Orion Pharma (UK) Limited

The SmPC and PL have been updated in line with agreed wording following PhVWP as published by CMD(h) for “Risk of psychiatric adverse drug reactions to inhaled and intranasal corticosteroids and risk of non-psychiatric systemic adverse drugs reactions to intranasal corticosteroids” (CMDh/PhVWP/027/2010).

(Note: Easyhaler Budesonide is not suitable for the treatment of acute asthma attacks has been added.

In section 4.2 (Posology and method of administration)

The dose should be adjusted until control is achieved and then titrated to the lowest dose at which effective control of asthma is maintained has been added.

'The dose should be adjusted until control is achieved and then titrated to the lowest dose at which effective control od asthma is maintained' has been removed

In section 5.1 (Pharmacological properties) the following has been added:

Budesonide is a glucocorticosteroid which possesses a high local anti-inflammatory action,

Topical anti-inflammatory effect

The exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions, such as inhibition of inflammatory mediator release and inhibition of cytokine-mediated immune response are probably important

Onset of effect

After a single dose of orally inhaled budesonide, delivered via dry powder inhaler,

improvement of the lung function is achieved within a few hours. After therapeutic use of orally inhaled budesonide delivered via dry powder inhaler, improvement in lung function has been shown to occur within 2 days of initiation of treatment, although maximum benefit may not be achieved for up to 4 weeks.

Airway reactivity

Budesonide has also been shown to decrease airway reactivity to histamine and methacholine in hyper-reactive patients.

Exercise-induced asthma

Therapy with inhaled budesonide has effectively been used for prevention of exercise-induced asthma.

Growth

Limited data from long term studies suggest that most children and adolescents treated with inhaled budesonide ultimately achieve their adult target height. However, an initial small but transient reduction in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment (see section 4.4).

HPA axis function

A study in healthy volunteers with Easyhaler Budesonide has shown dose-related effects on plasma and urinary cortisol. At recommended doses, budesonide causes less effect on the adrenal function than prednisolone 10mg, as shown by ACTH tests.

The following has been removed:

Budesonide is a non-halogenated corticosteroid. It has local anti-inflammatory effects on respiratory mucosa when administered topically.

Improvement in asthma control following inhalation of budesonide can occur within 24 hours of commencing the treatment although maximum benefit is achieved after a few weeks of continuous treatment.

The precise mechanism of corticosteroid actions on inflammation in asthma is not known. Budesonide has been shown to have a wide range of inhibitory effects against several cell types (e.g., eosinophils, macrophages, mast cells, lymphocytes, and neutrophils) and mediators (e.g., cytokines, leukotrienes, eicosanoids, and histamine) involved in allergic and non-allergic respiratory inflammation. These actions of corticosteroids may contribute to their efficacy in asthma.

In section 5.3 ( Preclinical safety data)

The following has been removed:

The toxicity observed in animal studies with budesonide was associated with exaggerated pharmacological activity.

No genotoxic effects of budesonide have been observed in conventional genotoxicity tests.

In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). Similar effects are considered unlikely to occur in humans at therapeutic doses.

The following has been added:

Preclinical data with budesonide reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, or carcinogenic potential.

In animal studies on reproductive toxicity, glucocorticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). However, these animal results do not seem to be relevant for humans given recommended doses.

In section 10 ( Date of revision of text)
04/2009