Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant capsules, hard

Public Assessment Report

Decentralised Procedure

Dutor 20 mg gastro-resistant capsules, hard



Dutor 60 mg gastro-resistant capsules, hard (Duloxetine hydrochloride)

Procedure No: UK/H/5865/001-004/DC

UK Licence No: PL 27755/0002-0005

Dr. Ebeling & Assoc. GmbH

Dutor 20 mg, 30 mg, 40 mg, and 60 mg gastro-resistant capsules, hard UK/H/5865/001-004/DC

2

LAY SUMMARY Dutor 20 mg gastro-resistant capsules, hard

PL 27755/0002


PL 27755/0003


PL 27755/0004


PL 27755/0005

(Duloxetine hydrochloride)

This is a summary of the Public Assessment Report (PAR) for Dutor 20 mg, 30 mg, 40 mg

and 60 mg gastro-resistant capsules, hard (UK/H/5865/001-004/DC; PL 27755/0002-0005).

Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant capsules, hard will be referred to as

Dutor gastro-resistant capsules throughout this report, for ease of reading. It explains how

Dutor gastro-resistant capsules 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 Dutor

gastro-resistant capsules.

For practical information about using Dutor gastro-resistant capsules, patients should read the

package leaflet or contact their doctor or pharmacist.

What are Dutor gastro-resistant capsules and what are they used for?

Dutor gastro-resistant capsules are generic medicines. This means that Dutor 20 mg and

40 mg gastro-resistant capsules are similar to ‘reference medicines’ already authorised in the

European Union (EU) called Yentreve 20 mg and 40 mg hard gastro-resistant capsules, and

Dutor 30 mg and 60 mg gastro-resistant capsules are similar to ‘reference medicines’ already

authorised in the European Union (EU) called Cymbalta 30mg and 60mg hard gastro-resistant

capsules.

Dutor 20 mg and 40 mg gastro-resistant capsules are used to treat Stress Urinary Incontinence

(SUI) in women. Stress urinary incontinence is a medical condition in which patients have

accidental loss or leakage of urine during physical exertion or activities such as laughing,

coughing, sneezing, lifting, or exercise.

Dutor 30 mg and 60 mg gastro-resistant capsules are used to treat:

- Depression

- Generalised anxiety disorder (chronic feeling of anxiety or nervousness), and

- Diabetic neuropathic pain. (This is often described as burning, stabbing, stinging,

shooting or aching, or like an electric shock. There may be loss of feeling in the

affected area, or sensations such as touch, heat, cold or pressure may cause pain).

How do Dutor gastro-resistant capsules work?

Dutor gastro-resistant capsules contain the active substance, duloxetine (as duloxetine

hydrochloride), which increases levels of serotonin and noradrenaline in the nervous system.

How are Dutor gastro-resistant capsules used?

Dutor gastro-resistant capsules should be swallowed whole with a drink of water. Dutor

gastro-resistant capsules can be taken with or without food.


3

Dutor 20 mg and 40 mg gastro-resistant capsules

The usual dose for Dutor 20 mg and 40 mg gastro-resistant capsules is 40 mg twice a day (to

be taken in the morning and late afternoon or evening). The prescribing doctor may decide to

start treatment with 20 mg twice a day for two weeks before increasing the dose to 40 mg

twice a day.

Dutor 30 mg and 60 mg gastro-resistant capsules

The usual dose for the treatment of depression and diabetic neuropathic pain is 60 mg once a

day but the prescribing doctor will decide on a dose that is correct for the patient.

The usual dose for the treatment of generalised anxiety disorder is 30 mg once a day but the

prescribing doctor will decide on a dose that is correct for the patient.

Please read Section 3 of the package leaflet for further information.

Dutor gastro-resistant capsules can only be obtained with a prescription.

What benefits of Dutor gastro-resistant capsules have been shown in studies? Because Dutor gastro-resistant capsules are generic medicines, studies in patients have been

limited to tests to determine that Dutor gastro-resistant capsules, are bioequivalent to the

reference medicines. Two medicines are bioequivalent when they produce the same levels of

the active substance in the body.

