fluticasone and salmeterol

Action and Spectrum

Actions and spectrum: 

fluticasone: 

• Action: fluticasone is a corticosteroid medication that has potent anti-inflammatory effects. It acts by reducing inflammation in the airways, thereby relieving symptoms such as wheezing, shortness of breath, and cough. 
• Spectrum: fluticasone primarily targets the airways, reducing inflammation and improving lung function. It is effective in treatment and prevention of asthma symptoms, including both acute exacerbations and chronic symptoms. It is also used in the maintenance treatment of COPD. 

salmeterol: 

• Action: salmeterol is a long-acting beta-2 adrenergic agonist (LABA) medication. It acts by relaxing the smooth muscles of the airways, which helps to open the air passages and make breathing easier. It provides long-lasting bronchodilation. 
• Spectrum: salmeterol primarily targets the smooth muscles of the airways, causing relaxation and bronchodilation. It is used as a maintenance treatment to prevent asthma symptoms and to improve lung function in patients with COPD. It should not be used as a rescue medication for acute symptoms. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Throat irritation (7-9%) 

Bronchitis (2-8%) 

respiratory Viral infections (4-6%) 

Cough (3-6%) 

dysphonia or Hoarseness (2-5%) 

Diarrhea (2-4%) 

Oral candidiasis (1-4%) 

Fatigue or malaise (2-3%) 

nonspecific site, Candidiasis (0-10%) 

Musculoskeletal pain (2-9%) 

vomiting or nausea (4-6%) 

Sinusitis (4-5%) 

Fever (3-4%) 

GI discomfort (1-4%) 

Muscle spasms or cramps (3%) 

GI Viral infections (0-3%)  

>10% 

Headache (12-21%) 

URTI (21-27%) 

Pharyngitis (10-13%)  

Post marketing Reports 

Endocrine:  cushingoid features, hyperadrenocorticism, Cushing syndrome 

GI: dyspepsia, Abdominal pain, xerostomia 

Metabolic: weight gain, Hyperglycemia  

Neurologic: restlessness, Paresthesia 

Reproductive: Dysmenorrhea 

Dermatologic: photodermatitis, Ecchymoses  

Cardiac: ventricular tachycardia, Arrhythmias 

Eye: cataracts, central serous chorioretinopathy, Glaucoma, and blurred vision 

Immunologic: anaphylactic reaction, hypersensitivity reaction 

Musculoskeletal: cramps, osteoporosis, Arthralgia, myositis 

Psychiatric: aggression, behavioral changes, Agitation, depression 

Respiratory: tightness, oropharyngeal and facial edema, paradoxical bronchospasm, wheezing, Congestion, dyspnea, immediate bronchospasm, tracheitis 

Vascular: Pallor 

Black Box Warning

Black Box Warning: 

The combination of fluticasone and salmeterol does not have a specific black box warning 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: The combination of fluticasone and salmeterol is contraindicated in patients with hypersensitivity or allergic to either fluticasone or salmeterol. If an allergic reaction occurs, the medication should be discontinued. 
• Status asthmaticus: fluticasone and salmeterol combination therapy are contraindicated during episodes of acute bronchospasm or status asthmaticus. It is not intended for immediate relief of acute symptoms and should not be used as a rescue medication. 
• Severe hypersensitivity reactions: fluticasone and salmeterol should not be used in patients who have experienced severe hypersensitivity reactions, such as anaphylaxis, to similar medications or excipients present in the formulation. 
• Monotherapy for asthma: The combination of fluticasone and salmeterol should not be used as monotherapy for asthma. It is indicated for the maintenance treatment of asthma in patients who are not controlled on other asthma-controller medications, such as inhaled corticosteroids. 
• Children under 4 years of age: The use of fluticasone and salmeterol combination therapy is not recommended in children under 4 years of age. The safety and efficacy of this medication have not been established in this age group.

