Class: Selective beta-2-Adrenergic Agonists
VA Class: RE103
CAS Number: 23031-32-5
Special Alerts:
[Posted 02/17/2011] ISSUE: FDA notified healthcare professionals that injectable terbutaline should not be used in pregnant women for prevention or prolonged treatment (beyond 48-72 hours) of preterm labor in either the hospital or outpatient setting because of the potential for serious maternal heart problems and death. In addition, oral terbutaline should not be used for prevention or any treatment of preterm labor because it has not been shown to be effective and has similar safety concerns.
Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women.
BACKGROUND: Terbutaline is approved to prevent and treat bronchospasm (narrowing of airways) associated with asthma, bronchitis, and emphysema. The drug is sometimes used off-label (an unapproved use) for acute obstetric uses, including treating preterm labor and treating uterine hyperstimulation. Terbutaline has also been used off-label over longer periods of time in an attempt to prevent recurrent preterm labor.
The decision to require the addition of a Boxed Warning and Contraindication is based on new safety information reviewed by the FDA, specifically postmarketing safety reports of terbutaline used for obstetrical indications (see Data Summary in Drug Safety Communication) as well as data from the medical literature. These label changes are consistent with statements from the American College of Obstetricians and Gynecologists (ACOG).
A Data Summary is provided in the Drug Safety Communication
RECOMMENDATION: Based on FDA review, FDA has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48-72 hours), or acute or prolonged treatment with oral terbutaline. FDA is requiring the addition of a new Boxed Warning and Contraindication to the terbutaline drug labels to warn healthcare professionals about these risks.
Healthcare professional and patients should follow the recommendations in the “Additional Information for Healthcare Professionals/Patients” sections of the Drug Safety Communication. For more information visit the FDA website at: and .
Introduction
Bronchodilator; relatively selective, short-acting β2-adrenergic agonist.a b c
Uses for Terbutaline Sulfate
Bronchospasm in Asthma
Symptomatic management or prevention of bronchospasm in patients with reversible, obstructive airway disease (e.g., asthma).a b
Current asthma management guidelines suggest use of oral β2-adrenergic agonist therapy principally in patients unable to use inhaled bronchodilators (e.g., young children).d Oral administration associated with slower onset of action and increased incidence of adverse effects.167 183 d
Sub-Q terbutaline generally used for relief of acute exacerbations of asthma in hospitalized patients.j No proven advantage of sub-Q administration compared with oral inhalation (no longer commercially available in US). j
Bronchospasm in COPD
Symptomatic management of reversible bronchospasm associated with chronic bronchitis and emphysema.a b c
Inhaled β2-adrenergic agonists preferred over oral β2-adrenergic agonist therapy for treatment of COPD;h i long-acting inhaled bronchodilators more effective and convenient than short-acting agents.h Oral β2-adrenergic agonist use associated with slower onset of action and increased incidence of adverse effects compared with inhaled therapy.h i
Role of oral β2-adrenergic agonists in treatment of COPD limited.
Antenatal Use in Preterm Labor
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Acute IV† and sub-Q therapy in selected women to inhibit uterine contractions in preterm labor† (tocolysis) and prolong gestation when beneficial.108 109 110 111 115 116 117 118 119 120 121 122 123 124 125 126 188 e
Manufacturers state that terbutaline should not be used for tocolysis.a b However, available data suggest that acute sub-Q β-adrenergic agonist treatment may forestall labor for 48 hours,108 111 119 120 121 122 123 124 126 providing time for patients to be transferred to other (e.g., tertiary-care) facilities and/or receive other agents (e.g., corticosteroids) to increase fetal maturation (e.g., lung maturation).124 125 126 188 189 e Any other potential benefits of such drugs in prolonging pregnancy are unclear.124 125 126 188 189
American College of Obstetricians and Gynecologists (ACOG) states that because of limited comparative studies, there is no clear first-line tocolytic agent.188
Maintenance therapy with sub-Q infusion or oral β-adrenergic agonists, including terbutaline, in women with arrested preterm labor not shown to decrease risk of preterm birth.124 125 f g Current evidence considered inadequate to support use of sub-Q infusion or oral maintenance therapy.188 f g FDA states that safety and efficacy of sub-Q infusion maintenance therapy not adequately demonstrated and that such therapy is potentially dangerous.161 (See Preterm Labor under Cautions.)
