How Effective Is Fluticasone for Asthma?

Fluticasone propionate inhaled aerosol is indicated for the preventive treatment of asthma by inhaled fluticasone propionate. Adults: · Mild asthma: Patients who need to be given intermittent bronchodilator medication to relieve asthma symptoms on the basis of regular daily treatment. Moderate asthma: Patients who are receiving preventive treatment or bronchodilator therapy but whose asthma is still unstable or continues to worsen. Severe asthma: Patients with severe chronic asthma who rely on systemic corticosteroids to adequately control their symptoms. Once the use of inhaled fluticasone propionate can significantly reduce or eliminate the need for oral corticosteroids in many patients. Child: Any child in need of preventive medication, including patients whose symptoms cannot be controlled with current preventive treatment.

Drug Name: Fluticasone propionate aerosol
Drug type: Prescription drugs, topical drugs, medical insurance workers' injuries

Special medicine: Doping
Use classification: Glucocorticoid

Fluticasone propionate inhalation aerosol drug name

[Common name] Fluticasone propionate aerosol

[Commodity name] Flixotide

[English name] Fluticasone Propionate Inhaled Aerosol

[Chinese Pinyin] Bing Suan Fu Ti Ka Song Xi Ru Qi Wu Ji

Fluticasone Propionate Inhalation Aerosol Ingredients

Fluticasone propionate chemical name: 6,9-difluoro-11hydroxy-16-methyl-3-oxo-17- (1-oxopropoxy) -androsta-1,4-diene-17- Chemical structure of thiocarboxylic acid (6, 11, 16, 17) -S- (fluoromethyl) ester:

Molecular formula: C ₂₅ H ₃₁ F ₃ O ₅ S

Molecular weight: 500.6
This product uses HFA134a as a propellant.

Characteristics of Fluticasone Propionate Inhalation Aerosol

This product is an aerosol for quantitative pressure administration and contains a white to off-white suspension.

Indications of fluticasone propionate inhalation aerosol

Administration of inhaled fluticasone propionate can prevent asthma.
adult:
Mild asthma: Patients who need to be given intermittent bronchodilator medication to relieve asthma symptoms on the basis of regular daily treatment.
Moderate asthma: Patients who are receiving preventive treatment or bronchodilator therapy but whose asthma is still unstable or continues to worsen.
Severe asthma: Patients with severe chronic asthma who rely on systemic corticosteroids to adequately control their symptoms. Once the use of inhaled fluticasone propionate can significantly reduce or eliminate the need for oral corticosteroids in many patients.
child:
Any child in need of prophylactic treatment, including patients whose symptoms cannot be controlled with current preventive treatment.

Fluticasone Propionate Inhalation Aerosol Specifications

50g / , 125g / , 250g /

Fluticasone propionate inhalation aerosol

Cosedone® inhalation aerosol can only be inhaled through the mouth. Patients who have difficulty synchronizing inhalation and inhalation can use the mist storage tank.
Patients should pay attention to cosedone® inhalation aerosol for preventative treatment, and should be used regularly even if asymptomatic. Significant effect within 4 to 7 days after administration.
Adults and children over 16 years: 100 to 1,000 micrograms each time, twice daily. Usually two tadpoles each time, twice daily.
Patients should be given an appropriate initial dose in the severity of the condition. Prescribers should be aware that fluticasone propionate may require lower doses for disease control than some other inhaled corticosteroids.
Usually the initial dose is:
Mild asthma: 100 to 250 mg twice daily.
· Moderate asthma: 250 to 500 mg twice daily.
Severe asthma: 500 to 1000 mg each time, twice daily.
Children over 4 years: 50 to 100 micrograms each time, twice daily. The starting dose should be based on the severity of the condition.
If this product does not reach the exact child's dose prescribed by your doctor, please use other formulations of cosedone®, such as Junner®, dish absorber® or other aerosols.
When the dose is more than 1000 micrograms (500 micrograms twice daily), a mist tank should be used to reduce side effects on the mouth and throat.
Special patients: No dosage adjustment is required for elderly patients, patients with liver or kidney impairment.
The dose should be gradually reduced to the lowest dose that can effectively control asthma.

