BUDESONIDE AND FORMOTEROL FUMARATE DIHYDRATE
Clinical safety rating: safe
Other adrenergic drugs can have additive cardiovascular effects Can cause paradoxical bronchospasm and increase the risk of asthma-related death.
Budesonide is a glucocorticoid receptor agonist that inhibits inflammatory mediators; formoterol is a long-acting beta2-adrenoceptor agonist that relaxes bronchial smooth muscle.
| Metabolism | Budesonide is extensively metabolized in the liver via CYP3A4 to 16α-hydroxyprednisolone and 6β-hydroxybudesonide; formoterol is metabolized via direct glucuronidation and O-demethylation by CYP2D6 and CYP2C19. |
| Excretion | Budesonide: Approximately 60% of the dose is excreted in urine as metabolites, with less than 10% as unchanged drug; about 40% is eliminated in feces via biliary excretion. Formoterol: Approximately 60% of the dose is excreted in urine (primarily as metabolites, with about 15-20% as unchanged drug) and 40% in feces. |
| Half-life | Budesonide: Terminal elimination half-life is approximately 2.5-4.5 hours in adults. Formoterol: Terminal elimination half-life is approximately 10-14 hours (after inhalation). The longer half-life of formoterol supports twice-daily dosing. |
| Protein binding | Budesonide: Approximately 85-90% bound to plasma proteins (primarily albumin). Formoterol: Approximately 50-61% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Budesonide: Volume of distribution (Vd) is approximately 2.5-4 L/kg, indicating extensive tissue distribution. Formoterol: Vd is approximately 3-4 L/kg after intravenous administration, also indicating wide distribution. |
| Bioavailability | Inhalation (via dry powder inhaler): Budesonide absolute bioavailability is approximately 25-35% (with 30-40% of the dose deposited in the lungs; swallowed fraction undergoes extensive first-pass metabolism). Formoterol absolute bioavailability from inhalation is approximately 46-61% (with about 30% of the dose reaching the lungs; oral bioavailability is low due to first-pass metabolism). |
| Onset of Action | Inhalation: Bronchodilation onset occurs within 1-3 minutes for formoterol; anti-inflammatory effects from budesonide begin within 24 hours but maximal benefit may take up to 2 weeks. |
| Duration of Action | Inhalation: Bronchodilation from formoterol lasts approximately 12 hours (supports twice-daily dosing). Budesonide provides sustained anti-inflammatory effect with regular use; duration exceeds 12 hours due to receptor occupancy. |
2 inhalations (160 mcg budesonide/4.5 mcg formoterol per inhalation) twice daily, morning and evening, for maintenance therapy of asthma. For COPD: 2 inhalations (160 mcg/4.5 mcg) twice daily.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No specific dose adjustment required for renal impairment. GFR-based modifications not established. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use with caution; consider dose reduction due to increased systemic exposure. Child-Pugh C: Not recommended due to lack of data. |
| Pediatric use | Children 6-11 years: 1 inhalation (80 mcg/4.5 mcg) twice daily. Children 12 years and older: same as adult dosing (160 mcg/4.5 mcg) twice daily. |
| Geriatric use | No specific dose adjustment required. Use with caution in elderly due to potential comorbidities and increased risk of adverse effects (e.g., pneumonia in COPD). Monitor for systemic corticosteroid effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other adrenergic drugs can have additive cardiovascular effects Can cause paradoxical bronchospasm and increase the risk of asthma-related death.
| FDA category | Animal |
| Breastfeeding | Budesonide: Excreted in breast milk in low amounts (M/P ratio ~0.2-0.3); infant dose <0.1% maternal weight-adjusted dose. Formoterol: Excreted in breast milk; unknown M/P ratio but likely low. Both are considered compatible with breastfeeding. Monitor infant for irritability or feeding difficulties. |
| Teratogenic Risk |
■ FDA Black Box Warning
Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death. Therefore, budesonide/formoterol should only be used in patients with asthma not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of both an inhaled corticosteroid and a LABA.
| Common Effects | COPD |
| Serious Effects |
Primary treatment of status asthmaticus or other acute episodes of asthma or COPD; hypersensitivity to budesonide, formoterol, or any ingredient.
| Precautions | Increased risk of asthma-related death with LABA use; paradoxical bronchospasm; cardiovascular effects including increased blood pressure and heart rate; hypokalemia; hyperglycemia; reduction in bone mineral density; adrenal insufficiency during stress or upon withdrawal; immunosuppression; oropharyngeal candidiasis; pneumonia in COPD patients; ocular effects like glaucoma and cataracts. |
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| Budesonide: Inhaled glucocorticoids are not associated with increased risk of major congenital malformations. Oral corticosteroids may increase risk. Formoterol: Beta-agonists are not teratogenic. Overall, low risk; avoid systemic exposure. First trimester: no increased malformations; second/third trimester: risk of maternal hypoglycemia, fetal tachycardia. Use if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal respiratory function (peak flow, FEV1). Assess fetal growth and well-being via ultrasound and non-stress tests if third trimester use. Monitor for maternal hyperglycemia, hypokalemia, or QT prolongation. Watch for signs of preterm labor. |
| Fertility Effects | No known adverse effects on fertility in humans. In animal studies, budesonide and formoterol did not impair fertility at clinically relevant doses. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase budesonide systemic exposure. No other specific food restrictions; however, maintaining a balanced diet is recommended. Grapefruit interaction is clinically significant. |
| Clinical Pearls | Budesonide/formoterol is a fixed-dose combination ICS/LABA indicated for maintenance therapy of asthma and COPD, not for acute bronchospasm. Use a spacer with metered-dose inhaler to optimize lung deposition. Rinse mouth after each dose to prevent oral candidiasis and dysphonia. Do not exceed recommended dose; excessive use may increase risk of pneumonia in COPD patients due to formoterol's rapid onset. For asthma, step-down therapy when well-controlled. Monitor for adrenal insufficiency during stress or if switching from systemic corticosteroids. Assess for paradoxical bronchospasm, hypokalemia, hyperglycemia, and QT prolongation. |
| Patient Advice | Use this inhaler exactly as prescribed every day, even if you feel well; do not use it for sudden breathing problems. · Rinse your mouth with water (do not swallow) after each use to reduce the risk of oral infections and hoarseness. · Contact your healthcare provider if your breathing worsens or you need more rescue inhaler puffs than usual. · Avoid foods or beverages that contain grapefruit or grapefruit juice, as they can affect how the medicine works. · Do not take more than the number of pips prescribed; doing so can increase side effects. · Tell your doctor about all medications you take, especially other asthma drugs, diuretics, beta-blockers, and antifungal or antiviral medicines. |