Terbutaline

R03C - Adrenergics for systemic use ATC R03AC03 Small molecule approved 1974 Oral Parenteral Topical Natural product Black-box warning

JFDA label: Neoterb

⚠ Black-Box Warning

Prolonged tocolysis:

Mechanism of Action

Relaxes bronchial and uterine smooth muscle by action on beta2-receptors with less effect on heart rate

Indications

Approved

Asthma/Bronchospasm

Off-label

Extravasation management, sympathomimetic vasoconstrictors
Premature labor (acute
short-term [≤72 hours] tocolysis)

Contraindications

Source: Lexicomp

Hypersensitivity to terbutaline, sympathomimetic amines, or any component of the formulation Injection: Additional contraindications: Prolonged (>48 to 72 hours) tocolysis, especially for maintenance in the outpatient setting Oral: Additional contraindications: Acute or maintenance tocolysis Bricanyl Turbuhaler [Canadian product]: History of tachyarrhythmias Absolute
as tocolytic in patients at risk of premature labor or threatened abortion Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (2)

Common Hypertension · tachycardia

Nervous system disorders (6)

Very Common Nervousness · restlessness

Common Dizziness · drowsiness · headache · insomnia

Metabolism and nutrition disorders (2)

Very Common Decreased serum potassium · increased serum glucose

Gastrointestinal disorders (4)

Common Dysgeusia · nausea · vomiting · xerostomia

Skin and subcutaneous tissue disorders (1)

Common Diaphoresis

Musculoskeletal and connective tissue disorders (3)

Very Common Tremor

Common Muscle cramps · weakness

Dosing

Source: Lexicomp

Asthma/bronchospasm: Oral: 5 mg 3 times daily (approximately every 6 hours); reduce dose to 2.5 mg 3 times daily if side effects occur; maximum: 15 mg/24 hours SubQ: Manufacturer's labeling: 0.25 mg/dose; may repeat in 15 to 30 minutes (maximum: 0.5 mg/4-hour period) Off-label dose: 0.25 mg/dose; may repeat every 20 minutes for 3 doses (maximum: 0.75 mg/1-hour period) (NAEPP 2007) Inhalation: Bricanyl Turbuhaler [Canadian product]: One inhalation (0.5 mg) as needed; if not effective after 5 minutes may repeat dose. If second dose is not effective, consult healthcare provider immediately. Additional doses may be administered however >6 inhalations in a 24 hour period should not be needed. Note: If adequate relief is not obtained with previously effective dose, or if effects of inhalation last Extravasation management, sympathomimetic vasoconstrictors (off-label use; based on limited case reports): SubQ: Large extravasations: Infiltrate extravasation area using a solution of 1 mg diluted in 10 mL of 0.9% sodium chloride; volume of terbutaline solution administered varied from 3 to 10 mL (Stier 1999). Small/distal extravasations: Infiltrate extravasation area using a solution of 1 mg diluted in 1 mL of 0.9% sodium chloride; volume of terbutaline solution administered varied from 0.5 to 1 mL (Stier 1999). Premature labor (acute; short-term [≤72 hours] tocolysis) (off-label use): IV: 2.5 to 5 mcg/minute; increased gradually every 20 to 30 minutes by 2.5 to 5 mcg/minute up to a maximum of 25 mcg/minute; decrease to the lowest effective dose once contractions are controlled (Mackeen 2014; Travis 1993). SubQ: 0.25 mg every 20 minutes to 3 hours; hold for pulse >120 beats per minute. Terbutaline has not been approved for and should not be used for prolonged tocolysis (beyond 48 to 72 hours) (ACOG 171 2016; Hearne 2000).

(For additional information see "Terbutaline: Pediatric drug information") Asthma/bronchospasm: Oral: Children ≥12 years to Adolescents ≤15 years: 2.5 mg 3 times daily (approximately every 6 hours); maximum: 7.5 mg/24 hours Adolescents >15 years: Refer to adult dosing. SubQ: Children and Adolescents: ≥12 years: Refer to adult dosing. Inhalation: Bricanyl Turbuhaler [Canadian product]: Children ≥6 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Bronchospasm

Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.

Hypersensitivity reactions

Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported.

Serious effects/fatalities

Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Disease-related concerns:

Asthma

Appropriate use: When used as a bronchodilator, optimize anti-inflammatory treatment before initiating maintenance treatment with terbutaline. Do not use as a component of chronic therapy without an anti-inflammatory agent. Only the mildest form of asthma (Step 1 and/or exercise-induced) would not require concurrent use based upon asthma guidelines.

Cardiovascular disease

Use with caution in patients with cardiovascular disease (arrhythmia or hypertension or HF); beta-agonists may cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta2-agonists may also increase risk of arrhythmias.

Diabetes

Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose.

