FURAMIST Nasal Spray (Fluticasone furoate )

Table of Content

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Qualitative and Quantitative Composition

FURAMIST Nasal spray

Each spray delivers:

Fluticasone Furoate…… 27.5 mcg

Dosage Form(s) and Strength(s)

Aqueous intranasal spray containing 27.5 mcg of fluticasone furoate.

Clinical Particulars

Therapeutic Indications

FURAMIST nasal spray is indicated for the treatment of the symptoms of seasonal and perennial allergic rhinitis in patients 2 years of age and older.

Posology and Method of Administration

FURAMIST nasal spray should be administered by the intranasal route only.

Adults and Adolescents (12 Years of Age and Over)

The recommended starting dosage is 110 mcg once daily administered as 2 sprays (27.5 mcg/spray) in each nostril. When the maximum benefit has been achieved and symptoms have been controlled, reducing the dosage to 55 mcg (1 spray in each nostril) once daily may be effective in maintaining control of allergic rhinitis symptoms.

Paediatric Patients (2 to 11 Years of Age)

The recommended starting dosage in children is 55 mcg once daily administered as 1 spray (27.5 mcg/spray) in each nostril. Children not adequately responding to 55 mcg may use 110 mcg (2 sprays in each nostril) once daily. Once symptoms have been controlled, the dosage may be decreased to 55 mcg once daily.

Contraindications

FURAMIST Nasal spray is contraindicated in patients with known hypersensitivity to fluticasone furoate or any of the excipients in this preparation.

Special Warnings and Precautions for Use

Systemic Corticosteroid Effects

Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and, more rarely, a range of psychological or behavioural effects, including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. Fluticasone furoate once daily was not associated with hypothalamic-pituitary-adrenal (HPA) axis suppression in adult, adolescent or paediatric subjects. However, the dose of this drug combination should be reduced to the lowest dose at which effective control of the symptoms of rhinitis is maintained. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently.

If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to fluticasone furoate nasal spray.

Visual Disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient present with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes that may include cataract, glaucoma, or rare diseases such as central serous chorioretinopathy (CSCR), which have been reported after the use of systemic and topical corticosteroids.

Growth Retardation

Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. A reduction in growth velocity has been observed in children treated with fluticasone furoate. Therefore, children should be maintained on the lowest possible efficacious dose that delivers adequate symptom control. It is recommended that the growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid, if possible, to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should be given to referring the patient to a paediatric specialist.

Patients on Ritonavir

Concomitant administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

Drug Interactions

Interaction with CYP3A Inhibitors

Fluticasone furoate is rapidly cleared by extensive first-pass metabolism mediated by cytochrome (CY) P450 3A4.

Based on data with another glucocorticoid (fluticasone propionate) that is metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors, including cobicistat-containing products, as an increase in the risk of systemic side effects is expected. Co-administration should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects, in which case patients should be monitored for systemic corticosteroid side effects. In a drug interaction study of intranasal fluticasone furoate with the potent CYP3A4 inhibitor ketoconazole, there were more subjects with measurable fluticasone furoate concentrations in the ketoconazole group (6 out of 20 subjects) compared with placebo (1 out of 20 subjects). This small increase in exposure did not result in a statistically significant difference in 24-hour serum cortisol levels between the two groups.

The enzyme induction and inhibition data suggest that there is no theoretical basis for anticipating metabolic interactions between fluticasone furoate and the CYP450-mediated metabolism of other compounds at clinically relevant intranasal doses. Therefore, no clinical studies have been conducted to investigate interactions of fluticasone furoate on other drugs.

Use in Special Populations

Pregnant Women

There are no adequate data from the use of fluticasone furoate in pregnant women. In animal studies, glucocorticoids have been shown to induce malformations, including cleft palate and intra-uterine growth retardation. This is not likely to be relevant for humans given recommended nasal doses that result in minimal systemic exposure. Fluticasone furoate should be used in pregnancy only if the benefits to the mother outweigh the potential risks to the foetus or child.

Nursing Mothers

It is unknown whether intranasally administered fluticasone furoate is excreted in human breast milk. Administration of fluticasone furoate 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.

Pediatric Use

The safety and effectiveness of fluticasone furoate nasal spray in children younger than 2 years have not been established.

Geriatric Use

Clinical studies of fluticasone furoate  nasal spray did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment

Fluticasone furoate is not detectable in urine from healthy volunteers after intranasal dosing. Less than 1% of dose-related material is excreted in urine and, therefore, renal impairment would not be expected to affect the pharmacokinetics of fluticasone furoate.

