The composition and form of issue:
Spray nasal. 1 dose contains active substance:
fluticasone furoate (micronized) 27,5 mcg
excipients: dextrose — 2750 mcg dispersible cellulose (containing 11% of sodium carmellose) — 825 mcg of Polysorbate 80 — of 13.75 µg of benzalkonium chloride solution 50%, and 16.5 mg of disodium edetate to 8.25 µg purified water up to 50 µl
in dark glass bottles for 30, 60 or 120 doses (complete with metering device) to the hard plastic in the paper cartons 1 case plastic.
Description pharmaceutical form:
Spray nasal dose: homogeneous white slurry.
Suction. Fluticasone furoate is not completely absorbed, exposed to primary hepatic metabolism, which leads to negligible systemic exposure. Intranasal dose of 110 mcg 1 time a day usually leads to the definition of immeasurable plasma concentrations (<10 PG/ml). Absolute bioavailability of fluticasone furoate when administered intranasally at a dose of 880 mcg 3 times daily (daily dose of 2640 g) is 0.5%.
Distribution. Fluticasone furoate binds to blood plasma proteins more than 99%. Upon reaching the Css Vd fluticasone furoate is an average of 608 L.
Metabolism. Fluticasone furoate is rapidly excreted from the systemic blood flow (total plasma clearance of 58.7 l.), mainly by metabolism in the liver to form the inactive 17&beta-carboxyl metabolite (GW694301X) with the participation of the enzyme CYP3A4 of cytochrome P450. The main route of metabolism is hydrolysis of the S-fermecelebrite group with the formation of 17&beta-carboxykinase metabolite. In vivo studies showed that cleavage of fluticasone furoate to fluticasone occurs.
Excretion. The excretion of fluticasone furoate and its metabolites after oral and/in the introduction is carried out mainly through the gut, reflecting their excretion in the bile. About 1 and 2% is excreted by the kidneys after oral and/in the introduction, respectively.
Special groups of patients
Elderly patients: the pharmacokinetic data are presented only for a small number of elderly patients (n=23/872 2.6 percent). There is no evidence that concentrations of fluticasone furoate, quantifiable, elderly patients is higher than in younger patients.
Children: fluticasone furoate typically found in concentrations not quantifiable (<10 PG/ml), with intra application at a dose of 110 mcg 1 time a day. Concentration determined quantitatively was less than 16% of children in intra application at a dose of 110 mcg 1 time a day and less than 7% of children who use 55 mcg 1 time a day. There is no evidence that children younger than 6 years were more often observed increase in the concentration of fluticasone furoate.
Patients with impaired renal function: fluticasone furoate was not determined in the urine of healthy volunteers during intra the reception. Less than 1% of metabolites are excreted through the kidneys, thus impaired renal function theoretically has no influence on the pharmacokinetics of fluticasone furoate.
Patients with abnormal liver function: study in patients with moderate hepatic impairment, administer 400 micrograms of fluticasone furoate once inhaled, showed increased Cmax by 42% and increase in AUC0–&infin by 172% in comparison with healthy volunteers. Based on the results of the study, on average, the estimated effect of fluticasone furoate at a dose of 110 µg in intra application in this group of patients will not lead to suppression of cortisol. Therefore, to mild disturbances of liver function likely will not lead to clinically important effects when you assign the standard dose for adults.
Other pharmacokinetic parameters: concentration of fluticasone furoate is typically not detected (<10 PG/ml) when administered intranasally at a dose of 110 mcg 1 time a day. Determined concentration was only observed in less than 31% of patients aged 12 years and older and less than 16% of patients under the age of 12 when assigning 110 mcg 1 once a day intranasally.
According to gender, age (including children), race was not mentioned in the cases, when the concentration was above or below the threshold.
Description pharmacological action:
Fluticasone furoate is a synthetic triptoreline GCS with high affinnostew to GCS receptors, has a pronounced anti-inflammatory action.
Symptomatic treatment of seasonal and perennial allergic rhinitis in adults and children older than 2 years.
Hypersensitivity to fluticasone furoate or any other component of the drug.
Caution: patients with severe liver dysfunction (pharmacokinetics of fluticasone furoate may change).
Application of pregnancy and breast-feeding:
Data on the use of fluticasone furoate in pregnancy and lactation for women is not enough. Fluticasone furoate may be used in pregnant women only if the expected benefit to the mother outweighs the potential risk to the fetus.
The excretion of fluticasone furoate with women’s breast milk has not been studied. Fluticasone furoate may be used in lactating women only if expected benefit for mother exceeds the potential risk to the child.
Adverse events below lists depending on the body systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very common (&GE. 1/10), often (&ge1/100 and <1/10), infrequently (&ge1/1000 and <1/100), rare (&ge1/10,000 and <1/1000), very rare (<1/10000, including individual cases). Categories of frequency were formed on the basis of clinical studies and post-marketing drug surveillance.
The respiratory system of the chest and mediastinum: often — nasal bleeding in adults and adolescents cases of epistaxis was observed more frequently with prolonged use (over 6 weeks) than in short course (6 weeks). In studies in children with duration of therapy up to 12 weeks the number of cases of nasal bleeding was similar in the group fluticasone furoate and placebo often ulceration of the mucous membrane of the nasal cavity.
Violations by the immune system: hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria.
Fluticasone furoate is rapidly metabolized in the liver by isoenzymes of cytochrome P450 CYP3A4. In a study of drug interactions fluticasone furoate and the CYP3A4 inhibitor — ketoconazole was observed more cases of concentrations of fluticasone furoate are above threshold in the plasma in the ketoconazole group (6 of 20 patients) compared to placebo (1 out of 20 patients). This slight increase does not lead to a statistically significant difference of cortisol in plasma during 24 h between the two groups.
