Symbicort - Drug Monograph

Introduction

Symbicort is a combination maintenance medication containing budesonide (an inhaled corticosteroid) and formoterol (a long-acting beta2-adrenergic agonist) indicated for the management of asthma and chronic obstructive pulmonary disease (COPD). It is delivered via pressurized metered-dose inhaler and represents a cornerstone therapy in respiratory disease management.

Mechanism of Action

Indications

• Maintenance treatment of asthma in patients 6 years and older
• Maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema
• Reduction of COPD exacerbations

• Exercise-induced bronchoconstriction (as preventive therapy)
• Step-down therapy in asthma management

Dosage and Administration

• Adults and adolescents (12+ years): 2 inhalations twice daily of either 80/4.5 mcg or 160/4.5 mcg strength
• Children (6-11 years): 2 inhalations twice daily of 80/4.5 mcg strength

• 2 inhalations twice daily of 160/4.5 mcg strength

• Shake well before each inhalation
• Prime before first use or if not used for 7 days
• Rinse mouth with water after inhalation to reduce risk of oropharyngeal candidiasis
• Not for relief of acute symptoms (requires separate short-acting bronchodilator)

• Hepatic impairment: No dosage adjustment required
• Renal impairment: No dosage adjustment required
• Elderly: No dosage adjustment required
• Pregnancy: Category C - use only if potential benefit justifies potential risk

Pharmacokinetics

• Budesonide: Systemic availability approximately 40% of metered dose
• Formoterol: Rapid absorption with peak plasma concentrations within 10-30 minutes

• Budesonide: Volume of distribution ~3 L/kg, 85-90% protein bound
• Formoterol: Volume of distribution ~4 L/kg, 50-65% protein bound

• Budesonide: Extensive first-pass metabolism via CYP3A4 to metabolites with minimal activity
• Formoterol: Metabolized via direct glucuronidation and O-demethylation via CYP2D6/2C19/2C9

• Budesonide: Primarily fecal elimination (60%), renal elimination (20%)
• Formoterol: 60% renal excretion, 40% fecal excretion
• Half-life: Budesonide ~2-3 hours, Formoterol ~10 hours

Contraindications

• Hypersensitivity to budesonide, formoterol, or any component
• Primary treatment of status asthmaticus or other acute episodes requiring intensive measures
• Acute exacerbations of asthma or COPD where intensive measures are required

Warnings and Precautions

• Long-acting beta2-adrenergic agonists may increase the risk of asthma-related death
• Not indicated for patients whose asthma is adequately controlled on low or medium-dose inhaled corticosteroids

• Paradoxical bronchospasm: Discontinue immediately if occurs
• Cardiovascular effects: May produce significant cardiovascular effects in some patients
• Reduction in bone mineral density with long-term corticosteroid use
• Glaucoma and cataracts with long-term use
• Adrenal insufficiency: Particularly during stress or after transfer from systemic corticosteroids
• Increased risk of pneumonia in COPD patients
• Hypersensitivity reactions: Anaphylaxis may occur
• Hypokalemia and hyperglycemia: May occur with beta-agonist component

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, ritonavir): May increase budesonide exposure and systemic effects
• Beta-blockers: May block bronchodilator effects and produce severe bronchospasm
• Diuretics: May potentiate hypokalemia and ECG changes
• MAO inhibitors, tricyclic antidepressants: May potentiate cardiovascular effects
• Other sympathomimetic agents: Additive effects may occur

Adverse Effects

• Headache (12%)
• Pharyngitis (8%)
• Upper respiratory tract infection (8%)
• Sinusitis (5%)
• Oral candidiasis (3%)
• Hoarseness/dysphonia (2%)
• Tremor (2%)
• Palpitations (2%)

• Pneumonia (COPD patients)
• Cardiovascular events (tachycardia, hypertension, arrhythmias)
• Severe bronchospasm
• Anaphylactic reactions
• Adrenal insufficiency
• Reduced bone mineral density
• Glaucoma and cataracts
• Hypokalemia

Monitoring Parameters

• Pulmonary function tests
• Height and weight (pediatric patients)
• Blood pressure and heart rate
• Oropharyngeal examination

• Pulmonary function regularly (FEV1, peak flow)
• Symptom control and exacerbation frequency
• Height monitoring in pediatric patients (every 3-6 months)
• Blood pressure and heart rate periodically
• Serum potassium in patients at risk
• Blood glucose in diabetic patients
• Signs of oral candidiasis
• Ophthalmologic exams with long-term use
• Bone mineral density with long-term use

• Signs of adrenal insufficiency

Patient Education

• Not for rescue of acute symptoms - always carry a short-acting bronchodilator
• Use regularly even when feeling well
• Rinse mouth with water after each use to prevent oral thrush
• Do not exceed prescribed dosage
• Recognize signs of worsening asthma/COPD
• Seek immediate medical attention for deteriorating respiratory status
• Inform all healthcare providers about Symbicort use
• Report palpitations, chest pain, or tremors
• Keep regular follow-up appointments
• Proper inhaler technique demonstration essential
• Storage: Room temperature, away from heat and flame
• Discard when counter reads 0 or after 3 months from opening

References

1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2023. 2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2024. 3. FDA Prescribing Information: Symbicort (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol. 4. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids. Eur Respir J. 2002;19(1):182-191. 5. Nelson HS, et al. The SMART study: results of a multicenter trial comparing the safety and efficacy of Symbicort with its monocomponents. J Allergy Clin Immunol. 2003;111:S218. 6. Calverley PM, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361(9356):449-456. 7. Pauwels RA, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet. 2003;361(9363):1071-1076.