Hepatic Impairment

Extensive first-pass metabolism by the hepatic cytochrome P450 isozyme, CYP3A4, the pharmacokinetics of fluticasone furoate may be altered in patients with hepatic impairment. The systemic exposure would be expected to be higher than that observed had the study been conducted after multiple doses and/or in patients with severe hepatic impairment. Therefore, use fluticasone furoate nasal spray with caution in patients with severe hepatic impairment.

Effect on Ability to Drive and Use Machines

FURAMIST nasal spray has no or negligible influence on the ability to drive and use machines.

Undesirable Effects

Summary of the Safety Profile

The most commonly reported adverse reactions during treatment with fluticasone furoate are epistaxis, nasal ulceration and headache. The most serious undesirable effects are rare reports of hypersensitivity reactions, including anaphylaxis (less than 1 case per 1,000 patients).

Tabulated List of Adverse Reactions

There were over 2,700 patients treated with fluticasone furoate in safety and efficacy studies for seasonal and perennial allergic rhinitis. Paediatric exposure to fluticasone furoate in safety and efficacy studies in seasonal and perennial allergic rhinitis included 243 patients 12 to <18 years of age, 790 patients 6 to <12 years of age, and 241 patients 2 to <6 years of age.

Data from large clinical trials were used to determine the frequency of adverse reactions.

The following convention has been used for the classification of frequencies: very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100; rare ≥1/10,000 to <1/1,000; very rare <1/10,000; and, not known (cannot be estimated from the available data).

Immune system disorders

Rare

Hypersensitivity reactions, including anaphylaxis, angio-oedema, rash, and urticaria

Nervous system disorders

Common

Headache

Eye disorders

Not known

Transient ocular changes, vision blurred

Respiratory, thoracic and mediastinal disorders

Very common

Epistaxis*

Common

Nasal ulceration, dyspnoea**

Uncommon

Rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness

Very rare

Nasal septum perforation

Not known

Bronchospasm

Musculoskeletal and connective tissue disorders (children)

Known

Growth retardation***

Description of selected adverse reactions

Epistaxis was generally mild to moderate in intensity. In adults and adolescents, the incidence of epistaxis was higher in longer-term use (more than 6 weeks) than in short-term use (up to 6 weeks).

Systemic effects

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.

**Dyspnoea cases were reported in more than 1% of patients during clinical trials with fluticasone furoate; similar rates were also observed in placebo groups.

***Growth retardation has been reported in children receiving nasal corticosteroids.

If case of any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting adverse events, you can help provide more information on the safety of this product.

Overdose

There are no data on the effects of acute or chronic overdosage with fluticasone furoate nasal spray. Because of low systemic bioavailability and an absence of acute drug-related systemic findings in clinical studies , overdose is unlikely to require any therapy other than observation.

Intranasal administration of up to 2,640 mcg/day (24 times the recommended adult dose) of fluticasone furoate was administered to healthy human volunteers for 3 days. Single- and repeat-dose studies with orally inhaled fluticasone furoate doses of 50–4,000 mcg have shown decreased mean serum cortisol at doses of 500 mcg or higher. Chronic overdosage with any corticosteroid may result in signs or symptoms of hypercorticism.

Pharmacological Properties

Mechanism of Action

Fluticasone furoate is a synthetic trifluorinated corticosteroid that possesses a very high affinity for the glucocorticoid receptor and has a potent anti-inflammatory action.

Pharmacodynamics

Clinical Efficacy and Safety

Seasonal allergic rhinitis in adults and adolescents

Compared with placebo, fluticasone furoate nasal spray 110 micrograms once daily significantly improved nasal symptoms (comprising rhinorrhoea, nasal congestion, sneezing and nasal itching) and ocular symptoms (comprising itching/burning, tearing/watering and redness of the eyes) in all four studies. Efficacy was maintained over the full 24-hour dosing period with once-daily administration.

Onset of therapeutic benefit was observed as early as 8 hours after initial administration, with further improvement observed for several days afterwards.

Fluticasone furoate nasal spray significantly improved patient perception of overall response to therapy, and patient disease-related quality of life (as per the Rhinoconjunctivitis Quality of Life Questionnaire ), in all the four studies.

Perennial allergic rhinitis in adults and adolescents

Fluticasone furoate nasal spray 110 micrograms once daily significantly improved nasal symptoms as well as patient perception of overall response to therapy compared with placebo in three studies.