What are the possible side effects from Dutor gastro-resistant capsules?

Because Dutor gastro-resistant capsules are generic medicines, and are bioequivalent to the

reference medicines, their benefits and possible side effects are taken as being the same as the

reference medicines.

For information about side effects that may occur with using Dutor gastro-resistant capsules,

please refer to the package leaflet or the Summaries of Product Characteristics (SmPCs)

available on the Medicines and Healthcare products Regulatory Agency website.

Why are Dutor gastro-resistant capsules approved?

It was concluded that, in accordance with EU requirements, Dutor 20 mg, 40 mg, 30 mg and

60 mg gastro-resistant capsules have been shown to have comparable quality and to be

bioequivalent to Yentreve 20 mg and 40 mg hard gastro-resistant capsules, and Cymbalta

30mg and 60 mg hard gastro-resistant capsules, respectively. The MHRA, therefore, decided

that, as for Yentreve 20 mg and 40 mg hard gastro-resistant capsules and Cymbalta 30mg and

60 mg hard gastro-resistant capsules, the benefits are greater than the risks and recommended

that Dutor gastro-resistant capsules can be approved for use.

What measures are being taken to ensure the safe and effective use of Dutor gastro-

resistant capsules?

A Risk Management Plan has been developed to ensure that Dutor gastro-resistant capsules

are used as safely as possible. Based on this plan, safety information has been included in the

SmPCs and the package leaflets for Dutor gastro-resistant capsules, including the appropriate

precautions to be followed by healthcare professionals and patients.


4

Other information about Dutor gastro-resistant capsules

Lithuania, Romania and the UK agreed to grant Marketing Authorisations for Dutor

gastro-resistant capsules on 05 August 2015.

The full PAR for Dutor gastro-resistant capsules follows this summary.

For more information about taking Dutor gastro-resistant capsules, read the package leaflet, or

contact your doctor or pharmacist.

This summary was last updated in October 2015.


5

Table of Contents

I Introduction Page 6

II Quality aspects Page 8

III Non-clinical aspects Page 11

IV Clinical aspects Page 12

V User consultation Page 17

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 17

Annex - Table of content of the PAR update for MRP and

DCP

Page 29


6

I Introduction

Based on the review of the data on quality, safety and efficacy, the Member States have

granted Marketing Authorisations (MAs) for the medicinal products Dutor 20 mg, 30 mg,

40 mg, and 60 mg gastro-resistant capsules (UK/H/5865/001-004/DC; PL 27755/0002-0005).

Dutor 20 mg and 40 mg gastro-resistant capsules are prescription-only medicines (legal status

POM) indicated for women for the treatment of moderate to severe Stress Urinary

Incontinence (SUI). Dutor 20 mg and 40 mg gastro-resistant capsules are indicated in adults.

Dutor 30 mg and 60 mg gastro-resistant capsules are prescription-only medicines (legal status

POM) indicated in the treatment of:

- major depressive disorder

- diabetic peripheral neuropathic pain

- generalised anxiety disorder.

Dutor 30 mg and 60 mg gastro-resistant capsules are indicated in adults.

The applications were submitted using the Decentralised Procedure (DCP), with the UK as

Reference Member State (RMS) and Lithuania and Romania as Concerned Member States

(CMSs).

The applications were made under Article 10(1) of Directive 2001/83/EC, as amended, as

generic medicinal products. For the reference medicinal products authorised for more than 10

years in the EEA, reference has been made to Yentreve 20 mg and 40 mg hard gastro-resistant

capsules authorised to Eli Lilly Nederland BV on 11 August 2004 through the centralised

procedure (EU/1/004/280/001, 007, 008 and EU/1/04/280/002-006).

The reference medicinal products for Dutor 20 mg and 40 mg gastro-resistant capsules, are

Yentreve 20 mg and 40 mg hard gastro-resistant capsules (EU/1/004/280/001, 007, 008 and

EU/1/04/280/002-006).

