DALMAN Aqueous Nasal Spray, 50 mcg is an aqueous suspension of microfine fluticasone propionate for topical administration to the nasal mucosa by means of metering, atomizing spray pump.
Excipients/Inactive Ingredients: DALMAN AQ Nasal Spray also contains microcrystalline cellulose and carboxymethylcellulose sodium, dextrose, polysorbate 80, benzalkonium chloride, hydrogen phosphate disodium, citric acid and purified water as excipients.
Pharmacology: Pharmacodynamics: Fluticasone propionate is a potent corticosteroid with high affinity to the glucocorticoid receptors and used for the treatment of allergic rhinitis. It has potent topical anti-inflammatory effect and weak systemic activity.
In a trial to evaluate the potential systemic and topical effects of nasal spray on allergic rhinitis symptoms, the benefits of comparable drug blood levels produced by nasal spray and oral fluticasone propionate were compared. The doses used were 200 mcg of nasal spray, the nasal spray vehicle (plus oral placebo) and 5 and 10 mg of oral fluticasone propionate (plus nasal spray vehicle) per day for 14 days. Plasma levels were undetectable in the majority of patients after intranasal dosing, but present at low levels in the majority after oral dosing. Nasal spray was significantly more effective in reducing symptoms of allergic rhinitis. This trial demonstrated that the therapeutic effect of nasal spray is attributed to the topical effect of fluticasone propionate.
Fluticasone propionate has no effect on the hypothalamic-pituitary-adrenal (HPA) axis. When fluticasone propionate is applied on intranasal mucosa, a part of the drug is absorbed by nasal mucosa then transferred to systemic circulation and the remainder is eliminated by the nasal mucosal activation and by swallowing.
Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, neutrophils) and mediators (e.g. histamine, eicosanoids, leukotrienes, and cytokines). Corticosteroids do not have sudden effect on allergic symptoms.
Pharmacokinetics: Absorption: After intranasal application, fluticasone propionate has an absolute bioavailability averaging less than 2%. After intranasal treatment of patients with allergic rhinitis for 3 weeks, fluticasone propionate plasma concentrations were above the level of detection (50 ρg/ml). Due to the low bioavailability by the intranasal route, the majority of the pharmacokinetic data was obtained via other routes of administration. Studies using oral dosing of radiolabeled drug have demonstrated that fluticasone propionate highly extracted from plasma and absorption is low. Oral bioavailability is negligible and the majority of the circulating radioactivity is due to an inactive metabolite.
Distribution: Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 l/kg. The percentage of fluticasone propionate bound to human plasma proteins averaged 91 % with no obvious concentration relationship. Fluticasone propionate is weakly and reversibly bound to erythrocytes and freely equilibrates between erythrocytes and plasma. Fluticasone propionate is not significantly bound to human transcortin.
Metabolism: The total blood clearance of fluticasone propionate is high (average, 1.093 ml/min), with renal clearance less than 0.02% of the total. The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the cytochrome P450 3A4 pathway. This inactive metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacologic activity in studies.
Elimination: Following intravenous dosing, fluticasone propionate showed a terminal elimination half-life of 7-8 hours. Less than 5% of the dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.
DALMAN AQ Nasal Spray is indicated for the prophylaxis and treatment of seasonal allergic rhinitis (including hay fever) and perennial rhinitis.
For intranasal use only.
Patients should use DALMAN AQ Nasal Spray at regular intervals for optimal effect.
Greater symptom control may be achieved with scheduled regular use for 3-4 days.
Adults and 12 years of age and older: Seasonal allergic rhinitis and perennial rhinitis prophylaxis and therapy: the recommended starting dosage in adults is 2 actuations (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 200 mcg).
In some conditions 2 actuations in each nostril for 2 times a day will be recommended.
Once adequate control is achieved, the dosage should be decreased to 100 mcg (1 actuation in each nostril) daily.
The maximum total daily dosage should not exceed 4 actuations in each nostril.
Geriatrics: Same with adult dosage.
Children between 4 and 11 years of age: Seasonal allergic rhinitis and perennial rhinitis prophylaxis and therapy: the recommended starting dosage is 1 actuation (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 100 mcg).
In some conditions 2 actuations in each nostril for once a day will be recommended.
The maximum total daily dosage should not exceed 2 actuations in each nostril.
There is no adequate information about acute and chronic over dosage of DALMAN AQ Nasal Spray. Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate twice daily for 7 days to healthy human volunteers was well tolerated and doesn't effect HPA axis.
DALMAN AQ Nasal Spray is contraindicated in patients with a hypersensitivity to any of its ingredients.
Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery or nasal trauma should not use a nasal corticosteroid until healing has occurred.
The full benefit of DALMAN AQ Nasal Spray therapy may not be achieved until treatment has been administered for several days.
Although systemic effects have been minimal with recommended doses of DALMAN AQ Nasal Spray, potential risk increases with larger doses.
Although DALMAN AQ Nasal Spray will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy.
Care must be taken while transferring patients from systemic steroid treatment to DALMAN AQ Nasal Spray if there is any reason to suppose that their adrenal function is impaired.
The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, and in addition some patients may experience symptoms of withdrawal, e.g. joint and/or muscular pain and depression.
In those patients who have asthma or other clinical conditions requiring long term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms. The concomitant use of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis.