Adverse effects of fluticasone propionate inhalation aerosol

Adverse events are listed according to different occurrence systems, organs, and incidences. Incidence rates are defined as: very common (1 / 10), common (1 / 100 and <1/10), uncommon (1 / 1000 and <1/100), and rare (1 / 10000 and <1 / 1000), very rare (less than 1/10000) including case reports. Very rare, common, and uncommon individuals are usually obtained from clinical trial data. Rare and very rare adverse events are usually spontaneous data.
Infections and invasive diseases < br are very common: candidiasis of the mouth and throat.
Some patients develop candidiasis (thrush) in the mouth and throat. Rinse mouth with water after medication may help patients. Symptomatic candidiasis can be treated topically with antifungal drugs, while cosedone® inhalation aerosol can be continued.
Immune System Disorders < br The following allergic reactions have been reported:
Uncommon: Skin allergic reactions are very rare: angio (neuro) edema (mainly facial and oropharyngeal edema), respiratory syndrome (dyspnea and / or bronchospasm), and allergic reactions.
Endocrine disorders < br Possible systemic reactions include (see [Cautions]):
Very rare: Cushing's Syndrome, Cushingoid's features, adrenal depression, growth retardation in children and adolescents, reduced bone mineral density, cataracts and glaucoma.
Metabolic and Nutrition Disorders br Very Rare: Hyperglycemia <br Mental Disorders < br Very Rare: Anxiety, Sleep Disorders, Behavior Changes including Hyperactivity, Irritability (Mainly seen in children)
Respiratory system, chest and mediastinum <br /> common: hoarseness Some patients inhale fluticasone propionate, which can cause hoarseness. It is helpful to rinse your mouth with water after medication.
Very rare: As with other inhaled therapies, abnormal bronchospasm may occur after administration and immediately increase with wheezing. It should be treated immediately with a fast-acting inhaled bronchodilator, and the use of cosedone® inhaled aerosol should be stopped immediately. Evaluate the patient and, if necessary, develop alternative treatment options.
Very rare reports of indigestion and joint pain have not been established for a causal relationship with fluticasone propionate.

Fluticasone propionate inhalation aerosol contraindications

It is contraindicated in patients who have an allergic reaction to any ingredient in the preparation.