Tocolytic therapy in general may be contraindicated by certain maternal or fetal conditions (e.g., advanced cervical dilation, acute fetal distress other than intrauterine resuscitation, placental insufficiency, chorioamnionitis, eclampsia or severe preeclampsia, fetal demise [singleton], lethal congenital or chromosomal abnormalities, fetal maturity, maternal hemodynamic instability, placental abruption, intrauterine infection), and specifically, β-adrenergic agonist therapy may be contraindicated by other conditions (e.g., maternal cardiac rhythm disturbances or certain other cardiac diseases, poorly controlled diabetes mellitus, thyrotoxicosis, hypertension).124 188
Terbutaline Sulfate Dosage and Administration
Administration
Administer orally or sub-Q.a b
Has been administered IV† to inhibit uterine contractions in preterm labor† (tocolysis).109 117 124 e Administration of sub-Q injection preparation by other routes (e.g., IV) or methods not recommended by manufacturer.a (See Preterm Labor under Cautions.)
Oral Administration
Administer orally 3 times daily during waking hours, at approximately 6-hour intervals,.b
Sub-Q Administration
For solution and drug compatibility information, see Compatibility under Stability.
Inject into lateral deltoid area.a
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Available as terbutaline sulfate; dosage expressed in terms of sulfate salt.a b
Pediatric Patients
Bronchospasm
Asthma
Oral
Children or adolescents 12–15 years of age: 2.5 mg 3 times daily. Do not exceed 7.5 mg in 24-hour period.b b
Sub-Q
Hospitalized children ≤12 years of age† with 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.j
Children or adolescents ≥12 years of age: 0.25 mg recommended by manufacturer.a Repeat dose (0.25 mg) if substantial clinical improvement does not occur ≤15–30 minutes.a If no response, consider other measures. a Manufacturer recommends total dosage of ≤0.5 mg within a 4-hour period.a
Hospitalized children or adolescents >12 years of age with asthma exacerbation: 0.25 mg every 20 minutes for a total of 3 doses suggested by some clinicians.j
Adults
Bronchospasm
Asthma
Oral
5 mg 3 times daily, given approximately every 6 hours.b If disturbing adverse effects occur, reduce dosage to 2.5 mg 3 times daily.b Do not exceed 15 mg in 24-hour period.b
Sub-Q
0.25 mg recommended by manufacturer.a Repeat dose (0.25 mg) if substantial clinical improvement does not occur ≤15–30 minutes.a If no response, consider other measures.a Manufacturer recommends total dosage of ≤0.5 mg within 4-hour period.a
Hospitalized adults with asthma exacerbation: 0.25 mg every 20 minutes for a total of 3 doses suggested by some clinicians.j
COPD
Oral
5 mg 3 times daily, given approximately every 6 hours.b If disturbing adverse effects occur, reduce dosage to 2.5 mg 3 times daily.b
Sub-Q
0.25 mg recommended by manufacturer.a Repeat dose (0.25 mg) if substantial clinical improvement does not occur ≤15–30 minutes.a If no response, consider other measures.a Manufacturer recommends total dosage of ≤0.5 mg within 4-hour period.a
Preterm Labor†
Sub-Q
0.25 mg every 0.3–3 hours has been recommended.188
Prolongs gestation for about 48 hours.e
Temporarily discontinue if pulse rate is >120 bpm.188
Prescribing Limits
Pediatric Patients
Bronchospasm
Asthma
Oral
Children 12–15 years of age: Maximum 7.5 mg daily.b
Sub-Q
Children ≥12 years of age: Maximum: 0.5 mg within 4-hour period.a
Adults
Bronchospasm
Asthma
Oral
Maximum 15 mg daily.b
Sub-Q
Maximum 0.5 mg within 4-hour period.a
COPD
Oral
Maximum 15 mg daily.b
Sub-Q
Maximum 0.5 mg within 4-hour period.a
Special Populations
Geriatric Patients
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.a
Cautions for Terbutaline Sulfate
Contraindications
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Known hypersensitivity to sympathomimetic agents or any ingredient in formulation.a b
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Acute or Worsening Asthma
Failure to respond to a previously effective dosage of terbutaline may indicate seriously worsening asthma.a b d Reevaluate asthma therapy, giving special consideration to possible need for anti-inflammatory treatment (e.g., corticosteroids).a b d Use of β-adrenergic agents alone not adequate to control mild to severe persistent asthma symptoms.d j
Cardiovascular Effects
