Public Assessment Report
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001-003/DC
PL 31752/0031-0033
Takeda GmbH
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Lay Summary
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
(ciclesonide)
This is a summary of the Public Assessment Report (PAR) for Alvesco Takeda 40, 80
and 160 Inhalers (PL 31752/0031-0033). Alvesco Takeda 40, 80 and 160 Inhalers will
be referred to as Alvesco 40, 80 and 160 Inhalers throughout this report, for ease of
reading. It explains how Alvesco 40, 80 and 160 Inhalers were assessed and their
authorisation recommended, as well as their conditions of use. It is not intended to
provide practical advice on how to use these products.
For practical information about using Alvesco 40, 80 and 160 Inhalers, patients
should read the Patient Information Leaflet (PIL) or contact their doctor or
pharmacist.
What are Alvesco 40, 80 and 160 Inhalers and what are they used for?
Alvesco 40, 80 and 160 Inhalers are the same as ‘Alvesco 40 Inhaler, 40 micrograms
Pressurised inhalation, solution’, ‘Alvesco 80 Inhaler, 80 micrograms Pressurised
inhalation, solution’, and ‘Alvesco 160 Inhaler, 160 micrograms Pressurised
inhalation, solution’, respectively, which are already authorised. The company that
owns these latter ‘reference products’ submitted applications for Alvesco 40, 80 and
160 Inhalers, using the reference products as bases for the grant of identical marketing
authorisations (informed consent).
Alvesco 40, 80 and 160 Inhalers are used to control persistent asthma in adult and
adolescent patients (12 years old and more).
How do Alvesco 40, 80 and 160 Inhalers work?
Alvesco 40, 80 and 160 Inhalers contain the active substance ciclesonide, which is a
corticosteroid. Ciclesonide helps a patient to breathe more easily by decreasing the
symptoms of the asthma and by lessening the chances of an asthma attack.
Ciclesonide is termed a ‘preventer’ medication; its effect builds up over a period of
time, so these medicines needs to be taken every day, even when the patient is feeling
well.
How are Alvesco 40, 80 and 160 Inhalers used?
Alvesco 40, 80 and 160 Inhalers are used by inhaling through the mouth into the
lungs. It is important that a doctor, nurse or pharmacist shows the patient first how to
use the Alvesco inhaler properly. A good technique will ensure that the patient is
receiving the correct amount of these medicines into their lungs.
Please read Section 3 of the PIL for detailed information on dosing recommendations,
the route of administration, and the duration of treatment.
2
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
The recommended dose of Alvesco is 160 micrograms once daily, which leads to
asthma control in the majority of patients. This dose may be increased or decreased by
the prescribing doctor.
Alvesco 40, 80 and 160 Inhalers can only be obtained with a prescription.
What benefits of Alvesco 40, 80 and 160 Inhalers have been shown in studies?
Alvesco 40, 80 and 160 Inhalers are considered identical to the previously granted
marketing authorisations for ‘Alvesco 40 Inhaler, 40 micrograms Pressurised
inhalation, solution’, ‘Alvesco 80 Inhaler, 80 micrograms Pressurised inhalation,
solution’ and ‘Alvesco 160 Inhaler, 160 micrograms Pressurised inhalation, solution’,
respectively, with the same benefits and risks. No new studies have been provided for
Alvesco 40, 80 and 160 Inhalers, but reference is made to the studies for ‘Alvesco 40
Inhaler, 40 micrograms Pressurised inhalation, solution’, ‘Alvesco 80 Inhaler, 80
micrograms Pressurised inhalation, solution’ and ‘Alvesco 160 Inhaler, 160
micrograms Pressurised inhalation, solution’.
What are the possible side effects from Alvesco 40, 80 and 160 Inhalers?
Like all medicines, these medicines can cause side-effects, although not everybody
gets them.
For information about side-effects that may occur with using Alvesco 40, 80 and 160
Inhalers, please refer to the PIL or the Summaries of Product Characteristics (SmPCs)
available on the Medicines and Healthcare products Regulatory Agency (MHRA)
website.
Why are Alvesco 40, 80 and 160 Inhalers approved?
No new or unexpected safety concerns arose from these applications. It was, therefore,
considered that the benefits of Alvesco 40, 80 and 160 Inhalers outweigh the risks, and
the grant of these marketing authorisations was recommended.
What measures are being taken to ensure the safe and effective use of Alvesco 40,
80 and 160 Inhalers?
A Risk Management Plan (RMP) has been developed to ensure that Alvesco 40, 80
and 160 Inhalers are used as safely as possible. Based on this plan, safety information
has been included in the SmPCs and the PIL for Alvesco 40, 80 and 160 Inhalers,
including the appropriate precautions to be followed by healthcare professionals and
patients.
