Rx Only

Terbutaline sulfate USP is a beta-adrenergic agonist bronchodilator available as tablets of 2.5 mg (2.05 mg of the free base) and 5 mg (4.1 mg of the free base) for oral administration. Terbutaline sulfate is ±-α-[(tert –butylamino) methyl]-3,5-dihydroxybenzyl alcohol sulfate (2:1) (salt). The molecular formula is (C12H19NO3)2 • H2SO4 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.

Inactive Ingredients: lactose monohydrate, pregelatinized starch, microcrystalline cellulose, povidone, and magnesium stearate.

In vitro and in vivo pharmacologic studies have demonstrated that 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% to 50%. The precise function of these receptors has not been established (see WARNINGS). In controlled clinical studies in patients given terbutaline sulfate 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.

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 3’, 5’-adenosine 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 relieves bronchospasm in chronic obstructive pulmonary disease by significantly increasing pulmonary function (e.g., an increase of 15% or more in FEV1 and in FEF25%-75%). After administration of terbutaline sulfate tablets, a measurable change in flow rate usually occurs within 30 minutes, and a clinically significant improvement in pulmonary function occurs within 60 to 120 minutes. The maximum effect usually occurs within 120 to 180 minutes. Terbutaline sulfate also produces a clinically significant decrease in airway and pulmonary resistance, which persists for 4 hours or longer. Significant bronchodilator action (as measured by airway resistance, FEF25%-75% or PEFR) has also been demonstrated for up to 8 hours in some studies.

In studies comparing the effectiveness of terbutaline sulfate with that of ephedrine for up to 3 months, both drugs maintained a significant improvement in pulmonary function throughout this period of treatment.

Terbutaline sulfate 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.

1. Tocolysis

Oral terbutaline sulfate has not been approved and should not be used for acute or maintenance tocolysis. [see Boxed Warning: Tocolysis.]

2. Hypersensitivity

Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product.

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 the treatment regimen, giving special consideration to the possible need for anti-inflammatory 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 anti-inflammatory 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 occur, the drug may need to be discontinued. In addition, beta-agonists 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.

Adverse reactions observed with terbutaline sulfate are similar to those commonly seen with other sympathomimetic amines. All of these reactions are generally transient in nature and usually do not require treatment. The frequency of these side effects appears to diminish with continued therapy.

The following table lists the adverse reactions seen in 199 patients treated with terbutaline sulfate tablets during six double-blind crossover studies and four double-blind parallel studies (short- and long-term) performed in the United States.

The following adverse effects each occurred in fewer than 1% of patients: hallucinations, rash, paresthesia, hypertonia, (muscle cramps), vomiting.

There have been rare reports of elevations in liver enzymes and of hypersensitivity vasculitis.

Adults

The usual oral dose of terbutaline sulfate for adults is 5 mg administered at approximately six-hour intervals, three times daily, during the hours the patient is usually awake. If side effects are particularly disturbing, the dose may be reduced to 2.5 mg three times daily, and still provide a clinically significant improvement in pulmonary function. The total dose within 24 hours should not exceed 15 mg.

Children

Terbutaline sulfate is not recommended for use in children below the age of 12 years. A dosage of 2.5 mg three times daily is recommended for children 12-15 years of age. The total dose within 24 hours should not exceed 7.5 mg.

If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately as this is often a sign of seriously worsening asthma that would require reassessment of therapy.

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 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.

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.

Terbutaline sulfate tablets, USP are packaged in bottles of 100 and 1000 tablets. Descriptions of the 2.5 and 5 mg tablets follow:

Tablets 2.5 mg - White to off-white, oval tablets, scored on one side and engraved with “T132” on the other side

Bottles of 30     NDC 71205-938-30

Bottles of 60     NDC 71205-938-60

Bottles of 90     NDC 71205-938-90

Bottles of 100   NDC 71205-938-00

Bottles of 500   NDC 71205-938-55

Tablets 5 mg - White to off-white, round, scored and engraved “T” above and “133” below the score on the scored side.

Bottles of 30     NDC 71205-939-30

Bottles of 60     NDC 71205-939-60

Bottles of 90     NDC 71205-939-90

Bottles of 100   NDC 71205-939-00

Bottles of 500   NDC 71205-939-55

Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure

Manufactured for:

TWi Pharmaceuticals USA, Inc.
Paramus, NJ 07652

Manufactured by:

TWi Pharmaceuticals, Inc.
Taoyuan City, 32063, Taiwan

Rev. 07/19

Repackaged and Relabeled by:

Proficient Rx LP
Thousand Oaks, CA 91320

NDC 71205-938-30

TERBUTALINE SULFATE TABLETS, USP

2.5 mg

Rx Only

30 TABLETS

NDC 71205-939-30

TERBUTALINE SULFATE TABLETS, USP

5 mg

Rx Only

30 TABLETS