Pharmacological action Alvesco Inhaler
SCS for inhalation use. Ciclesonide has low affinity glucocorticoid receptor (approximately 8 times lower than that of dexamethasone). After oral inhalation Ciclesonide enzymatically converted in the lungs to the active metabolite – deztsiklezonid. Deztsiklezonid has a pronounced anti-inflammatory effect due to the high affinity glucocorticoid receptor (approximately 12 times higher than that of dexamethasone).
Application Alvesco at the recommended doses shows a satisfactory correlation between the local and systemic anti-inflammatory effect of corticosteroids, due to these pharmacokinetic and pharmacodynamic properties of the active substance: a high ground clearance, a very small amount of tissue compared with light, a relatively short T1 / 2, the low oral bioavailability, high level of protein binding, low affinity metabolites (except deztsiklezonida) to the receptors of the SCS and the low interaction with other drugs.
Prolonged retention in the lungs deztsiklezonida (up to 24 hours) allows you to use the drug 1 time /
Inhaler use Ciclesonide also slows the growth of inflammatory cells (eosinophils, total) and inflammatory mediators in saliva.
Pharmacokinetics Alvesco Inhaler
Absorption
Oral or / in the introduction of radiolabeled Ciclesonide showed that when administered extent of absorption was 24.5%. Before the drug inside the bioavailability Ciclesonide as well as the active metabolite is negligible (<0.5% for Ciclesonide , and <1% for the metabolite) in relation to the significant influence of first-pass metabolism.
Ciclesonide accumulation in healthy subjects in the lungs – over 50%. In line with this figure for the systemic bioavailability of the active metabolite after inhalation – over 50%. Since the bioavailability of the active metabolite at the reception inside Ciclesonide less than 1%, a drug taken by inhalation has no systemic effects.
Distribution
After i / v administration in healthy volunteers Ciclesonide quickly distributed because of its high lipophilicity. Vd averaged 2.9 l / kg and 12.1 Ciclesonide L / kg for deciclesonide. Percentage Ciclesonide associated with plasma proteins, about 99% and the percentage of the active metabolite – 98-99%, show an almost complete binding of circulating Ciclesonide / active metabolite to plasma proteins.
Metabolism
Ciclesonide hydrolyzed to the biologically active metabolite by esterase enzymes in the lung. The active metabolite Ciclesonide mainly metabolized to hydroxylated inactive metabolites by CYP3A4 catalysis. Clearance Ciclesonide is about 152 l / h and deciclesonide – about 228 l / h, which indicates a high degree of extraction of a substance liver.
Breeding
Ciclesonide output, mainly in the feces, both after oral and after the / in the introduction, indicating that the preferential allocation of its bile.
Pharmacokinetics in separate groups of patients
Pharmacokinetics Ciclesonide patients with mild asthma compared with healthy patients does not change.
Since the active metabolite is not eliminated via the kidneys, studies in patients with impaired renal function were not conducted.
In patients with liver failure have been noted long T1 / 2 and a slight increase in retention time deciclesonide (active metabolite) in blood. As a result does not exclude the accumulation of this substance while taking the drug at high doses.
Indications for use of the drug Alvesco Inhaler
- Bronchial asthma.
Dosage regimen Alvesco Inhaler
Alvesco is used only by inhalation. The drug should be taken daily over a long period of time. It is not recommended to stop treatment abruptly.
Alvesco dosed individually. The initial dose should be adjusted depending on the severity of the condition. When you reach the desired clinical effect, the dose should be reduced to the minimum necessary to control symptoms of the disease.
Recommended dose for adults, adolescents and elderly patients over 12 years in the table.
Bronchial asthma is mild 160 mg 1 time /
Asthma medium 160-320 mg 1 time /
Bronchial asthma, severe 320 – 640 mg 1 time / 2 or 320 mg
Bronchial asthma, independent of oral GCS 320 – 640 mg 2
Relief of symptoms occurs within 24 hours after receiving Alvesco . Effective maintenance dose for adults and adolescents is 80 mg 1 time /
The recommended daily intake for children older than 6 years of age is 80-160 mg 1 time / or 80 mg 2 If bronchial asthma in children is well controlled, you can decide to move to a dose of 40 mg 1 time /
No need for dose adjustment in elderly patients or patients with hepatic and / or renal failure.
In adults and adolescents with asthma, severe, who regularly take oral corticosteroids (eg prednisone), a dose of 640 Alvesco 2 mg for oral translation from SCS to Alvesco patients need to be in remission. Dose Alvesco (640 mcg 2) should apply within 10 days in combination with oral corticosteroids. Dose oral corticosteroids should be gradually reduced each week to the lowest possible level, with a decrease in the daily dose of no more than 2.5 mg each time.
Alvesco dose should be reduced in patients requiring oral corticosteroids.
Switching from other inhaled corticosteroids on Alvesco
Patients with asthma symptoms were successfully controlled with the help of previous treatment, the initial dose Alvesco can make half the daily dose combination product containing beclomethasone and bronchodilator. Patients whose symptoms of asthma is poorly controlled, can proceed with the admission of previous drug use on Alvesco Dose calculation of micrograms per micrograms, up to a maximum dose allowed for adults, teens and children.
Alvesco can be used with or without a spacer. If you use a spacer is necessary to use a spacer is recommended AeroChamberPlus.
How to use an inhaler
Patients should be instructed about the correct handling of the inhaler.
If the inhaler is new or has not been used more than one week, then the first three pressing the valve should be in the air. There is no need to shake the container, as it dissolved aerosol.
