Terbutaline (injection)

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Terbutaline (injection)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

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Black Box Warning

PROLONGED TOCOLYSIS
See full prescribing information for complete Boxed Warning.
Terbutaline sulfate has not been approved and should not be used for prolonged tocolysis (beyond 48 - 72 hours). In particular, terbutaline sulfate should not be used for maintenance tocolysis in the outpatient or home setting. Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration.

Overview

Terbutaline (injection) is a Beta-2 adrenergic agonist, bronchodilator and sympathomimetic that is FDA approved for the treatment of bronchospasm in patients 12 years of age and older with asthma and reversible bronchospasm associated with bronchitis and emphysema. There is a Black Box Warning for this drug as shown here. Common adverse reactions include palpitations, tachyarrhythmia, headache, seizure, tremor and nervousness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Terbutaline (injection) FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Terbutaline in adult patients.

Non–Guideline-Supported Use

Prophylaxis of Exercise Induced Asthma[1]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • Terbutaline Sulfate Injection, USP is indicated for the prevention and reversal of bronchospasm in patients 12 years of age and older with asthma and reversible bronchospasm associated with bronchitis and emphysema.
Dosage
  • Ampules should be used only for subcutaneous administration and not intravenous infusion. Sterility and accurate dosing cannot be assured if the ampules are not used in accordance with DOSAGE AND =====ADMINISTRATION=====
  • The usual subcutaneous dose of Terbutaline Sulfate Injection, USP is 0.25 mg injected into the lateral deltoid area. If significant clinical improvement does not occur within 15-30 minutes, a second dose of 0.25 mg may be administered. If the patient then fails to respond within another 15-30 minutes, other therapeutic measures should be considered. The total dose within 4 hours should not exceed 0.5 mg.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Terbutaline in pediatric patients.

Non–Guideline-Supported Use

Prophylaxis of Exercise Induced Asthma[1]

Contraindications

Tocolysis
  • Oral terbutaline sulfate has not been approved and should not be used for acute or maintenance tocolysis.
Hypersensitivity
  • Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any components of this drug product.

Warnings

PROLONGED TOCOLYSIS
See full prescribing information for complete Boxed Warning.
Terbutaline sulfate has not been approved and should not be used for prolonged tocolysis (beyond 48 - 72 hours). In particular, terbutaline sulfate should not be used for maintenance tocolysis in the outpatient or home setting. Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration.
Deterioration of Asthma
  • Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of terbutaline sulfate tablets, USP than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
Use of Anti-Inflammatory Agents
Cardiovascular Effects
Seizures
  • There have been rare reports of seizures in patients receiving terbutaline; seizures did not recur in these patients after the drug was discontinued.

Precautions

(Terbutaline, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, including ischemic heart disease, hypertension, and cardiac arrhythmias; in patients with hyperthyroidism or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines or who have convulsive disorders. Significant changes in systolic and diastolic blood pressure have been seen and could be expected to occur in some patients after use of any beta-adrenergic bronchodilator.

  • Immediate hypersensitivity reactions and exacerbations of bronchospasm have been reported after terbutaline administration.
  • Beta-adrenergic agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.
  • Large doses of intravenous terbutaline have been reported to aggravate pre-existing diabetes mellitus and ketoacidosis.

Adverse Reactions

Clinical Trials Experience

  • Adverse reactions observed with Terbutaline Sulfate Injection, USP are similar to those commonly seen with other sympathomimetic agents. All these reactions are transient in nature and usually do not require treatment.
  • The following table compares adverse reactions seen in patients treated with terbutaline sulfate Injection (0.25 mg and 0.5 mg), with those seen in patients treated with epinephrine injection (0.25 mg and 0.5 mg), during eight double-blind crossover studies involving a total of 214 patients.

Postmarketing Experience

There is limited information regarding Terbutaline (injection) Postmarketing Experience in the drug label.

