Terbutaline

Terbutaline is an Anti-Asthmatic agent belonging to the Short-Acting Beta 2 Adrenergic Receptor Agonist Pharmacological class.Terbutaline is approved for the treatment of Bronchospasm, Emphysema, and Bronchial Asthma. Terbutaline achieved Tmax 0.5 hours and Cmax 9.6 ± ng/mL during subcutaneous injection of 0.5mg, whereas Terbutaline achieved Tmax 1.5 hours and Cmax 8.6 ± 3.6 ng/mL during oral administration of 0.5mg. The Volume of Distribution of Terbutaline was found to be 1.6L/kg. Terbutaline under sulphation or glucuronidation undergoes elimination. The subcutaneous dose elimination of Terbutaline is 40% after 72 hrs. While the Intravenous dose eliminated is 90% in urine.

The common side effects associated with Terbutaline are Headache, palpitations, nausea, nervousness, anxiety, dry mouth, etc.

Terbutaline is available in the form of oral tablets, Intravenous injections, subcutaneous injection powder, metered-dose inhalers, and syrups.

Terbutaline is available in Turkey, Thailand, the U.S., India, and Japan.

Terbutaline belonging to the pharmacological class of Short-Acting Beta 2 Adrenergic Receptor Agonist, acts as an Anti-asthmatic/Bronchodilator therapeutic agent. Terbutaline acts via a series of pathways causing increasing cAMP, thereby deactivating myosin light chain kinase and activating myosin light chain phosphate leading to smooth muscle relaxation in the bronchioles.Terbutaline hence leads to Bronchodilation of the smooth muscles and reverses bronchospasm in patients less than 12 yrs old.Terbutaline has a quick onset of action of 5 minutes, and the duration of action lasts up to 6 hours.Terbutaline achieved Tmax 0.5 hours and Cmax 9.6 ± ng/mL during subcutaneous injection of 0.5mg, whereas Terbutaline achieved Tmax 1.5 hours and Cmax 8.6 ± 3.6 ng/mL during oral administration of 0.5mg.

• Terbutaline oral tablet to be swallowed whole with water/liquid.
• Terbutaline subcutaneous injection should be administered under the skin subcutaneously.
• Terbutaline oral syrup is to be taken orally.
• Terbutaline Inhalation Powder should be used with the help of a inhalation device

Terbutaline can be used in the treatment of bronchospasm in patients more than 12 yrs old, bronchial asthma, and emphysema.

Terbutaline can help to relax bronchial smooth muscle leading to Bronchodilation and improving the patient's respiration.

Terbutaline is approved for use in the following clinical indications:

• Bronchospasm
• Emphysema
• Bronchial Asthma
• Premature Labor (OFF-LABEL INDICATION)

Asthma:

Oral dosage:

Patients above 16 yrs: 5 mg orally thrice a day at 6 hours intervals. If there are side effects occur, reduce to 2.5 mg orally 3 times daily. Max: 15 mg/day

Patients between 12-15 yrs: 2.5 mg orally 3 times daily (given every 6 hours while awake). Max: 7.5 mg/day.

For the treatment of bronchospasm, example- episodic wheezing or an asthma exacerbation, primary care or acute care management.

Subcutaneous dose

Patients 12 yrs. and above: 0.25 mg Terbutaline is administered subcutaneously once; In case of no significant improvement, it is repeated in 15 to 30 minutes. Consider alternative therapy if the patient fails to respond within another 15 to 30 minutes, But 0.5 mg should not be exceeded the total dose within a 4-hour period.

Patients between 02 -11 yrs: 0.01 mg/kg/dose (Max: 0.25 mg) is administered subcutaneously at an interval of 10 to 20 minutes up to 3 doses, or it is continued until IV infusion is initiated. One can repeat intermittent injection at an interval of 2 to 6 hours as per the need.

It is used for the treatment of bronchospasm due to chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis and emphysema).

Oral dosage

In Pregnant females

As per the FDA  oral Terbutaline should not be used for prevention as serious maternal cardiovascular safety concerns, increased fetal heart rate, and neonatal hypoglycemia can occur.

In Pregnant females

As per the FDA  oral Terbutaline should not be used for the prevention as serious maternal cardiovascular safety concerns, increased fetal heart rate, and neonatal hypoglycemia.

Subcutaneous dosage

In Pregnant females

In case of prolonged tocolysis (beyond 48 to 72 hours) of preterm labor due to the potential for serious maternal cardiovascular events, hence Terbutaline should not be used.

The duration and dosage of treatment should be as per the clinical judgment of the treating physician.