1. Necessary to remove the cap from the sprayer and check the mouthpiece inside and outside. Make sure it is clean and dry.
2. It is necessary to turn the inhaler upside down (bottom cylinder up), place your index finger on the bottom of the cylinder, and the thumb – a mouthpiece.
3. Make maximum exhalation as much as possible. You should not breathe into the inhaler.
4. Place the mouthpiece in your mouth and close my lips around it.
5. Only after the breath has begun, press your index finger on top of the inhaler to release medication during a slow and deep breaths. Care should be taken to remedy could not pass through the space between the lips and the mouthpiece.
6. Hold your breath, remove the mouthpiece from the mouth and remove your finger from the top of the inhaler. We must continue to hold their breath for about 10 seconds or as long as possible. Slowly exhale through your mouth. Should be avoided to exhale through the mouthpiece.
It is important not to rush at the time of items 3-6.
7. If you need to make an extra breath, wait 30 seconds and repeat steps 3-6.
8. After use, always need to wear a protective cap to protect from dust. Cover tightly and lock in place.
9. For reasons of hygiene:
- Clean the mouthpiece regularly, inside and out with a dry cloth;
- Using a dry folded napkin to wipe the surface with a small hole where the medicine comes out;
- Do not use water or any other liquid.
Side effect Alvesco Inhaler
In most cases, side effects were mild and did not require discontinuation.
From the digestive system: Sometimes (> 1 / 1000, <1 / 100) – nausea, vomiting, unpleasant taste, rare (> 1 / 10, 000, <1 / 1000) – abdominal pain, dyspepsia.
The respiratory system: sometimes – dyspnea, cough after inhalation, paradoxical bronchospasm.
Central nervous system: sometimes – a headache.
Cardio-vascular system: rarely – palpitations, hypertension.
Dermatological reactions: sometimes – eczema and skin rash.
Allergic reactions: seldom – angioedema, hypersensitivity reactions.
Local reactions: sometimes – Application site reactions, dry place of application.
Other: sometimes – fungal infection of the mouth.
Inhaled corticosteroids can cause systemic effects, especially with prolonged use at high doses.
Contraindications to the use of the drug Alvesco Inhaler
- Hypersensitivity to the drug.
Use of the drug Alvesco Inhaler during pregnancy and lactation
Controlled studies in pregnant women has not been conducted. However, after inhalation of the drug level in blood serum Ciclesonide very low, therefore, the effect on the embryo and the potential toxicity to reproduction are negligible.
Isolation Ciclesonide or its metabolites in breast milk has not been investigated.
As with other inhaled corticosteroids, Alvesco can be used during pregnancy and lactation on prescription, if the expected therapeutic effect is greater than the risk of possible side effects. Newborns whose mothers used corticosteroids during pregnancy should be under medical supervision to avoid hypoadrenalism.
Cautions
Alvesco is not indicated for the treatment of status asthmaticus or other acute asthma attacks requiring intensive therapeutic measures.
Alvesco is not intended to relieve acute asthma symptoms for the treatment of which requires the use of inhaled short-acting bronchodilators. Patients should be encouraged to have always with these medications.
As with other inhaled corticosteroids, Alvesco should be administered with caution in patients with active tuberculosis or remission, with fungal, viral or bacterial infections, and only under the condition that patients receive adequate treatment.
May enhance the action of the drug in severe liver failure, so you must carefully observe the emergence of adverse effects.
Against the background of inhalation Ciclesonide should decrease the need for oral corticosteroids. However, patients transferred from oral corticosteroids to inhaled Ciclesonide , for a considerable period of time may be at risk for adrenal insufficiency. The possibility of development of the symptoms will persist for some time.
These patients may need to determine the extent of damage to the adrenal glands in front of some procedures. In an emergency (medical, surgical), and in some stressful situations should always take into account the possibility of residual adrenal response, as well as pay attention to adequate treatment with corticosteroids.
The transfer of patients to treatment with oral corticosteroids on Alvesco , as well as their subsequent treatment should be under strict medical supervision. During the transition from drug to drug, perhaps a slight deterioration of general condition the patient, despite some improvement in respiratory function even. In such cases it is necessary to convince the patient to continue receiving inhaled Ciclesonide and continue the gradual elimination of systemic corticosteroids, unless objective signs of adrenal insufficiency.
In case of paradoxical bronchospasm shows the use of inhaled short-acting bronchodilator, which usually leads to rapid relief of symptoms.
Should be checked regularly as the patient uses the inhaler to make sure that the very same breath inhalation for better penetration into the lungs.
Use in Pediatrics
Data on the use of the drug in children under 6 years are currently unavailable.
Effects on ability to drive and control mechanisms
Inhaler use Ciclesonide not have a negative impact on ability to drive and operate machinery.
Overdose Alvesco Inhaler
Symptoms: may increase side effects.
Treatment: Special treatment is required, it is recommended to control of adrenocortical function.
Drug Interactions Alvesco Inhaler
CYP3A4 is the major enzyme involved in the metabolism of the active metabolite Ciclesonide – M1 (deciclesonide).
In studies of drug interactions between ketoconazole and Ciclesonide, as a strong inhibitor of CYP3A4, the influence of the active metabolite deciclesonide increasing by around 3.5 times, whereas the effect on Ciclesonide noted. On this basis, should avoid the simultaneous use of potential inhibitors of CYP3A4 and Ciclesonide as long as the benefits outweigh the potential risks are not of systemic side effects of corticosteroids.
Investigation of the interaction of the substrate and Ciclesonide CYP3A4 erythromycin showed no interaction between them.
