Avamys鼻眼適

Avamys

fluticasone

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Contents
Fluticasone furoate.
Description
Each spray of the suspension delivers approximately 27.5 micrograms of micronised fluticasone furoate as an ex-device dose.
Action
Pharmacology: Clinical Studies: Adult and Adolescent Seasonal Allergic Rhinitis: Once daily 110 micrograms AVAMYS Nasal Spray resulted in a significant improvement in daily reflective (how patient felt over the preceding 12 hours) and instantaneous (how patient felt at the time of assessment) pre-dose total nasal symptom scores (rTNSS and iTNSS, comprising rhinorrhea, nasal congestion, sneezing and nasal itching) and daily reflective and instantaneous total ocular symptom scores (rTOSS, comprising itching/burning, tearing/watering and redness of the eyes) versus placebo (see table as follows). The improvement in nasal and ocular symptoms was maintained over the full 24 hours after once daily administration. (See Table 1.)

Click on icon to see table/diagram/image

The distribution of the patients' perception of overall response to therapy (using a 7-point scale ranging from significantly improved to significantly worse) favoured AVAMYS Nasal Spray 110 micrograms over placebo, with a statistically significant treatment difference. Onset of action was experienced as early as eight hours after initial administration in two studies. Significant improvement in symptoms was observed in the first 24 hours in all four studies, and continued to improve over several days. The patients' quality of life (as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire – RQLQ), was significantly improved from baseline with AVAMYS Nasal Spray compared to placebo (Minimum Important Difference in all studies = improvement of at least -0.5 over placebo; treatment difference -0.690, p<0.001, 95% CI -0.84, -0.54).
Adult and Adolescent Perennial Allergic Rhinitis: AVAMYS Nasal Spray 110 micrograms once daily resulted in a significant improvement in daily rTNSS (LS mean difference = -0.706, P=0.005, 95% CI -1.20, -0.21). The improvement in nasal symptoms was maintained over the full 24 hours after once daily administration. The distribution of patients' perception of overall response to therapy was also significantly improved compared to placebo.
In a two-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 [time to increase in posterior subcapsular opacity (≥0.3 from baseline in Lens Opacities Classification System, Version III (LOCS III grade)) and time to increase in intraocular pressure (IOP; ≥7 mmHg from baseline)] were not statistically significant between the two groups. Increases in posterior subscapsular opacity (≥0.3 from baseline) were more frequent in subjects treated with fluticasone furoate 110 micrograms [14 (4%)] versus placebo [4 (2%)] and were transient in nature for ten subjects in the fluticasone furoate group and two subjects in the placebo group. Increases in 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 six subjects in the fluticasone furoate group and one 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 and, 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 ± 5mmHg of the baseline value. Increases in posterior subcapsular opacity or IOP were not accompanied by any adverse events of cataracts or glaucoma.
Children: The paediatric posology is based on assessment of the efficacy data across the allergic rhinitis population in children. In a seasonal allergic rhinitis study in children, AVAMYS Nasal Spray 110 micrograms over two weeks was effective on primary (daily rTNSS LS mean difference = -0.616, P=0.025, 95% CI -1.15, -0.08) and all secondary nasal endpoints, except the individual reflective score for rhinorrhea. No significant differences were observed between 55 micrograms AVAMYS Nasal Spray and placebo on any endpoint.
In a perennial allergic rhinitis study, AVAMYS Nasal Spray 55 micrograms was effective on daily rTNSS (LS mean difference = -0.754, P=0.003, 95% CI -1.24, -0.27). Although there was a trend towards improvement in rTNSS in 110 micrograms, this did not reach statistical significance (LS mean difference = -0.452, P=0.073, 95% CI -1.24, -0.04). Post-hoc analysis of efficacy data over 6 and 12 weeks from this study, and a 6 week HPA-axis safety study, each showed that the improvement in rTNSS for AVAMYS Nasal Spray 110 micrograms nasal spray over placebo was statistically significant.
A randomised, double-blind, parallel-group, multicenter, one-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 to placebo (5.46 cm/year). The mean treatment difference was -0.27 cm per year [95% CI -0.48 to -0.06].