Fluticasone furoate nasal spray 110 micrograms once daily significantly improved ocular symptoms as well as the patient disease-related quality of life (as per the RQLQ) compared with placebo in one study.

Efficacy was maintained over the full 24-hour dosing period with once-daily administration.

In a 2-year study designed to assess the ocular safety of fluticasone furoate (110 micrograms once-daily intranasal spray), adults and adolescents with perennial allergic rhinitis received either fluticasone furoate (n=367) or placebo (n=181). The primary outcomes were not statistically significant between the two groups. Increases in posterior subcapsular opacity (≥0.3 from baseline) were more frequent in subjects treated with fluticasone furoate 110 micrograms versus placebo and were transient in nature for 10 subjects in the fluticasone furoate group and 2 subjects in the placebo group. Increases in the IOP (≥7 mmHg from baseline) were more frequent in subjects treated with fluticasone furoate 110 micrograms: 7 (2%) for fluticasone furoate 110 micrograms once daily and 1 (<1%) for placebo. These events were transient in nature for 6 subjects in the fluticasone furoate group and 1 placebo subject. At weeks 52 and 104, 95% of subjects in both treatment groups had posterior subcapsular opacity values within ±0.1 of baseline values for each eye; at week 104, ≤1% of subjects in both treatment groups had ≥0.3 increase from baseline in posterior subcapsular opacity. At weeks 52 and 104, the majority of subjects (>95%) had IOP values of within ±5 mmHg of the baseline value. Increases in posterior subcapsular opacity or IOP were not accompanied by any adverse events of cataracts or glaucoma.

Paediatric Patients

Seasonal and perennial allergic rhinitis

The paediatric posology is based on assessment of the efficacy data across the paediatric population having allergic rhinitis.

In seasonal allergic rhinitis, fluticasone furoate nasal spray 110 micrograms once daily was effective, but no significant differences were observed between fluticasone furoate nasal spray 55 micrograms once daily and placebo with respect to any endpoint.

In perennial allergic rhinitis, fluticasone furoate nasal spray 55 micrograms once daily exhibited a more consistent efficacy profile than fluticasone furoate nasal spray 110 micrograms once daily over 4 weeks of treatment. Post hoc analysis over 6 and 12 weeks in the same study, as well as a 6-week HPA axis safety study, supported the efficacy of fluticasone furoate nasal spray 110 micrograms once daily.

A 6-week study that assessed the effect of fluticasone furoate nasal spray 110 micrograms once daily on adrenal function in children aged 2 to 11 years showed that there was no significant effect on 24-hour serum cortisol profiles, compared with placebo.

A randomised, double-blind, parallel-group, multicentre, 1-year, placebo-controlled clinical growth study evaluated the effect of fluticasone furoate nasal spray 110 micrograms daily on growth velocity in 474 prepubescent children (5 to 7.5 years of age for girls and 5 to 8.5 years of age for boys) with stadiometry. Mean growth velocity over the 52-week treatment period was lower in the patients receiving fluticasone furoate (5.19 cm/year) compared with placebo (5.46 cm/year). The mean treatment difference was –0.27 cm per year .

Pharmacokinetics

Absorption

Following intranasal administration of fluticasone furoate, most of the dose is eventually swallowed and undergoes incomplete absorption and extensive first-pass metabolism in the liver and gut, resulting in negligible systemic exposure. At the highest recommended intranasal dosage of 110 mcg once daily for up to 12 months in adults and up to 12 weeks in children, plasma concentrations of fluticasone furoate are typically not quantifiable despite the use of a sensitive HPLC-MS/MS assay with a lower limit of quantification (LOQ) of 10 pg/mL. However, in a few isolated cases (<0.3%) fluticasone furoate was detected in high concentrations above 500 pg/mL, and in a single case, the concentration was as high as 1,430 pg/mL in the 52-week study. There was no relationship between these concentrations and cortisol levels in these subjects. The reasons for these high concentrations are unknown.

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 solution and intravenous dosing of radiolabelled drug have demonstrated that at least 30% of fluticasone furoate is absorbed and then rapidly cleared from plasma. Oral bioavailability is on average 1.26%, and the majority of the circulating radioactivity is due to inactive metabolites.

Distribution

Following intravenous administration, the mean volume of distribution at steady state is 608 L. Binding of fluticasone furoate to human plasma proteins is greater than 99%.