Inhalation powder Dose

In Adults

0.5 mg i.e. one inhalation orally, as needed. Repeated doses should be taken five minutes apart.

The maximum dose recommended is 3 mg i.e. six inhalations in 24 hours.

Patients 12 yrs. and above

0.5 mg i.e. one inhalation orally, as needed. Repeated doses should be taken five minutes apart.

The maximum dose recommended is 3 mg i.e. six inhalations in 24 hours.

Tablets: 2.5mg, 5mg,

Subcutaneous Injection: 0.5mg/ml,1 mg/ml

Inhalation: 0.5mg, 2.5mg

Tablets, syrups. Subcutaneous injection, Inhalation Powder, Turbuhaler.

To maintain good respiratory health, smoking cessation is a must.

Diet containing refined and high energy-dense foods, red and processed meat, added sugar, salt, preservatives, low antioxidants and vitamins, low fiber, food with a high glycemic index, and saturated and trans fat food needs to be restricted.

The dietary restriction should be individualized as per patient requirements.

Terbutaline may be contraindicated in the following:

• Hypersensitive to Sympathomimetic amines
• Hypersensitive to any components of the medication
• Paradoxical bronchospasm
• Patients with Pheochromocytoma, as sympathomimetic amines, cause increased heart rate and blood pressure.
• Used with caution in Hyperthyroidism patients
• In Diabetes Mellitus, as may lead to Ketoacidosis
• In pregnancy as it may cause fetal tachycardia, and cardiac issues in the pregnant woman, and therefore the drug should be withdrawn in case of prolonged tocolysis.
• Monoamine Oxidase Inhibitors/Antidepressants

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• Deterioration of Asthmatic Condition:

There might be a deterioration of the asthma condition over a period of time. The increased usage of Terbutaline is a noted marker for the destabilization of the condition. Therefore a re-evaluation of the patient’s condition should be considered and the usage of anti-inflammatory agents such as corticosteroids should be considered.

• Anti-Inflammatory agent’s usage:

The use of Terbutaline alone might not be adequate to control asthmatic conditions, therefore early consideration of Corticosteroids should be taken.

• Cardiovascular events:

Terbutaline has a potential of causing Myocardial Ischemia , Cardiac Arrest , changes in the ECG curve such as flattening of the T segment, prolongation of Q-Tc segment and ST segment depression has been found to be associated with the beta 2 adrenergic agonist.

• Seizures:

Rare cases of seizures have been reported with the usage of Terbutaline.

• Hypokalemia:

Terbutaline causes a decrease in potassium levels which potentially produces adverse cardiac events. In acute asthma conditions, the use of Xanthine, Steroids and Diuretics should be avoided or closely monitored as it may lead to hypoxia

• Diabetes Mellitus:

During Terbutaline usage, a patient with Diabetes Mellitus condition, might suffer from hyperglycemia and will be unable to compensate in the condition of ketoacidosis

No established data for alcohol warning has been reported for Terbutaline

Terbutaline or the components of the drug medication has not been known to be excreted in milk but a decision should be made by the treating physician whether to continue or discontinue this medication and should be only used if the benefits outweigh the risks.

Pregnancy Category C

There is no well-known established data on Terbutaline use in pregnant women. Terbutaline dose of 15mg approximately 6.5 times the human dose in Animal studies shows alterations in behavior and brain development.

Oral Terbutaline has not been approved for acute or maintenance of Tocolysis, yet off-label, I.V. Administration is been done by an Obstetrician. Severe adverse effects have been reported while administering Terbutaline to pregnant women. These adverse effects include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia. No fetal abnormalities have been reported in animal studies, but a decision should be made by the treating physician whether to continue or discontinue this medication and should be only used if the benefits outweigh risks.

No known interactions with food is noted.

The adverse reactions related to Terbutaline can be categorized as :

Common

• Tremor
• Anxiety
• Nervousness
• Somnolence
• Dizziness
• Nausea

Less Common

• Palpitations
• Cramps
• Hypokalemia

Rare

• Increased Heart Rate
• Irregular Heart Rate
• Flushing of face
• High levels of sugar/lactic acid in blood
• Fluid accumulation in lungs

The clinically relevant drug interactions of Terbutaline is briefly summarized here:

Monoamine Oxidase Inhibitors or Anti-Depressants: Patients should be monitored closely or an alternate therapy must be considered while using Terbutaline as it might lead to some cardiovascular events in patients.

Beta-blockers or Sympathomimetics: Terbutaline should not be concomitantly administered with the beta-blockers as it might worsen the patient’s respiratory condition. In the condition of myocardial infraction use of cardio selective beta-blockers should be considered with caution

Diuretics: The use of loop diuretics and thiazide diuretics might worsen the condition of the patient under the treatment of Terbutaline such as hypokalemia and ECG changes.

