Aroflo-HFA

Uses

Inhaler:

This is used for the regular treatment of asthma where use of a combination product (long-acting ß2-agonist and inhaled corticosteroid) is appropriate:

• patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short acting ß2-agonist or
• patients already adequately controlled on both inhaled corticosteroid and long-acting ß2-agonist.

Inhalation Powder in Capsule:

Treatment of asthma: Fluticasone Propionate & Salmeterol Xinafoate combination is used for the treatment of asthma in patients aged 4 years and older. It is used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. It is not used for the relief of acute bronchospasm.

Maintenance treatment of chronic obstructive pulmonary disease: Fluticasone Propionate & Salmeterol Xinafoate combination is used for the maintenance treatment of airflow obstruction and to reduce exacerbations in patients with chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema.

Aroflo-HFA is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Allergy to Mold, Allergy; Dander, Asthma, Bacterial Sinusitis, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), Chronic Sinusitis, Dermatitis, Emphysema, House Dust Mite Allergy, House dust allergy, Itching of the nose, Nasal Congestion, Nonallergic Rhinitis, Oesophagitis, Eosinophilic, Perennial Rhinitis, Pollen Allergy, Rhinitis, Rhinorrhoea, Seasonal Allergic Rhinitis, Sneezing, Moderate, severe Perennial Allergic Rhinitis (PAR), Moderate, severe Seasonal Allergic RhinitisAsthma, Chronic Obstructive Pulmonary Disease (COPD), Exercise-Induced Bronchospasm

How Aroflo-HFA works

Fluticasone propionate works through an unknown mechanism to affect the action of various cell types and mediators of inflammation. Fluticasone propionate activates glucocorticoid receptors and inhibits lung eosinophilia in rats.

Beta-2 adrenoceptor stimulation causes relaxation of bronchial smooth muscle, bronchodilation, and increased airflow.

Salmeterol is hypothesized to bind to 2 sites on the beta-2 adrenoceptor. The saligenin moiety binds to the active site of the beta-2 adrenoceptor. The hydrophilic tail of salmeterol binds to leucine residues in the exo-site of the beta-2 adrenoceptor almost irreversibly, allowing salmeterol to persist in the active site, which is responsible for it's long duration of action.

Another hypothesis is that the lipophilic drug diffuses into lipid bilayer of smooth muscle cells and provides a depot of drug to the cells over a longer period of time.

Dosage

Aroflo-HFA dosage

Inhalation Aerosol:

Adults and adolescents 12 years and older: 2 puffs of 25 µg Salmeterol and 50 µg Fluticasone Propionate twice daily or 2 puffs of 25 µg Salmeterol and 125 µg Fluticasone Propionate twice daily or 2 puffs of 25 µg Salmeterol and 250 µg Fluticasone Propionate twice daily.

Children (4-12 years):2 puffs of 25 µg salmeterol and 50 µg Fluticasone Propionate twice daily.

Inhalation Powder in Capsule (For Asthma):

Adult and Adolescent (12 Years and Older): Salmeterol 50 µg & Fluticasone 100 µg orSalmeterol50 µg & Fluticasone 250 µg twice daily (morning and evening, approximately 12 hours apart).The recommended starting dosages forSalmeterol50 µg & Fluticasone100 µg &Salmeterol50 µg & Fluticasone 250 µg for patients aged 12 years and older are based upon patients asthma severity.The maximum recommended dosage isSalmeterol50 µg & Fluticasone 500 µg twice daily.

Pediatric Patients (4 to 11 Years): For patients with asthma who are not controlled on an inhaled corticosteroid, the dosage is Salmeterol50 µg & Fluticasone100 µg twice daily (morning and evening, approximately 12 hours apart).

Chronic obstructive pulmonary disease: Salmeterol50 µg & Fluticasone 250 µg twice daily (morning and evening, approximately 12 hours apart). Rinsing the mouth after each inhalation is advised

Side Effects

The common side effects experienced are oral candidiasis, pneumonia, immunosuppression hypercorticism, adrenal suppression, growth retardation, glaucoma and cataracts etc. The few side effects have been reported infrequently like ear signs and symptoms; nasal signs and symptoms; nasal sinus disorders; keratitis and conjunctivitis; dental discomfort and pain; gastrointestinal signs and symptoms; oral ulcerations; oral discomfort and pain; lower respiratory signs and symptoms; muscle stiffness, tightness, and rigidity; bone and cartilage disorders; sleep disorders; compressed nerve syndromes; chest symptoms; fluid retention; unusual taste; viral skin infections; disorders of sweat and sebum.