Known side-effects are continuously monitored. Furthermore, new safety signals
reported by patients and healthcare professionals will be monitored and reviewed
continuously as well.
Other information about Alvesco 40, 80 and 160 Inhalers
The Netherlands and the UK agreed to grant marketing authorisations for Alvesco 40,
80 and 160 Inhalers on 13 November 2014. The marketing authorisations in the UK
were granted on 15 December 2014.
For more information about taking Alvesco 40, 80 and 160 Inhalers, read the PIL, or
contact your doctor or pharmacist.
3
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
This summary was last updated in February 2015.
The full PAR for Alvesco 40, 80 and 160 Inhalers follows this summary.
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Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Table of Contents
I
II
III
IV
V
VI
Introduction
Quality aspects
Non-clinical aspects
Clinical aspects
User consultation
Overall conclusion, benefit/risk assessment and
recommendation
Page 6
Page 7
Page 8
Page 8
Page 9
Page 10
Table of content of the PAR update
Page 17
5
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
I
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Introduction
Based on the review of the data on quality, safety and efficacy, the member states
granted marketing authorisations for the medicinal products Alvesco 40, 80 and 160
Inhalers. These applications were submitted using the Decentralised Procedure (DCP),
with the UK as Reference Member State (RMS) and the Netherlands as a Concerned
Member State (CMS).
Alvesco 40, 80 and 160 Inhalers are prescription-only medicines (POM), indicated to
control persistent asthma in adults and adolescents (12 years and older).
These applications were made under Article 10c of Directive 2001/83/EC, as
amended. These applications cross-refer, and claim to be identical, to ‘Alvesco 40
Inhaler, 40 micrograms Pressurised inhalation, solution’ (PL 31752/0004), ‘Alvesco
80 Inhaler, 80 micrograms Pressurised inhalation, solution’ (PL 31752/0005) and
‘Alvesco 160 Inhaler, 160 micrograms Pressurised inhalation, solution’ (PL
31752/0006), which were originally granted to Altana Pharma AG (PL 20141/00040006) on 16 April 2004. The marketing authorisation holder subsequently underwent
a change of ownership to the new marketing authorisation holder, Takeda GmbH, on
17 January 2008 (PL 31752/0004-0006).
These medicinal products contain the active substance ciclesonide. Ciclesonide is an
inhaled corticosteroid that exhibits low binding affinity to the glucocorticoid-receptor.
Once orally inhaled, ciclesonide is enzymatically converted in the lungs to the
principal metabolite (C21-des-methylpropionyl-ciclesonide), which has a pronounced
anti-inflammatory activity and is thus considered as the active metabolite.
No new data have been submitted and none are required for these simple applications,
as the data are identical to those of the previously granted, cross-referred products.
6
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
II
Quality aspects
II.1
Introduction
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
These are simple, piggyback (informed consent) applications for Alvesco 40, 80 and
160 Inhalers submitted under Article 10c of Directive 2001/83/EC, as amended.
The applications cross-refer to ‘Alvesco 40 Inhaler, 40 micrograms Pressurised
inhalation, solution’ (PL 31752/0004), ‘Alvesco 80 Inhaler, 80 micrograms
Pressurised inhalation, solution’ (PL 31752/0005) and ‘Alvesco 160 Inhaler, 160
micrograms Pressurised inhalation, solution’ (PL 31752/0006).
Alvesco 40, 80 and 160 Inhalers contain the active substance ciclesonide at
concentrations of 40 micrograms, 80 micrograms and 160 micrograms per actuation,
respectively. The excipients present in Alvesco 40, 80 and 160 Inhalers are norflurane
(HFA-134a) and anhydrous ethanol. The qualitative and quantitative composition of
these excipients is identical to those of the respective cross-reference product.
The inhalers each comprise a pressurised container made from aluminium that is
sealed with a metering valve, mouthpiece and cap. The inhalers are available in sizes
of 30, 60 and 120 metered actuations
This packaging is identical to those of the cross-reference products.
II.2
Drug Substance
Ciclesonide
The drug substance specification is identical to those of the cross-reference products
and is acceptable.
II.3
Medicinal Product
Pharmaceutical development
The drug products are non-aqueous metered dose inhalers, presented as ciclesonide in
40 micrograms/actuation, 80 micrograms/actuation and 160 micrograms/actuation
strengths. These applications are direct copies of the dossiers for the cross-reference
medicinal products and, therefore, the information provided here, including the
formulation, is identical to that of the respective cross-reference products.
Manufacture of the product
The manufacture of the drug product together with in-process controls has been
adequately described, and it is confirmed that this process is identical to that of the
currently approved cross-reference products. With respect to Good Manufacturing
Practice (GMP) certification, valid EU GMP certificates have been provided for both
the finished product manufacturer, and batch release site. The certificates are
acceptable and no further requests for inspection are requested during these
procedures.