Possible clinically important cardiovascular effects, including changes in BP, heart rate, and ECG (e.g., flattening of the T wave, prolongation of the QTc interval, ST-segment depression).a b
Cautious use recommended in patients with cardiovascular disorders, including ischemic heart disease, coronary insufficiency, cardiac arrhythmias, and hypertension.a b May require drug discontinuance.a b
Nervous System Effects
Possible CNS stimulation (e.g., nervousness, tremor).a b c d Seizures reported rarely; did not recur following drug discontinuance.a b
Cautious use recommended in patients with seizure disorders and those unusually responsive to sympathomimetic amines.a b
Sensitivity Reactions
Immediate hypersensitivity reactions and exacerbations of bronchospasm reported.a b
General Precautions
Preterm Labor
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Potentially serious adverse effects, including transient hyperglycemia, usually transient hypokalemia, increased heart rate, cardiac arrhythmias, pulmonary edema, and myocardial ischemia, have occurred during preterm labor†.124 a b e g In addition, increased fetal heart rate and neonatal hypoglycemia reported.a b e
Not recommended by manufacturer for management of preterm labor because of risk of such effects.a b Maintenance sub-Q infusion therapy considered potentially dangerous, particularly on an outpatient basis.161
Endocrine and Metabolic Effects
Large IV† doses may aggravate preexisting diabetes and ketoacidosis.a b
Use with caution in patients with diabetes mellitus or hyperthyroidism.a b
Possible hypokalemia;a b may increase risk of cardiovascular effects.a b Hypokalemia usually transient, not requiring supplementation.a b
Specific Populations
Pregnancy
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Category B.a b Restrict use for relief of bronchospasm during labor to women in whom benefits clearly outweigh risks.a b (See Preterm Labor under Cautions.)
Lactation
Distributed into milk, but in amounts generally considered insufficient to affect nursing infants.c Administer to nursing women only if potential benefits to woman outweigh possible risk to infant.a b
Pediatric Use
Safety and efficacy not established in children <12 years of age.a b
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a (See Geriatric Patients under Dosage and Administration.)
Common Adverse Effects
Oral: Nervousness,b tremor,b headache,b somnolence,b palpitations,b dizziness,b tachycardia,b nausea.b
Sub-Q: Nervousness,a drowsiness,a tremor,a headache,a palpitations.a
Interactions for Terbutaline Sulfate
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Antidepressants, tricyclic
|
Potentiation of vascular effectsa b
|
Extreme caution recommended with concomitant therapy or in patients receiving terbutaline ≤2 weeks after discontinuance of tricyclic antidepressantsa b
|
β-Adrenergic blocking agents
|
Potential antagonism of pulmonary effects resulting in severe bronchospasm in asthmatic patientsa b
|
If concomitant therapy required, consider cautious use of cardioselective β-adrenergic blocking agentsa b
|
Diuretics, potassium depleting
|
Potential for decreased serum potassium concentrations and/or ECG changes, especially when recommended β-adrenergic agonist dosage exceededa b
|
Use concomitantly with cautiona b
|
MAO inhibitors
|
Potentiation of vascular effectsa b
|
Extreme caution recommended with concomitant therapy or in patients receiving terbutaline ≤2 weeks after discontinuance of MAO inhibitorsa b
|
Sympathomimetic agents
|
Potential for additive adverse cardiovascular effectsa b c
|
Concomitant use not recommendeda b
Does not preclude use of an inhaled adrenergic agonist bronchodilator to relieve acute bronchospasm during long-term oral terbutaline therapyb
|
Terbutaline Sulfate Pharmacokinetics
Absorption
Bioavailability
Oral: About 30-50%.b
Sub-Q: Well absorbed.c
Onset
Sub-Q, patients with COPD: Measurable changes in expiratory flow rate occur ≤5 minutes.a Clinically important bronchodilation occurs ≤15 minutes.a Peak effects occur ≤30–60 minutes.a
Oral, patients with COPD: Measurable changes in pulmonary flow rate usually occur ≤30 minutes.b Substantial clinical improvement in pulmonary function occurs ≤1–2 hours.b Peak effects occur ≤2–3 hours.b
Duration
Sub-Q: 1.5–4 hours.a Duration of clinical improvement similar to equivalent doses (mg for mg) of epinephrine.a
Oral: ≤8 hours.b
Distribution
Extent
Crosses placentaa b e g and distributes into milk.c (See Preterm Labor under Cautions.)