Toxicity

Fluticasone propionate's use in specific populations has not been well studied. Fluticasone propionate is not carcinogenic, mutagenic, or clastogenic, nor did it affect fertility in animal studies. Subcutaneous fluticasone propionate has been shown to produce teratogenic effects in rats though oral administration does not. Generally, there are no reported adverse effects with fluticasone in pregnancy. Fluticasone propionate in human milk may cause growth suppression, effects on endogenous corticosteroid production, or other effects. Pediatric patients treated with fluticasone propionate ointment experienced adrenal suppression. Geriatric patients treated with fluticasone propionate did not show any difference in safety or efficacy compared to other patient groups, though older patients may be more sensitive to adverse effects. There is no difference in the clearance of fluticasone propionate across genders or race. Patients with hepatic impairment should be closely monitored due to the elimination mechanism.

Patients experiencing an overdose have presented with metabolic acidosis, hyperlactatemia, anxiety, palpitations, chest pain, sinus tachycardia, ST depression, hypokalemia, hypophosphatemia. Though patients may also present with seizures, angina, hypertension or hypotension, arrhythmia, headache, tremor, muscle cramps, dry mouth, nausea, dizziness, fatigue, malaise, insomnia, and hyperglycemia. Patients should be given symptomatic and supportive treatment which may include intravenous fluids, potassium supplementation, a cardioselective beta-blocker, and cardiac monitoring.

Data regarding the LD₅₀ of salmeterol is not readily available.

Precaution

Fluticasone Propionate & Salmeterol Xinafoate combination should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or chronic obstructive pulmonary disease.

Fluticasone Propionate & Salmeterol Xinafoate combination should not be used for the relief of acute bronchospasm.

Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Interaction

The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate & Salmeterol Xinafoate combination is contraindicated because increased systemic corticosteroid and increased cardiovascular adverse effects may occur. Ketoconazole, beta-adrenergic receptor blocking agents and nonpotassium-sparing diuretics are also contraindicated.

Volume of Distribution

The volume of distribution of intravenous fluticasone propionate is 4.2L/kg. A study of 24 healthy Caucasian males showed a volume of distribution at steady state of 577L following intravenous administration.

In asthmatic patients, the volume of distribution of the central compartment is 177L and the volume of distribution of the peripheral compartment is 3160L.

Elimination Route

Intranasal bioavailability of fluticasone propionate is 10. Intranasal exposure results in the majority of the dose being swallowed. Topical absorption of fluticasone propionate is very low but can change depending on a number of factors including integrity of the skin and the presence of inflammation or disease. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 9.0%.

In asthmatic patients, a 50µg dose of inhaled salmeterol powder reaches a C_max of 47.897pg/mL, with a T_max of 0.240h, and an AUC of 156.041pg/mL/h.

Half Life

7.8 hours for intravenous fluticasone propionate. A study of 24 healthy Caucasian males shows a half life of 14.0 hours following intravenous administration and 10.8 hours following inhalation.

The half life of salmeterol is 5.5h.

Clearance

1093mL/min for fluticasone propionate. A study of 24 healthy Caucasian males showed a clearance of 63.9L/h following intravenous administration.

The average clearance of salmeterol in a group of asthmatic patients was 392L/h. Further data regarding the clearance of salmeterol is not readily available.

Elimination Route

Fluticasone propionate is mainly eliminated in the feces with 10,5.

Salmeterol is 57.4% eliminated in the feces and 23% in the urine. Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.

Pregnancy & Breastfeeding use

Pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration of Fluticasone Propionate & Salmeterol Xinafoate combination to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Contraindication

The use of Fluticasone Propionate & Salmeterol Xinafoate combination is contraindicated in the following conditions:

• Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required.
• Severe hypersensitivity to milk proteins.

Special Warning

Hepatic Impairment: Because Salmeterol is extensively metabolised by the liver, patients with hepatic impairment receiving the drug should be closely monitored.

Acute Overdose

Symptoms: Dizziness, HTN or hypotension, tremor, headache, tachycardia, hypokalaemia, seizures, angina, arrhythmias, nervousness, muscle cramps, dry mouth, palpitations, nausea, fatigue, malaise, insomnia, hyperglycaemia, metabolic acidosis.

Management: Symptomatic and supportive treatment. β-blockers may be considered but should be used with caution.

Storage Condition

• Protect from light, store in cool & dry place
• Do not store above 30° C.
• Keep out of the reach of children
• Protect from freezing
• Insert the ConviCap in the ConviHaler just prior to use to protect from deterioration by moisture.

Innovators Monograph

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