Caution: 

• Infections: fluticasone and salmeterol can increase the risk of respiratory tract infections, including pneumonia. It is important to monitor for signs and symptoms of infection and to use caution in patients with a history of recurrent infections. 
• Immunocompromised patients: Patients who are immunocompromised or taking immunosuppressive medications may be at increased risk of infections. Close monitoring is necessary in these individuals. 
• Cardiovascular effects: fluticasone and salmeterol may cause cardiovascular effects such as increased heart rate, blood pressure, and arrhythmias. It is important to monitor patients with cardiovascular conditions closely and adjust therapy, as necessary. 
• Ocular effects: Glaucoma and cataracts have been reported with the use of inhaled corticosteroids, including fluticasone. Regular eye examinations are recommended in patients with a history of increased intraocular pressure or glaucoma. 
• Hypokalemia: salmeterol, a long-acting beta-agonist, may cause hypokalemia (low potassium levels) in some individuals. Close monitoring of potassium levels is advised, especially in patients with a history of hypokalemia or those taking medications that can lower potassium levels. 
• Systemic corticosteroid effects: Prolonged use of high-dose inhaled corticosteroids may lead to systemic effects such as adrenal suppression. It is important to use the lowest effective dose of fluticasone and to monitor adrenal function in patients who are transitioning from systemic corticosteroid therapy. 
• Growth effects in children: Long-term use of inhaled corticosteroids, including fluticasone, may affect growth in children. Regular monitoring of growth is recommended, and the benefits of treatment should be carefully weighed against the potential risks.

Comorbidities: 

• Cardiovascular disease: Patients with a history of cardiovascular disease, like heart failure, coronary artery disease, or arrhythmias, may be at an increased risk of cardiovascular effects associated with long-acting beta-agonists (LABAs) like salmeterol. Close monitoring is advised in these individuals. 
• Hypertension: fluticasone and salmeterol may cause transient increases in blood pressure. Patients with poorly controlled hypertension should be closely monitored during treatment. 
• Diabetes: Glucocorticoids, including fluticasone, can affect glucose metabolism and may lead to hyperglycemia in patients with diabetes.  
• Osteoporosis: Prolonged use of high-dose inhaled corticosteroids, such as fluticasone, may increase the risk of osteoporosis and fractures. This is of particular concern in postmenopausal women and older adults.  
• Immunosuppression: Patients who are immunosuppressed or taking immunosuppressive medications may have an increased susceptibility to infections. Close monitoring and caution are advised in these individuals. 
• Liver disease: fluticasone is metabolized by the liver. Patients with severe liver impairment may have reduced clearance of the drug, and cautious use is recommended. Dose adjustments may be necessary. 
• Thyroid disorders: fluticasone can affect the hypothalamic-pituitary-adrenal (HPA) axis and may suppress the production of endogenous cortisol. Patients with thyroid disorders, including hypothyroidism or adrenal insufficiency, should be closely monitored during treatment. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

fluticasone: 

• fluticasone is a synthetic glucocorticoid with potent anti-inflammatory and immunosuppressive properties. 
• It acts by binding to glucocorticoid receptors, which results in the inhibition of multiple inflammatory pathways. 
• fluticasone reduces the production and release of pro-inflammatory cytokines, chemokines, and other mediators involved in the inflammatory response. 
• It also inhibits the infiltration of inflammatory cells into the airways and reduces mucus production. 
• fluticasone has a high affinity for glucocorticoid receptors, allowing for potent anti-inflammatory effects while minimizing systemic side effects. 

salmeterol: 

• salmeterol is a long-acting beta-agonist (LABA) that acts as a selective agonist for beta-2 adrenergic receptors. 
• It stimulates these receptors in the smooth muscle cells of the bronchioles, leading to bronchodilation. 
• salmeterol has a longer duration of action compared to short-acting beta-agonists, providing sustained bronchodilation for up to 12 hours. 
• It also has some anti-inflammatory effects by inhibiting the inflammatory mediators release from mast cells and other cells involved in the inflammatory response. 
• salmeterol is considered a controller medication and is used to prevent asthma symptoms and improve lung function over the long term. 

Pharmacodynamics: 

fluticasone: 

• fluticasone is a synthetic glucocorticoid that binds to glucocorticoid receptors in target cells. 
• Upon binding, fluticasone forms a complex with the glucocorticoid receptor and translocates to the nucleus. 
• In the nucleus, the fluticasone-glucocorticoid receptor complex binds to specific DNA sequences, known as glucocorticoid response elements (GREs). 
• This binding leads to the modulation of gene expression, resulting in various anti-inflammatory and immunosuppressive effects. 
• fluticasone reduces the production and release of pro-inflammatory cytokines, chemokines, and other mediators involved in the inflammatory response. 
• It also inhibits the activation and migration of inflammatory cells to the site of inflammation, thereby reducing airway inflammation. 
• Fluticasone has a local effect within the airways, minimizing systemic exposure and reducing the risk of systemic side effects associated with glucocorticoids. 