The reference medicinal products for Dutor 30 mg and 60 mg gastro-resistant capsules are

Cymbalta 30 mg and 60 mg hard gastro-resistant capsules, which were authorised to Eli Lilly

Nederland BV on 17 December 2004 through the centralised procedure (EU/1/004/296/002-

005&007-008).

Dutor gastro-resistant capsules contain the active ingredient duloxetine (as duloxetine

hydrochloride). Duloxetine hydrochloride is a selective serotonin and norepinephrine reuptake

inhibitor (SSNRI) for oral administration.

No new non-clinical studies were conducted, which is acceptable given that the applications

are based on being generic medicinal products of originator products that has been licensed

for over 10 years.

Since Dutor gastro-resistant capsules are intended for generic substitution, their use will not

lead to an increased exposure to the environment. An Environmental Risk Assessment (ERA)

is, therefore, not deemed necessary.

With the exception of two bioequivalence studies, no new clinical data were provided with

these applications. Two bioequivalence studies were performed, which compared the


7

pharmacokinetics of the Applicant’s Dutor 60 mg gastro-resistant capsules with those of the

reference product, Cymbalta 60 mg hard gastro-resistant capsules, in healthy subjects under

fasting and fed conditions. The bioequivalence studies were conducted in line with current

Good Clinical Practice (GCP).

The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP)

are in place for this product type at all sites responsible for the manufacture, assembly and

batch release of these products.

For manufacturing sites within the Community, the RMS has accepted copies of current

manufacturer authorisations issued by inspection services of the competent authorities as

certification that acceptable standards of GMP are in place at those sites.

For manufacturing sites outside the Community, the RMS has accepted copies of current

GMP Certificates of satisfactory inspection summary reports issued by the inspection services

of the MHRA as certification that acceptable standards of GMP are in place at those

non-Community sites.

A Risk Management Plan (RMP) and a summary of the pharmacovigilance system have been

provided with these applications and are satisfactory.

The RMS and CMSs considered that the applications could be approved at the end of

procedure (Day 206) on 05 August 2015. After a subsequent National phase, licences were

granted in the UK on 03 September 2015.


8

II Quality aspects

II.1 Introduction These applications are submitted according to Article 10(1) of Directive 2001/83/EC, as

amended.

Dutor 20 mg gastro-resistant capsules

Dutor 20 mg gastro-resistant capsules are formulated as size ‘4’ hard gelatin capsules having

a light blue cap and body, imprinted with ‘20 mg’ on the body, and ‘1109’ on the cap, with

black ink. The gelatin capsules contain off-white to reddish brown coloured pellets.

Dutor 20 mg gastro-resistant capsules contain 20 mg of the active substance duloxetine (as

hydrochloride). The excipients present in the capsule contents are: hypromellose 2910,

hypromellose acetate succinate, sucrose, sugar spheres (consisting of sucrose, maize starch,

liquid glucose and purified water), talc, titanium dioxide (E 171), triethyl citrate and macrogol

400.

The excipients present in the capsule shell for Dutor 20 mg gastro-resistant capsules are:

gelatin, sodium lauryl sulphate, titanium dioxide (E 171) and indigo carmine (E 132).

The excipients present in the black printing ink are: shellac, black iron oxide (E 172) and

potassium hydroxide.



a blue cap and a milky white body, imprinted with ‘30 mg’ on the body with black ink, and

‘30 mg’ on the cap with white ink. The gelatin capsules contain off-white to reddish brown

coloured pellets.





400.


gelatin, sodium lauryl sulphate, titanium dioxide (E 171) and indigo carmine (E 132).



The excipients present in the white printing ink are: shellac, titanium dioxide (E 171) and




a light blue cap and an orange body, imprinted with ’40 mg’ on the body, and ‘1112’ on the

cap, with black ink. The gelatin capsules contain off white to reddish brown coloured pellets.


