Nazofan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Nasofan (Nasofan)

Composition:

Active substance: fluticasone propionate;

One dose contains fluticasone propionate 50 mcg;

Excipients: anhydrous glucose, microcrystalline cellulose and sodium carmellose (Avicel RC 591), phenethyl alcohol, benzalkonium chloride solution, polysorbate 80, purified water.

Pharmaceutical form. Nasal spray, suspension.

Main physicochemical characteristics: opaque thixotropic suspension, white or almost white.

Pharmacotherapeutic group. Anti-inflammatory and other agents for local use in nasal cavity disorders. Corticosteroids. ATC code R01AD08.

Pharmacological properties.

Pharmacodynamics.

Fluticasone propionate exerts a pronounced anti-inflammatory effect, but its systemic activity is minimal when administered intranasally. Fluticasone propionate does not suppress or suppresses to a very small extent the hypothalamic-pituitary-adrenal function. After intranasal administration of fluticasone propionate (at a dose of 200 mcg/day) over 24 hours, no significant change in plasma cortisol AUC was observed compared to placebo.

Pharmacokinetics.

After intranasal administration of fluticasone propionate (200 mcg/day), Cmax in plasma is not detectable in most patients (less than 0.01 ng/mL). The extent of direct absorption of the drug from the nasal cavity is negligible. Overall systemic absorption of the drug, including the portion of the dose that is swallowed, is also negligible.

Fluticasone propionate has a large volume of distribution—approximately 318 L. Plasma protein binding is moderately high at 91%.

Fluticasone propionate is rapidly eliminated from systemic circulation, primarily via hepatic metabolism into an inactive carboxylic acid metabolite by cytochrome P450 CYP3A4. Caution should be exercised when co-administering with strong CYP3A4 inhibitors, such as ketoconazole and ritonavir, due to the potential for increased systemic exposure to fluticasone propionate.

The main route of elimination is fecal excretion, primarily as unchanged, unabsorbed drug. Renal clearance of fluticasone propionate is very low (less than 0.2%).

Clinical characteristics.

Indications.

Prophylaxis and treatment of perennial and seasonal allergic rhinitis (including hay fever).

Contraindications.

Hypersensitivity to fluticasone propionate or to any of the other components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Experimental studies have not revealed any significant effect of fluticasone propionate on the pharmacokinetics of terfenadine and erythromycin.

Under normal conditions, very low plasma concentrations of fluticasone propionate are achieved after intranasal administration due to extensive first-pass metabolism and high systemic clearance of the drug mediated by cytochrome P450 3A4 in the liver and intestine. Therefore, the likelihood of clinically significant drug interactions mediated by fluticasone propionate is very low.

Caution should be exercised when administering fluticasone propionate to patients who are concurrently taking medicinal products that are strong inhibitors of the cytochrome P450 3A4 system (e.g., protease inhibitors such as ritonavir). It has been reported that co-administration of intranasal fluticasone propionate with ritonavir (a strong inhibitor of cytochrome P450 3A4) at a dose of 100 mg twice daily to healthy volunteers may result in a significant increase in plasma concentrations of fluticasone propionate (by several hundred-fold), leading to a substantial reduction in serum cortisol concentration. Clinically significant interactions have been observed in patients treated with intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.

Concomitant use of CYP3A inhibitors, including medicinal products containing cobicistat, is expected to increase the risk of systemic adverse effects. Such combination should be avoided, except when the benefit outweighs the increased risk of systemic corticosteroid adverse effects. In such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse effects.

It has been reported that concomitant use of fluticasone propionate with other P450 3A4 inhibitors leads to minor (erythromycin) or weak (ketoconazole) increases in plasma concentrations of fluticasone propionate, which do not cause a noticeable reduction in serum cortisol concentration.

Interaction studies have been conducted only in adults.

Special precautions for use.

Infectious-inflammatory processes of the nasal passages require appropriate treatment but are not a specific contraindication for the use of fluticasone propionate.

It may take several days to achieve the effect of fluticasone propionate.