The proposed manufacturing sites are consistent with those registered for the
cross-reference products. Evidence of GMP compliance has been provided, which is
identical to that of the cross-reference products.
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Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
None of the excipients contain materials of animal or human origin.
Finished Product Specification
The finished product specifications are identical to the cross-reference medicinal
products, for both the shelf-life and release acceptance parameters.
Stability of the product
The proposed shelf-lives of 1 year for a 30 actuation presentation and 3 years for the
60 and 120 actuation presentations are acceptable.
These are identical to those of the cross-reference products.
Alvesco 40, 80 and 160 Inhalers do not require any special storage conditions, which
is identical to that of the cross-reference products.
II.4
Discussion on chemical, pharmaceutical and biological aspects
The quality data for these applications are consistent with those previously assessed
for the marketing authorisations for ‘Alvesco 40 Inhaler, 40 micrograms Pressurised
inhalation, solution’ (PL 31752/0004), ‘Alvesco 80 Inhaler, 80 micrograms
Pressurised inhalation, solution’ (PL 31752/0005) and ‘Alvesco 160 Inhaler, 160
micrograms Pressurised inhalation, solution’ (PL 31752/0006) and, as such, have been
judged to be satisfactory. The grant of marketing authorisations is recommended.
III Non-clinical aspects
As these are abridged applications, submitted under Article 10c of Directive
2001/83/EC, as amended, no new non-clinical data has been supplied and none are
required.
The grant of marketing authorisations is recommended.
IV Clinical aspects
As these are abridged applications, submitted under Article 10c of Directive
2001/83/EC, as amended, no new clinical data have been supplied and none are
required.
Risk Management Plan (RMP)
The applicant has submitted an RMP, in accordance with the requirements of
Directive 2001/83/EC as amended, describing the pharmacovigilance activities and
interventions designed to identify, characterise, prevent or minimise risks relating to
Alvesco 40, 80 and 160 Inhalers.
A summary of safety concerns and risk minimisation measures, as approved in the
RMP, are listed below:
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Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Summary table of safety concerns
Summary of safety concerns
Important identified
risks
Important potential
risks
Missing information
None
Local oropharyngeal adverse events
Paradoxical bronchospasm
Hypothalamic-pituitary-adrenal (HPA) axis effects
Decreased bone density
Effects on growth in children
Eye disorders (cataract, lens opacities and glaucoma)
Use in patients with underlying pulmonary infection
(tuberculosis, viral, fungal or bacterial)
Immediate or delayed hypersensitivity reactions
Psychiatric Events
Interactions with potent CYP3A4 inhibitors
Experience in pregnancy and lactation
Use in patients with severe hepatic impairment
Summary table of risk minimisation measures
Routine Pharmacovigilance and routine risk minimisation is proposed for all safety
concerns, which is considered acceptable.
The grant of a marketing authorisation is recommended.
V
User consultation
A User Testing report is provided from 9 July 2006 based upon the readability testing
of the leaflet for the cross-reference products. The PIL of the cross-reference products
was evaluated via a user consultation study in accordance with the requirements of
Articles 59(3) and 61(1) of Directive 2001/83/EC.
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Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
The results show that the package leaflet meets the criteria for readability as set out in
the Guideline on the readability of the label and package leaflet of medicinal products
for human use.
As the proposed leaflet for the current applications will be identical to that of the
cross-reference products, upon this basis an additional User Testing report is not
required.
VI Overall conclusion, benefit/risk assessment and
recommendation
The quality of these products is acceptable, and no new non-clinical or clinical safety
concerns have been identified. The applicant’s products are identical to the
cross-reference products. The benefit/risk assessment is, therefore, considered to be
positive.
The Summaries of Product Characteristics (SmPCs), Patient Information Leaflet (PIL)
and labelling are satisfactory, in line with current guidelines and consistent with the
cross-reference products. In accordance with Directive 2012/84/EU, the current
approved UK versions of the SmPCs and PIL for these products are available on the
MHRA website.
The currently approved labels are listed below:
10
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Labelling text for Alvesco 40 Inhaler
11
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
12
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
13
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Labelling for Alvesco 80 Inhaler
14
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Labelling text for Alvesco 160 Inhaler
15
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
16
Alvesco Takeda 40 Inhaler
Alvesco Takeda 80 Inhaler
Alvesco Takeda 160 Inhaler
UK/H/5699/001/DC
UK/H/5699/002/DC
UK/H/5699/003/DC
Table of content of the PAR update
Steps taken after the initial procedure with an influence on the Public Assessment
Report (Type II variations, PSURs, commitments)
Scope
Product
information
affected
Date of
start of the
procedure
Date of end
of
procedure
Approval/
non
approval
Assessment
report
attached
Y/N
(version)
17