Elimination
Metabolism
Partially metabolized in liver, principally to inactive sulfate conjugate.a b
Elimination Route
Following sub-Q administration, excreted principally as unchanged drug (60%) in urine.a b
Half-life
Sub-Q administration: Mean 5.7 hours.a
Oral single-dose administration in patients with asthma: Approximately 3.4 hours.b
Stability
Storage
Oral
Tablets
15–30°C.b Protect from light.b
Parenteral
Solution for Injection
20–25°C.a Protect from light by storing in original carton until use.a
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution CompatibilityHID
Compatible
|
|---|
Dextrose 5% in water
|
Sodium chloride 0.45 or 0.9%
|
Drug Compatibility
Admixture CompatibilityHID
Compatible
|
|---|
Aminophylline
|
Incompatible
|
|---|
Bleomycin sulfate
|
ActionsActions
Stimulates β-adrenergic receptors of sympathetic nervous system with little or no effect on α-adrenergic receptors.a b c
Less selective than relatively selective β2-agonists (e.g., albuterol).c
No apparent preferential β2-adrenergic effect following sub-Q administration in controlled clinical studies.a
Stimulates the production of cyclic adenosine-3′,5′-monophosphate (cAMP), which mediates numerous cellular responses, including bronchial smooth muscle relaxation and inhibition of release of mediators from mast cells in airways.a b
Decreases resistance of airways.a b
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 a c g (See Antenatal Use in Preterm Labor under Uses and see Preterm Labor under Cautions.)
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of understanding proper storage and administration techniques.a b
Importance of adherence to dosing schedules, including not exceeding the recommended dose or frequency of use unless otherwise instructed by clinician.a b
If decreased effectiveness occurs and/or symptoms become worse, contact clinician immediately; do not increase dose or frequency of administration.b
Importance of using inhaled or other anti-asthma agents only as directed by clinician.b
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a b
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., inhaled drugs, other anti-asthma agents) and OTC drugs.a b
Importance of informing patients of other important precautionary information.a b (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Terbutaline Sulfate
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Tablets
|
2.5 mg
|
Terbutaline Sulfate Tablets
|
Global, Lannett
|
|
|
5 mg
|
Terbutaline Sulfate Tablets
|
Global, Lannett
|
Parenteral
|
Injection, for subcutaneous use only
|
1 mg/mL
|
Terbutaline Sulfate Injection
|
Abraxis, Bedford, Sicor
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Brethine 2.5MG Tablets (AAIPHARMA): 90/$45.99 or 270/$119.97
Terbutaline Sulfate 1MG/ML Solution (APP PHARMACEUTICAL): 1/$13.99 or 3/$19.97
Terbutaline Sulfate 2.5MG Tablets (GLOBAL PHARMACEUTICAL CORP): 90/$44.99 or 270/$125.98
Terbutaline Sulfate 5MG Tablets (GLOBAL PHARMACEUTICAL CORP): 90/$47.99 or 270/$125.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions March 17, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
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