Usage
Fluticasone propionate + salmeterol is prescribed for the maintenance treatment of asthma in patients aged 4 years and older and for the long-term treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, in adults. This combination is indicated for patients whose asthma is not adequately controlled on inhaled corticosteroids alone or whose disease warrants the use of both an inhaled corticosteroid and a long-acting beta2-adrenergic agonist (LABA). It is not for the relief of acute bronchospasm or status asthmaticus.
This drug is classified as a combination corticosteroid and long-acting beta2-adrenergic agonist.
The combination works by reducing inflammation in the airways (fluticasone) and relaxing the airway muscles (salmeterol) to improve airflow and prevent asthma and COPD symptoms.
Alternate Names
This combination is commonly known as fluticasone/salmeterol. Brand names include Advair, Advair Diskus, Advair HFA, AirDuo Respiclick, and Wixela Inhub.
How It Works
Pharmacodynamics: Fluticasone propionate exerts its anti-inflammatory effects by binding to glucocorticoid receptors in the airways, leading to a reduction in inflammatory cell activation and mediator release. Salmeterol, a LABA, activates beta2-adrenergic receptors, relaxing airway smooth muscle and promoting bronchodilation.
Pharmacokinetics: Both drugs are administered via inhalation. Fluticasone propionate is absorbed systemically, primarily through the lungs, with limited oral bioavailability due to extensive first-pass metabolism in the gut and liver. Salmeterol reaches peak plasma concentration after inhalation with lipophilic distribution and metabolism mainly by CYP3A4 to inactive metabolites. Both drugs are excreted primarily in the feces, with a small portion through renal clearance.
Dosage
Standard Dosage
Adults:
- Asthma: 1 inhalation of fluticasone/salmeterol (100/50 mcg, 250/50 mcg, or 500/50 mcg) twice daily, approximately 12 hours apart. Maximum dose: 500/50 mcg twice daily.
- COPD: 1 inhalation of fluticasone/salmeterol 250/50 mcg twice daily, approximately 12 hours apart.
Children:
- Asthma (4–11 years): 1 inhalation of fluticasone/salmeterol 100/50 mcg twice daily, approximately 12 hours apart.
- Asthma (12 years and older): Same as adult asthma dosing.
- COPD: Not recommended for children.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required. Monitor for age-related organ dysfunction.
- Patients with Renal Impairment: No dosage adjustment is typically needed.
- Patients with Hepatic Dysfunction: Use with caution. Monitor for adverse events.
- Patients with Comorbid Conditions: Exercise caution in patients with diabetes, cardiovascular disease, hyperthyroidism, seizures, or osteoporosis.
Clinical Use Cases
Fluticasone/salmeterol is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations requiring immediate bronchodilation. For acute exacerbations of asthma or COPD, a short-acting beta2-agonist (SABA) should be used as a rescue medication.
Dosage Adjustments
Dosage adjustments may be necessary based on patient response and tolerance. If patients with asthma experience inadequate control on the starting dose, an increase in the dose strength can be considered. In COPD patients with an increased risk of inhaled corticosteroid side effects, a lower strength of fluticasone/salmeterol (125/25 mcg) can be considered.
Side Effects
Common Side Effects
Headache, throat irritation, upper respiratory tract infection, hoarseness, voice changes, thrush (oral candidiasis), cough, runny nose, nasal congestion, nausea, vomiting, muscle and bone pain.
Rare but Serious Side Effects
Severe allergic reactions (e.g., anaphylaxis, angioedema), paradoxical bronchospasm, pneumonia, adrenal suppression, hyperglycemia, increased risk of bone loss (osteoporosis), glaucoma, cataracts, effects on heart rhythm (QT prolongation).
Long-Term Effects
Prolonged use of inhaled corticosteroids can contribute to decreased bone mineral density and an increased risk of osteoporosis, especially at higher doses. Regular bone density monitoring may be considered in long-term users, particularly those at risk.