9





400.


gelatin, sodium lauryl sulphate, titanium dioxide (E 171), indigo carmine (E 132), yellow iron

oxide (E172) and red iron oxide (E172).





an opaque blue cap and a yellow body, imprinted with ‘60 mg’ on the body, and ‘1111’ on the

cap, with white ink. The gelatin capsules contain off white to reddish brown coloured pellets.


hydrochloride). The excipients present in the capsule contents, common to all strengths, are:

hypromellose 2910, hypromellose acetate succinate, sucrose, sugar spheres (consisting of

sucrose, maize starch, liquid glucose and purified water), talc, titanium dioxide (E 171),

triethyl citrate, macrogol 400.


gelatin, sodium lauryl sulphate, titanium dioxide (E 171), indigo carmine (E 132) and yellow

iron oxide (E172).

The excipients present in the white printing ink are: shellac, sodium hydroxide, povidone K16

and titanium dioxide (E 171).

Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant capsules are packed into:

- oriented polyamide (OPA)/aluminium (Al)/ polyvinyl chloride (PVC)/aluminium (Al)

blisters in pack sizes of 7, 28 and 56 capsules. Additionally, the 40 mg and 60 mg

strengths are packed in OPA/Al/PVC/Al blisters in pack sizes of 98, 140 and 196 (2 x

98) capsules and the 60 mg strength is packed in OPA/Al/PVC/Al blisters in pack

sizes 84 capsules.

- High Density Polyethylene (HDPE) bottles with a polypropylene screw cap in pack

sizes of 28, 98 and 100 or 30 capsules.


10

II.2 Drug Substance Duloxetine

rINN: Duloxetine Hydrochloride

Structure:

Molecular formula: C18H20ClNOS

Molecular weight: 333.9

Appearance: White or almost white powder

Solubility: Sparingly soluble in water, freely soluble in methanol, practically

insoluble in hexane.

Duloxetine hydrochloride is the subject of a European Pharmacopoeia (Ph. Eur) monograph.

The manufacture and control of the active substance, duloxetine hydrochloride, are covered

by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate

of Suitability. Satisfactory information has been provided on the stability of the active

substance.

II.3 Medicinal Product Pharmaceutical development

The objective of the development studies was to develop a stable, scalable, bioequivalent and

robust formulation of Duloxetine hydrochloride 20 mg, 30 mg, 40 mg and 60 mg

gastro-resistant capsules.

The development of the products has been adequately described. Satisfactory justification for

the excipients used in the final formulation and the manufacturing process has been provided.

Comparative dissolution was demonstrated between the test product and reference product

used in the bioequivalence studies and between the Dutor 60 mg gastro-resistant capsules and

Dutor 20 mg, 30mg and 40mg gastro-resistant capsules under a variety of pH conditions.

All of the excipients used in the manufacture of the finished product, with the exception of

hypromellose acetate succinate and the gelatin capsules, comply with their respective Ph. Eur.

monograph. Hypromellose acetate succinate complies with its United States Pharmacopoeia-

National Formulary (USP-NF) monograph and the gelatin capsules are controlled by suitable

in house specifications. Colourants used in the gelatin capsules comply with EC requirements

for colorants.

Satisfactory Certificates of Analysis have been provided for the excipients showing

compliance with their proposed specifications.

None of the excipients are sourced from animal or human origin, except for gelatin. The

suppliers of gelatin have provided certificates of suitability from the European Directorate for

the Quality of Medicines and Healthcare (EDQM) to show that it is manufactured in line with


11

current European guidelines concerning the minimising of risk of transmission of Bovine

Spongiform Encephalopathy/Transmissible Spongiform Encephalopathies (BSE/TSE).

No genetically modified organisms (GMO) have been used in the preparation of this product.

Manufacture of the product

Satisfactory batch formulae have been provided for the manufacture of the Dutor

gastro-resistant capsules, together with appropriate accounts of the manufacturing process.

