ISOBUTALINE

Terbutaline was first synthesized in 1966 12 and described in the literature in the late 1960s and early 1970s.

It is a selective beta-2 adrenergic agonist used as a bronchodilator in asthmatic patients. 12, 16, 17 Terbutaline was granted FDA approval on 25 March 1974.

Terbutaline is indicated for prevention and reversal of bronchospasm in patients at least 12 years old, with asthma and reversible bronchospasm associated with bronchitis and emphysema. 16,

Terbutaline is a beta-2 adrenergic receptor agonist indicated to treat reversibly bronchospasm in asthmatic patients with bronchitis and emphysema. 16, 17 It has a short duration as the inhaled form is taken up to three times daily, and the therapeutic window is wide. 16, 17.

A 0.5 mg subcutaneous dose of terbutaline reaches a mean C max of 9.6 ± ng/mL, with a median T max of 0.5 hours, and a mean AUC of 29.4 ± 14.2 h*ng/mL.

A 5 mg oral terbutaline tablet reaches a mean C max of 8.3 ± 3.9 ng/mL with a median T max of 2 hours, and a mean AUC of 54.6 ± 26.8 h*ng/mL.

A 5 mg oral terbutaline solution reaches a mean C max of 8.6 ± 3.6 ng/mL, with a median T max of 1.5 hours, and a mean AUC of 53.1 ± 23.5 h*ng/mL.

Oral terbutaline has an oral bioavailability of 14-15%.

Terbutaline has a mean volume of distribution of 1.6 L/kg.

Terbutaline is sulphated or glucuronidated prior to elimination. 4, 5, 6, 9 Hover over products below to view reaction partners Terbutaline Terbutaline Sulfate Terbutaline Glucuronide.

An oral dose of terbutaline is 40% eliminated in the urine after 72 hours.

The major metabolite in the urine was the sulphate conjugated form of terbutaline.

Parenteral doses of terbutaline are 90% eliminated in the urine, with approximately 2/3 as the unchanged parent drug.

Less than 1% of a dose of terbutaline is eliminated in the feces.

An oral dose of terbutaline has an elimination half life of 3.4 hours, 17 while a subcutaneous dose has an elimination half life of 2.9 hours.

The average clearance of terbutaline is 3.0 mL/min/kg.

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Patients experiencing an overdose may present with abdominal pain, agitation, palpitations, seizures, angina, hypertension, hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, nausea, dizziness, fatigue, malaise, insomnia. 10, 16, 17 Discontinue treatment with terbutaline and initiate symptomatic and supportive therapy. 16, 17.

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.

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.

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.

There have been rare reports of seizures in patients receiving terbutaline; seizures did not recur in these patients after the drug was discontinued.

Oral terbutaline sulfate has not been approved and should not be used for acute or maintenance tocolysis. 2.

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

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.

Terbutaline sulfate tablets, USP are packaged in bottles of 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) .

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.

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/m 2 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 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 and 65 times, respectively, the maximum recommended daily oral dose for adults, on a mg/m 2 basis.

Terbutaline sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug is excreted in human milk.

Therefore, terbutaline sulfate should be used during nursing only if the potential benefit justifies the possible risk to the newborn.

Terbutaline sulfate is not recommended for patients under the age of 12 years because of insufficient clinical data to establish safety and effectiveness See DOSAGE AND ADMINISTRATION.

Clinical studies of terbutaline sulfate did not include sufficient numbers of subjects aged 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.