Introduction
Wixela Inhub is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) medication delivered via a breath-actuated dry powder inhaler device. It contains fluticasone propionate (an ICS) and salmeterol (a LABA) in fixed-dose combination. Wixela Inhub is the first FDA-approved generic version of Advair Diskus, providing a more affordable option for patients requiring this maintenance therapy for respiratory conditions.
Mechanism of Action
Fluticasone propionate: A synthetic trifluorinated corticosteroid with potent anti-inflammatory effects. It inhibits multiple inflammatory cytokines, reduces mucosal inflammation, decreases airway hyper-responsiveness, and inhibits inflammatory cell activation and migration. Salameterol xinafoate: A long-acting selective beta2-adrenergic receptor agonist that stimulates intracellular adenyl cyclase, increasing cyclic AMP levels. This results in relaxation of bronchial smooth muscle and inhibition of immediate-release mediators from mast cells.The combination provides complementary mechanisms: fluticasone addresses underlying inflammation while salmeterol provides prolonged bronchodilation.
Indications
- Asthma: Maintenance treatment of asthma in patients aged 4 years and older
- COPD: Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema
- Reduction of exacerbations: To reduce exacerbations in patients with COPD with a history of exacerbations
Dosage and Administration
Available strengths: 100/50 mcg, 250/50 mcg, and 500/50 mcg (fluticasone/salmeterol) Asthma:- Adults and adolescents ≥12 years: 1 inhalation twice daily (approximately 12 hours apart)
- Children 4-11 years: 100/50 mcg strength only, 1 inhalation twice daily
- Use the Inhub device without shaking
- Open the device fully until click is heard
- Slide lever away until click is heard
- Exhale fully away from mouthpiece
- Place mouthpiece between lips and inhale deeply and forcefully
- Hold breath for 10 seconds if possible
- Close device and rinse mouth after use
- Hepatic impairment: Use with caution
- Renal impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
Pharmacokinetics
Fluticasone propionate:- Absorption: Systemic bioavailability is low (18%) due to extensive first-pass metabolism
- Distribution: Extensive tissue distribution, volume of distribution ~4.2 L/kg
- Metabolism: Extensive hepatic metabolism via CYP3A4
- Elimination: Primarily fecal excretion (<5% renal excretion), terminal half-life ~8 hours
- Absorption: Systemic exposure is low due to extensive first-pass metabolism
- Distribution: Highly protein bound (96%) to albumin and alpha-1-acid glycoprotein
- Metabolism: Extensive hepatic metabolism via CYP3A4
- Elimination: Primarily fecal excretion, terminal half-life ~5.5 hours
Contraindications
- Primary treatment of status asthmaticus or other acute episodes of asthma or COPD
- Hypersensitivity to fluticasone propionate, salmeterol, or any component
- Significant hypersensitivity to milk proteins (contains lactose)
Warnings and Precautions
Boxed Warning:- LABA monotherapy increases risk of asthma-related death. Wixela Inhub should only be used in patients not adequately controlled on other asthma-controller medications or whose disease severity clearly warrants initiation of treatment with both an ICS and LABA.
- Paradoxical bronchospasm: Discontinue immediately if occurs
- Cardiovascular effects: May produce clinically significant cardiovascular effects
- Immunosuppression: Increased risk of infections
- Adrenal insufficiency: May occur after transfer from systemic corticosteroids
- Bone mineral density: Long-term administration may be associated with loss
- Glaucoma/cataracts: Long-term use may increase risk
- Hyperglycemia: May occur in some patients
- Hypokalemia: Beta-agonist may produce significant hypokalemia
Drug Interactions
Strong CYP3A4 inhibitors:- Ketoconazole, ritonavir, clarithromycin - may increase fluticasone and salmeterol concentrations
- Use with caution; consider alternative treatments
- May block bronchodilator effects and produce severe bronchospasm
- Use cardioselective beta-blockers with caution
- May worsen hypokalemia or ECG changes
- Monitor potassium levels
- May potentiate cardiovascular effects
- Use with extreme caution
Adverse Effects
Common adverse reactions (>1%):- Upper respiratory tract infection
- Pharyngitis
- Headache
- Hoarseness/dysphonia
- Oral candidiasis
- Throat irritation
- Cough
- Nausea/vomiting
- Asthma-related death
- Pneumonia in COPD patients
- Severe bronchospasm
- Cardiovascular effects
- Adrenal insufficiency
- Hypersensitivity reactions
- Immunosuppression
- Reduced bone mineral density
Monitoring Parameters
- Pulmonary function tests (FEV1, PEF)
- Asthma/COPD symptom control
- Exacerbation frequency
- Oral examination for candidiasis
- Growth velocity in pediatric patients
- Bone mineral density with long-term use
- Serum potassium and glucose levels
- Blood pressure and heart rate
- Signs/symptoms of adrenal insufficiency
- Ophthalmic exams with long-term use
Patient Education
- Not for rescue: This is a maintenance medication, not for acute symptoms
- Proper technique: Demonstrate and have patient demonstrate inhaler use
- Rinse mouth: After each use to prevent oral candidiasis
- Regular use: Use consistently twice daily, even when feeling well
- Device care: Keep dry; do not wash mouthpiece or any part of device
- Missed dose: Take as soon as remembered, but not if almost time for next dose
- Seek medical attention: If breathing problems worsen, need more rescue inhaler use, or experience chest pain, rapid heartbeat, or tremors
- Carry rescue inhaler: Always have a short-acting bronchodilator available
- Medical alert: Inform all healthcare providers about all medications being taken
- Never stop abruptly: Especially if switching from oral corticosteroids
References
1. FDA Prescribing Information: Wixela Inhub (fluticasone propionate and salmeterol inhalation powder). 2019. 2. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2022. 3. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2023. 4. Nelson HS, et al. The salmeterol multicentre asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129(1):15-26. 5. 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. 6. Peters SP, et al. Serious asthma events with budesonide plus formoterol vs. budesonide alone. N Engl J Med. 2016;375(9):850-860. 7. US National Library of Medicine. DailyMed - Wixela Inhub label. Accessed January 2023.