Fluticasone (Spray) Instructions for Use

Marketing Authorization Holder

Savapharm, LLC (Russia)

Manufactured By

Sava Medica, Ltd. (India)

ATC Code

R01AD08 (Fluticasone)

Active Substance

Fluticasone (Rec.INN registered by WHO)

Dosage Form

Fluticasone

Dosed nasal spray 50 mcg/dose: 12 ml (120 doses) bottle

Dosage Form, Packaging, and Composition

Dosed nasal spray as a white or almost white suspension.

Excipients: benzalkonium chloride – 10 mcg, phenylethanol – 250 mcg, polysorbate 80 – 100 mcg, avicel RC-591 – 1250 mcg, anhydrous dextrose – 5000 mcg, purified water – 0.1 ml.

12 ml (120 doses) – dark glass bottles (1) with a dosing device – plastic trays (1) – cardboard packs.

Clinical-Pharmacological Group

Inhaled corticosteroids

Pharmacotherapeutic Group

Topical glucocorticosteroid

Pharmacological Action

Mechanism of action

Fluticasone propionate is a substance with a strong anti-inflammatory effect. When administered intranasally, no significant systemic action or suppression of the hypothalamic-pituitary-adrenal system is observed.

No significant change in the daily area under the pharmacokinetic curve of serum cortisol was detected after administration of fluticasone propionate at a dose of 200 mcg/day compared to placebo (ratio: 1.01, 90% CI – confidence interval from 0.9 to 1.14).

Fluticasone propionate exerts an anti-inflammatory effect by interacting with glucocorticosteroid receptors. It suppresses the proliferation of mast cells, eosinophils, lymphocytes, macrophages, neutrophils; reduces the production of inflammatory mediators and other biologically active substances (histamine, prostaglandins, leukotrienes, cytokines) during the early and late phases of an allergic reaction. Fluticasone propionate has a rapid anti-inflammatory effect on the nasal mucosa, and its anti-allergic effect appears within 2-4 hours after the first application. It reduces sneezing, nasal itching, runny nose, nasal congestion, discomfort in the paranasal sinuses, and pressure sensation around the nose and eyes. In addition, it alleviates eye symptoms associated with allergic rhinitis. The reduction in symptom severity (especially nasal congestion) persists for 24 hours after a single spray administration at a dose of 200 mcg. Fluticasone propionate improves the quality of life of patients, including physical and social activity.

Pharmacokinetics

Absorption

After intranasal administration of fluticasone propionate at a dose of 200 mcg/day, the maximum equilibrium concentrations in plasma are quantitatively undetectable in most patients (less than 0.01 ng/ml). The highest plasma concentration was recorded at 0.017 ng/ml. Direct absorption from the nasal cavity is unlikely due to low water solubility and swallowing of most of the drug. Absolute oral bioavailability is low (less than 1%) due to a combination of incomplete absorption from the gastrointestinal tract and active first-pass metabolism in the liver. Thus, total systemic absorption is extremely low.

Distribution

Fluticasone propionate has a large volume of distribution at steady state (approximately 318 L). Plasma protein binding is high (91%).

Metabolism

Fluticasone propionate is rapidly eliminated from the systemic circulation primarily through metabolism in the liver to form an inactive carboxylic acid via the cytochrome P450 isoenzyme CYP3A4. The metabolism of the swallowed fraction of fluticasone propionate during first-pass through the liver occurs in the same way.

Excretion

The elimination of fluticasone propionate is linear in the dose range from 250 to 1000 mcg and is characterized by a high plasma clearance value (1.1 L/min). The maximum plasma concentration decreases by approximately 98% within 3-4 hours, and only at very low plasma concentrations was a terminal half-life of 7.8 h observed. The renal clearance of fluticasone propionate is insignificant (less than 0.2%), and that of the inactive metabolite, carboxylic acid, is less than 5%. Fluticasone propionate and its metabolites are mainly excreted in the bile through the intestines.

Indications

• Prevention and treatment of seasonal and perennial allergic rhinitis.

ICD codes

Dosage Regimen

For intranasal use only.

To achieve the full therapeutic effect, the drug must be used regularly. The maximum therapeutic effect may be achieved after 3-4 days of therapy.

