TENTAVAIR 80MCG

Indications

• Asthma maintenance therapy
• Chronic obstructive pulmonary disease (COPD)

Dosage

Children: For children aged 12–17 years: 160 micrograms once daily, reduced to 80 micrograms once daily if control is maintained; may increase if necessary up to 320 micrograms twice daily.

Adults: 160 micrograms once daily, reduced to 80 micrograms once daily if control is maintained; may increase to 320 micrograms twice daily if necessary.

Mechanism of action

Ciclesonide is a pro-drug that is converted into its active metabolite, des-ciclesonide, which binds to glucocorticoid receptors. This receptor-ligand complex translocates to the nucleus, where it interacts with glucocorticoid response elements in the DNA, leading to altered gene expression. This results in the suppression of pro-inflammatory cytokines such as IL-2, reduced synthesis of inflammatory mediators like prostaglandins and leukotrienes, and decreased infiltration of inflammatory cells in the airways.

Pharmacodynamics

As a glucocorticoid, ciclesonide exhibits potent anti-inflammatory properties. The active metabolite, des-ciclesonide, has a significantly higher affinity for glucocorticoid receptors than the parent compound, enhancing its efficacy. Ciclesonide affects various immune cell types, including eosinophils and mast cells, thereby reducing inflammatory responses in asthma and allergic conditions.

Pharmacokinetics

Ciclesonide undergoes extensive first-pass metabolism, resulting in a low systemic bioavailability. The active metabolite, des-ciclesonide, is responsible for its therapeutic effects. The drug is primarily eliminated via hepatic metabolism. The onset of action occurs within a few hours, but optimal effects may take several days of consistent use. Peak plasma concentrations are typically reached shortly after inhalation.

Contra-indications

• Hypersensitivity to ciclesonide or any of its components
• Untreated systemic fungal infections
• Untreated tuberculosis

Adverse effects

• Oral thrush
• Dysphonia
• Cough
• Headache
• Nausea
• Respiratory tract infection
• Cushing's syndrome (with high doses)
• Adrenal suppression

Interactions

• Cobicistat increases exposure to ciclesonide (unknown mechanism)
• Idelalisib increases exposure to ciclesonide (unknown mechanism)
• Clarithromycin increases exposure to ciclesonide (unknown mechanism)

Precautions

• Use with caution in patients with a history of serious mental health issues
• May cause hypercorticism or adrenal suppression at high doses or prolonged use
• Patients should be monitored for signs of infection
• Consider potential drug interactions with other corticosteroids or medications affecting the CYP3A4 pathway

Pregnancy

Ciclesonide is a Category C medication. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Ciclesonide is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Do not freeze.

Formulations

• {'name': 'Pressurised inhalation', 'dosage': '160 micrograms per dose', 'packaging': '60 doses'}
• {'name': 'Pressurised inhalation', 'dosage': '80 micrograms per dose', 'packaging': '120 doses'}
• {'name': 'Pressurised inhalation', 'dosage': '320 micrograms per dose', 'packaging': '120 doses'}

Mechanism of action

Glucocorticoids such as ciclesonide can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Ciclesonide reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Ciclesonide is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.

Pharmacodynamics

Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.