Metabolism

In vivo studies have revealed no evidence of cleavage of the furoate moiety to form fluticasone. Fluticasone furoate is cleared (total plasma clearance of 58.7 L/h) from systemic circulation principally by hepatic metabolism via the cytochrome P450 isozyme, CYP3A4. The principal route of metabolism is hydrolysis of the S-fluoromethyl carbothioate function to form the inactive 17beta-carboxylic acid metabolite.

Elimination

Fluticasone furoate and its metabolites are eliminated primarily in the faeces, accounting for approximately 101% and 90% of the orally and intravenously administered dose, respectively. Urinary excretion accounted for approximately 1% and 2% of the orally and intravenously administered dose, respectively. The elimination phase half-life averaged 15.1 hours following intravenous administration.

Special Populations

Hepatic impairment

Since fluticasone furoate undergoes extensive first-pass metabolism by the hepatic cytochrome P450 isozyme, CYP3A4, the pharmacokinetics of fluticasone furoate may be altered in patients with hepatic impairment. The systemic exposure would be expected to be higher than that observed had the study been conducted after multiple doses and/or in patients with severe hepatic impairment. Therefore, use fluticasone furoate nasal spray with caution in patients with severe hepatic impairment.

Renal Impairment

Fluticasone furoate is not detectable in urine from healthy subjects following intranasal dosing. Less than 1% of dose-related material is excreted in the urine. No dosage adjustment is required in patients with renal impairment.

Nonclinical Properties

Animal Toxicology or Pharmacology

Findings in general toxicology studies were similar to those observed with other glucocorticoids and are associated with exaggerated pharmacological activity. These findings are not likely to be relevant for humans given recommended nasal doses that result in minimal systemic exposure. No genotoxic effects of fluticasone furoate have been observed in conventional genotoxicity tests. Further, there were no treatment-related increases in the incidence of tumours in 2-year inhalation studies in rats and mice.

Description

Fluticasone furoate is a trifluorinated corticosteroid that consists of 6alpha,9-difluoro-11beta,17alpha-dihydroxy-17beta-{carbonyl}-16-methyl-3-oxoandrosta-1,4-diene bearing a 2-furoyl substituent at position 17. It has a molecular weight of 538.6  and the empirical formula is C27H29F3O6S

The chemical structure of fluticasone furoate

Pharmaceutical Particulars

Incompatibilities

Not applicable.

Shelf-Life

As on the pack.

Packaging Information

FURAMIST nasal spray: Each sales pack contains 120 metered doses

Storage and Handling Instructions

Store in a cool place. Protect from light. Do not freeze.

Patient Counselling Information

What is FURAMIST nasal spray and what is it used for?

FURAMIST nasal spray belongs to a group of medicines called glucocorticoids. FURAMIST nasal spray works to decrease inflammation caused by allergy (rhinitis) and, therefore, reduces symptoms of allergy.

FURAMIST nasal spray is used to treat symptoms of allergic rhinitis, including stuffy, runny, or itchy nose, sneezing and watery, itchy, or red eyes, in adults and children 2 years of age and over.

Allergy symptoms can occur at specific times of the year and be caused by allergy to pollen from grass or trees (hay fever), or they can occur all year round and be caused by allergy to animals, house-dust mites, or moulds.

What do I need to know before using FURAMIST Nasal spray?

  • Do not use FURAMIST nasal spray if you are allergic to fluticasone furoate or any of the other ingredients of this medicine.

Using FURAMIST Nasal spray may cause the following:

  • Slow growth in children when used for a long time. The doctor will check your child’s height regularly, and make sure he or she is taking the lowest possible effective dose.
  • Eye conditions such as glaucoma (increase in pressure in the eye) or cataracts (clouding of the lens of the eye). Tell your doctor if you had these conditions in the past, or if you notice blurred vision or other visual disturbances while you are using FURAMIST Nasal spray.

u Who should not use FURAMIST Nasal spray?

  • If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
  • Do not use FURAMIST Nasal spray if you are pregnant, or planning to become pregnant, unless your doctor or pharmacist tells you to.
  • Do not use FURAMIST Nasal spray if you are breastfeeding unless your doctor or pharmacist tells you to.
  • FURAMIST Nasal spray is unlikely to affect your ability to drive and use machines.

Tell your doctor or pharmacist if you are taking, or have recently taken, or might take any other medicines, including medicines obtained without a prescription. It is especially important to tell your doctor if you are taking, or have recently taken any of the following medicines:

  • Steroid tablets or injected steroids,
  • Steroid creams,
  • Medicines for asthma,
  • Ritonavir or cobicistat (used to treat HIV)
  • Ketoconazole (used to treat fungal infections).

u How should I use FURAMIST Nasal spray?