Toxicology: Pre-clinical Safety Data: Carcinogenesis, mutagenesis: There were no treatment-related increases in the incidence of tumours in two year inhalation studies in rats and mice.
AVAMYS Nasal Spray was not genotoxic in vitro or in vivo.
Reproductive Toxicology: The potential for reproductive toxicity was assessed in animals by inhalation administration to ensure high systemic exposure to fluticasone furoate. There were no effects on mating performance or fertility of male or female rats. In rats, developmental toxicity was confined to an increased incidence of incompletely ossified sternabrae in association with lower foetal weight. High doses in rabbits induced abortion. These findings are typical following systemic exposure to potent corticosteroids. There were no major skeletal or visceral abnormalities in either rats or rabbits, and no effect on pre- or post-natal development in rats.
Animal toxicology and/or pharmacology: Findings in general toxicology studies were similar to those observed with other glucocorticoids and are not considered to be clinically relevant to intranasal use of AVAMYS Nasal Spray.
Indications/Uses
Treatment of Allergic Rhinitis: AVAMYS Nasal Spray is indicated for the treatment of the symptoms of seasonal and perennial allergic rhinitis in patients 2 years of age and older.
Dosage/Direction for Use
Avamys nasal spray is for administration by the intranasal route only.
For full therapeutic benefit regular, scheduled usage is recommended. Onset of action has been observed as early as 8 hours after initial administration. However, it may take several days of treatment to achieve maximum benefit, and the patient should be informed that their symptoms will improve with continuous regular use. The duration of treatment should be restricted to the period that corresponds to allergenic exposure.
Adults and Adolescents 12 Years of Age and Older: The recommended starting dosage is 110 micrograms once daily administered as 2 sprays (27.5 micrograms/spray) in each nostril. Titrate an individual patient to the minimum effective dosage to reduce the possibility of side effects. When the maximum benefit has been achieved and symptoms have been controlled, reducing the dosage to 55 micrograms (1 spray in each nostril) once daily may be effective in maintaining control of allergic rhinitis symptoms.
Children 2 to 11 Years of Age: The recommended starting dosage in children is 55 micrograms once daily administered as 1 spray (27.5 micrograms/spray) in each nostril. Children not adequately responding to 55 micrograms may use 110 micrograms (2 sprays in each nostril) once daily. Once symptoms have been controlled, the dosage may be decreased to 55 micrograms once daily.
Children (under 2 years of age): There are no data to recommend use of AVAMYS Nasal Spray for the treatment of seasonal or perennial allergic rhinitis in children under two years of age.
Elderly: No dose adjustment is required in this population.
Renal Impairment: No dosage adjustment is required in patients with renal impairment.
Hepatic Impairment: No dose adjustment is required in patients with hepatic impairment. Caution should be exercised when dosing patients with severe hepatic impairment as patients with hepatic impairment may be more at risk of systemic adverse reactions associated with corticosteroids (see Precautions).
Overdosage
Symptoms and Signs: In a bioavailability study, intranasal doses of up to 24 times the recommended daily adult dose were studied over three days with no adverse systemic effects observed.
Treatment: Acute overdose is unlikely to require any therapy other than observation.
Contraindications
AVAMYS Nasal Spray is contraindicated in patients with hypersensitivity to any of the ingredients.
Special Precautions
Based on data with another glucocorticoid metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the potential risk of increased systemic exposure to fluticasone furoate. (See Interactions).
Systemic effects with nasal corticosteroids have been reported, 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. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year (see Adverse Reactions and Pharmacology: Clinical Studies under Actions). Therefore, children should be maintained on the lowest dose which delivers adequate symptom control (see Dosage & Administration). As with other intranasal corticosteroids, physicians should be alert to potential systemic steroid effects including ocular changes (see Pharmacology: Clinical Studies under Actions).
Effects on Ability to Drive and Use Machines: Based on the pharmacology of fluticasone furoate and other intranasally administered steroids, there is no reason to expect an effect on ability to drive or to operate machinery with AVAMYS Nasal Spray.
