Alvesco, 80 mcg/dose aerosol, 60 doses

Alvesco is a GKS for topical application by inhalation.

Cyclisonide has low affinity for glucocorticoid receptors.

After inhalation, with the participation of enzymes, it is converted in the lungs to the main metabolite (desciclesonide, C21-desmethylpropionylcyclonide), which has pronounced anti-inflammatory activity and is therefore considered an active metabolite.

Ciclesonide suppresses inflammatory responses in the respiratory tract and thus alleviates bronchial asthma symptoms and improves lung function.

Indications

Bronchial asthma.

Active ingredient

Composition

1 dose contains cyklesonide 80 µg.

The excipients:

Norflurane (HFA-134a) – 54.46 mg,

Ethanol – 4.74 mg.

How to take, the dosage

For oral inhalation.

Alvesco should be taken for a long period of time daily. The drug is dosed individually. The initial dose should be adjusted according to the severity of the condition. When the desired clinical effect is achieved, the dose should be reduced to the minimum necessary to control the manifestations of the disease.

Adults, elderly patients, and adolescents over 12 years of age

Mild to moderate asthma: the recommended daily dose is 160 to 640 mcg; the 640 mcg dose should be divided into 2 doses daily.

Severe asthma: the dose may be increased to a maximum of 2 × 640 mcg, daily.

An improvement in the manifestations of the disease occurs within 24 hours after taking Alvesco. It is expected that the maximum effect of treatment – as with other inhaled GHBs – is achieved after 2-3 months of using the drug.

Patients should not stop treatment, even in the absence of asthma symptoms.

Children over 6 years of age

The recommended daily dose is 80-160 mcg once or 80 mcg twice daily.

Alvesco can be used with or without a spacer. If the use of a spacer is necessary, the AeroChamberPlus spacer is recommended.

Spacer guidelines

There is no need to adjust the dose for elderly patients or patients with hepatic or renal impairment.

Adults and adolescents taking oral GCS continuously

In patients with severe bronchial asthma who are dependent on oral GCS therapy (e.g., prednisolone), the dose of Alvesco is 640 mcg twice daily. To switch patients from oral GCS to Alvesco, patients must be in remission. The dose of Alvesco (640 mcg twice daily) must be used for 10 days in combination with oral GCS. The oral GCS dose should then be gradually reduced each week to as low a level as possible, with the daily dose reduced by no more than 2.5 mg each time.

Interaction

CYP3A4 is the main enzyme involved in the metabolism of the active metabolite of cyclezonide, M1 (decyclezonide).

In drug interaction studies between cyclizonide and ketoconazole, as a strong CYP3A4 inhibitor, the effect on the active metabolite dezciclesonide was increased by about 3.5 times, whereas no effect on cyclizonide was noted. Therefore, concomitant use of potential CYP3A4 inhibitors and ciclesonide should be avoided until the benefit outweighs the possible risk of systemic side effects of GCS.

The study of interactions between cyklezonide and the CYP3A4 substrate erythromycin showed no interactions between them.

Special Instructions

Alvesco is not indicated for the treatment of asthmatic status or other acute asthma episodes requiring intensive therapeutic measures.

The effects of inhaled GCSs on long-term use in children are not fully understood. The physician should constantly monitor the growth of children with long-term use of GCS. If growth slows down, therapy should be revised to reduce the dose of inhaled GCS. If possible, to the lowest dose with which to maintain constant control of asthma manifestations. The dose of Alvesco may be reduced in patients who require oral GCS.

For patients transferred from oral GCS therapy to inhaled treatment with Alvesco, decreased adrenal cortical function may persist for a significant period of time after transfer. The possibility of adverse effects from the use of oral GCSs may persist for some time after their withdrawal. In such cases, monitoring of adrenal reserve function is recommended. The possibility of residual worsening of adrenocortical response in a critical situation (therapeutic or surgical) and in other individual cases, which may be caused by a stress reaction, should always be taken into account; consequently, appropriate GCS treatment should be initiated.

In case of insufficient adrenocortical response or severe exacerbations, the dose of Alvesco should be increased; if necessary, oral GCS should be used. In cases of infection, antibiotics should be used. Paradoxical bronchospasm with increased wheezing and other symptoms of bronchoconstriction occurring immediately after inhalation should be treated with a rapid-acting bronchodilator, usually resulting in rapid relief. The patient should be examined, and therapy with Alvesco should be continued only if, after careful consideration, the expected effect is greater than the possible risk. The relationship between asthma severity and a general predisposition to acute bronchial reactions should be taken into account.