salmeterol: 

• salmeterol is a long-acting beta-agonist (LABA) that selectively stimulates beta-2 adrenergic receptors in the smooth muscle cells of the bronchioles. 
• Activation of beta-2 adrenergic receptors leads to the activation of adenylate cyclase, which increases intracellular levels of cyclic adenosine monophosphate (cAMP). 
• Elevated cAMP levels activate protein kinase A, which results in the phosphorylation of various proteins involved in smooth muscle relaxation. 
• The net effect is relaxation of the bronchial smooth muscle, leading to bronchodilation and improved airflow in the lungs. 
• salmeterol has a longer duration of action compared to short-acting beta-agonists, providing sustained bronchodilation for up to 12 hours.

Pharmacokinetics: 

Absorption 

• fluticasone: After inhalation, fluticasone is primarily absorbed into the lungs, where it exerts its local anti-inflammatory effects. The systemic absorption of inhaled fluticasone is minimal due to its low oral bioavailability. 
• salmeterol: Like fluticasone, salmeterol is also administered via inhalation. It is absorbed into the lungs and acts locally on the bronchial smooth muscles. Systemic absorption is limited, resulting in low oral bioavailability. 

Distribution 

• fluticasone: After absorption, fluticasone binds extensively to plasma proteins, to albumin. It has a high distribution volume, indicating its widespread distribution throughout the body tissues. 
• salmeterol: salmeterol also binds extensively to plasma proteins, primarily to albumin. It has a large distribution volume, suggesting its extensive distribution into the extravascular spaces. 

Metabolism 

• fluticasone: fluticasone undergoes extensive first-pass metabolism in the liver by the cytochrome P450 enzyme system, primarily CYP3A4. It is metabolized to inactive metabolites, which are further eliminated from the body. 
• salmeterol: salmeterol is metabolized in the liver by the cytochrome P450 enzyme system, primarily CYP3A4. It undergoes biotransformation to form its active metabolite, 4-hydroxy-salmeterol, which contributes to its prolonged duration of action. 

Elimination and excretion 

• fluticasone: The metabolites of fluticasone and a small portion of unchanged drug are eliminated primarily through the bile and feces. The renal excretion of fluticasone is minimal. 
• salmeterol: Following metabolism, the elimination of salmeterol and its metabolites occurs primarily through the feces. 

Adminstartion

Administration: 

• Shake the inhaler: Before each use, shake the inhaler well to ensure proper mixing of the medication. 
• Prepare the inhaler: If it is a new inhaler or has not been used for a while, prime the inhaler by releasing a few test sprays into the air. Follow the instructions provided with the inhaler for the priming process. 
• Breathe out: Exhale completely to ensure your lungs are empty before using the inhaler. 
• Use proper technique: Hold the inhaler in a level, horizontal position, with the mouthpiece facing away from you.  
• Inhale deeply: While breathing in slowly and deeply through mouth, press down on the canister to release the medication. Continue to inhale until your lungs are full. 
• Hold breath: After inhaling, remove the inhaler from mouth and hold breath upto 10 seconds to reach the airways. 
• Exhale slowly: Exhale slowly and comfortably away from the inhaler. 
• Repeat if necessary: If instructed to take multiple inhalations, wait for about 30 seconds to 1 minute between inhalations and repeat the process. 
• Rinse mouth (if applicable): If instructed by your healthcare provider, rinse your mouth with water and spit it out after using the inhaler. This helps reduce the risk of oral thrush or other side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fluticasone and salmeterol 

Pronounced: (flute-i-KAY-zone/sal-ME-teh-rol)  

Why do we use fluticasone and salmeterol? 

• Asthma: fluticasone and salmeterol combination inhaler are used as a long-term controller medication for the prevention and management of asthma symptoms in adults and children over the age of 4. It helps to reduce airway inflammation and improve lung function, thus reducing the frequency and severity of asthma attacks. 
• COPD: fluticasone and salmeterol combination inhaler are also prescribed for the maintenance treatment of COPD, including chronic bronchitis and emphysema, in adults. It helps to improve lung function, reduce symptoms such as shortness of breath and cough, and prevent exacerbations or flare-ups.