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: There are no data with intranasal fluticasone furoate in patients with hepatic impairment. Data are available following inhaled administration of fluticasone furoate (as fluticasone furoate or fluticasone furoate/vilanterol) to subjects with hepatic impairment that are also applicable for intranasal dosing. A study of a single 400 microgram dose of orally inhaled fluticasone furoate in patients with moderate hepatic impairment (Child-Pugh B) resulted in increased Cmax (42%) and AUC(0-∞) (172%) and a modest (on average 23%) decrease in cortisol levels in patients compared to healthy subjects. Following repeat dosing of orally inhaled fluticasone furoate/vilanterol for 7 days, there was an increase in fluticasone furoate systemic exposure (on average two-fold as measured by AUC(0-24)) in subjects with moderate or severe hepatic impairment (Child-Pugh B or C) compared with healthy subjects. The increase in fluticasone furoate systemic exposure in subjects with moderate hepatic impairment (fluticasone furoate/vilanterol 200/25 micrograms) was associa ted with an average 34% reduction in serum cortisol compared with healthy subjects. There was no effect on serum cortisol in subjects with severe hepatic impairment (fluticasone furoate/vilanterol 100/12.5 micrograms).
Based on these findings the average p redicted exposure of 110 micrograms of intranasal fluticasone furoate in this patient population would not be expected to result in suppression of cortisol.
Other pharmacokinetic: Fluticasone furoate is typically not quantifiable (less than 10 picograms/mL) following intranasal dosing of 110 micrograms once daily. Quantifiable levels were only observed in less than 31% of patients aged 12 years and above and in less than 16% of paediatric patients following intranasal dosing of 110 micrograms once daily. There was no evidence for gender, age (including paediatrics), or race to be related to those subjects with quantifiable levels, when compared to those without.
Use in Elderly: Only a small number of elderly subjects (n=23/872; 2.6%) provided pharmacokinetic data. There was no evidence for a higher incidence of subjects with quantifiable fluticasone furoate concentrations in the elderly, when compared to the younger subjects.
Use in Children: Fluticasone furoate is typically not quantifiable (less than 10 picograms/mL) following intranasal dosing of 110 micrograms once daily. Quantifiable levels were observed in less than 16% of paediatric patients - following intranasal dosing of 110 micrograms once daily and only less than 7% of paediatric patients following 55 micrograms once daily. There was no evidence for a higher incidence of quantifiable levels of fluticasone furoate in younger children (less than 6 years of age).
Use In Pregnancy & Lactation
Adequate data are not available regarding the use of AVAMYS Nasal Spray during pregnancy and lactation in humans. AVAMYS Nasal Spray should be used in pregnancy only if the benefits to the mother outweigh the potential risks to the foetus.
Fertility: There are no data in humans. (See Pharmacology: Toxicology: Preclinical Safety Data: Reproductive Toxicology under Actions.)
Pregnancy: Following intranasal administration of AVAMYS Nasal Spray at the maximum recommended human dose (110 micrograms/day), plasma fluticasone furoate concentrations were typically non-quantifiable and therefore potential for reproductive toxicity is expected to be very low (see Pharmacology: Toxicology: Preclinical Safety Data: Reproductive Toxicology under Actions).
Lactation: The excretion of fluticasone furoate into human breast milk has not been investigated.
Adverse Reactions
Data from large clinical trials were used to determine the frequency of adverse reactions. The following convention has been used for the classification of frequency: 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). (See Tables 2 and 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image
Drug Interactions
Fluticasone furoate is rapidly cleared by extensive first-pass metabolism mediated by the cytochrome P450 3A4. In a drug interaction study of intranasal fluticasone furoate with the potent CYP3A4 inhibitor ketoconazole, there were more subjects with measurable fluticasone furoate plasma concentrations in the ketoconazole group (6 of the 20 subjects) compared to placebo (1 of the 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 cytochrome P450-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. (See Precautions)
Caution For Usage
Instructions for Use/Handling: Patients should be instructed that the device must be primed before first use and re-primed if the cap is left off or the device does not seem to be working. In order to prime the device, the nasal spray needs to be shaken vigorously for about 10 seconds with the cap on. This is important as AVAMYS Nasal Spray is a thick suspension that becomes liquid when vigorously shaken. It will only spray when it becomes liquid. The patient must then press the button firmly all the way in, approximately 6 times until a fine mist is seen, (to ensure a full-dose is delivered). Once primed the patient must shake the nasal spray vigorously each time before use. The cap must be replaced after use to keep the nozzle clean and to prevent the need for re-priming.
