Tulobuterol Hydrochloride

• Approved Indications:
• Bronchial asthma: For symptomatic relief and maintenance treatment of bronchial asthma.
• Chronic obstructive pulmonary disease (COPD): To relieve bronchospasm and improve airflow in COPD patients.
• Bronchospasm associated with reversible airway obstruction: Including chronic bronchitis with bronchospasm.
• Clinically accepted off-label uses:
• Adjunct therapy in exercise-induced bronchospasm prevention.
• Maintenance therapy to reduce frequency and severity of asthma exacerbations.

• Adults:
• Transdermal patch: One patch applied once daily to intact, clean, dry skin on the chest or upper arm.
• Patch contains 2 mg or 4 mg of tulobuterol, depending on severity and physician discretion.
• Typically applied in the morning and worn for 24 hours; replaced daily.
• Elderly:
• Same dosing as adults; use with caution due to potential increased sensitivity to β2-agonists.
• Pediatrics:
• Safety and efficacy not well established; use only if clearly needed and under strict medical supervision.
• Special Populations:
• Renal impairment: No specific dose adjustments recommended; monitor clinical response.
• Hepatic impairment: Use cautiously; no formal dosage adjustment guidelines.
• Administration notes:
• Avoid application to irritated or broken skin.
• Do not apply heat sources (heating pads, electric blankets) over the patch as it may increase drug absorption.

Tulobuterol is a selective β2-adrenergic receptor agonist that stimulates β2 receptors on airway smooth muscle, leading to activation of adenylate cyclase and increased cyclic AMP levels. Elevated cAMP results in relaxation of bronchial smooth muscle, causing bronchodilation and improved airflow. The transdermal delivery provides sustained β2 stimulation, reducing bronchospasm frequency and severity. Additionally, β2 agonists may inhibit mediator release from mast cells, reducing airway inflammation indirectly.

• Absorption:
  Tulobuterol is absorbed transdermally; steady-state plasma concentrations are achieved after repeated daily patch application.
• Distribution:
  Moderate plasma protein binding (~30%).
• Metabolism:
  Extensively metabolized in the liver mainly by CYP enzymes into inactive metabolites.
• Elimination:
  Primarily renal excretion of metabolites.
• Half-life: Approximately 7 hours after transdermal administration.
• Onset of action: Within 30 minutes post-application, with effects lasting up to 24 hours.

• Pregnancy:
  Classified as FDA Pregnancy Category C. Animal studies have shown adverse effects at high doses; no adequate human studies. Use only if potential benefit justifies potential risk to fetus.
• Lactation:
  Unknown if excreted in human milk. Caution advised when administered to breastfeeding mothers; weigh benefits against potential infant risks.

• Primary class: Bronchodilator
• Subclass: Selective β2-adrenergic receptor agonist
• Delivery form: Transdermal β2-agonist

• Known hypersensitivity to tulobuterol or any component of the patch.
• Concurrent use with non-selective β-blockers (may reduce efficacy or precipitate bronchospasm).
• Severe cardiac arrhythmias or recent myocardial infarction where β2-agonists are contraindicated.

• Use cautiously in patients with cardiovascular disorders (e.g., hypertension, arrhythmias, ischemic heart disease).
• Monitor for signs of hypokalemia, which may be potentiated by β2-agonists.
• Risk of paradoxical bronchospasm; discontinue if occurs.
• Avoid abrupt discontinuation; taper if possible.
• Potential for tachycardia, palpitations, and tremor.
• Monitor skin at patch site for irritation or allergic dermatitis.

• Common:
• Nervous system: Tremor, headache
• Cardiovascular: Tachycardia, palpitations
• Skin: Local erythema, itching, rash at patch site
• Gastrointestinal: Nausea
• Less common:
• Dizziness, muscle cramps
• Insomnia
• Rare/Serious:
• Paradoxical bronchospasm
• Hypersensitivity reactions including angioedema
• Arrhythmias or worsening of pre-existing cardiac conditions

• Beta-blockers: May antagonize bronchodilatory effects of tulobuterol.
• MAO inhibitors and tricyclic antidepressants: May potentiate cardiovascular effects such as tachycardia and hypertension.
• Diuretics (non-potassium sparing): Increased risk of hypokalemia.
• Other sympathomimetics: Additive effects on heart rate and blood pressure.
• CYP450 inducers or inhibitors: May alter metabolism, though clinically significant interactions are rare with transdermal use.

• Guidelines continue to recommend tulobuterol as an effective transdermal β2-agonist option for maintenance therapy in asthma and COPD, especially in patients with difficulty using inhalers.
• Recent studies support its use for sustained bronchodilation with improved patient compliance due to once-daily application.
• No major new safety warnings; however, monitoring for cardiovascular effects remains emphasized.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from excessive moisture and heat.
• Keep patches in original sealed pouch until use.
• Avoid freezing or exposure to direct sunlight.
• Dispose of used patches safely to prevent accidental exposure.