On the basis of theoretical data make no assumptions about any drug interactions fluticasone furoate used intranasally, and other drugs that are metabolized with participation of cytochrome P450. Thus, clinical studies to investigate interactions of fluticasone furoate and other drugs have not been conducted.
On the basis of the data obtained in the study with another medication containing corticosteroids, which also undergoes metabolism via the isoenzyme cytochrome CYP3A4 is not recommended joint appointment with ritonavir because of the potential risk of increasing systemic exposure of fluticasone furoate.
Method of application and dose:
The intranasal route.
To achieve maximum therapeutic effect it is necessary to adhere to regular patterns of use. Onset of action can occur within 8 h after the first injection. To achieve maximum effect may take several days. The lack of an immediate effect should be carefully explained to the patient.
For the symptomatic treatment of seasonal and perennial allergic rhinitis
Adults and adolescents (aged 12 years and older): the recommended initial dose — 2 inject (with 27.5 mcg of fluticasone furoate in 1 injection) in each nostril 1 time a day (110 mcg/day). In achieving adequate control of symptoms a dose reduction to 1 inject into each nostril 1 time per day (55 mcg/day) may be effective for maintenance treatment.
Children aged 2 to 11 years: the recommended starting dose — 1 spray in between (to 27.5 mcg of fluticasone furoate in 1 injection) in each nostril 1 time per day (55 mcg/day). In the absence of the desired effect, with 1 injection in each nostril 1 time a day may increase dose to 2 vspryskivaniu in each nostril 1 time a day (110 mcg/day). In achieving adequate control of symptoms is recommended to reduce the dose to 1 inject into each nostril 1 time per day (55 mcg/day).
Children under 2 years of age: insufficient data to recommend use of fluticasone furoate intranasal treatment of seasonal and perennial allergic rhinitis in children aged under 2 years.
Elderly patients: dose adjustment is not required.
Patients with impaired renal function: dose adjustment is not required.
Patients with hepatic impairment: dose adjustment in patients with slight and moderate impaired liver function is not required. No data on use in patients with severely impaired liver function.
Instructions for use nasal spray
Description nasal spray: the product is available in orange glass bottles of 30, 60 and 120 doses, which are in plastic boxes.
Display window in the plastic packaging allows you to control the level of drug in the vial. In bottles of 30 or 60 doses, drug levels will be visible immediately, but in bottles of 120 doses of the initial level of drug is above the upper boundary of the viewing window.
To produce an injection, you must press the button to spray. A removable cap protects the atomizer against dust and debris.
Six important facts about the drug
1. Nasal spray is produced in orange glass bottles. In order to check the level of the drug in the vial, you need to look through it into the light. The level will be visible in the viewing window.
2. If nasal spray is used for the first time, you should shake the bottle well for 10 seconds without removing the cap. The drug is a fairly heavy suspension and becomes more liquid when shaken. Injection is possible only after the shaking.
3. To make an injection, it is necessary to press the button.
4. If you are not able to click on one thumb, you must use the fingers of both hands.
5. You should always keep a bottle of nasal spray closed. The cap protects the atomizer against dust and debris and seal the vial. In addition, the cap prevents accidental pressing.
6. Do not attempt to clean the hole of the tip with a pin or other sharp objects. They can damage the bottle with the spray.
Preparation for application should be carried out if:
- spray used for the first time
- or the bottle was left open.
Proper preparation of the application of the spray will ensure the injection of the required dose of the drug.
- without removing the cap, you should shake the bottle well for 10 seconds
- remove the cap, gently pulling it between thumb and forefinger
- it is necessary to hold the vial vertically and guide tip from myself
- to press the button to make several clicks (at least 6) until the tip appears a little cloud.
The use of nasal spray
1. Carefully shake the bottle.
2. To remove the cap.
3. To unclog the nose and tilt the head slightly forward.
4. To enter a tip in one nostril, continuing to keep the bottle vertical.
5. To direct the tip of the sprayer on the outer wall of the nose, not on the nasal septum. This will ensure proper injection of the drug.
6. Begin to inhale through the nose and make a single tap of your finger for injection of the drug.
7. Avoid getting spray in the eyes! If the product enters eyes, rinse thoroughly with water.
8. Remove the atomizer from the nostril and exhale through the mouth.
9. If, according to the advice of a doctor, you need to make for 2 injection in each nostril, repeat the paragraphs 4-6.
10. Repeat the procedure for the other nostril.
11. Close the bottle cap.
After each use:
- wet the tip and the inner surface of the cap with a clean dry cloth avoid contact with water
- never attempt to clean the hole of the tip with a pin or other sharp objects
- you must always close the bottle cap protects the atomizer against dust and debris and seal the vial.
If the sprayer is not working:
- to check the level of remaining medication in the bottle through the viewing window, if there are very small amount of fluid, it may not be enough to operate the sprayer
- check bottle for damage
- check for clogging of the inlet of the tip do not attempt to clean the hole of the tip with a pin or other sharp objects
- it is necessary to try to bring the device into action, repeating the procedure for the preparation of nasal spray for use.
Symptoms: the study of the bioavailability of the drug when administered intranasally applied dose 24 times higher than recommended dose for adults for more than 3 days, with adverse system reactions were observed.
Treatment: it is unlikely that acute overdosage would require other measures in addition to medical supervision.
Fluticasone furoate undergoes primary hepatic metabolism by the isozyme cytochrome CYP3A4. Thus, the pharmacokinetics of fluticasone furoate in patients with severe liver dysfunction may change.
Effects on ability to drive or other mechanisms. Based on the pharmacological properties of fluticasone furoate and other local GCS, effects on ability to drive or other mechanisms is not expected.