Process validation data provided on the lower scale batches is satisfactory. The Applicant has

committed to provide full process validation data on three consecutive maximum batch sizes

of each strength product after completion.

Product Specifications

The finished product specifications are satisfactory. Satisfactory batch analysis has been

submitted, for each capsule strength. Certificates of Analysis have been provided for all

working standards used.

Stability of the product

Stability studies were performed in accordance with current guidelines on three batches each

of Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant capsules, packed in the packaging

proposed for marketing. The data from these studies support a shelf life for of 2 years. After

the first opening of the bottle, the shelf life for the 28 capsule HDPE bottle is 30 days and the

shelf life for the 98 and 100 capsule HDPE bottle is 100 days.

There are no special storage conditions for Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-

resistant capsules.

Suitable post approval stability commitments have been provided.

II.4 Discussion on chemical, pharmaceutical and biological aspects The grant of Marketing Authorisations is recommended.

III Non-clinical aspects No new non-clinical studies have been submitted in support of these applications. The

pharmacodynamic, pharmacokinetic and toxicological properties of duloxetine are

well-known. As duloxetine is a widely used, well-known active substance, the Applicant has

not provided additional studies and further studies are not required. A satisfactory non-clinical

overview, based on a review of the literature, has been supplied.

The non-clinical sections of the SmPCs are in line with the reference product SmPCs.

There are no objections to approval of Dutor gastro-resistant capsules from a non-clinical

point of view.

Environmental Risk Assessment (ERA)

Since Dutor gastro-resistant capsules are intended to be used in place of other similar

products, this will not lead to an increased exposure to the environment. An ERA is, therefore,

not deemed necessary.


12

IV Clinical aspects

IV.1 Introduction The applications have been submitted under Article 10(1) according to Directive 2001/83/EC,

as amended. With the exception of bioequivalence data for Dutor 60 mg gastro-resistant

capsules, no new clinical data was submitted with these applications and none are required.

The Applicant sought a biowaver of clinical studies for Dutor 20 mg, 30 mg and 40 mg

gastro-resistant capsules and this was accepted – please see Section and IV.2.

The clinical overview has been written by an appropriately qualified person and provides an

adequate summary of published literature on the clinical pharmacology, efficacy and safety of

duloxetine. This is considered acceptable.

IV.2 Pharmacokinetics In support of these applications, the Marketing Authorisation holder has submitted two

bioequivalence studies:

Study 1 - 60 mg single dose crossover study, under fasting conditions.

Study 2 - 60 mg single dose crossover study under fed conditions.

Study 1

An Open Label, Randomised, 2-Period, 2-Treatment, 2-Sequence, Crossover,

Single-Dose Bioequivalence Study of Dutor 60 mg gastro-resistant capsules (Test) versus

Cymbalta 60 mg Hard Gastro-Resistant Capsules (Reference) in Healthy Human

Volunteers under Fasting Condition.

After an overnight fast of at least 10 hours the subjects received a single dose of either the test

or reference treatment with 200 ml water at room temperature. Blood samples were taken for

the measurement of pharmacokinetic parameters pre-dose and up to 72 hours post-dose. The

two treatment periods were separated by a 12-day washout period.

The main pharmacokinetic results are presented below:

PK - Pharmacokinetics

LSM – least square mean

CV – Coefficient of variation


13

Study 2

An Open Label, Randomised, 2-Period, 2-Treatment, 2-Sequence, Crossover,

Single-Dose Bioequivalence Study of Dutor 60 mg gastro-resistant capsules (Test) versus

Cymbalta 60 mg Hard Gastro-Resistant Capsules (Reference) in Healthy Human

Volunteers under Fed Condition.

After an overnight fast of at least 8 hours, and 30 minutes after starting a high-fat high-calorie

breakfast, the subjects received a single oral dose of the test or reference treatment with

200 ml water at room temperature. Blood samples were taken for the measurement of

pharmacokinetic parameters pre-dose and up to 72 hours post-dose. The two treatment periods

were separated by a 10-day washout period.

