Pharmacological properties
Pharmacodynamics. Fluticasone propionate - GCS. By inhalation in powder form, it has a pronounced anti-inflammatory effect on the lungs and alleviates the symptoms and frequency of attacks of BA, significantly reduces the severity of COPD symptoms, which significantly improves the quality of life of patients. The drug normalizes lung function regardless of the age and gender of patients and the initial functional parameters, the presence of a history of bad habits (cigarette smoking) or allergic status.
Pharmacokinetics. Systemic absorption of the drug occurs through the respiratory system, initially absorption is rapid, then slows down. The remainder of the dose is swallowed and enters the esophagus, having minimal effect due to the low solubility of fluticasone propionate in water and presystemic metabolism of the drug.
A linear increase in the severity of systemic action with increasing inhalation dose of the drug was noted. Fluticasone propionate is characterized by high plasma clearance (1150 ml/min), a large volume of distribution (≈300 l) and a terminal T ½ of ≈8 h. The level of protein binding is moderately high (91%).
Fluticasone propionate is rapidly eliminated from the systemic circulation by metabolism to an inactive metabolite by the cytochrome P450 CYP3A4 enzyme. Renal clearance of fluticasone propionate is low (0.2%), with 5% of the drug excreted as metabolites. Caution should be exercised when co-administering CYP3A4 inhibitors due to the potential for increased systemic exposure to fluticasone propionate.
When fluticasone propionate is administered orally, 87-100% of the dose is excreted in the feces. Up to 75% is excreted unchanged due to minimal systemic absorption. An inactive metabolite is also excreted. After intravenous administration, rapid clearance was observed, indicating extensive metabolism in the liver.
Indication
Ba. adults and children over 16 years of age
Preventive treatment:
mild asthma: patients who require periodic symptomatic treatment with bronchodilators; moderate asthma: patients who require regular anti-asthma treatment, and patients with unstable asthma or worsening asthma on existing preventive therapy or bronchodilator therapy alone; severe asthma: patients with severe chronic asthma. After starting inhaled fluticasone propionate, patients with systemic steroid dependence can significantly reduce the dose of oral corticosteroids or completely abandon them.
Symptomatic therapy of COPD.
Application
Fluthixone is intended for inhalation use. There is no need to change the dose in elderly patients and patients with renal or hepatic insufficiency.
Asthma: the therapeutic effect becomes noticeable after 4-7 days from the start of treatment, although positive dynamics are noted after 24 hours, especially in patients who have not previously received inhaled steroids. The drug Fluticasone has a prophylactic effect, it must be taken regularly, even in the absence of asthma attacks. The dose of fluticasone propionate depends on the severity of the disease and the individual patient's response to treatment.
BA (adults and children over 16 years old)
Mild form of asthma: 125 mcg 2 times a day.
Moderate asthma: 125-250 mcg 2 times a day.
Severe asthma: 250-500 mcg 2 times a day.
The onset of therapeutic effect usually occurs after 4-7 days. If the symptoms of asthma disappear, the dose should be reduced depending on the response to treatment in such a way as to obtain a state of optimal disease control, using the minimum daily dose of the drug.
COPD. Adults: 250 mcg 2 times a day.
For optimal effect, the drug should be taken daily. Improvement is noted after approximately 3-6 months of treatment. If there is no improvement during this time, the patient should be clinically examined and the treatment regimen reviewed.
How to use the inhaler
1. Remove the cap from the inhaler.
2. Holding the inhaler by the bottom, open by turning the tip (body) in the direction of the arrow.
3. Place the capsule into the capsule-shaped chamber at the bottom of the inhaler. The capsule should be removed from the packaging immediately before use.
4. Turn the tip to the closed position.
5. Simultaneously press the button at the bottom of the inhaler all the way down (once!), holding the inhaler in an upright position.
WARNING! At this point, the capsule may break and small pieces may enter the mouth or throat. This is not harmful. The likelihood of the capsule breaking will be minimal if it is pierced once, if storage conditions are observed and if the capsule is unpacked immediately before use.
6. Take a deep breath.
8. When you hear a characteristic sound (buzzing), hold your breath as long as you can without feeling discomfort and remove the inhaler from your mouth. Exhale. Then open the inhaler and check if there is any powder left in the capsule. If there is any powder left, repeat steps 6-8.
9. Open the inhaler, remove the empty used capsule, return the tip to its original position and put on the cap-nozzle.
Cleaning the inhaler: To remove powder residue, wipe the tip and capsule chamber with a dry cloth or a clean, soft brush.
Any unused product or waste material should be disposed of in accordance with local requirements.
Contraindication
Hypersensitivity to any of the components of the drug.
