Terbutaline Sulfate

Hikma Pharmaceuticals Usa Inc.
Human Prescription Drug
NDC 0143-9375

Terbutaline Sulfate is a human prescription drug labeled by 'Hikma Pharmaceuticals Usa Inc.'. National Drug Code (NDC) number for Terbutaline Sulfate is 0143-9375. This drug is available in dosage form of Injection. The names of the active, medicinal ingredients in Terbutaline Sulfate drug includes Terbutaline Sulfate - 1 mg/mL . The currest status of Terbutaline Sulfate drug is Active.

Drug Information:

Drug NDC:	0143-9375
The labeler code and product code segments of the National Drug Code number, separated by a hyphen. Asterisks are no longer used or included within the product code segment to indicate certain configurations of the NDC.
Proprietary Name:	Terbutaline Sulfate
Also known as the trade name. It is the name of the product chosen by the labeler.
Product Type:	Human Prescription Drug
Indicates the type of product, such as Human Prescription Drug or Human OTC Drug. This data element corresponds to the “Document Type” of the SPL submission for the listing.
Non Proprietary Name:	Terbutaline Sulfate
Also known as the generic name, this is usually the active ingredient(s) of the product.
Labeler Name:	Hikma Pharmaceuticals Usa Inc.
Name of Company corresponding to the labeler code segment of the ProductNDC.
Dosage Form:	Injection
The translation of the DosageForm Code submitted by the firm. There is no standard, but values may include terms like `tablet` or `solution for injection`.The complete list of codes and translations can be found www.fda.gov/edrls under Structured Product Labeling Resources.
Status:	Active
FDA does not review and approve unfinished products. Therefore, all products in this file are considered unapproved.
Substance Name:	TERBUTALINE SULFATE - 1 mg/mL
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.
Route Details:	SUBCUTANEOUS
The translation of the Route Code submitted by the firm, indicating route of administration. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Marketing Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.

Marketing Category:	ANDA
Product types are broken down into several potential Marketing Categories, such as New Drug Application (NDA), Abbreviated New Drug Application (ANDA), BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
Marketing Start Date:	20 May, 2009
This is the date that the labeler indicates was the start of its marketing of the drug product.
Marketing End Date:	22 Dec, 2025
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.
Application Number:	ANDA078630
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
Listing Expiration Date:	31 Dec, 2023
This is the date when the listing record will expire if not updated or certified by the firm.

OpenFDA Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.

Manufacturer Name:	Hikma Pharmaceuticals USA Inc.
Name of manufacturer or company that makes this drug product, corresponding to the labeler code segment of the NDC.
RxCUI:	857635
The RxNorm Concept Unique Identifier. RxCUI is a unique number that describes a semantic concept about the drug product, including its ingredients, strength, and dose forms.
Original Packager:	Yes
Whether or not the drug has been repackaged for distribution.
UNII:	576PU70Y8E
Unique Ingredient Identifier, which is a non-proprietary, free, unique, unambiguous, non-semantic, alphanumeric identifier based on a substance’s molecular structure and/or descriptive information.

Packaging Information:

Package NDC	Description	Marketing Start Date	Marketing End Date	Sample Available
0143-9375-10	10 VIAL in 1 CARTON (0143-9375-10) / 1 mL in 1 VIAL (0143-9375-01)	20 May, 2009	N/A	No
Package NDC number, known as the NDC, identifies the labeler, product, and trade package size. The first segment, the labeler code, is assigned by the FDA. Description tells the size and type of packaging in sentence form. Multilevel packages will have the descriptions concatenated together.

Other medicines with the same generic name

Product Elements:

Terbutaline sulfate terbutaline sulfate terbutaline sulfate terbutaline edetate disodium hydrochloric acid sodium chloride

Drug Interactions:

Drug interactions the concomitant use of terbutaline sulfate injection with other sympathomimetic agents is not recommended, since the combined effect on the cardiovascular system may be deleterious to the patient. monoamine oxidase inhibitors or tricyclic antidepressants: terbutaline 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 on the vascular system may be potentiated. beta-blockers: beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as terbutaline sulfate injection, but may produce severe bronchospasm in asthmatic patients. therefore, patients with asthma should not normally be treated with betaâblockers. however, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergi Read more...

c blocking agents in patients with asthma. in this setting, cardioselective beta-blockers could be considered, although they should be administered with caution. diuretics: the ecg changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics.