Drug Interactions

Drug Interactions

  • The concomitant use of terbutaline sulfate tablets, USP with other sympathomimetic agents is not recommended, since the combined effect on the cardiovascular system may be deleterious to the patient. However, this does not preclude the use of an aerosol bronchodilator of the adrenergic-stimulant type for the relief of an acute bronchospasm in patients receiving chronic oral therapy with terbutaline sulfate tablets, USP.
Monoamine Oxidase Inhibitors and Tricyclic Antidepressants
  • Terbutaline sulfate should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, since the action of terbutaline sulfate on the vascular system may be potentiated.
Beta-Blockers
Diuretics

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • There are no adequate and well-controlled studies of terbutaline sulfate in pregnant women. Published animal studies show that rat offspring exhibit alterations in behavior and brain development, including decreased cellular proliferation and differentiation when dams were treated subcutaneously with terbutaline during the late stage of pregnancy and lactation period. Terbutaline exposures in rat dams were approximately 6.5 times the common human dose in adults of 15 mg/day, on a mg/m2 basis.
  • Oral terbutaline sulfate has not been approved and should not be used for acute or maintenance tocolysis. In particular, terbutaline sulfate should not be used for tocolysis in the outpatient or home setting. Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration.
  • In animal embryofetal development studies, no teratogenic effects were observed in offspring when pregnant rats and rabbits received terbutaline sulfate at oral doses up to 50 mg/kg/day, approximately 32 and 65 times, respectively, the maximum recommended daily oral dose for adults, on a mg/m2 basis.
  • Terbutaline sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Terbutaline (injection) in women who are pregnant.

Labor and Delivery

  • Because of the potential for beta-agonist interference with uterine contractility, use of Terbutaline Sulfate Injection, USP for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. Terbutaline crosses the placenta. After single dose IV administration of terbutaline to 22 women in late pregnancy who were delivered by elective Cesarean section due to clinical reasons, umbilical blood levels of terbutaline were found to range from 11% to 48% of the maternal blood levels.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Therefore, Terbutaline Sulfate Injection, USP should be used during nursing only if the potential benefit justifies the possible risk to the newborn.

Pediatric Use

  • Terbutaline sulfate tablets, USP are not recommended for patients under the age of 12 years because of insufficient clinical data to establish safety and effectiveness.

Geriatic Use

  • Clinical Studies of terbutaline sulfate injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Gender

There is no FDA guidance on the use of Terbutaline (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Terbutaline (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Terbutaline (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Terbutaline (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Terbutaline (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Terbutaline (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Terbutaline (injection) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Terbutaline (injection) and IV administrations.

Overdosage

  • The median subcutaneous lethal dose of terbutaline sulfate in mature rats is approximately 165 mg/kg (approximately 90 times the maximum recommended daily oral dose for adults on a mg/m2 basis). The median subcutaneous lethal dose of terbutaline sulfate in young rats is approximately 2000 mg/kg (approximately 1100 times the maximum recommended daily oral dose for adults on a mg/m2 basis).
  • The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under adverse reactions, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Hypokalemia may also occur.
  • There is no specific antidote. Treatment consists of discontinuation of terbutaline sulfate tablets, USP together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of terbutaline sulfate tablets.
  • In the alert patient who has taken excessive oral medication, the stomach should be emptied by induced emesis followed by lavage. In the unconscious patient, the airway should be secured with a cuffed endotracheal tube before lavage, and emesis should not be induced. Instillation of activated charcoal slurry may help reduce absorption of terbutaline. Adequate respiratory exchange should be maintained, and cardiac and respiratory support provided as needed. The patient should be monitored until signs and symptoms of overdosage have subsided.

Pharmacology

Template:Px
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1 : 1 mixture (racemate)Terbutaline
Systematic (IUPAC) name
(RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol
Identifiers
CAS number 23031-25-6
ATC code R03AC03 R03CC03 (WHO)
PubChem 5403
DrugBank DB00871
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 225.284 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Protein binding 25%
Metabolism GI tract (oral), liver; CYP450: unknown
Half life 11-16 hours
Excretion urine 90% (60% unchanged), bile/faeces
Therapeutic considerations
Pregnancy cat.

C

Legal status

POM(UK)

Routes SQ, Oral, Inhaled

Mechanism of Action

  • Terbutaline exerts a preferential effect on beta2-adrenergic receptors. While it is recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta2-receptors in the human heart, existing in a concentration between 10%-50%. The precise function of these receptors has not been established. In controlled clinical studies in patients given terbutaline sulfate tablets, USP orally, proportionally greater changes occurred in pulmonary function parameters than in heart rate or blood pressure. While this suggests a relative preference for the beta2-receptors in man, the usual cardiovascular effects commonly associated with other sympathomimetic agents were also observed with terbutaline sulfate tablets.