Precautions for Fluticasone Propionate Inhalation Aerosol

The control of asthma should be carried out according to the principle of step treatment, and the patient's condition should be monitored through clinical and pulmonary function tests. If a fast-acting inhaled 2-agonist is added to reduce symptoms, this indicates a worsening of asthma control. In this case, the patient's treatment regimen should be re-evaluated and additional anti-inflammatory treatments should be considered (for example, inhalation of higher doses or a course of oral corticosteroids). Severely worsening asthma must be treated routinely. In the control of asthma, sudden and progressive exacerbations of asthma are fatal, and increasing doses of glucocorticoids should be considered. If the patient is at risk, consideration should be given to monitoring the daily peak flow rate in the morning.
Ineffective or severe exacerbation of asthma, the dose of fluticasone propionate should be increased. If necessary, systemic glucocorticoid therapy and / or antibiotics should be given (if infected).
Cosedone® inhalation aerosol is mainly used for long-term routine treatment of asthma and is not suitable for alleviating the symptoms of acute asthma. At this time, patients should choose a fast and short-acting inhaled bronchodilator. It is recommended that patients have the above-mentioned first aid.
Sudidone® inhalation aerosol treatment must not be interrupted abruptly.
Very rare reports of elevated blood glucose levels (see [Adverse Reactions]). For patients with a history of diabetes, the possibility should be considered.
Like other inhaled glucocorticoids, it should be used with caution in patients with active or stationary tuberculosis.
A clinical trial of drug interactions in healthy volunteers showed that ritonavir (a strong CYP3A4 liver enzyme inhibitor) can cause clinically significant patients treated with fluticasone propionate and ritonavir Drug interactions lead to systemic glucocorticoid effects, including Cushing's Syndrome and suppression of adrenal function. Therefore, the combination of fluticasone propionate with ritonavir should be avoided. Concomitant administration of fluticasone propionate and ritonavir may only be considered when the patient's expected benefit from the drug exceeds a systemic glucocortic side effect.
The technique of the patient using an aerosol device should be checked frequently to confirm that the administration and inhalation are performed at the same time to ensure that the drug can reach the lungs to the greatest extent.
Possible systemic effects, including adrenal function, bone density and growth: [/ u]
Inhaled glucocorticoids can cause systemic effects, especially when used in large doses for long periods of time (participate in [drug overdose]). But its incidence is much less than oral glucocorticoids. Possible systemic effects include Cushing's Syndrome, Cushingoid's features, adrenal depression, growth retardation in children and adolescents, reduced bone mineral density, cataracts and glaucoma. Therefore, it is important to reduce the dose to the lowest dose that can effectively control asthma (see [Adverse Reactions]).
Regular monitoring of the height of children receiving long-term inhaled corticosteroids is recommended. If growth reduction occurs, consideration should be given to whether inhaled glucocorticoids can be reduced to the lowest dose effective in controlling asthma, and a child respiratory specialist should be considered for evaluation.
Long-term high-dose inhalation of glucocorticoids, especially above the recommended dose, can cause clinically significant adrenal suppression. In addition, in emergency situations or elective procedures, additional systemic glucocorticoid therapy should be considered.
Medication for children:
The growth and development of children receiving corticosteroid therapy, including fluticasone propionate, should be monitored. The potential impact on growth and development from long-term medication should be weighed against the clinical benefits obtained. To minimize the systemic effects of inhaled corticosteroids, including fluticasone propionate, patients should gradually adjust the dose used to the lowest dose effective to control symptoms. (See [Usage and dosage]).
Children inhaled fluticasone propionate at the recommended dose, and adrenal function and reserve usually remained within normal ranges. Nonetheless, there may be no reduction in systemic effects from previous or intermittent oral steroids. However, the benefit of inhaled fluticasone propionate is that it minimizes the need for oral steroids.
Medical and surgical emergencies:
For patients who have previously received other high-dose inhaled corticosteroids and / or intermittent oral corticosteroids for medical and surgical emergencies, the risk of impaired adrenal reserve will persist for some time when changing to inhaled fluticasone propionate . The possibility of adverse reactions will continue for quite some time. Such patients should undergo special tests to confirm the extent of adrenal damage before selecting a protocol. During emergencies and elective treatments that may cause stress, the possibility of adrenal damage should be considered and the appropriate glucocorticoid treatment should be selected.
For patients who have received oral glucocorticoid therapy:
For oral hormone-dependent patients, special care should be given when switching to cositone® inhalation aerosol and its subsequent treatment, as the recovery of adrenal function impairment caused by long-term systemic hormone therapy may take a long time. In patients with long-term or high-dose systemic hormone therapy, adrenal function may be inhibited. For such patients, their adrenal cortical function should be monitored regularly and the dose of systemic hormones carefully reduced.
After about 1 week, the effects of systemic hormones can be gradually removed. The reduction should be performed at intervals of not less than 1 week, depending on the maintenance dose level of systemic hormones, as appropriate. Patients who use prednisolone (or an equivalent drug) at a daily maintenance dose of 10 mg or less should not reduce the dose by more than 1 mg per day or at intervals of less than 1 week. Patients who use prednisolone at a maintenance dose of more than 10 mg per day can carefully reduce the dose by a large interval at 1 week intervals.
In the process of withdrawing systemic hormones, some patients may feel bad although they can maintain their respiratory function or even their lung function is improved. They should be encouraged to adhere to inhaled fluticasone propionate and continue to withdraw systemic glucocorticoids unless objective signs of adrenal insufficiency appear.
Patients who have been withdrawn from hormone therapy, if their adrenal cortical function has not recovered, should carry a hormone warning card to indicate that the patient is under stress, such as exacerbation of asthma, lung infections, major complications, surgery or trauma Supplement systemic hormones.
Switching from systemic glucocorticoid therapy to inhaled therapy sometimes exposes allergic conditions such as allergic rhinitis or eczema that has been controlled with systemic administration. Symptomatic treatment with antihistamines and / or topical formulations, including topical corticosteroids. Rare examples show that inhalation therapy can cause the onset of underlying eosinophilic diseases such as Churg-Strauss syndrome. This is mostly related to the reduction or withdrawal of oral glucocorticoid therapy. No direct causality has been established.
Fluticasone propionate has no effect on driving and operating machinery.
Use with caution by athletes.