Always use this medicine exactly as your doctor or pharmacist has told you. Don’t exceed the recommended dose. Check with your doctor or pharmacist if you’re not sure.

  • When to use FURAMIST Nasal spray
  • Use once a day
  • Use at the same time each day.

This will treat your symptoms throughout the day and night.

  • Time taken for FURAMIST Nasal spray to work

Some people will not feel the full effects until several days after first using FURAMIST Nasal spray. However, it is usually effective within 8 to 24 hours of use.

  • How much to use

Adults and children (12 years of age and over)

  • The usual starting dose is two sprays in each nostril once every day.
  • Once symptoms are controlled, your doctor may recommend decreasing your dose to one spray in each nostril, once every day.

Children (6 to 11 years of age)

  • The usual starting dose is one spray in each nostril once a day.
  • If symptoms are very bad, your doctor may increase the dose to two sprays in each nostril once every day until the symptoms are under control. It may then be possible for the dose to be reduced to one spray in each nostril once every day.
  • Directions for use
  • FURAMIST Nasal spray has virtually no taste or smell. It is in the form of a fine mist and is to be sprayed into the nose. Be careful not to get any spray into your eyes. If you do, rinse your eyes with water.
  • If you use more FURAMIST Nasal spray than you should, talk to your doctor or pharmacist.
  • If you miss a dose, take it when you remember.
  • If it is nearly time to take your next dose, wait until then. Do not take a double dose to make up for a forgotten dose.
  • If you have any further questions on the use of this medicine or if you have any discomfort using the nasal spray, get advice from your doctor or pharmacist or nurse.

u What are the possible side effects of FURAMIST Nasal spray?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

  • Allergic reactions: Get a doctor’s help straight away.

Allergic reactions to FURAMIST Nasal spray are rare and affect less than 1 person in 1,000. In a small number of people, allergic reactions can develop into a more serious, even life-threatening problem if not treated. Symptoms include the following:

  • Becoming very wheezy, coughing or having difficulty with breathing
  • Suddenly feeling weak or lightheaded (which may lead to collapse or loss of consciousness)
  • Swelling around the face
  • Skin rashes or redness.

In many cases, these symptoms can be signs of less serious side effects. But any side effect could potentially turn serious – so, if you notice any of these symptoms, contact a doctor as soon as possible.

  • Very common side effects (may affect more than 1 in 10 people)
  • Nosebleeds (generally minor), particularly if you use FURAMIST Nasal spray for more than 6 weeks continuously.
  • Common side effects (may affect up to 1 in 10 people)
  • Nasal ulceration – which may cause irritation or discomfort in your nose. You may also get streaks of blood when you blow your nose.
  • Headache.
  • Shortness of breath
  • Uncommon side effects (may affect up to 1 in 100 people)
  • Pain, burning, irritation, soreness or dryness in the inside of the nose.
  • Very rare side effects (may affect up to 1 in 10,000 people)
  • Small holes (perforations) in the ridge inside the nose that separates the nostrils.
  • Not known (frequency cannot be estimated from the available data)
  • Slowing of growth in children.
  • Blurred vision or temporary changes in vision with long-term use.
  • Chest tightness, causing difficulty in breathing.

Nasal corticosteroids can affect the normal production of hormones in your body, particularly if you use high doses for a long time. In children, this side effect can cause them to grow more slowly than others.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national Pharmacovigilance Programme of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 1800 267 7779. By reporting side effects, you can help provide more information on the safety of this product.

u How should I store FURAMIST Nasal spray?

  • Keep this medicine out of the sight and reach of children.
  • It is best to store FURAMIST Nasal spray upright. Always keep the cap on.
  • Do not use this medicine after the expiry date, which is stated on the label and carton. The expiry date refers to the last day of the month. FURAMIST Nasal spray should be used within 2 months after first opening.
  • Do not refrigerate or freeze.
  • Do not throw away any medicines via wastewater or household waste. Ask your healthcare provider about how to throw away medicines you no longer use. These measures will help protect the environment.

Details of The Manufacturer

Sava Healthcare Ltd,

Plot No. 507-B to 512,

GIDC Estate, Wadhwan city,

District- Surendranagar, Gujrat

Details of Permission or Licence Number with Date

G/25/536 Dated 31/12/2017

Date of Revision

04/10/2021