Adverse Drug Reactions (ADR)
Immediate hypersensitivity reactions, including urticaria, angioedema, and bronchospasm. Paradoxical bronchospasm manifested as increased wheezing and shortness of breath shortly after inhalation. Cardiac arrhythmias, including palpitations and tachycardia.
Contraindications
Absolute contraindications include primary treatment of status asthmaticus, severe hypersensitivity to milk proteins, and demonstrated hypersensitivity to either fluticasone propionate or salmeterol.
Drug Interactions
Clinically significant interactions can occur with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir), some antibiotics (e.g., clarithromycin, erythromycin), and beta-blockers. Concomitant use with other LABAs should be avoided. Interactions with OTC medications and supplements are possible.
Pregnancy and Breastfeeding
Pregnancy Safety Category: B3 (Australia), Not assigned (US FDA). Fluticasone/salmeterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. While studies in pregnant women are lacking, animal studies have shown adverse effects. The lowest effective dose should be used if deemed necessary during pregnancy.
Both fluticasone and salmeterol are excreted in breast milk, albeit at low concentrations after inhaled therapeutic doses. A decision to discontinue breastfeeding or the drug should be made considering the importance of the drug to the mother and potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Fluticasone: Inhaled corticosteroid reducing airway inflammation. Salmeterol: LABA relaxing airway smooth muscle.
- Side Effects: Common: Headache, throat irritation, thrush. Serious: Paradoxical bronchospasm, allergic reactions.
- Contraindications: Status asthmaticus, milk protein hypersensitivity.
- Drug Interactions: Strong CYP3A4 inhibitors (ketoconazole, ritonavir), some antibiotics.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Asthma/COPD: See detailed dosage section.
- Monitoring Parameters: Pulmonary function tests (FEV1, PEF), blood glucose (in diabetic patients), bone mineral density (long-term use).
Popular Combinations
Fluticasone/salmeterol is itself a combination product. Combining it with other LABAs is contraindicated. Short-acting beta2-agonists (SABAs) are used as rescue medications for acute exacerbations.
Precautions
- General Precautions: Assess for allergies, asthma severity, concomitant medications.
- Specific Populations: Monitor pregnant/breastfeeding women and pediatric patients.
- Lifestyle Considerations: Smoking cessation is crucial. Advise patients on proper inhaler technique.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluticasone Propionate + Salmeterol?
A: See the detailed dosage section above for adult, pediatric, and special population dosing recommendations.
Q2: Can Fluticasone/Salmeterol be used for acute asthma attacks?
A: No. It is a maintenance medication and not a rescue inhaler. Use a SABA like albuterol for acute attacks.
Q3: What are the most common side effects?
A: Common side effects include headache, throat irritation, and oral thrush.
Q4: Are there any serious drug interactions?
A: Yes, strong CYP3A4 inhibitors and some macrolide antibiotics can interact. Avoid concomitant use of other LABAs.
Q5: Can this combination be used during pregnancy?
A: Use with caution if the potential benefit justifies the potential risk. Consult with a specialist.
Q6: What should I monitor in patients using this medication long-term?
A: Monitor for adverse effects like oral thrush, lung function, blood glucose levels (in diabetic patients), and consider bone mineral density assessment.
Q7: Can patients stop taking Fluticasone/Salmeterol abruptly?
A: No, especially in asthma patients, gradual dose reduction under medical supervision is essential to avoid exacerbations.
Q8: What should I do if a patient experiences paradoxical bronchospasm?
A: Discontinue the medication immediately and prescribe a rescue inhaler (SABA). Consider alternative maintenance therapy.
Q9: What strength should I start with in patients with asthma not previously on ICS?
A: Consider starting with the low strength of fluticasone/salmeterol based on asthma severity.
Q10: How should patients clean their inhaler device?
A: Consult the manufacturer’s instructions for the specific inhaler device being used. Generally, the mouthpiece can be wiped with a dry cloth or tissue as needed.