Adults and children over 12 years

For the prevention and treatment of seasonal and perennial allergic rhinitis, 2 sprays into each nostril once a day, preferably in the morning (200 mcg per day). In some cases, 2 sprays into each nostril twice a day (400 mcg per day) can be used for a short time to achieve symptom control, after which the dose should be reduced.

Maximum daily dose – 400 mcg (no more than 4 sprays into each nostril).

Special patient groups

Elderly patients

Usual adult dose.

Children from 4 to 12 years

For the prevention and treatment of seasonal and perennial allergic rhinitis, 1 spray (50 mcg) into each nostril once a day, preferably in the morning. In some cases, 1 spray into each nostril twice a day may be required. Maximum daily dose – 200 mcg (no more than 2 sprays into each nostril).

Use of the inhaler

Before use, shake the bottle gently, hold it by placing the index and middle fingers on either side of the tip and the thumb under the bottom.

When using the drug for the first time or after a break in use of more than 1 week, check the sprayer’s functionality: point the tip away from you and press several times until a small cloud appears from the tip. Then, clear the nose (blow your nose). Close one nostril and insert the tip into the other nostril. Tilt your head slightly forward, continuing to hold the bottle vertically. Then, begin to inhale through the nose and, while continuing to inhale, press once with your fingers to spray the drug. Exhale through the mouth. Repeat the procedure for the second spray into the same nostril if necessary. Then completely repeat the described procedure, inserting the tip into the other nostril. After use, wipe the tip with a clean tissue or handkerchief and close it with the cap. The sprayer should be cleaned at least once a week. To do this, carefully remove the tip and rinse it in warm water. Shake off excess water and leave to dry in a warm place. Avoid overheating. Then carefully reattach the tip to its original place on the top of the bottle. Put on the protective cap. If the tip hole is clogged, the tip should be removed as described above and left in warm water for some time. Then rinse under a stream of cold water, dry, and reattach to the bottle. Do not clean the tip hole with a pin or other sharp objects.

Adverse Reactions

The adverse events listed below are presented according to the anatomical-physiological classification and frequency of occurrence. Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000), very rare (≥ 1/10,000, including isolated cases). Very common, common, and uncommon adverse events are mainly established based on clinical trial data. Events occurring rarely and very rarely are mainly determined from spontaneous reports. When determining the frequency of adverse events, background rates in the placebo group were not taken into account, as they were generally comparable to the active treatment group.

Immune system disorders

Very rare: hypersensitivity reactions (including bronchospasm, rash, facial and tongue swelling, anaphylactic reactions), anaphylactoid reactions.

Nervous system disorders

Common: headache, unpleasant taste and smell sensation. Headache, unpleasant taste and smell have also been reported with the use of other nasal sprays.

Eye disorders

Very rare: glaucoma, increased intraocular pressure, cataract. A causal relationship between intranasal use of fluticasone propionate and these events was not identified in clinical trials lasting up to one year.

Respiratory, thoracic and mediastinal disorders:

Very common: nosebleed.

Common: dryness in the nasal cavity and pharynx, irritation of the nasal and pharyngeal mucosa (reported as with the use of other intranasal drugs).

Very rare: nasal septum perforation (reported with the use of intranasal glucocorticosteroids).

Contraindications

• Hypersensitivity to fluticasone propionate or any other component of the drug;
• Children under 4 years of age.

With caution

• Concomitant use with strong inhibitors of the CYP3A4 isoenzyme, such as ritonavir and ketoconazole, may cause an increase in the plasma concentration of fluticasone propionate;
• With simultaneous use of other dosage forms of glucocorticosteroids;
• In the presence of nasal cavity or paranasal sinus infections. In this case, infectious diseases of the nose require appropriate treatment but are not a contraindication to the use of the nasal spray;
• After a recent nasal injury or surgery in the nasal cavity, or in the presence of ulcerations of the nasal mucosa.

Use in Pregnancy and Lactation

The drug can be prescribed to pregnant and breastfeeding women only in cases where the expected benefit to the patient outweighs any possible risk to the fetus or child.