Fluticasone propionate inhalation aerosol for pregnant and lactating women

There is insufficient evidence for the safety of fluticasone propionate in humans during pregnancy. Corticosteroids have been found to induce fetal toxicity and teratogenesis in rodent trials. Nevertheless, the same effects of such compounds on pregnant women have not been found. In the teratogenicity test of mice and rats with subcutaneous injections of fluticasone propionate at 100-150 mg / kg / day and above, the expected fetal toxicity and teratogenesis were seen. In the inhalation teratogenicity test in rats, inhalation of fluticasone propionate at a dose of 68.7ug / kg / day did not show any deformity, but the mother animal was administered at a dose of 25.7ug / kg / day and a larger dose, and fetal animals appeared Weight loss and stunted growth. With early compounds of this class, these effects are unlikely to be relevant to human treatment. Nonetheless, as with other medicines, the administration of fluticasone propionate during pregnancy can only be considered if the expected benefit to the mother outweighs the potential danger to the fetus.
Studies on the secretion of fluticasone propionate in human milk have not been performed. Radioactively labeled quantified drugs are injected subcutaneously into lactating rats. Radioactivity can be detected in plasma and milk after 1-8 hours (concentration in milk is 3-7 times that in plasma).
However, given the low blood concentration of fluticasone propionate in the mother's body, the amount of fluticasone propionate taken up by the newborn is estimated to be very small.

Fluticasone propionate inhalation aerosol for children

See [Indications], [Usage and Dosage] and Precautions for details.

Fluticasone propionate inhalation aerosol for elderly use

For details, please refer to [Usage and Dosage].

Fluticasone Propionate Inhalation Aerosol Drug Interactions

Due to first-pass metabolism and the high systemic clearance of cytochrome P4503A4 in the intestine and liver, usually fluticasone propionate has a low blood concentration after inhalation. Therefore, there is no clinically significant drug interaction caused by fluticasone propionate.
A clinical trial of drug interactions in healthy volunteers has shown that ritonavir (a strong inhibitor of CYP3A4 liver enzymes) can significantly increase fluticasone propionate blood levels, leading to serum cortisol concentrations Significantly reduced. Patients who have been treated with both fluticasone propionate and ritonavir have clinically significant drug interactions that lead to systemic glucocorticoid effects, including Cushing's Syndrome and adrenal function inhibition. Therefore, the combination of fluticasone propionate with ritonavir should be avoided. Concomitant administration of fluticasone propionate and ritonavir may only be considered when the patient's expected benefit from the drug exceeds a systemic glucocortic side effect.
Studies have shown that other inhibitors of cytochrome P4503A4 have no effect on the increase of fluticasone propionate system exposure (erythromycin) and a slight effect (ketoconazole), and there is no significant decrease in serum cortisol concentration. However, when taking P4503A4 liver enzyme inhibitors (such as ketoconazole) at the same time, care should be taken that may increase the exposure of fluticasone propionate system.

Fluticasone propionate inhaled aerosol overdose

Acute inhalation above the recommended dose can cause temporary adrenal depression. No emergency measures are required. These patients should continue to be treated with fluticasone propionate, which effectively controls asthma; adrenal function can be restored within a few days, and this can be confirmed by testing plasma cortisol.
If long-term use of fluticasone propionate exceeds the recommended dose, it will cause some degree of adrenal function inhibition. Adrenal reserve should be monitored. Adrenal crises have been reported very rarely in children over a long period (months or years) of using fluticasone propionate (usually 1000 g or more per day). The observed features are hypoglycemia, with a diminished consciousness Or the sequelae of convulsions. Once fluticasone propionate is used in excess, treatment can still be continued at an appropriate dose that effectively controls symptoms.
Patients using more than the recommended dose of fluticasone propionate should be closely monitored and the dose gradually reduced.