Nasal Spray: The medicine comes in a brown glass bottle inside a plastic casing. It will contain 120 sprays, depending on the pack size that has been prescribed.
A window in the plastic casing allows the patient to see how much medicine is left. The patient will not be able to see the liquid level for a new 120 spray bottle because the liquid level is above the window.
The medicine sprays out of the nozzle when the button on the side is pressed firmly all the way in.
A removable cap protects the nozzle from dust and prevents it from blocking up.
Important information about Avamys Nasal Spray: The nasal spray comes in a brown glass bottle. To check how much is left hold the nasal spray upright against a bright light. The patient will then be able to see the level through the window.
In the first use of the nasal spray, shake it vigorously with the cap on for about 10 seconds. This is important as Avamys Nasal Spray is very thick and becomes more liquid when the patient shakes it well. It will only spray when it becomes liquid.
The button on the side must be pressed firmly all the way in, to release a spray through the nozzle.
If the patient has difficulty pressing the button with the thumb, the patient can use two hands. Alternatively, hold the device back to front (or the other way around) and press the button using the forefinger, middle finger and ring finger.
Always keep the cap on the nasal spray when not in use. The cap keeps the dust out, seals in the pressure and stops the nozzle from blocking up. When the cap is in place, the button on the side cannot be pressed accidentally.
Never use a pin or anything sharp to clear the nozzle. It will damage the nasal spray.
Patient Counseling Information
Preparing the nasal spray: Prepare the nasal spray before using it for the first time and/or if the patient has left the cap off.
Preparing the nasal spray helps to make sure that the patient always get the full dose of medicine.
With the cap on, shake the nasal spray vigorously for about 10 seconds.
Remove the cap by gently squeezing the sides of the cap with the thumb and forefinger and pulling it straight off.
Hold the nasal spray upright and point the nozzle away.
Press the button firmly all the way in. Do this at least 6 times to release a fine spray into the air.
Using the nasal spray: 1. Shake the nasal spray vigorously.
2. Remove the cap.
3. Blow nose to clear nostrils, and then tilt head forward a little bit.
4. Hold the nasal spray upright and carefully place the nozzle in one of the nostrils.
5. Point the end of the nozzle toward the outside of the nose, away from the center ridge of the nose. This helps direct the medicine to the right part of the nose.
6. As the patient breathes in through the nose, press the button once firmly all the way in.
7. Be careful not to get any spray in the eyes. If this happens, rinse the eyes with water.
8. Take the nozzle out and breathe out through mouth.
9. If the physician instructed to take 2 sprays per nostril, repeat steps 4 to 6.
10. Repeat steps 4 to 6 for the other nostril.
11. Replace the cap on the nasal spray.
Cleaning the Nasal Spray: After each use: Wipe the nozzle and the inside of the cap. Don’t use water to do this. Wipe with a clean, dry tissue.
Never use a pin or anything sharp on the nozzle.
Always replace the cap once finished to keep out dust, seal in the pressure and stop the nozzle from blocking up.
If the nasal spray does not seem to be working: Check if there is medicine left. Look at the level through the window. If the level is very low there may not be enough left to work the nasal spray.
Check the nasal spray for damage.
If the nozzle may be blocked, don’t use a pin or anything sharp to clear it.
Try to reset it by following the instructions under Preparing the Nasal Spray.
If it is still not working, or if it produces anything other than a fine mist (such as a jet of liquid), or if there is any discomfort using the spray, return it to the pharmacist.
ATC Classification
R01AD12 - fluticasone furoate ; Belongs to the class of topical corticosteroids used for prophylaxis and treatment of allergic rhinitis.
Presentation/Packing
Nasal spray (white, uniform susp) 27.5 mcg/spray x 120 sprays x 1's.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Sign up for free
Already a member? Sign in