Glaucoma

Use with caution in patients with glaucoma; may elevate intraocular pressure.

Hyperthyroidism

Use with caution in hyperthyroidism; may stimulate thyroid activity.

Hypokalemia

Use with caution in patients with hypokalemia or taking concomitant drugs that cause hypokalemia; beta2-agonists may decrease serum potassium.

Preterm labor

Terbutaline is not FDA approved for and should not be used for prolonged tocolysis (>48 to 72 hours). Use for maintenance tocolysis should not be done in the outpatient setting. Adverse events observed in pregnant women include arrhythmias, increased heart rate, hyperglycemia (transient), hypokalemia, myocardial ischemia, and pulmonary edema. Heart rate may be increased in the fetus and hypoglycemia may occur in the neonate. Oral terbutaline is contraindicated for acute or chronic use in the management of preterm labor.

Seizures

Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation. Other warnings/precautions:

Patient information

Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use may indicate deterioration of asthma, and treatment must not be delayed.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies. Terbutaline crosses the placenta; umbilical cord concentrations are ~11% to 48% of maternal blood levels. Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Terbutaline is not recommended for the treatment of asthma during pregnancy; inhaled beta2-receptor agonists are preferred (NAEPP 2005). [US Boxed Warning]: Terbutaline is not FDA approved for and should not be used for prolonged tocolysis (>48 to 72 hours). Use for maintenance tocolysis should not be done in the outpatient setting. Adverse events observed in pregnant women include arrhythmias, increased heart rate, hyperglycemia (transient), hypokalemia, myocardial ischemia, and pulmonary edema. Heart rate may be increased in the fetus and hypoglycemia may occur in the neonate. Terbutaline has been used in the management of preterm labor. Tocolytics

Lactation

Terbutaline is excreted in breast milk; concentrations are similar to or higher than those in the maternal plasma. Based on information from four cases, exposure to the breast-fed infant would be 2-receptor agonists are not considered a contraindication to breast-feeding (NAEPP 2005).

Monitoring

Clinical pearl	Serum potassium, glucose; intake/output; heart rate, blood pressure, respiratory rate; chest pain, shortness of breath; monitor for signs and symptoms of pulmonary edema (when used as a tocolytic); monitor FEV1, peak flow, and/or other pulmonary function tests (when used as bronchodilator). If used for extravasation management, monitor and document extravasation site.

Chemistry & Properties

Formula	C12H19NO3
Molecular weight	225.29 g/mol
IUPAC name	5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol
CAS	23031-25-6
PubChem CID	5403
InChIKey	`XWTYSIMOBUGWOL-UHFFFAOYSA-N`
logP	1.52 (XLogP 0.9)
Polar surface area	72.72 Å²
H-bond acceptors / donors	4 / 4
Drug-likeness (QED)	0.63
Lipinski violations	0

SMILES

CC(C)(C)NCC(O)c1cc(O)cc(O)c1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2D6	Substrate	—

Receptor binding (top 3)

Target	Action	Affinity
β2-adrenoceptor (ADRB2)	Agonist	pEC50 7.3
β1-adrenoceptor (ADRB1)	Agonist	pEC50 5.8
adrenergic Beta2 (ADRB2)	Binding	pKi 5.6

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OCT1 (Substrate)OCT2 (Substrate)OCTN2 (Substrate)P-gp (Substrate)Transporter(unspecified) (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Amiodarone	major
Amisulpride	major
Anagrelide	major
Arsenic trioxide	major
Bedaquiline	major
Bepridil	major
Cabozantinib	major
Carteolol	major
Carteolol (ophthalmic)	major
Carvedilol	major
Ceritinib	major
Cisapride	major
Citalopram	major
Clozapine	major
Cocaine (nasal)	major
Cocaine (topical)	major
Crizotinib	major
Disopyramide	major
Dofetilide	major
Dolasetron	major
Dronedarone	major
Droperidol	major
Efavirenz	major
Escitalopram	major
Gatifloxacin	major
Grepafloxacin	major
Halofantrine	major
Haloperidol	major
Ibutilide	major
Iloperidone	major
Ivosidenib	major
Labetalol	major
Lefamulin	major
Levacetylmethadol	major
Levobunolol (ophthalmic)	major
Lumefantrine	major
Macimorelin	major
Mesoridazine	major
Methadone	major
Metipranolol (ophthalmic)	major

Showing 40 of 100+.

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Talin syrup	Syrup 1.5 mg/5 ml	60 ml	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	0.950
Neoterb	Suspension 1.5 mg/5 ml	100 ml	Reda Jardaneh Drug Store	1.080
Talin	Tablet 2.5 mg	30 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	1.300
Talin	Tablet 5 mg	30 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	2.000
Talin	Tablet 5 mg	1000 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	53.330