The conversion of patients taking oral GCS to Alvesco.

The transfer of patients treated with oral GCS to Alvesco and their follow-up management needs attention, as it can take time to recover the decreased adrenal function caused by prolonged systemic GCS therapy.

In patients who have taken systemic GCS for a long period of time or at a high dose, adrenal function may be inhibited. Adrenal function in these patients should be monitored regularly, and the dose of systemic GCS should be reduced gradually. After approximately one week, gradual elimination of systemic GCSs may be initiated with a reduction in the daily dose by 1 mg of prednisolone or its equivalent. For maintenance doses of prednisolone greater than 10 mg daily, cautious, larger dose reductions over weekly intervals may be appropriate.

Some patients may not feel well during drug withdrawal despite maintaining or even improving respiratory function. They should be evaluated for adrenocortical insufficiency.

Allergic reactions (e.g., allergic rhinitis, eczema) that were previously suppressed by systemic medications may occur when patients are switched from systemic GCS to inhaled therapy. These allergies should be treated symptomatically with antihistamines and/or topical agents including topical GCS.

The effect on the ability to drive or perform work requiring increased speed of physical and mental reactions. There are no data on the effect of the drug on the ability to drive vehicles and machines.

Drug interactions
According to in vitro data CYP3A4 is the main enzyme involved in the metabolism of the active metabolite of cyclasonide – M1 (dezciclesonide) in humans.

In drug interaction studies between ciclesonide and ketoconazole, as a strong CYP3A4 inhibitor, the effect on the active metabolite dezciclesonide was increased by approximately 3.5-fold, whereas no effect on ciclesonide was noted. Therefore, concomitant use of potential CYP3A4 inhibitors and ciclesonide should be avoided.

A study of the interaction between cyklesonide and the CYP3A4 substrate erythromycin showed no interaction between them.

Contraindications

With caution: patients with active or chronic pulmonary tuberculosis; patients with bacterial, viral or fungal respiratory infections.

Side effects

In most cases, the side effects were mild and did not require discontinuation of Alvesco.

– Digestive system disorders: sometimes (> 1/1000, < 1/100) – nausea, vomiting, unpleasant taste; rarely (> 1/10 000, – Respiratory system disorders: sometimes – dyspnea, cough after inhalation, paradoxical bronchospasm.

– CNS side: sometimes – headache.

– Cardiovascular system: rarely – palpitations, arterial hypertension.

Dermatological reactions: sometimes – eczema and skin rash.

– Allergic reactions: rarely – angioedema, hypersensitivity reactions.

– Local reactions: sometimes – reactions at the site of application, dryness at the site of application.

Others: sometimes – fungal infections of the oral cavity.

Inhaled GCSs may cause systemic effects, especially when used in high doses for a long time.

Overdose

Acute overdose

Symptoms: Inhalation administration of a single dose of 2880 mcg of ciclesonide in healthy volunteers was well tolerated. The possibility of acute toxic effects following an overdose of inhaled cyclesonide is low. Increased dryness of the mucous membranes of the oral cavity and pharynx, sensations of irritation or farting in the throat, and dysphonia are possible.

Treatment: after acute overdose there is no need for specific treatment.

Chronic overdose

Symptoms: no clinical signs of adrenal suppression have been observed after prolonged administration of 1280 µg cyclesonide. However, if exceeding the recommended dose continues for an ultra-long period of time, some degree of adrenal suppression cannot be ruled out.

Treatment: Adrenal function monitoring is recommended.

Pregnancy use

Controlled studies in pregnant women have not been performed.

However, after inhalation administration of the drug, the serum concentration of cyklesonide is very low, therefore, the effect on the embryo and the potential toxicity affecting reproductive function is negligible.

The excretion of cyklesonide or its metabolites through breast milk has not been studied.

Like other inhaled GCSs, ciclesonide may be used during pregnancy and lactation by prescription if the expected treatment effect exceeds the risk of possible side effects.

Newborns from mothers treated with GCS should be monitored by a physician to rule out adrenal hypofunction.