Caution should be exercised when transferring patients from systemic corticosteroid therapy to treatment with fluticasone propionate, especially if there is reason to suspect impaired adrenal cortex function.

In most cases of seasonal allergic rhinitis, administration of a single nasal spray of Nazofan is sufficient; however, in severe disease (e.g., during periods of high allergen concentration in the summer), additional appropriate treatment may be required.

Systemic effects may occur with the use of nasal corticosteroids, especially when high doses are used over prolonged periods. The likelihood of such effects is lower than with oral corticosteroids and varies depending on the specific corticosteroid and individual patient response. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, and glaucoma, as well as, in rare cases, psychiatric disorders and behavioral changes, including psychomotor hyperactivity, sleep disturbances, restlessness, depression, and aggression (mainly in children).

Visual disturbances

Visual disturbances have been reported with the use of systemic or topical corticosteroids.

If a patient experiences symptoms such as blurred vision or other visual disturbances, referral for ophthalmological evaluation should be considered to assess possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSC), which has been reported after use of systemic or topical corticosteroids.

Long-term use of the drug requires regular monitoring of adrenal cortex function. Patients should be advised that if there is no improvement after 7 days of continuous use, they should consult a physician. Continuous use of the drug for more than 6 months requires medical supervision of the patient's condition.

When using the drug in patients with tuberculosis, any untreated infections, ocular infections, recent nasal or oral surgery, or trauma to the nasal or oral cavity, the benefits of therapy should be weighed against potential risks.

Cases of growth retardation in children treated with approved doses of nasal corticosteroids have been reported. Regular monitoring of growth is recommended in children undergoing long-term treatment with intranasal corticosteroids. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of intranasal corticosteroid to the lowest effective dose that maintains adequate symptom control. Additionally, consultation with a pediatrician should be considered.

Treatment with intranasal corticosteroids at doses higher than recommended may cause clinically significant suppression of adrenal function. In cases of use at higher-than-recommended doses, consideration should be given to the need for additional systemic corticosteroid therapy during periods of stress or surgical procedures.

Ritonavir may greatly increase plasma concentrations of fluticasone propionate. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, except when the benefit outweighs the risk of systemic corticosteroid effects. Increased risk of systemic effects has also been reported with co-administration of fluticasone propionate and other strong CYP3A inhibitors (see section "Interaction with other medicinal products and other forms of interactions").

Nazofan Aqueous 50 mcg nasal spray contains benzalkonium chloride. This substance is an irritant and may cause skin reactions. With prolonged use, the preservative benzalkonium chloride may cause nasal mucosal swelling. In case of such a reaction (persistent nasal congestion), switching, if possible, to medicinal products without preservatives is recommended; however, if preservative-free products are unavailable, switching to other dosage forms should be considered.

Use during pregnancy or breastfeeding.

Fluticasone propionate should be used during pregnancy or breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus/child.

There is insufficient evidence of safety during pregnancy in humans. Direct intranasal administration results in minimal systemic exposure.

Excretion of fluticasone propionate into human breast milk has not been studied. It is unlikely that the drug would be detected in breast milk following intranasal administration.

Ability to affect reaction speed when driving or operating machinery.

The effect of this medicinal product on the ability to drive or operate machinery is negligible or absent.

Method of Administration and Dosage

Nasofan is intended for intranasal use only.

Before the first use, Nasofan must be primed by pressing and releasing the pump 6 times. If the nasal spray has not been used for 7 days or more, it should be re-primed by pressing and releasing the pump an adequate number of times until a fine mist appears.

Adults and children aged 12 years and older: 2 sprays into each nostril once daily, preferably in the morning. In some cases, the dose may be increased to 2 sprays into each nostril twice daily. The maximum daily dose should not exceed 4 sprays into each nostril (400 mcg). The lowest effective dose sufficient to control symptoms should be used.

Children aged 4 to 11 years: 1 spray into each nostril once daily, preferably in the morning. In some cases, the dose may be increased to 1 spray into each nostril twice daily.

The maximum daily dose should not exceed 2 sprays into each nostril (200 mcg).

The lowest effective dose sufficient to control symptoms should be used.

