Terbutaline Sulfate

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.

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 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 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 1.3 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.

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 beta‐blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic 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.

DESCRIPTION Terbutaline Sulfate, USP, the active ingredient of Terbutaline Sulfate Injection, USP, is a beta‐adrenergic 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 (±)-a-[( tert ‐butylamino) methyl]-3,5-dihydroxybenzyI alcohol sulfate (2:1) (salt). The molecular formula is (C 12 H 19 N0 3 ) 2 •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

OVERDOSAGE The median sc lethal dose of terbutaline sulfate in mature rats was approximately 165 mg/‌kg (approximately 2,700 times the maximum recommended daily sc dose for adults on a mg/‌m 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/‌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 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.

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 20° to 25°C (68° to 77°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 FARMACÊUTICA (PORTUGAL), S.A.. Estrada do Rio da Mó, no 8, 8A e 8B - Fervença, 2705 – 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