Side effects
The frequency of detection is defined as follows: very common (≥1/10), common (≥1/100 to 1/10), uncommon (≥1/1000 to 1/100), rare (≥1/10,000 to 1/1000), very rare (1/10,000), including isolated cases.
Information on side effects that occur very often, often and infrequently is obtained during clinical trials. Side effects that occur rarely and very rarely are data from episodic reports.
On the part of the immune system: infrequently - hypersensitivity skin reactions; very rarely - angioedema (face, mouth and throat), respiratory symptoms (dyspnea and/or bronchospasm), anaphylactic reactions.
On the part of the endocrine system: very rarely - Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineralization, the occurrence of cataracts and glaucoma.
Infections and infestations: very common: candidiasis of the oral cavity and pharynx (to prevent candidiasis, rinsing the mouth immediately after inhalation is indicated). If necessary, an antifungal drug is prescribed locally, continuing the use of the drug.
From the side of the central nervous system: very rarely - anxiety, sleep disturbances, changes in behavior, including hyperactivity and agitation (mainly in children).
Metabolic disorders: very rarely - hyperglycemia.
Respiratory, thoracic and mediastinal disorders: often - hoarseness (to prevent this, gargling with water immediately after inhalation is indicated); very rarely - paradoxical bronchospasm (in this case, inhalation of the drug is immediately stopped, fast-acting inhaled bronchodilators are used). The patient is examined and, if necessary, alternative therapy is prescribed.
From the gastrointestinal tract: very rarely - dyspepsia.
From the musculoskeletal system: very rarely - pain in the joints.
Skin: often - slight bruising.
Special instructions
The doctor should periodically monitor the patient's ability to use the inhaler.
Fluticone is not intended for the relief of acute asthma attacks, it is prescribed for long-term preventive treatment. In order to stop an acute asthma attack, inhalation of drugs that quickly dilate the bronchi should be used, so the patient should always have such drugs with him.
Severe asthma requires regular monitoring of lung function, as there is a risk of severe attacks and potential life-threatening complications.
If the patient uses rapid-acting bronchodilators more often, this indicates a complicated course of asthma. In such cases, the patient's treatment regimen should be reviewed, taking into account that a sudden and severe increase in asthma symptoms can be life-threatening. In this case, the dose of corticosteroids should be increased. Patients at risk of this course of the disease should measure the maximum volume of air exhaled during forced expiration daily.
As with other inhaled medications, paradoxical bronchospasm may occur. In such cases, Flutixone should be discontinued immediately, a rapid-acting inhaled bronchodilator should be administered immediately, the patient assessed and, if necessary, alternative treatment instituted.
In the absence of a response to treatment or a severe exacerbation of asthma, the dose of fluticasone propionate should be increased and, if necessary, oral steroids should be prescribed and/or an antibiotic should be used in the event of infection.
Systemic effects may occur with all inhaled steroids, for example, when used in high doses for long-term therapy. Systemic effects are less likely to occur with inhaled steroids than with oral steroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineralization, glaucoma and cataracts. It is important to use the lowest possible dose that effectively controls symptoms.
When using the drug in recommended doses, adrenal function and reserve remain within normal limits. The effect of inhaled Fluthixone allows to minimize the need for oral steroids. However, the possibility of side effects in patients who have previously taken oral steroids persists for some time. The degree of adrenal dysfunction in individual situations may require specialist assessment.
Prolonged use of inhaled corticosteroids in high doses can lead to suppression of the function of the adrenal cortex and acute adrenal crisis. Very rare cases of suppression of the function of the adrenal cortex and acute adrenal crisis have been noted when using doses of 250-500 mcg of fluticasone propionate. Sudden situations (trauma, surgery, infection or a sharp decrease in dose) can cause acute adrenal crisis. Then patients develop such uncharacteristic symptoms as fatigue, loss of appetite, nausea, vomiting, weight loss, abdominal pain, headache, hypoglycemia, epileptic seizures, loss of consciousness, decreased blood pressure, confusion. During periods of threat of stress or before elective surgery, the possibility of impaired adrenal function should be considered and appropriate GCS therapy should be carried out.
Switching from oral to inhaled steroids may cause allergic manifestations, such as allergic rhinitis or rash, that were previously treated with systemic steroids. In this case, allergic manifestations should be treated symptomatically with antihistamines or topical agents, including topical steroids.
Patients with COPD should be monitored particularly closely for the development of pneumonia or other lower respiratory tract infections, as the clinical manifestations of these infections and COPD exacerbations are often similar.
Very rare cases of increased plasma glucose concentration have been reported. When prescribing Fluticone to patients with a history of diabetes, it should be noted that the dose of Fluticone contains ≈25 mg of lactose. In patients with lactose intolerance, this amount does not cause any problems.