May cause suppression of HPA axis, particularly in younger children or in patients receiving high doses for prolonged periods. Fluticasone may cause less HPA axis suppression than therapeutically equivalent oral doses of prednisone. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving 20 mg per day of prednisone (or equivalent) may be more susceptible.
To minimize the systemic effects of orally-inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose.
May suppress the immune system; patients may be more susceptible to infection. Use with caution, if at all, in patients with systemic infections, active or quiescent tuberculosis infection, or ocular herpes simplex. Avoid exposure to chickenpox and measles.
How the dose, route, and duration of corticosteroid administration effect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Rare cases of vasculitis (Churg-Strauss syndrome) or other eosinophilic conditions can occur.
Fluticasone must not be inhaled in acute bronchospasm Status asthmaticus.
May also cause suppression of HPA axis, especially when used on large areas of the body, denuded areas, for prolonged periods of time or with an occlusive dressing.
Avoid spray to the eyes.
Effect on Driving or Machinery Operation: Any effect has not been observed.
Use in Children: Controlled clinical studies have shown that orally-inhaled or intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients.
Pediatric patients may be more susceptible to systemic toxicity. Safety and efficacy in pediatric patients < 3 months of age have not been established.
Pregnancy Category C.
Pregnancy: There are no adequate and well controlled studies using fluticasone in pregnant women. In reproduction studies, special adverse reactions of strong corticosteroids to application of high doses was observed.
After direct application systemic effect is minimum. DALMAN AQ Nasal Spray should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother.
Lactation: Excretion in breast milk unknown. But other corticosteroids are excreted to breast milk. There are no adequate and well-controlled studies using fluticasone in nursing women, usage is contraindicated in nursing mothers.
Oral or nasal inhalation:
Frequency depends upon population studied and dosing used. Reactions reported are representative of multiple oral formulations (> 3 %).
Central Nervous System:
Headache (2% to 22%), fever (1% to 7%).
Nausea / vomiting (1% to 8%).
Neuromuscular & skeletal:
Muscle injury (1% to 5%), musculoskeletal pain (1% to 5%), back problems (<1% to 4%).
Upper respiratory tract infection (14% to 22%), throat irritation (3% to 22%), nasal congestion (4% to 16%), pharyngitis (6% to 14%), oral candidiasis (<1% to 11%), sinusitis / sinus infection (3% to 10%), rhinitis (1% to 9%), dysphonia (<1% to 8%).
Viral infection (2% to 5%).
< 3 % (Limited to important or life threatening):
Aggression, agitation, cataracts, cholecystitis, Churg Strauss syndrome, Cushingoid features, depression, dyspnea, eosinophilic conditions, fungal skin infection, gastroenteritis, glaucoma, goiter, growth velocity reduction (in children / adolescents), increased intraocular pressure, lower respiratory infections, migraine, mood disorders, nasopharyngitis, nervousness, nose/throat polyps, oral ulcerations, paradoxical bronchospasm, paralysis of cranial nerves, photodermatitis, pruritus, skin rash, throat constriction, urticaria, vasculitis.
Contact the physician immediately in case of an unexpected effect.
Cytochrome P450 Effect: Substrate of CYP3A4.
Increased Effect / Toxicity: CYP3A4 inhibitors: Serum level and/or toxicity of fluticasone may be increased, this effect was shown with ketoconazole, but not erythromycin. Other potential inhibitors include amiodarone, cimetidine, clarithromycin, delavirdine, diltiazem, dirithromycin, disulfiram, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nevirapine, propoxyphene, quinupristin-dalfopristin, ritonavir, saquinavir, verapamil, zafirlukast, zileuton.
Salmeterol: The addition of salmeterol has been demonstrated to improve response to inhaled corticosteroids (as compared to increasing steroid dosage).
Ethanol / Nutrition / Herb Interactions: Herb / Nutraceutical: In theory, St John's Wort may decrease serum levels of fluticasone by inducing CYP3A4 isoenzymes.
Before using: 1. Shake the bottle gently and then remove the dust cover.
2. It is necessary to prime the pump into air the first time it is used, or when it has not been used for a week or more. To prime the pump, hold the bottle with the nasal applicator pointing away and with the forefinger and middle finger on either side of the nasal applicator and the thumb underneath the bottle. When the pump is primed for the first time, press down and release the pump for several times.
Using the spray: 3. Blow the nose to clear the nostrils.
4. Close one nostril. Tilt the head forward slightly and, keeping the bottle upright, carefully insert the nasal applicator into the other nostril.
5. Start to breathe in through the nose, and while breathing in, press firmly down once on the applicator to release the spray.
6. Breathe out through the mouth. If a second spray is required in that nostril, repeat steps 5 through 6.
7. Repeat the same steps in the other nostril.
After using: 8. Wipe the nasal applicator with a clean tissue and replace the dust cover.
Cleaning: 1. Remove the dust cover and wash the applicator under warm tap water.
2. Allow to dry at room temperature, avoid too hot.
3. Replace the applicator and dust cover back on the bottle.
4. If the nasal applicator becomes blocked, it can be removed as previously mentioned and left to soak in warm water. Rinse with cold tap water, dry, and refit. Do not try to unblock the nasal applicator by inserting a pin or other sharp object.
Keep in a dry place at room temperature below 25°C.
R01AD08 - fluticasone ; Belongs to the class of topical corticosteroids used for prophylaxis and treatment of allergic rhinitis.
Nasal spray 50 mcg/metered dose x 120 metered doses.