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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYMBICORT AEROSPHERE (SYMBICORT AEROSPHERE).
| Breastfeeding | Both budesonide and formoterol are excreted in breast milk in low amounts. Budesonide has an estimated M/P ratio of approximately 0.4. Formoterol M/P ratio is not well defined. At therapeutic doses, unlikely to cause adverse effects in breastfed infants. Caution with high doses due to potential beta-agonist effects (e.g., tachycardia). Consider risk-benefit. |
| 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. |
■ 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 |
["Status asthmaticus or other acute episodes of asthma where intensive measures are required","Hypersensitivity to any ingredient of SYMBICORT AEROSPHERE"]
| 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"] |
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| 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. |