects of intramuscular and oral administration of ritodrine in pregnancy. Obstet Gynecol . 1981; 57:730-3. [PubMed 7231825]
114. Finley J, Katz M, Rojas-Perez M et al. Cardiovascular consequences of β-agonist tocolysis: an echocardiographic study. Obstet Gynecol . 1984; 64:787-91. [PubMed 6150456]
115. Ingemarsson I, Bengtsson B. A five-year experience with terbutaline for preterm labor: low rate of severe side effects. Obstet Gynecol . 1985; 66:176-80. [PubMed 4022480]
116. Main EK, Main DM, Gabbe SG. Chronic oral terbutaline tocolytic therapy is associated with maternal glucose intolerance. Am J Obstet Gynecol . 1987; 157:644-7. [PubMed 3631165]
117. Parilla BV, Dooley SL, Minogue JP et al. The efficacy of oral terbutaline after intravenous tocolysis. Am J Obstet Gynecol . 1993; 169:965-9. [PubMed 8238158]
118. How HY, Hughes SA, Vogel RL et al. Oral terbutaline in the outpatient management of preterm labor. Am J Obstet Gynecol . 1995; 173:1518-22. [PubMed 7503194]
119. Adkins RT, Van Hooydonk JE, Bressman PL et al. Prevention of preterm birth: early detection and aggressive treatment with terbutaline. South Med J . 1993; 86:157-64. [PubMed 8240475]
120. Allbert JR, Johnson C, Roberts WE et al. Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump. J Reprod Med . 1994; 39:614-8. [PubMed 7996525]
121. Fischer JR, Kaatz BL. Continuous subcutaneous infusion of terbutaline for suppression of preterm labor. Clin Pharm . 1991; 10:292-6. [PubMed 2032446]
122. Lam F, Gill P, Smith M et al. Use of the subcutaneous terbutaline pump for long-term tocolysis. Obstet Gynecol . 1988; 72:810-3. [PubMed 3173932]
123. Perry KG Jr, Morrison JC, Rust OA et al. Incidence of adverse cardiopulmonary effects with low-dose continuous terbutaline infusion. Am J Obstet Gynecol . 1995; 173:1273-7. [PubMed 7485336]
124. American College of Obstetricians and Gynecologists (ACOG) Committee on Technical Bulletins. Preterm labor. Technical Bulletin No. 206. Washington, DC: American College of Obstetricians and Gynecologists; 1995 Jun.
125. Macones GA, Berlin M, Berlin JA. Efficacy of oral beta-agonist maintenance therapy in preterm labor: a meta-analysis. Obstet Gynecol . 1995; 85:313-7. [PubMed 7824252]
126. King JF, Grant A, Keirse MJ et al. Beta-mimetics in preterm labour: an overview of the randomized controlled trials. Br J Obstet Gynaecol . 1988; 95:211-22. [PubMed 2897207]
127. Canadian Preterm Labor Investigators Group. Treatment of preterm labor the beta-adrenergic agonist ritodrine. N Engl J Med . 1992; 327:308-12. [PubMed 1620169]
128. Wilkins IA, Lynch L, Mehalek KE et al. Efficacy and side effects of magnesium sulfate and ritodrine as tocolytic agents. Am J Obstet Gynecol . 1988; 159:685-9. [PubMed 3048103]
129. Astra USA, Inc. Yutopar® (ritodrine hydrochloride) injection prescribing information dated April 1995. In: Physicians' desk reference. 51st ed. Montvale, NJ; Medical Economics Company Inc; 1997:566-7.
130. CibaGeneva. Brethine® (terbutaline sulfate) tablets prescribing information. In: Physicians' desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1997:831.2.
131. Meyer JM, Wenzel CL, Kradjan WA. Salmeterol: a novel, long-acting beta 2-agonist. Ann Pharmacother . 1993; 27:1478-87. [PubMed 7905757]
132. Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs . 1991; 42:895-912. [PubMed 1723379]
133. Kelly HW. Issues and advances in the pharmacotherapy of asthma. J Clin Pharm Ther . 1992; 17:271-81. [PubMed 1361192]
134. Lipworth BJ. Risks versus benefits of inhaled β2-agonists in the management of asthma. Drug Safety . 1992; 7:54-70. [PubMed 1346963]
135. Sears MR, Taylor DR, Print CG et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet . 1990; 336:1391-6. [PubMed 1978871]
136. Anon. Warnings from the CSM. Int Pharm J . 1991; 5:247-8.
137. Spitzer WO, Sussa S, Ernst P et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med . 1992; 326:501-6. [PubMed 1346340]
