rolenium

Uses

Fluticasone propionate is a glucocorticoid used to treat asthma, inflammatory pruritic dermatoses, and nonallergic rhinitis.

Fluticasone propionate is indicated as an inhaler for the treatment and management of asthma by prophylaxisas well as inflammatory and pruritic dermatoses. Fluticasone propionate nasal spray is indicated for managing allergic and nonallergic rhinitis.

Inhaled Salmeterol exerts a significant bronchodilating effect within 10 to 20 minutes of single-dose administration with asthma and this effect lasts for up to 12 hours or more. Salmeterol has a beneficial effect on airway mucociliary clearance that will reduce the incidence of respiratory tract infections.

Salmeterol produces a significant protective effect against Exercise Induced Asthma (EIA) for up to 9 to 12 hours in both adolescents and adults.

Salmeterol improves the overnight PEFR (Peak Expiratory Flow Rate) and controls the symptoms of the patients with nocturnal asthma. The use of Salmeterol avoids exposure of children to theophylline or high-dose corticosteroid, with their attendants risks.

Addition of Salmeterol to inhaled corticosteroid therapy is significantly more effective in terms of an improvement in lung function, symptom control and a reduction in the use of rescue bronchodilator therapy (use of short acting beta2-agonist).

Addition of Salmeterol to inhaled corticosteroid therapy also significantly reduces the use of inhaled corticosteroids

rolenium 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 rolenium 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

rolenium dosage

Inhalation/Respiratory-

Chronic asthma:

• Adult: As metered dose aerosol or dry powder inhaler: 50 mcg bid, or up to 100 mcg bid if necessary, in asthma patients with more severe airways obstruction.
• Child: 4-12 yr 50 mcg bid.

Prophylaxis of exercise-induced asthma:

• Adult: As metered dose aerosol or dry powd inhaler: 50 mcg at least 30 min prior to exercise.
• Child: ≥4 yr Same as adult dose.

Chronic obstructive pulmonary disease:

• Adult: As metered dose aerosol or dry powder inhaler: 50 mcg bid.

Side Effects

Dose related tremor, subjective palpitations and headaches are usually mild and transient. Skin reactions, muscle cramps, non-specific chest pain, local irritation and arthralgia have been reported.

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

Patient with CV disease, CNS disorders, DM, hyperthyroidism, hypokalaemia, seizure disorders, ketoacidosis. Not intended for the relief of acute bronchospasm. Hepatic impairment. Pregnancy and lactation.

Interaction

As with all the other beta2-agonists there may be interaction with betablocking agents at the receptor site when given concomitantly.

Monoamino Oxidase Inhibitors and Tricyclic Antidepressants : These agent should be used with caution because Salmeterol may be potentiated by these agents.

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. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Monotherapy in the treatment of asthma. Treatment of status asthmaticus, other acute episodes of asthma or COPD.

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

Store between 20-25° C. Protect from heat or sunlight.

Innovators Monograph

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