Boxed Warning:

Warning: prolonged tocolysis 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 (see contraindications: prolonged tocolysis ).

Indications and Usage:

Indications and usage 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.

Warnings:

Warnings 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 than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for antiâinflammatory treatment, e.g., corticosteroids. use of anti-inflammatory agents the use of beta-adrenergic agonist bronchodilators alone may not be adequate to control asthma in many patients. early consideration should be given to adding antiâinflammatory agents, e.g., corticosteroids. cardiovascular effects terbutaline sulfate, like all other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. although such effects are uncommon after administration of terbutaline sulfate at recommended doses, if they oc Read more...

cur, the drug may need to be discontinued. in addition, betaâagonists have been reported to produce electrocardiogram (ecg) changes, such as flattening of the t wave, prolongation of the qtc interval, and st segment depression. the clinical significance of these findings is unknown. therefore, terbutaline sulfate, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. seizures there have been rare reports of seizures in patients receiving terbutaline; seizures did not recur in these patients after the drug was discontinued.

General Precautions:

General 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-exi Read more...

sting diabetes mellitus and ketoacidosis.

Dosage and Administration:

Dosage and administration vials should be used only for subcutaneous administration and not intravenous infusion. sterility and accurate dosing cannot be assured if the vials are not used in accordance with dosage and administration . discard unused portion after single patient use. the usual subcutaneous dose of terbutaline sulfate injection is 0.25 mg injected into the lateral deltoid area. if significant clinical improvement does not occur within 15 to 30 minutes, a second dose of 0.25 mg may be administered. if the patient then fails to respond within another 15 to 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.

Contraindications:

Contraindications 1. prolonged tocolysis 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 (see boxed warning: prolonged tocolysis ). 2. hypersensitivity terbutaline sulfate injection is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product.

Adverse Reactions:

Adverse reactions adverse reactions observed with terbutaline sulfate injection 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. incidence (%) of adverse reactions terbutaline (%) epinephrine (%) 0.25 mg n = 77 0.5 mg n = 205 0.25 mg n = 153 0.5 mg n = 61 reaction central nervous system tremor 7.8 38.0 16.3 18.0 nervousness 16.9 30.7 8.5 31.1 dizziness 1.3 10.2 7.8 3.3 headache 7.8 8.8 3.3 9.8 drowsiness 11.7 9.8 14.4 8.2 cardiovascular palpitations 7.8 22.9 7.8 29.5 tachycardia 1.3 1.5 2.6 0.0 respiratory dyspnea 0.0 2.0 2.0 0.0 chest discomfort 1.3 1.5 2.6 0.0 gastrointestinal nausea/vomiting 1. Read more...

3 3.9 1.3 11.5 systemic weakness 1.3 0.5 2.6 1.6 flushed feeling 0.0 2.4 1.3 0.0 sweating 0.0 2.4 0.0 0.0 pain at injection site 2.6 0.5 2.6 1.6 note: some patients received more than one dosage strength of terbutaline sulfate and epinephrine. in addition, there were reports of anxiety, muscle cramps, and dry mouth (< 0.5%). there have been rare reports of elevations in liver enzymes and of hypersensitivity vasculitis with terbutaline administration. to report suspected adverse reactions, contact hikma pharmaceuticals usa inc.. at 1-877-233-2001, or the fda at 1-800-fda-1088 or www.fda.gov/medwatch.