138. Palmer JBD, Jenkins MM. β2-agonists in asthma. Lancet . 1991; 337:43. [PubMed 1670660]
139. Dahl R. β2-agonists in asthma. Lancet . 1991; 337:43. [PubMed 1670660]
140. Löfdahl CG, Svedmyr N. Beta agonists—friends or foes? Eur Respir J . 1991; 4:1161-5. Editorial.
141. Kamada AK, Spahn JD, Blake KV. Salmeterol: its place in asthma management. Ann Pharmacother . 1994; 28:1100-2. [PubMed 7803888]
142. Wanner A. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? Yes. Am J Respir Crit Care Med . 1995; 151:597-9. [PubMed 7881643]
143. Sears MR. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? No. Am J Respir Crit Care Med . 1995; 151:600-1. [PubMed 7881644]
144. Lai CKW, Twentyman OP, Holgate ST. The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the associated change in nonspecific bronchial responsiveness. Am Rev Respir Dis . 1989; 140:917-23. [PubMed 2572192]
145. Suissa S, Ernst P, Boivin JF et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med . 1994; 149(3 Part 1):604-10. [PubMed 8118625]
146. O'Connor BJ, Aikman SL, Barnes PJ. Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma. N Engl J Med . 1992; 327:1204-8. [PubMed 1357551]
147. Cockcroft DW, McParland CP, Britto SA et al. Regular inhaled salbutamol and airway responsiveness to allergen. Lancet . 1993; 342:833-7. [PubMed 8104272]
148. Mullen ML, Mullen B, Carey M. The association between β-agonist use and death from asthma: a meta-analytic integration of case-control studies. JAMA . 1993; 270:1842-5. [PubMed 8105113]
149. Reviewers' comments (personal observations) on Salmeterol Xinafoate 12:12.08.12.
150. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 1995 Jan:77-100. NIH/NHLBI Publication No. 95-3659.
151. Devoy MAB, Fuller RW, Palmer JBD. Are there any detrimental effects of the use of inhaled long-acting β2-agonists in the treatment of asthma? Chest . 1995; 107:1116-24.
152. McFadden ER Jr. Perspectives in β2-agonist therapy: vox clamantis in deserto vel lux in tenebris? J Allergy Clin Immunol . 1995; 95:641-51.
153. Crane J, Burgess C, Pearce N et al. Asthma deaths in New Zealand. BMJ . 1992; 304:1307. [PubMed 1606438]
154. Crane J, Pearce N, Flatt A et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet . 1989; 1:917-22. [PubMed 2565417]
155. Löfdahl CG, Svedmyr N. Beta agonists—friends or foes? Eur Respir J . 1991; 4:1161-5. Editorial.
156. Sisson MC. Preventing preterm labor. Is terbutaline our best option? AWHONN Lifelines . 1997; 1:42-6.
157. Allbert JR, Johnson C, Roberts WE et al. Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump. J Reprod Med . 1994; 39:614-8. [PubMed 7996525]
158. Moise KJ, Sala DJ, Zurawin RK et al. Continuous subcutaneous terbutaline pump therapy for premature labor: safety and efficacy. South Med J . 1992; 85:255-60. [PubMed 1546349]
159. Wenstrom KD, Weiner CP, Merrill D et al. A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery. Am J Perinatol . 1997;14:87-91. [PubMed 9259905]
160. Perry KG, Morrison JC, Rust OA et al. Incidence of adverse cardiopulmonary effects with low dose continuous terbutaline infusion. Am J Obset Gynecol . 1995;173:1273-7.
161. Nightingale SL. Dear healthcare provider letter. Rockville, MD: US Food and Drug Administration; 1997 (Nov 13. Available from website. [Web]
162. Hudgens DR, Conradi SE. Sudden death associated with terbutaline sulfate Am J Obstet Gynecol . 1993;169:120-1.
163. Lindenbaum C, Ludmir J, Teplick FB et al. Maternal glucose intolerance and the subcutaneous terbutaline pump. Am J Obstet Gynecol . 1992: 166: 925-8. (IDIS 293989)
164. Adkins RT. Terbutaline pump treatment of premature labor. South Med J . 1993; 86: 1076. [PubMed 8240475]
165. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.
166. National Asthma Education Program. Executive summary: guidelines for the diagnosis and management of asthma. NIH Publ. No.94-3042A. Washington, DC: US Government Printing Office; 1994 Jul.
167. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 1995 Jan:77-100. NIH/NHLBI Publication No. 95-3659.
168. British Thoracic Society/Scottish Intercollegiate Guidelines Network. Guideline no. 101: British guideline on the management of asthma, a national clinical guideline. London, Eng; British Thoracic Society. 2008 May. Available from website. [Web]
169. Allen & Hanburys. Serevent® (salmeterol xinafoate) inhalation aerosol prescribing information. Research Triangle Park, NC; 1994 Dec.
170. Allen & Hanburys. Serevent® (salmeterol xinafoate) inhalation aerosol patient instructions. Research Triangle Park, NC; 1994 Feb.
