SYMBICORT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMBICORT (SYMBICORT).
Symbicort is a combination product containing budesonide, a corticosteroid, and formoterol fumarate dihydrate, a long-acting beta2-adrenergic agonist (LABA). Budesonide reduces inflammation by inhibiting inflammatory mediators and suppressing airway hyperresponsiveness. Formoterol stimulates beta2-adrenergic receptors in bronchial smooth muscle, leading to bronchodilation via increased cyclic AMP. The combination provides anti-inflammatory and bronchodilatory effects.
| Metabolism | Budesonide undergoes extensive first-pass metabolism in the liver via CYP3A4 (major pathway), forming metabolites with minimal glucocorticoid activity. Formoterol is metabolized primarily by direct glucuronidation and O-demethylation via CYP2D6 and CYP2C19, with subsequent conjugation. |
| Excretion | Budesonide: 60% renal (as metabolites), 40% fecal; Formoterol: 60% renal (as metabolites), 40% fecal. |
| Half-life | Budesonide: 2–3 hours (terminal); Formoterol: 10 hours (terminal). Clinical context: Twice-daily dosing maintains bronchodilation. |
| Protein binding | Budesonide: 85–90% (primarily albumin); Formoterol: 61–64% (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Budesonide: 2.7–4.3 L/kg (large, extensive tissue distribution); Formoterol: 3.4 L/kg (large, indicates wide distribution). |
| Bioavailability | Inhalation: Budesonide: 10–20% of metered dose (due to first-pass metabolism); Formoterol: ~50% of swallowed dose (low oral bioavailability, mostly from inhalation). |
| Onset of Action | Inhalation: Budesonide: 1–2 weeks for clinical effect; Formoterol: 1–3 minutes for bronchodilation. |
| Duration of Action | Inhalation: Budesonide: 12 hours (anti-inflammatory); Formoterol: 12 hours (bronchodilation). Note: Formoterol has a fast onset with prolonged duration. |
| Molecular Weight | Budesonide: 430.53 Da; Formoterol: 344.4 Da; Combination product: Not applicable. |
| Action Class | Inhaled Corticosteroid/Long-Acting Beta Agonist (ICS/LABA) |
1-2 inhalations (80/4.5 mcg or 160/4.5 mcg) twice daily; maximum 2 inhalations twice daily of 160/4.5 mcg.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; use caution in Child-Pugh C (not studied). |
| Pediatric use | Children 6-11 years: 1 inhalation of 80/4.5 mcg twice daily; Children ≥12 years: same as adult. |
| Geriatric use | No specific adjustment; use lowest effective dose due to potential for increased systemic effects. |
| 1st trimester | Limited data; use only if benefit justifies risk. Budesonide is preferred inhaled corticosteroid based on safety data. |
| 2nd trimester | Use if clearly needed; budesonide has favorable safety profile. Monitor fetal growth. |
| 3rd trimester | Use if indicated; formoterol may cause uterine contractions and fetal tachycardia; budesonide generally safe. |
Clinical note
Comprehensive clinical and safety monograph for SYMBICORT (SYMBICORT).
| Placental transfer | Budesonide undergoes incomplete placental metabolism (12-40% crosses). Formoterol crosses placenta in animal studies; human data limited. Both are considered to have low to moderate transfer. |
| Breastfeeding | Both budesonide and formoterol are excreted in breast milk in low amounts. Budesonide levels are negligible; formoterol levels are low. Benefits of asthma control outweigh theoretical risks. Use with caution, monitor infant for irritability or feeding issues. |
■ FDA Black Box Warning
WARNING: Long-acting beta2-adrenergic agonists (LABAs) such as formoterol increase the risk of asthma-related death. Data from a large placebo-controlled safety study (SMART) showed increased risk of asthma-related deaths in patients using salmeterol, another LABA. Therefore, Symbicort should only be used in asthma patients not adequately controlled on low- or medium-dose inhaled corticosteroids, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Symbicort is not indicated for the relief of acute bronchospasm.
| Common Effects | Nasopharyngitis, Headache, Upper respiratory tract infection, Pharyngolaryngeal pain, Sinusitis, Oral candidiasis, Dysphonia |
| Serious Effects | Increased risk of asthma-related death (LABA component), Adrenal insufficiency, Pneumonia in patients with COPD, Hypersensitivity reactions (anaphylaxis, angioedema), Cardiovascular effects (tachycardia, hypertension, QT prolongation) |
Hypersensitivity to budesonide, formoterol, or lactose (contains milk protein)Status asthmaticus or acute asthma exacerbation requiring intensive careSevere hypersensitivity reactions to any component
| Precautions |
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| Lactation Rating | L2 (Limited data - probably compatible) |
| Teratogenic Risk | Pregnancy Category C. Budesonide: increased risk of orofacial clefts and preterm birth in epidemiological studies. Formoterol: animal studies show fetal harm at high doses; no adequate human studies. Use only if potential benefit justifies risk. First trimester: consider risk of orofacial clefts. Second/third trimester: may cause fetal tachycardia, hypoglycemia with beta-agonist effects. |
| Fetal Monitoring | Monitor maternal asthma control, FEV1, peak flow, and symptoms. Fetal monitoring: ultrasound for growth restriction, preterm labor; nonstress test in third trimester if concerns. Monitor for maternal tachycardia, hyperglycemia, hypokalemia with formoterol. |
| Fertility Effects | No known adverse effects on human fertility from budesonide or formoterol. Animal studies show no impairment. |
| Increased risk of asthma-related death with LABA use; use only as recommended., Serious cardiovascular events including hypertension, tachycardia, and arrhythmias due to beta2-agonist effects., Hypersensitivity reactions including anaphylaxis, angioedema, and skin reactions., Adrenal insufficiency during stress or withdrawal of corticosteroid therapy., Candida albicans infections of the mouth and pharynx; rinse mouth after use., Pneumonia risk in COPD patients., Hypercorticism and adrenal suppression with excessive use or prolonged treatment., Paradoxical bronchospasm with immediate wheezing; discontinue therapy., Reduced bone mineral density with long-term use., Hypokalemia and hyperglycemia may occur., Not for acute bronchospasm. |
| Food/Dietary | No significant food interactions. Grapefruit juice is not known to interact with budesonide or formoterol. Maintain a balanced diet. Avoid excessive caffeine if you experience tremor or palpitations. |
| Clinical Pearls | Symbicort (budesonide/formoterol) is a fixed-dose combination of an inhaled corticosteroid (ICS) and a long-acting beta-2 agonist (LABA) for maintenance therapy of asthma and COPD. It should not be used for acute bronchospasm. Formoterol has a rapid onset of action (1-3 minutes), making it useful for as-needed use in some protocols. Monitor for adrenal insufficiency during stress. Rinse mouth after use to prevent oral candidiasis. Advise patients to be aware of paradoxical bronchospasm. |
| Patient Advice | Use Symbicort exactly as prescribed, usually twice daily (morning and evening) every day. · Do not use Symbicort to treat sudden breathing problems; always have a rescue inhaler (e.g., albuterol) available. · Rinse your mouth with water or brush teeth after each use to prevent thrush (yeast infection) and hoarseness. · Do not stop taking Symbicort without talking to your doctor, as your breathing may worsen. · Tell your doctor if your breathing does not improve or if you need to use your rescue inhaler more often. · Avoid foods that may trigger an allergic reaction if you have known allergies. No specific food interactions for this drug. · Store at room temperature away from moisture and heat. Keep the inhaler away from eyes. |