The common side effects of Terbutaline include the following:

• Dizziness
• Tremors
• Palpitations
• Anxiety
• Insomnia
• Tachycardia
• Headache
• Dry mouth

The use of molecule Terbutaline should be prudent in the following group of special populations

• Breastfeeding Warning of Terbutaline

Terbutaline or the components of the drug medication has not been known to be excreted in milk but a decision should be made by the treating physician whether to continue or discontinue this medication and should be only used if the benefits outweigh the risks.

• Pregnancy warning

Pregnancy Category C

There is no well-known established data on Terbutaline use in pregnant women. Terbutaline dose of 15mg approximately 6.5 times the human dose in Animal studies shows alterations in behavior and brain development.

Oral Terbutaline has not been approved for acute or maintenance of Tocolysis, yet off-label, I.V. Administration is been done by an Obstetrician. Severe adverse effects have been reported while administering Terbutaline to pregnant women. These adverse effects include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia. No fetal abnormalities have been reported in animal studies, but a decision should be made by the treating physician whether to continue or discontinue this medication and should be only used if the benefits outweigh the risks

Use in labor or delivery

The use of Terbutaline to provide relief from bronchospasm during uterine contractions should be restricted unless the benefits clearly outweigh the risks. Terbutaline is clearly known to cross the placenta, as the umbilical blood of the patients who underwent caesarian showed 11% to 48% of Terbutaline presence.

Pediatric use

Terbutaline is clearly not indicated in patients less than 12 yrs. of age as there is no enough clinical data.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of molecule Terbutaline.

Signs and symptoms associated with the over dosage include the following:

• Shakiness
• Tremor
• Hypoxia
• Seizures
• Angina
• Hypertension or Hypotension
• Dry mouth
• Palpitation
• Fatigue
• Malaise
• Insomnia
• Hypokalemia
• Lactic acidosis
• Metabolic acidosis

Treatment of overdosage includes:

• Immediate discontinuation of the treatment.
• Use of cardioselective beta-blocker eg: metoprolol, atenolol.
• Monitoring serum potassium levels

Pharmacodynamics

Terbutaline is indicated to treat reversibly bronchospasm in asthmatic patients with bronchitis and emphysema. Terbutaline is a beta-2 adrenergic receptor agonist .It has quick onset of action of 5 mins and the duration of action extends upto 6 hrs.

Pharmacokinetics

• Absorption:

A subcutaneous dose of Terbutaline of about 0.5 mg achieves a median Tmax of 0.5 hours, a mean Cmax of 9.6 ± ng/mL, and a mean AUC of 29.4 ± 14.2 h*ng/mL. While a 5 mg oral Terbutaline tablet achieves a median Tmax of 2 hours, mean Cmax of 8.3 ± 3.9 ng/mL and a mean AUC of 54.6 ± 26.8 h*ng/mL. A 5 mg oral Terbutaline solution achieved a median Tmax of 1.5 hours, mean AUC achieved about 53.1 ± 23.5 h*ng/mL and a mean Cmax of 8.6 ± 3.6 ng/mL.

Oral Terbutaline achieved an oral bioavailability of 14-15%.

• Volume of distribution:

Terbutaline achieved mean volume of distribution of 1.6 L/kg.

• Protein binding

Terbutaline protein binding is not highly bound.

• Metabolism:

Terbutaline is sulfated or glucuronidated prior to elimination.

• Terbutaline Sulfate
• Terbutaline Glucuronide

• Route of elimination:

Terbutaline oral dose is 40% eliminated in the urine after 72 hours. Sulfate is the major metabolite found in the urine which is said to be the 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.

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• Spiller H (2014). Terbutaline. In Encyclopedia of Toxicology (Third Edition) (3rd ed., pp. 484-485). Elsevier.
• FDA Approved Drug Products: Bricanyl (Terbutaline Sulfate) Injection
• Dailymed: Terbutaline Sulfate Subcutaneous Injection
• Dailymed: Terbutaline Sulfate Oral Tablet

1. https://www.pdr.net/drug-summary/Terbutaline-Sulfate-Tablets-terbutaline-sulfate-1659#:~:text=Terbutaline sulfate is contraindicated in,been reported after terbutaline administration.
2. go.drugbank.com/drugs/DB00871
3. https://docs.boehringeringelheim.com/Prescribing Information/PIs/Ben Venue_Bedford Labs/55390-101-10 TBT 1MG/5539010110