Adverse Reactions Table:

Incidence (%) of Adverse Reactions
	Terbutaline (%)		Epinephrine (%)
	0.25 mg N = 77	0.5 mg N = 205	0.25 mg N = 153	0.5 mg N = 61
Reaction Central Nervous System
Tremor	7.8	38.0	16.3	18.0
Nervousness	16.9	30.7	8.5	31.1
Dizziness	1.3	10.2	7.8	3.3
Headache	7.8	8.8	3.3	9.8
Drowsiness	11.7	9.8	14.4	8.2
Cardiovascular
Palpitations	7.8	22.9	7.8	29.5
Tachycardia	1.3	1.5	2.6	0.0
Respiratory
Dyspnea	0.0	2.0	2.0	0.0
Chest discomfort	1.3	1.5	2.6	0.0
Gastrointestinal
Nausea/vomiting	1.3	3.9	1.3	11.5
Systemic
Weakness	1.3	0.5	2.6	1.6
Flushed feeling	0.0	2.4	1.3	0.0
Sweating	0.0	2.4	0.0	0.0
Pain at injection site	2.6	0.5	2.6	1.6

Drug Interactions:

Use in Pregnancy:

Pregnancy -teratogenic effects pregnancy category 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 24 to 48 times the common human dose in adults of 2-4 mg/day, on a mg/m 2 basis. 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 hyperglycemi Read more...

a, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration (see boxed warning: prolonged tocolysis and contraindications: prolonged tocolysis ). in animal embryofetal developmental 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 810 and 1,600 times, respectively, the maximum recommended daily subcutaneous dose for adults, on a mg/m 2 basis. terbutaline sulfate should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.

Pediatric Use:

Pediatric use terbutaline sulfate injection is not recommended for patients under the age of 12 years because of insufficient clinical data to establish safety and effectiveness.

Geriatric Use:

Geriatric 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.

Overdosage:

Overdosage the median sc lethal dose of terbutaline sulfate in mature rats was approximately 165 mg/âkg (approximately 2,700 times the maximum recommended daily sc dose for adults on a mg/âm 2 basis). the median sc lethal dose of terbutaline sulfate in young rats was approximately 2,000 mg/kg (approximately 32,000 times the maximum recommended daily sc dose for adults on a mg/m 2 basis). the expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/âor 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 injection 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 injection.

Description:

Description terbutaline sulfate, usp, the active ingredient of terbutaline sulfate injection, usp, is a betaâadrenergic agonist bronchodilator available as a sterile, nonpyrogenic, aqueous solution in vials, for subcutaneous administration. each milliliter of solution contains 1 mg of terbutaline sulfate, usp (0.82 mg of the free base), sodium chloride for isotonicity, 0.055% edetate disodium dihydrate as a stabilizing agent, and hydrochloric acid for adjustment to a target ph of 4. terbutaline sulfate is (Â±)-a-[( tert âbutylamino) methyl]-3,5-dihydroxybenzyi alcohol sulfate (2:1) (salt). the molecular formula is (c 12 h 19 n0 3 ) 2 â¢h 2 so 4 and the structural formula is: terbutaline sulfate, usp is a white to gray-white crystalline powder. it is odorless or has a faint odor of acetic acid. it is soluble in water and in 0.1n hydrochloric acid, slightly soluble in methanol, and insoluble in chloroform. its molecular weight is 548.65. terbutaline sulfate structure

Clinical Pharmacology:

Clinical pharmacology terbutaline sulfate injection is a beta-adrenergic receptor agonist. in vitro and in vivo pharmacologic studies have demonstrated that terbutaline exerts a preferential effect on beta 2 âadrenergic receptors. while it is recognized that beta 2 -adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta 2 -receptors in the human heart, existing in a concentration between 10% to 50%. the precise function of these receptors has not been established (see warnings ). controlled clinical studies in patients given terbutaline subcutaneously have not revealed a preferential beta 2 -adrenergic effect. the pharmacologic effects of beta-adrenergic agonists, including terbutaline, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (atp) to cyclic 3â,5â-adenosine Read more...