Treatment with Fluticone should not be stopped suddenly.
It is recommended to exercise special caution when treating patients with active or latent pulmonary tuberculosis.
There is individual hypersensitivity to inhaled corticosteroids.
Switching from oral steroids to inhaled fluticasone propionate. Because of the potential for adrenal dysfunction, patients who are switched from oral steroids to inhaled fluticasone propionate should remain under close observation, with adrenal function monitored. After fluticasone propionate is introduced into the treatment regimen, the dose of oral systemic steroids should be gradually reduced, and patients should carry a steroid card that informs them of the need for additional systemic steroids in stressful situations.
Dose reduction of oral steroid should be initiated after one week of concomitant use of fluticasone propionate. Dose reduction should not be performed more frequently than once a week. Maintenance doses of 10 mg/day or less in terms of prednisolone should not be reduced more rapidly than by 1 mg once a week. For maintenance doses of prednisolone 10 mg/day, dose reductions of more than 1 mg/day once a week may be tolerated.
Some patients experience atypical symptoms of malaise during the tapering period of oral steroids, even though respiratory function has improved. These patients should continue treatment with Fluticasone and taper their oral steroids unless there are objective symptoms of adrenal insufficiency.
Patients who, after stopping oral steroids, have symptoms of adrenal dysfunction, should carry a document informing them of the need for additional systemic steroids in case of stress, such as increased asthma attacks, respiratory, thoracic and mediastinal infections, severe concomitant diseases, surgical interventions, injuries, etc.
Use during pregnancy and breastfeeding. There are no data on the use of fluticasone propionate during pregnancy. The drug should be prescribed to pregnant women only if the expected benefit to the mother outweighs the potential risk to the fetus. There is no data on the penetration of fluticasone propionate and its metabolites into breast milk. In humans, after inhalation of recommended doses of the drug, the concentration in the blood plasma will be low.
Children: Not intended for use in children under 16 years of age.
The ability to influence the reaction rate when driving vehicles or working with mechanisms. The use of the drug does not affect.
Under normal conditions, after inhalation of fluticasone propionate, low plasma concentrations are achieved due to extensive first-pass metabolism and high clearance, dependent on cytochrome P450 3A4 activity in the intestine and liver. Therefore, significant clinical interactions of fluticasone propionate with other drugs are unlikely. Studies have shown that concomitant administration of cytochrome P450 3A4 inhibitors (e.g. erythromycin or terfenadine) causes a slight increase in systemic fluticasone propionate concentrations without a significant decrease in plasma cortisol concentrations.
Concomitant use of strong inhibitors of cytochrome P450 3A4 (e.g. ritonavir) and fluticasone propionate, including nasal, increases the plasma concentration of fluticasone propionate many times, reducing the plasma concentration of cortisol. According to a post-marketing study, a clinically significant drug interaction in patients taking fluticasone propionate and ritonavir resulted in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the benefit outweighs the risk of systemic corticosteroid effects. This interaction has not been observed with inhaled fluticasone propionate, but its occurrence cannot be excluded.
Studies with other cytochrome P450 3A4 inhibitors have shown that they have a minor (erythromycin) effect on increasing the systemic concentration of fluticasone propionate in the blood plasma without a significant decrease in cortisol concentration. Ketoconazole, an inhibitor of CYP 3A isoenzymes, increases the concentration of fluticasone propionate after a single dose by up to 150%. This causes a significant decrease in the concentration of cortisol in the blood plasma. The detection of an interaction of fluticasone propionate with other CYP 3A inhibitors (e.g. itraconazole) cannot be excluded. However, special care should be taken and, if possible, long-term use of fluticasone propionate with strong cytochrome P450 3A4 inhibitors (e.g. ketoconazole) should be avoided, given the possibility of increasing the systemic concentration of fluticasone and the risk of developing undesirable systemic manifestations.
Overdose
A single use of fluthixone in doses exceeding the recommended ones can cause acute poisoning, manifested by temporary suppression of the hypothalamic-pituitary-adrenal system. This does not require special measures, and the function of the adrenal cortex returns to normal on its own after a few days. When using fluthixone in doses exceeding the recommended ones, significant suppression of the function of the adrenal cortex is possible for a long time. Factors that can provoke an acute adrenal crisis can be injuries, surgical interventions, infections or a sharp decrease in the dose. Patients taking fluthixone doses higher than recommended should be under special supervision, and their dose should be reduced gradually. In such cases, monitoring of adrenal reserve may be required. In cases of overdose, treatment with the drug should be continued in doses that provide effective control of BA.
Storage conditions
Store below 30°C.
