SYMBICORT AEROSPHERE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMBICORT AEROSPHERE (SYMBICORT AEROSPHERE).
Budesonide is a corticosteroid with anti-inflammatory activity; its mechanism includes inhibition of multiple inflammatory cell types and mediators. Formoterol is a long-acting beta2-adrenergic agonist that relaxes bronchial smooth muscle by increasing cyclic AMP.
| Metabolism | Budesonide is extensively metabolized in the liver via CYP3A4 to its major metabolite, 16α-hydroxyprednisolone, with minimal glucocorticoid activity. Formoterol is metabolized via direct glucuronidation and O-demethylation, primarily by CYP2D6 and CYP2C19. |
| Excretion | Budesonide: 60% renal metabolites, 40% fecal. Formoterol: 60% renal, 40% fecal via biliary, with 10% unchanged drug. |
| Half-life | Budesonide: 2-3 hours. Formoterol: 10-14 hours. Clinically, twice-daily dosing maintains effect due to active metabolite accumulation. |
| Protein binding | Budesonide: 85-90% bound, primarily to albumin. Formoterol: 61-64% bound, to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Budesonide: 2.9-4.7 L/kg, indicating extensive tissue distribution. Formoterol: 2.0-2.5 L/kg, moderate distribution. |
| Bioavailability | Inhalation: lung deposition gives effective local bioavailability; oral bioavailability: budesonide 11% (first-pass), formoterol 46% (low oral bioavailability because of extensive metabolism). |
| Onset of Action | Inhalation: bronchodilation begins within 5 minutes for formoterol; full clinical effect within 15 minutes. Budesonide anti-inflammatory onset: hours to days. |
| Duration of Action | Formoterol: 12 hours (bronchodilation maintained over twice-daily interval). Budesonide: 12 hours or longer with regular use; anti-inflammatory effect persists with dosing. |
| Molecular Weight | Budesonide: 430.53 Da; Formoterol: 344.40 Da |
| Action Class | Inhaled Corticosteroid/Long-Acting Beta Agonist (ICS/LABA) |
Two inhalations (budesonide 160 mcg/formoterol 4.5 mcg per inhalation) twice daily (morning and evening). Maximum dose: 2 inhalations twice daily.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Consider reducing to 1 inhalation twice daily due to increased systemic exposure. Child-Pugh C: Not recommended; contraindicated as formoterol exposure may be significantly increased. |
| Pediatric use | Approved for ages 12 years and older: 2 inhalations of 160/4.5 mcg twice daily. For ages 6-11 years (SYMBICORT 80/4.5 mcg): 2 inhalations twice daily. Not indicated below 6 years. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Monitor for increased systemic corticosteroid effects and cardiovascular effects of formoterol, especially in patients with comorbid conditions. |
| 1st trimester | Insufficient human data; animal studies show no teratogenic effects at clinically relevant doses. Use only if potential benefit justifies risk. |
| 2nd trimester | Insufficient human data; potential risk of fetal growth restriction due to systemic corticosteroid exposure. |
| 3rd trimester | Insufficient human data; risk of neonatal adrenal suppression if used near term. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for SYMBICORT AEROSPHERE (SYMBICORT AEROSPHERE).
| Placental transfer | Budesonide crosses placenta; formoterol possibly crosses. Animal studies show transfer; human data limited. |
| Breastfeeding | Inhaled budesonide and formoterol are excreted into breast milk in low amounts. Consider risk-benefit; monitor infant for possible adrenal suppression or beta-adrenergic effects. |
■ FDA Black Box Warning
LABA monotherapy for asthma increases the risk of asthma-related death. SYMBICORT AEROSPHERE contains formoterol, a LABA. Its use should be reserved for patients not adequately controlled on low or medium dose inhaled corticosteroids or whose disease severity warrants initiation of both products. Data from a large placebo-controlled US study that compared safety of another LABA (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol.
| Common Effects | Headache Nausea Vomiting Stomach discomfort Dizziness Cough Nasopharyngitis inflammation of the throat and nasal passages Upper respiratory tract infection Sinus inflammation Fungal infection of oropharynx Tremors Palpitations Voice change |
| Serious Effects | Increased risk of asthma-related death, Adrenal insufficiency, Hypercorticism and adrenal suppression, Reduced bone mineral density, Cataracts and glaucoma, Pneumonia in patients with COPD, Hypersensitivity reactions including anaphylaxis, Cardiovascular effects (e.g., increased blood pressure, tachycardia) |
Severe hypersensitivity to budesonide, formoterol, or any excipientStatus asthmaticus or acute episodes of asthma requiring intensive measuresPrimary treatment of acute asthma exacerbation
Loading safety data…
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Pregnancy Category B. No teratogenic effects in animal studies. In humans, no increased risk of major congenital malformations has been observed. However, inhaled corticosteroids (budesonide) are associated with a minimal risk of low birth weight and potential adrenal suppression in neonates if used long-term at high doses. Formoterol is a beta-2 agonist; limited human data show no increased malformation risk. Use only if clearly needed, especially during first trimester. |
| Fetal Monitoring | Monitor maternal asthma control and lung function (e.g., peak expiratory flow). Assess fetal growth via serial ultrasound if poor maternal asthma control. Monitor for signs of adrenal insufficiency in neonates if maternal long-term high-dose use. No routine fetal heart rate monitoring required unless maternal hypoxia or severe asthma exacerbation. |
| Fertility Effects | No evidence of impaired fertility in animal or human studies with budesonide/formoterol. Asthma itself may impact fertility if poorly controlled; Symbicort improves asthma control and may indirectly improve fertility outcomes. No direct reproductive toxicity. |
| Precautions | Risk of asthma-related death with LABA use, Deterioration of disease and acute episodes should be treated with a short-acting beta2-agonist, Cardiovascular effects (e.g., increased heart rate, blood pressure, arrhythmias) due to formoterol, Hypersensitivity reactions including anaphylaxis, angioedema, urticaria, Adrenal insufficiency, particularly in patients transferring from systemic corticosteroids, Reduced bone mineral density with long-term use, Glaucoma, increased intraocular pressure, and cataracts, Eosinophilic conditions and Churg-Strauss syndrome, Hypercorticism and adrenal suppression with high doses or prolonged use, Paradoxical bronchospasm |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice with budesonide (potential to increase systemic corticosteroid exposure via CYP3A4 inhibition). |
| Clinical Pearls | SYMBICORT AEROSPHERE is a fixed-dose combination of budesonide (an inhaled corticosteroid) plus formoterol (a long-acting beta2-agonist). It is approved for maintenance treatment of asthma (ages ≥6 years) and COPD (including chronic bronchitis and/or emphysema). Rinse mouth with water (do not swallow) after each use to reduce oral candidiasis risk. It is not indicated for acute bronchospasm; use a rescue inhaler (SABA) for acute symptoms. Formoterol has a rapid onset (within 1-3 minutes) similar to albuterol but duration of 12 hours. Monitor for increased respiratory adverse events with LABA use in asthma (black box warning; only use in combination with an ICS). |
| Patient Advice | Use exactly as prescribed; do not stop or change dose without consulting your doctor. · Rinse mouth with water after each inhalation to prevent thrush. · Do not use for sudden breathing problems; have a rescue inhaler available at all times. · Shake the inhaler well for 5 seconds before each use. · Prime the inhaler with 4 test sprays into the air if new or not used for more than 7 days. · Do not exceed the recommended number of inhalations per day. · Contact your doctor if your breathing worsens or you need more rescue inhaler than usual. · Store at room temperature (20-25°C); avoid extreme heat or cold; do not freeze. |