monophosphate (camp). increased camp levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. controlled clinical studies have shown that terbutaline sulfate injection relieves bronchospasm in acute and chronic obstructive pulmonary disease by significantly increasing pulmonary flow rates (e.g., an increase of 15% or more in fev 1 ). after subcutaneous administration of 0.25 mg of terbutaline sulfate injection, a measurable change in expiratory flow rate usually occurs within 5 minutes, and a clinically significant increase in fev 1 occurs within 15 minutes. the maximum effect usually occurs within 30 to 60 minutes, and clinically significant bronchodilator activity may continue for 1.5 to 4 hours. the duration of clinically significant improvement is comparable to that observed with equimilligram doses of epinephrine. preclinical studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histological evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. the clinical significance of these findings is unknown. pharmacokinetics subcutaneous administration of 0.5 mg of terbutaline sulfate to 17 healthy, adult, male subjects resulted in 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 to 1.0) hours after dosing. the mean (sd) auc (0 to 48) and total body clearance values were 29.4 (14.2) hrâ¢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. after subcutaneous administration of 0.25 mg of terbutaline sulfate to two male subjects, peak terbutaline serum concentrations of 5.2 and 5.3 ng/ml were observed at about 20 minutes after dosing. elimination half-life of the drug in 10 of 14 patients was approximately 2.9 hours after subcutaneous administration, but longer elimination half-lives (between 6 to 14 hours) were found in the other 4 patients. about 90% of the drug was excreted in the urine at 96 hours after subcutaneous administration, with about 60% of this being unchanged drug. it appears that the sulfate conjugate is a major metabolite of terbutaline and urinary excretion is the primary route of elimination.

Pharmacokinetics:

Pharmacokinetics subcutaneous administration of 0.5 mg of terbutaline sulfate to 17 healthy, adult, male subjects resulted in 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 to 1.0) hours after dosing. the mean (sd) auc (0 to 48) and total body clearance values were 29.4 (14.2) hrâ¢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. after subcutaneous administration of 0.25 mg of terbutaline sulfate to two male subjects, peak terbutaline serum concentrations of 5.2 and 5.3 ng/ml were observed at about 20 minutes after dosing. elimination half-life of the drug in 10 of 14 patients was approximately 2.9 hours after subcutaneous administration, but longer elimination half-lives (between 6 to 14 hours) were found in the other 4 patients. about 90% of the drug was excreted in the urine at 96 hours after subcutaneous admi Read more...

nistration, with about 60% of this being unchanged drug. it appears that the sulfate conjugate is a major metabolite of terbutaline and urinary excretion is the primary route of elimination.

Carcinogenesis and Mutagenesis and Impairment of Fertility:

Carcinogenesis, mutagenesis, impairment of fertility in a 2-year study in sprague-dawley rats, terbutaline sulfate caused a significant and doseârelated increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 50 mg/âkg and above (approximately 810 times the maximum recommended daily subcutaneous (sc) dose for adults on a mg/m 2 basis). in a 21-month study in cd-1 mice, terbutaline sulfate showed no evidence of tumorigenicity at dietary doses up to 200 mg/kg (approximately 1,600 times the maximum recommended daily sc dose for adults on a mg/m 2 basis). the mutagenicity potential of terbutaline sulfate has not been determined. reproduction 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/m 2 basis).

How Supplied:

How supplied terbutaline sulfate injection, usp, 1 mg/ml, is supplied at a volume of 1 ml contained in a 2 ml amber glass vial. each vial contains 1 mg of terbutaline sulfate per 1 ml of solution; 0.25 ml of solution will provide the usual clinical dose of 0.25 mg. ndc 0143-9375-10 carton of 10 vials. store at 20Â° to 25Â°c (68Â° to 77Â°f) [see usp controlled room temperature]. protect from light by storing vials in original carton until dispensed. do not use if solution is discolored. discard unused portion after single patient use. manufactured by: hikma farmacÃutica (portugal), s.a.. estrada do rio da mÃ³, nÂº 8, 8a e 8b - fervenÃ§a, 2705 â 906 terrugem snt, portugal distributed by: hikma pharmaceuticals usa inc. eatontown, nj 07724 usa novaplus is a registered trademark of vizient, inc. revised: october 2020 pin552-nov/2

Package Label Principal Display Panel:

Principal display panel ndc 0143-9375-01 rx only terbutaline sulfate injection, usp 1 mg/ml for subcutaneous use only plb488-nov.1

Principal display panel ndc 0143-9375-10 rx only terbutaline sulfate injection, usp 1 mg/ml for subcutaneous use only 10 x 1 ml single dose vials sterile, nonpyrogenic, aqueous solution for subcutaneous injection. do not use if solution is discolored. note: usual single dose is one-fourth of the vial contents. see prescribing information . pbx794-nov.1

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