Pharmacology and Toxicology of Fluticasone Propionate Inhalation Aerosol

1. Pharmacodynamics After inhaling fluticasone propionate at the recommended dose, it shows a strong anti-inflammatory effect of glucocorticoids in the lungs, which can improve the control of asthma symptoms and reduce the use of other drugs, such as first aid bronchodilators. And can prevent the decline of lung function. The lower systemic bioavailability of fluticasone propionate makes the incidence and severity of side effects significantly lower than that of systemic corticosteroids.
2. Preclinical safety toxicology shows that the typical effect of this class of corticosteroids appears only when the dosage is much higher than the recommended therapeutic dose. No new toxicological effects were found in long-term toxicity, reproductive toxicity and teratogenicity studies. Fluticasone propionate has no mutagenic activity in vivo and in vitro, and no carcinogenic effect of this product has been found in rodent studies; no irritation and sensitization of this product has been seen in animal models.
The Freon-free propellant-HFA134a did not show toxic effects in a two-year exposure test in a variety of animal species at high gaseous concentrations far exceeding patient dosage.

Pharmacokinetics of Fluticasone Propionate Inhalation Aerosol

In a 14-day trial on healthy volunteers, the inhaled dose was 2000 ug per day (1000 ug each time, twice daily), and the plasma concentration of the drug was about 0.3 ng / mL after 30-60 minutes of administration.
After inhalation in healthy volunteers, fluticasone propionate has a systemic bioavailability of 10-30% depending on the dosage form. Since the bioavailability of the inhaled dose swallowed through the digestive tract is almost zero, the overall absorption of the drug can be determined by the amount of the drug reaching the lungs.
Fluticasone propionate shares many similar characteristics with other inhaled glucocorticoids in the pharmacokinetics and pharmacodynamics of asthma treatment. But compared with other similar corticosteroids, due to its incomplete gastrointestinal absorption and significant first-pass effect, fluticasone propionate after inhalation is almost zero when swallowed into the systemic circulation.
Studies on oral radiolabeled and unlabeled fluticasone propionate in human volunteers have shown that most doses (87-100%) are excreted from feces, with as much as 75% of the original drug depending on the dose used. The 1-5% dose is excreted in urine as metabolites.
A 16 mg single dose of the drug was orally administered to healthy volunteers, resulting in a blood concentration of less than 0.5 ng / mL.
Healthy volunteers received a single intravenous injection of 2 mg of the drug, showing that the clearance rate of fluticasone propionate was close to the rate of liver blood flow (900 mL / min), while the renal clearance rate was less than 1%. These results indicate that liver clearance is almost complete. Oral bioavailability is close to zero.
When administered intravenously, the pharmacokinetics of fluticasone propionate is proportional to the dose administered. Fluticasone propionate is widely distributed throughout the body. The steady-state distribution volume is close to 300L, and its clearance rate is as high as 1.1L / min, suggesting extensive liver clearance.
The peak plasma concentration of fluticasone propionate decreased by nearly 98% within 3-4 hours, and after the terminal half-life (about 8 hours), the concentration of the drug in the plasma was very low.
In animal and human tests, the propellant HFA-134a was rapidly cleared by respiration, and no significant metabolism or accumulation was observed in humans. Due to the extremely short peak time (tmax) and average residual time, HFA-134a has a short residence time in plasma without accumulation.

Fluticasone propionate inhalation aerosol storage

Store below 30 ° C (86 ° F) and avoid freezing and direct sunlight. As with most drugs stored in pressure vessels, the therapeutic effect of the drug may decrease as the tank cools.

Fluticasone Propionate Inhalation Aerosol Packaging

The inhaler includes an aluminum can sealed with a dosing valve, a snap button and a dust cap. Each jar contains 60 or 120 g of fluticasone propionate.

Validity of Fluticasone Propionate Inhalation Aerosol

24 months

Standard for Fluticasone Propionate Inhalation Aerosol

50g / Import drug registration standard: JX20070120
125g / Import drug registration standard: JX20070120
250g / Import drug registration standard: JX20070120 ^[1]