The main pharmacokinetic results are presented below:

Pharmacokinetic conclusion For both studies the 90% confidence intervals for the primary variables AUC0-t, AUC0-inf and

Cmax are well within the acceptance range of 80.00-125.00%. Based on the submitted

bioequivalence studies bioequivalence of Dutor 60 mg gastro-resistant capsules to Cymbalta

60 mg hard gastro-resistant capsules may be concluded.

Although the indications and strengths for Yentreve and Cymbalta are different, they belong

to the same global marketing authorisation. Therefore the Applicant’s approach to use

Cymbalta 60 mg for the purpose of demonstrating bioequivalence is acceptable.

Biowaiver

The Applicant has justified conducting the bioequivalence study with the highest strength, in

accordance with the CPMP “Guideline on the investigation of bioequivalence”

(CPMP/EWP/QWP/1401/98 Rev. 1/Corr**) for products with linear pharmacokinetics.

A biowaiver for Dutor 20 mg, 30 mg and 40 mg gastro-resistant capsules has been requested

based on the following:

1. The pharmaceutical products Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant

capsules are manufactured by the same manufacturing process.

2. The qualitative composition of the different strengths (Dutor 20 mg, 30 mg, 40 mg and

60 mg gastro-resistant capsules) is the same.

3. The composition of the strengths is quantitatively proportional for Dutor 20 mg, 30

mg, 40 mg and 60 mg gastro-resistant capsules i.e. the ratio between the amount of

each excipient to the amount of active substance(s) is the same for 20 mg, 30 mg,

40 mg and 60 mg strengths.


14

4. Appropriate in vitro dissolution data confirms the adequacy of waiving additional in

vivo bioequivalence testing.

Based on the known pharmacokinetics characteristics of duloxetine, the highest strength of

the product is the appropriate choice for the biostudies. The bioequivalence package of two

single dose crossover studies under fasting and fed conditions on the highest 60 mg strength is

in compliance with guidelines (CPMP/EWP/QWP/1401/98 Rev. 1/Corr** and EMA/CPMP/EWP/280/96 Corr1).

The justification for biowaiver for the 20 mg, 30 mg and 40 mg strengths of the product can

be accepted as the Applicant’s 20 mg, 30 mg, 40 mg and 60 mg strength gastro-resistant

capsules meet the biowaiver criteria specified in the Guideline on the Investigation of

Bioequivalence (CPMP/EWP/QWP/1401/98 Rev 1/Corr**).

IV.3 Pharmacodynamics No new pharmacodynamic data are required and none have been submitted. The Applicant’s

review of the literature in the clinical overview is acceptable.

IV.4 Clinical efficacy No new clinical efficacy data are required and none have been submitted. The Applicant’s

review of the literature in the clinical overview is acceptable.

IV.5 Clinical safety With the exception of the bioequivalence studies, no new data have been provided and none

are required for these applications.

IV.6 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 Dutor gastro-resistant

capsules.

A summary of safety concerns and risk minimisation measures, as approved in the RMP, are

listed below:


15


16

Summary table of risk minimisation measures

The grant of Marketing Authorisations is recommended.


17

V User consultation The package leaflet has been evaluated via a user consultation study in accordance with the

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the

purpose of user testing the PIL was English.

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.

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 test product, Dutor 60 mg gastro-resistant capsules, can be

considered bioequivalent with the reference product, Cymbalta 60 mg Hard Gastro-Resistant

capsules. A justification for a biowaver for Dutor 20 mg. 30 mg and 40 mg gastro-resistant

capsules has been accepted.

The benefit/risk assessment is, therefore, considered to be positive.

The Summaries of Product Characteristics (SmPCs), package leaflets and labelling are

satisfactory, in line with current guidelines and consistent with the reference product. In

accordance with Directive 2012/84/EU, the current approved UK versions of the SmPCs and

package leaflets for these products are available on the Medicines and Healthcare products

Regulatory Agency website.