Pediatric Use

For the prevention and treatment of seasonal and perennial allergic rhinitis, 1 spray (50 mcg) into each nostril once a day, preferably in the morning. In some cases, 1 spray into each nostril twice a day may be required. Maximum daily dose – 200 mcg (no more than 2 sprays into each nostril). Contraindicated in children under 4 years of age.

Geriatric Use

Usual adult dose.

Special Precautions

The drug is indicated for intranasal use only.

Without medical supervision, the nasal spray should not be used continuously for more than 6 months.

With long-term use, regular monitoring of adrenal cortex function is necessary.

There are reports of systemic effects with the use of nasal glucocorticosteroids in very high doses for a long time. These effects are much less likely than with oral forms of glucocorticosteroids and may vary among individual patients and between different glucocorticosteroid drugs.

Possible systemic effects may include Cushing’s syndrome, adrenal suppression, cataract, glaucoma, and, even more rarely, mental or behavioral disorders, including psychomotor hyperactivity, sleep disturbance, anxiety, depression, or aggression.

In children receiving glucocorticosteroids intranasally, a decrease in growth rate has been observed. Therefore, the lowest dose that provides adequate control of disease symptoms should be used as the maintenance dose in children.

The full effect of fluticasone propionate nasal spray may only appear after several days of treatment. To achieve the maximum therapeutic effect, it is necessary to adhere to a regular application schedule.

Caution should be exercised when transferring patients from systemic glucocorticosteroid therapy to treatment with fluticasone propionate nasal spray if there is reason to suspect adrenal dysfunction.

In most patients, fluticasone propionate nasal spray relieves the symptoms of seasonal allergic rhinitis, but in some cases, with very high concentrations of allergens in the air, additional therapy may be needed.

To relieve ophthalmic manifestations against the background of successful therapy for seasonal allergic rhinitis, additional therapy may be required.

Post-marketing surveillance has reported cases of systemic corticosteroid effects, such as Cushing’s syndrome and adrenal suppression, with the combined use of fluticasone propionate and ritonavir. Thus, concomitant use of ritonavir and fluticasone propionate should be avoided, except in cases where the potential benefit to the patient outweighs the possible risk of systemic corticosteroid side effects.

Effect on ability to drive vehicles and operate machinery

No data on the effect of the drug on the ability to drive vehicles have been obtained, but the side effects that the drug may cause should be taken into account.

Overdose

There are no data on acute or chronic overdose of fluticasone propionate.

In healthy volunteers, intranasal administration of 2 mg of fluticasone propionate twice daily for 7 days did not affect the function of the hypothalamic-pituitary-adrenal system (doses 20 times higher than the therapeutic dose). Use of the drug in doses higher than recommended for a long period of time may lead to temporary suppression of adrenal function.

In such patients, treatment with fluticasone propionate should be continued at doses necessary to control symptoms; recovery of adrenal function takes several days, its monitoring is carried out by measuring plasma cortisol levels.

Drug Interactions

Due to the very low plasma concentrations of fluticasone propionate after the use of the nasal spray, clinically significant interactions are unlikely.

Ritonavir (a highly active inhibitor of the cytochrome P450 enzyme system coenzyme CYP3A4) can significantly increase the plasma concentrations of fluticasone propionate, resulting in a sharp decrease in serum cortisol levels, and the occurrence of systemic side effects, including Cushing’s syndrome and adrenal suppression.

Inhibitors of the cytochrome P450 enzyme system isoenzyme CYP3A4 cause a negligible (erythromycin) or slight (ketoconazole) increase in the plasma concentrations of fluticasone propionate, which do not lead to any noticeable decrease in serum cortisol concentrations. Nevertheless, caution should be exercised when co-administering inhibitors of the cytochrome P450 enzyme system isoenzyme CYP3A4 (e.g., ketoconazole) and fluticasone propionate due to the possible increase in the plasma concentration of the latter. Post-marketing surveillance has reported cases of systemic corticosteroid effects, such as Cushing’s syndrome and adrenal suppression, with the combined use of fluticasone propionate and ritonavir. Thus, concomitant use of ritonavir and fluticasone propionate should be avoided, except in cases where the potential benefit to the patient outweighs the possible risk of systemic corticosteroid side effects.

Storage Conditions

Store in a dry place at a temperature not exceeding 25°C (77°F). Do not freeze. Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.