171. Bone RC. Another word of caution regarding a new long-acting bronchodilator. JAMA . 1995; 273:967-8. [PubMed 7884959]
172. Reviewers' comments (personal observations) on salmeterol.
173. Anon. Warnings from the CSM. Int Pharm J . 1991; 5:247-8.
174. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 1995; 152: s77-120.
175. Siafakas NM, Vermeire P, Pride NB et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J . 1995: 8; 1398-1420.
176. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 1993 June.
177. Pearlman DS, Chervinsky P, LaForce C et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992; 327:1420-5.
178. D'Alonzo GE, Nathan RA, Henochowicz S et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994; 271:1412-6.
179. Drazen JM, Israel E, Boushey HA et al. Comparison of regularly scheduled with as- needed use of albuterol in mild asthma. N Engl J Med. 1996; 335:841-7.
180. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma-update on selected topics 2002. Bethesda, Md: National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Coordinating Committee; 2003 Jun. Available from National Heart, Lung, and Blood Institute Information Center, NIH Publication No. 02-5074. Also available from website. Accessed 2004 Sep. 15. [Web]
181. Papageorgiou AN, Doray JL, Ardila R et al. Reduction of mortality, morbidity, and respiratory distress syndrome in infants weighing less than 1,000 grams by treatment with betamethasone and ritodrine. Pediatrics . 1989; 83:493-7. [PubMed 2927987]
182. Veterans' Health Administration Department of Veteran Affairs. The pharmacologic management of chronic obstructive pulmonary disease. Washington, DC: Veterans' Health Administration; 1999 June. Pharmacy Benefits Management No. 99-0012. Available from website. Accessed Sep. 30, 2002. [Web]
183. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2009 Dec. Available from website. Accessed 2010 Sep 23. [Web]
184. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2001. Available from website. Accessed Sep. 26, 2002. [Web]
185. Boehringer Ingelheim. Atrovent® (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Mar.
186. Snow V, Lascher S, Mottur-Pilson C for the Joint Expert Panel of Chronic Obstructive Pulmonary Disease of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Clinical Practice Guideline, pt.1. Ann Intern Med . 2001; 134:595-9. [PubMed 11281744]
187. Veterans' Health Administration, Department of Veterans' Affairs. VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease: complete summary. Washington, DC: Veterans' Health Administration; 1999 Aug.
188. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins. Management of preterm labor. Washington, DC; American College of Obstetricians and Gynecologists: 2003 May. Practice Bulletin No. 43.
189. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev . 2006; 3:CD004454.
191. American Thoracic Society / European Respiratory Society Task Force. Standards for the diagnosis and management of patients with COPD. Version 1.2, for health professionals. New York, NY: American Thoracic Society, European Respiratory Society; 2005 Sep 8. Available from website. Accessed Aug 10, 2007. [Web]
192. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2006 Nov. Available from website. Accessed Jun. 13, 2007. [Web]
193. O'Donnell DE, Aaron S, Bourbeau J et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease-2003. Can Respir J . 2003; 10(Suppl. A):11A-65A. [PubMed 12861361]
194. Celli BR, Macnee W. Standard for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J . 2004; 23:932-46. [PubMed 15219010]
195. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 1995; 152: s77-120.
196. Siafakas NM, Vermeire P, Pride NB et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J . 1995: 8; 1398-1420.
197. Anotayanonth S, Subhedar NV, Garner P et al. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev . 2004; :CD004352.
198. Bedford Laboratories. Terbutaline sulfate injection prescribing information. Bedford, OH; 2011 Apr.
199. Global Pharmaceuticals. Terbutaline sulfate tablets prescribing information. Philadelphia, PA; 2011 Feb.
200. Nanda K, Cook LA, Gallo MF et al. Terbutaline pump maintenance therapy after threatened preterm labor for preventing preterm birth. Cochrane Database Syst Rev . 2002; :CD003933.
201. Dodd JM, Crowther CA, Dare MR et al. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database Syst Rev . 2006; :CD003927.
202. Tafreshi MJ, Weinacker AB. Beta-adrenergic-blocking agents in bronchospastic diseases: a therapeutic dilemma. Pharmacotherapy . 1999; 19(8):974-8. [PubMed 10453968]
205. American Thoracic Society/European Respiratory Society. Standards for the diagnosis and management of patients with COPD: patient version. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available from website. Accessed Aug 20, 2007. [Web]
209. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Jul. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available from website. Accessed Jul 27, 2008. [Web]
210. US Food and Drug Administration. FDA drug safety communication: New warnings against use of terbutaline to treat preterm labor. Rockville, MD; 2011 Feb 17. From FDA website. Accessed 2011 Jul 6. [Web]
211. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med . 2007; 357:477-87. [PubMed 17671256]
212. Berkman ND, Thorp JM, Lohr KN et al. Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol . 2003; 188:1648-59. [PubMed 12825006]
213. Sayres WG. Preterm labor. Am Fam Physician . 2010; 81:477-84. [PubMed 20148502]
249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]