Structure

Terbutaline sulfate is ±-alpha-[(tert-butylamino)methyl]-3,5-dihydroxybenzyl alcohol sulfate (2:1) (salt). The empirical formula is (C12H19NO3)2H2SO4 and the structural formula is:

Pharmacodynamics

There is limited information regarding Terbutaline (injection) Pharmacodynamics in the drug label.

Pharmacokinetics

Absorption
  • Oral administration of 5-mg terbutaline sulfate tablets, USP or 5 mg terbutaline sulfate in solution in 17 healthy, adult, male subjects, resulted in mean (SD) peak plasma terbutaline concentration of 8.3 (3.9) and 8.6 (3.6) ng/mL, which were observed at median (range) times of 2 (1-3) and 1.5 (0.5-3.0) hours after dosing. The mean (SD) AUC(0-48) values were 54.6 (26.8) and 53.1 (23.5) hr∙ng/mL, and corresponded to a bioavailability of 103% for the tablet relative to the solution.
Distribution
  • After oral administration of terbutaline, 51 to 62 mcg/kg of body weight, to 3 healthy male subjects, peak serum levels of 3.1 to 6.2 ng/mL were observed 1 to 3 hours later. In the same study, after 3 days only 30%-50% of the dose was recovered from urine and the remainder from the feces, which may indicate poor absorption.
  • After an oral dose to asthmatic patients, the elimination half-life of terbutaline was approximately 3.4 hours. In comparison to oral dosing, subcutaneous administration of 0.5 mg of terbutaline sulfate to 17 healthy, adult, male subjects resulted in a mean (SD) peak plasma terbutaline concentration of 9.6 (3.6) ng/mL, which was observed at a median (range) time of 0.5 (0.08-1.0) hours after dosing. The mean (SD) AUC (0-48) and total body clearance values were 29.4 (14.2) hr∙ng/mL, and 311 (112) mL/min, respectively. The terminal half-life was determined in 9 of the 17 subjects and had a mean (SD) of 5.7 (2.0) hours.
Excretion
  • About 90% of the drug was excreted in the urine at 96 hours after subcutaneous administration, with about 60% of this being unchanged drug. The sulfate conjugate is a major metabolite of terbutaline, and urinary excretion is the primary route of elimination.
  • There are no reports of any clinical pharmacokinetic studies investigating dose proportionality, effect of food, or special population studies with terbutaline.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility
  • In a 2-year study in Sprague-Dawley rats, terbutaline sulfate caused a significant and dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 50 mg/kg and above (approximately 810 times the maximum recommended daily subcutaneous (sc) dose for adults on a mg/m2 basis). In a 21 month study in CD-1 mice, terbutaline sulfate showed no evidence of tumorigenicity at dietary doses of up to 200 mg/kg (approximately 1,600 times the maximum recommended daily sc dose for adults on a mg/m2 basis). The mutagenicity potential of terbutaline sulfate has not been determined.
  • Reproductive studies in rats using terbutaline sulfate demonstrated no impairment of fertility at oral doses up to 50 mg/kg (approximately 810 times the maximum recommended daily sc dose for adults on a mg/m2 basis.)

Clinical Studies

There is limited information regarding Terbutaline (injection) Clinical Studies in the drug label.

How Supplied

  • Ampules 1 mg/mL – The drug is supplied at a volume of 1 mL contained in a 2 mL clear glass ampule. Each ampule contains 1 mg of terbutaline sulfate per 1 mL of solution; 0.25 mL of solution will provide the clinical dose of 0.25 mg.
  • Ampules are expiration-dated
  • Discard unused portion after single patient use.
  • Terbutaline Sulfate Injection, USP, 1 mg/mL is available as a 1 mL ampule in packs of 10.
  • NDC 17478-933-01
  • Store at 20° to 25° C (68º to 77°F). [See USP Controlled Room Temperature].
  • Protect from light by storing ampules in original carton until dispensed.
  • Do not use if solution is discolored.

Storage

  • Store at controlled room temperature 15° to 30°C (59° to 86°F). Dispense in tightly-closed, light-resistant container (USP).

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Terbutaline (injection) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Terbutaline interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • TERBUTALINE SULFATE

Look-Alike Drug Names

There is limited information regarding Terbutaline (injection) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ 1.0 1.1 Sly RM, O'Brien SR (1982). "Effect of oral terbutaline on exercise-induced asthma". Ann Allergy. 48 (3): 151–5. PMID 7065478.

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