Tervent

Approved Indications

• Bronchial Asthma: For the relief and prevention of bronchospasm in adults and children with reversible obstructive airway diseases.
• Chronic Obstructive Pulmonary Disease (COPD): Including chronic bronchitis and emphysema, to manage acute episodes of bronchospasm.
• Premature Labor (Tocolysis) (Injectable formulation only in certain countries): Used as a tocolytic agent to delay preterm labor in specific clinical situations, although this use is restricted or not recommended in many regions due to safety concerns.

Clinically Accepted Off-Label Uses

• Exercise-Induced Bronchospasm (EIB): Used prior to exercise in individuals known to experience exercise-induced bronchospasm.
• Bronchiolitis (Pediatric): Occasionally used as a bronchodilator in infants, though evidence for efficacy is limited.

Route: Oral, subcutaneous, intravenous (IV), or inhalation (metered-dose inhaler or nebulizer).

Adults

• Oral Tablets: 2.5–5 mg three times daily. Maximum: 15 mg/day.
• Subcutaneous Injection: 0.25 mg every 15–30 minutes as needed; max: 0.5 mg in 4 hours.
• Nebulization: 2.5–5 mg diluted in 3 mL normal saline every 4–6 hours.

Pediatrics

• Oral Syrup/Tablets:
• Age 2–6 years: 0.05 mg/kg (max 2.5 mg) three times daily.
• Age 6–15 years: 2.5 mg three times daily.
• Inhalation (Nebulizer): 0.05–0.15 mg/kg/dose (max 5 mg) every 4–6 hours.

Geriatrics

• Initiate at the lower end of dosing range due to increased sensitivity. Monitor cardiovascular effects closely.

Renal/Hepatic Impairment

• Use with caution; no formal dosage adjustment established. Monitor adverse effects closely.

Tocolysis (IV infusion)

• Initial rate: 2.5 mcg/min IV infusion, titrated by 2.5 mcg/min every 20–30 minutes to max 25 mcg/min. Discontinue if maternal heart rate exceeds 120 bpm or signs of pulmonary edema occur.

Terbutaline sulfate is a selective β2-adrenergic receptor agonist. It binds to β2-receptors located primarily on bronchial smooth muscle, stimulating adenylate cyclase to convert ATP to cyclic AMP (cAMP). Increased cAMP activates protein kinase A, which inhibits phosphorylation of myosin and lowers intracellular calcium, leading to bronchial smooth muscle relaxation. This action results in bronchodilation, relief from bronchospasm, and improved airflow. In the uterus, β2 stimulation decreases myometrial contractility, leading to uterine relaxation, which underlies its tocolytic action.

• Absorption: Rapidly absorbed from the gastrointestinal tract after oral administration.
• Bioavailability: Approximately 14–15% due to extensive first-pass metabolism.
• Onset of Action:
• Oral: 30–60 minutes
• Inhaled: 5–15 minutes
• IV: Immediate
• Peak Effect:
• Oral: 2–3 hours
• Inhaled: 30–60 minutes
• Half-life: 3–6 hours
• Metabolism: Primarily hepatic via conjugation.
• Excretion: Mostly via urine (unchanged and metabolized); <1% in feces.
• Distribution: Widely distributed; crosses the placenta and may enter breast milk.

• Pregnancy:
• FDA Category B (Oral/inhaled): Animal studies do not show fetal risk; however, caution advised due to limited human data.
• IV Use for Tocolysis: Not recommended beyond 48–72 hours due to potential maternal cardiovascular risks (FDA warning).
• Lactation:
• Excreted into breast milk in small amounts. Use with caution; potential effects on the infant are minimal but monitor for irritability or tachycardia.
• Consider benefits versus risks for nursing mothers.

• Primary Class: Beta-2 Adrenergic Agonist (Bronchodilator)
• Subclass: Short-Acting Beta-2 Agonist (SABA)

• Known hypersensitivity to terbutaline sulfate or formulation excipients
• Use for prolonged tocolysis (beyond 48–72 hours of IV use)
• Significant cardiac arrhythmias or uncontrolled ischemic heart disease
• Preeclampsia or eclampsia when used for tocolysis
• Hyperthyroidism (relative contraindication; may exacerbate symptoms)

• Cardiovascular Risks: May cause tachycardia, palpitations, arrhythmias, or chest pain. Use with caution in patients with cardiac disorders.
• Tocolysis: Avoid prolonged use due to risk of maternal pulmonary edema, myocardial ischemia, and death.
• Diabetes: May cause transient hyperglycemia. Monitor blood glucose.
• Hypokalemia: Beta-agonists can cause potassium shift into cells, leading to hypokalemia. Monitor serum levels if used chronically or with diuretics.
• Seizures: Caution in seizure-prone individuals.
• Paradoxical Bronchospasm: Rare but life-threatening; discontinue immediately if this occurs.
• Elderly Patients: Higher risk of cardiac adverse effects. Start at lower doses.

Common Side Effects

• Nervous system: Tremor, headache, dizziness, nervousness
• Cardiovascular: Palpitations, tachycardia, chest pain
• Respiratory: Throat irritation (inhaled), cough
• Gastrointestinal: Nausea, vomiting
• Musculoskeletal: Muscle cramps

Serious Adverse Effects

• Cardiac arrhythmias
• Myocardial ischemia
• Pulmonary edema (especially with IV use)
• Severe hypokalemia
• Paradoxical bronchospasm

Rare Side Effects

• Seizures
• Allergic reactions (rash, urticaria, anaphylaxis)

Onset is usually within minutes to hours after dosing. Severity often dose-dependent and more prominent with systemic use.

• Beta-blockers (e.g., propranolol): Antagonize bronchodilatory effects; may provoke bronchospasm.
• MAO Inhibitors & Tricyclic Antidepressants: May enhance cardiovascular effects; avoid concurrent use or allow 2-week washout.
• Diuretics: Increased risk of hypokalemia, especially with loop or thiazide diuretics.
• Other Sympathomimetics: Increased risk of additive toxicity (tachycardia, hypertension).
• Digoxin: May decrease serum digoxin levels and increase risk of arrhythmia.
• Enzyme Involvement: Not extensively metabolized by CYP450; interactions mainly pharmacodynamic.

• FDA Warning (Tocolysis): Terbutaline should not be used for prolonged tocolysis (>48–72 hours) due to risk of maternal cardiac events.
• GINA Guidelines for Asthma: Terbutaline remains an option for relief of acute symptoms but is not recommended as monotherapy for maintenance.
• Pediatric Use: Some updated guidelines caution against routine use in infants with bronchiolitis due to limited efficacy.

• Oral Tablets/Syrup: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Inhalation Solutions: Store below 25°C; protect from light. Discard unused portion after use.
• Injection: Store at 20°C to 25°C; do not freeze. Protect from excessive heat.
• Handling Precautions: Do not use discolored solutions. Shake oral liquid before use. Use sterile technique for injections.