Elderly patients: the usual adult dosage should be used.

For optimal therapeutic effect, the medication should be used regularly. The absence of an immediate effect is explained by the fact that the maximum therapeutic effect is not achieved earlier than 3–4 days after the start of treatment.

The duration of treatment is determined by the physician based on the patient’s clinical condition and response to therapy.

Before Using the Nasal Spray

The dust-protective cap prevents contamination of the bottle neck: it should be removed before use and replaced after use.

If the medication bottle is being opened for the first time, prepare it as follows:

1. Gently shake the bottle and remove the dust-protective cap.
2. Hold the bottle vertically, supporting it with the thumb underneath and the index and middle fingers around the neck. Ensure the nozzle is not directed toward the patient.
3. To perform the initial priming spray, press the pump with the fingers.
4. Repeat steps 2 and 3 five more times. The bottle is now ready for use.

If Nasofan has not been used for 7 days, re-prime the bottle until a fine mist is produced.

If, after attempts to prepare the bottle for use, it still does not function and the patient suspects it is clogged, it can be cleaned using the following procedure.

Cleaning

1. Remove the dust-protective cap.

2. Pull the white collar upward to remove the nozzle.

3. Place the nozzle and dust-protective cap in warm water and soak for several minutes. Then rinse them under running water.

4. Shake off excess water and place the nozzle and dust-protective cap to dry in a warm (but not hot) place.

5. Reattach the nozzle.

6. Prime the bottle by pumping until a fine mist is produced.

To prevent clogging, the bottle should be cleaned at least once a week. Additional cleaning should be performed as needed if clogging occurs.

NEVER attempt to clean or enlarge the spray orifice with a pin or any other sharp object, as this may damage the spray mechanism.

Using the Spray

1. Shake the bottle and remove the dust-protective cap.
2. Breathe out gently.
3. Close one nostril by pressing it with a finger and insert the bottle nozzle into the other nostril. Tilt the head slightly forward so that the bottle remains in a vertical position.
4. Inhale slowly through the open nostril while simultaneously pressing firmly on the collar with the fingers to deliver a full spray.
5. Exhale through the mouth. Repeat step 4 to administer the second spray into the same nostril.
6. Remove the nozzle from this nostril and exhale through the mouth.
7. Repeat steps 3–6 for the other nostril.

After using the spray, carefully wipe the nozzle with a clean tissue and replace the dust-protective cap.

Children

The medication is not recommended for children under 4 years of age due to insufficient experience with use in this age group.

Overdose

No cases of acute or chronic overdose with Nasofan have been reported.

Prolonged use of doses higher than recommended may lead to temporary suppression of adrenal gland function. In such patients, treatment with fluticasone propionate should continue at doses sufficient to control symptoms. Adrenal function recovers within a few days, which can be confirmed by measuring plasma cortisol levels.

Adverse Reactions.

Immune system disorders: anaphylactoid/anaphylactic reactions, hypersensitivity reactions, skin rash, angioneurotic edema (mainly of the face and tongue).

Nervous system disorders: headache, unpleasant taste, perception of unpleasant odor.

Eye disorders: cataract, glaucoma (observed with prolonged use), increased intraocular pressure, blurred vision (see also section "Special precautions for use").

Skin and subcutaneous tissue disorders: skin ulcers.

Respiratory system disorders: epistaxis, dryness and irritation in the nose and throat, nasal septum perforation, mucosal ulcers (usually in patients who have previously undergone nasal surgery).

Systemic effects of some nasal corticosteroids are possible, especially when used in high doses over prolonged periods.

There have been reports that certain nasal corticosteroids may cause growth retardation in children even when used at recommended doses. Regular monitoring of growth is recommended in children receiving long-term treatment with nasal corticosteroids.

Shelf life. 2 years.

After first opening – 3 months.

Storage conditions. Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging. 1 bottle containing 120 doses or 150 doses of the medicinal product, in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Teva Czech Industries s.r.o.

Manufacturer's address and place of business.
Ostravska 305/29, Komarov, 747 70 Opava, Czech Republic.