The currently approved labels are listed below:


18

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

blister packs

1. NAME OF THE MEDICINAL PRODUCT





Duloxetine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Dr Ebeling & Assoc GmbH

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot:

5. OTHER


19

PARTICULARS TO APPEAR ON THE INNER PACKAGING (HDPE BOTTLES)






Duloxetine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each gastro-resistant capsule, hard contains 20 mg duloxetine (as hydrochloride).




3. LIST OF EXCIPIENTS

Contains sucrose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Gastro-resistant capsule, hard


28 capsules

98 capsules

100 capsules


28 capsules

98 capsules

100 capsules


28 capsules

98 capsules

100 capsules


28 capsules

98 capsules

100 capsules


20

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE

STORED OUT OF THE REACH AND SIGHT OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

Shelf life after first opening of the bottle:

28’s container: 30 days

98’s and 100’s container: 100 days

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL

PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH

MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER


Isestrasse 5

Hamburg

D-20144

Germany

12. MARKETING AUTHORISATION NUMBER(S)

PL 27755/0002

PL 27755/0003

PL 27755/0004

PL 27755/0005


21

13. BATCH NUMBER

Lot:

14. GENERAL CLASSIFICATION FOR SUPPLY

POM

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE






22

PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER WRAPPER LABEL

ON MULTIPACKS (2 X 98 CAPSULES, 40/60 MG) WRAPPED IN FOIL




Duloxetine







Multipack comprising 2 packs, each containing 98 capsules


Oral use.






8. EXPIRY DATE

EXP


100 days



23






Isestrasse 5

Hamburg

D-20144

Germany


PL 27755/0002

PL 27755/0003

PL 27755/0004

PL 27755/0005

13. BATCH NUMBER

Lot:


POM




24

PARTICULARS TO APPEAR ON THE OUTER PACKAGING (CARTON FOR BLISTER

AND BOTTLES)






Duloxetine










<OPA/Al/PVC//Al blister>

<Dutor> 20 mg

7 capsules

28 capsules

56 capsules

98 capsules

<Dutor> 30 mg

7 capsules

28 capsules

56 capsules

98 capsules

<Dutor> 40 mg

7 capsules

28 capsules

56 capsules

98 capsules

140 capsules

196 (2 x 98) capsules

<Dutor> 60 mg


25

7 capsules

28 capsules

56 capsules

84 capsules

98 capsules

140 capsules

196 (2x98) capsules

<HDPE-bottles>

<Product name> 20, 30, 40, 60 mg

28 capsules

98 capsules

100 capsules


Oral use.






8. EXPIRY DATE

EXP

only bottles:


28’s container: 30 days

98’s and 100’s container: 100 days






26



Isestrasse 5

Hamburg

D-20144

Germany


PL 27755/0002

PL 27755/0003

PL 27755/0004

PL 27755/0005

13. BATCH NUMBER

Lot:


POM








27

PARTICULARS TO APPEAR ON THE OUTER PACKAGING CARTON FOR 98

CAPSULES (40/60 MG) AS INTERMEDIATE PACK / COMPONENT OF A MULTIPACK




Duloxetine








98 capsules

Component of a multipack comprising 2 packs, each containing 98 capsules.


Oral use.






8. EXPIRY DATE

EXP


100 days



28






Isestrasse 5

Hamburg

D-20144

Germany


PL 27755/0004

PL 27755/0005

13. BATCH NUMBER

Lot:


POM



Dutor 40 mg gastro-resistant capsules, hard Dutor 60 mg gastro-resistant capsules, hard


29

Annex - Table of content of the PAR update for MRP and

DCP

Steps taken after the initial procedure with an influence on the Public Assessment Report

(Type II variations, PSURs, commitments)

Scope Procedure

number

Product

information

affected

Date of

start of the

procedure

Date of end

of

procedure

Approval/

non

approval

Assessment

report

attached

Y/N

(version)

Documents

Dutor 20 mg, 30 mg, 40 mg and 60 mg gastro-resistant capsules, hard