public assessment report decentralised procedure assessment report decentralised procedure...

Public Assessment Report

Decentralised Procedure

TELMISARTAN/HYDROCHLOROTHIAZIDE

40 MG/12.5 MG TABLETS


80 MG/12.5 MG TABLETS


80 MG/25 MG TABLETS

(telmisartan, hydrochlorothiazide)

Procedure No: UK/H/4966/001-003/DC

UK Licence No: PL 20075/0323-24 & PL 20075/0439

Accord Healthcare Limited

PAR Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg

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LAY SUMMARY Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg tablets

Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets

Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets

(telmisartan, hydrochlorothiazide)

This is a summary of the Public Assessment Report (PAR) for Telmisartan/Hydrochlorothiazide 40

mg/12.5 mg tablets (PL 20075/0323; UK/H/4966/001/DC), Telmisartan/Hydrochlorothiazide 80

mg/12.5 mg tablets (PL 20075/0324; UK/H/4966/002/DC) and Telmisartan/Hydrochlorothiazide 80

mg/25 mg tablets (PL 20075/0439; UK/H/4966/003/DC). It explains how the applications for these

tablets 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 Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80

mg/12.5 mg and 80 mg/25 mg tablets.

For practical information about using Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg

and 80 mg/25 mg tablets, patients should read the package leaflet or contact their doctor or pharmacist.

What are Telmisartan/Hydrochlorothiazide tablets and what are they used for?

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets are ‘generic

medicines’. This means that Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80

mg/25 mg tablets are similar to ‘reference medicines’ already authorised in the European Union (EU)

called Micardis Plus 40 mg/12.5 mg tablets, Micardis Plus 80 mg/12.5 mg tablets and Micardis Plus 80

mg/25 mg tablets.

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg and 80 mg/12.5 mg tablets are used to treat high blood

pressure (essential hypertension) in adults whose blood pressure is not controlled enough when

telmisartan is used alone.

Telmisartan/Hydrochlorothiazide 80 mg/25mg tablets are used to treat high blood pressure (essential

hypertension) in adults whose blood pressure is not adequately controlled by

Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets or in patients who have been previously

stabilised by telmisartan and hydrochlorothiazide, when given separately.

How do Telmisartan/Hydrochlorothiazide tablets work?

These products contain a combination of two active substances in one tablet - telmisartan and

hydrochlorothiazide. Both of these substances help to control high blood pressure. Telmisartan belongs

to a group of medicines called angiotensin II receptor antagonists. Angiotensin-II is a substance

produced in the body which causes blood vessels to narrow thus increasing the blood pressure.

Telmisartan blocks the effect of angiotensin II so that the blood vessels relax, and the blood pressure is

lowered. Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics, which cause the

urine output to increase, leading to a lowering of the blood pressure.

How are Telmisartan/Hydrochlorothiazide tablets used?

These medicines can only be obtained with a prescription.

The recommended dose of Telmisartan/Hydrochlorothiazide tablets is one tablet a day. Patients should

try to take the tablet at the same time each day. Telmisartan/Hydrochlorothiazide tablets can be taken

with or without food. The tablets should be swallowed with some water or other non-alcoholic drink. It

is important that patients take Telmisartan/Hydrochlorothiazide tablets every day until otherwise advised

by a doctor.


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What benefits of Telmisartan/Hydrochlorothiazide tablets have been shown in studies?

Because Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets are

generic medicines, studies in patients have been limited to tests to determine that they are bioequivalent

to the reference medicines, Micardis Plus 40 mg/12.5 mg tablets, 80 mg/12.5 mg tablets and 80 mg/25

mg tablets. Two medicines are bioequivalent when they produce the same levels of the active substance

in the body.

What are the possible side effects of Telmisartan/Hydrochlorothiazide tablets?

Because Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets are

generic medicines, their possible side effects are taken as being the same as those of the reference

medicines, Micardis Plus 40 mg/12.5 mg tablets, 80 mg/12.5 mg tablets and 80 mg/25 mg tablets.

For the full list of all side effects reported with Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80

mg/12.5 mg and 80 mg/25 mg tablets, see section 4 of the package leaflet.

For the full list of restrictions, see the package leaflet.

Why were Telmisartan/Hydrochlorothiazide tablets approved?

It was concluded that, in accordance with EU requirements, Telmisartan/Hydrochlorothiazide 40

mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets have been shown to have comparable quality and

to be bioequivalent to Micardis Plus 40 mg/12.5 mg tablets, 80 mg/12.5 mg tablets and 80 mg/25 mg

tablets. Therefore, the MHRA decided that, as for Micardis Plus 40 mg/12.5 mg tablets, 80 mg/12.5 mg

tablets and 80 mg/25 mg tablets, the benefits outweigh the identified risks and recommended that

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets can be

approved for use.

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

Telmisartan/Hydrochlorothiazide tablets?

A risk management plan (RMP) has been developed to ensure that Telmisartan/Hydrochlorothiazide 40

mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets are used as safely as possible. Based on this plan,

safety information has been included in the Summaries of Product Characteristics (SmPCs) and the

package leaflet for these products, 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/healthcare professionals will be monitored and reviewed continuously.

Other information about Telmisartan/Hydrochlorothiazide tablets

Austria, Germany, Estonia, Finland, France, Ireland, Italy, Lithuania, Latvia, the Netherlands, Poland,

Slovakia and UK agreed to grant Marketing Authorisations for Telmisartan/Hydrochlorothiazide 40

mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets (PL 20075/0323-24, PL 20075/0439;

UK/H/4966/001-3/DC) on 10 February 2016.

Marketing Authorisations were granted in the UK on 03 March 2016.

The full PAR for Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg

tablets follows this summary. For more information about treatment with

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets read the

package leaflet, or contact your doctor or pharmacist.

This summary was last updated in April 2016.


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SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

I Introduction Page 6

II Quality aspects Page 8

III Non-clinical aspects Page 16

IV Clinical aspects Page 17

V User consultation Page 24

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 24


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I INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the member states considered that the

applications for Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg tablets (PL 20075/0323;

UK/H/4966/001/DC), Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets (PL 20075/0324;

UK/H/4966/002/DC) and Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets (PL 20075/0439;

UK/H/4966/003/DC) could be approved. The applications were submitted via the Decentralised

Procedure, with the UK as Reference Member State (RMS), and Austria, Germany, Estonia, Finland,

France, Ireland, Italy, Lithuania, Latvia, the Netherlands, Poland and Slovakia as Concerned Member

States (CMS).

These products are prescription-only medicines (legal classification POM).

These were applications made under the Decentralised Procedure (DCP), according to Article 10(1) of

Directive 2001/83/EC, as amended, claiming to be generic medicinal products of Micardis Plus 40

mg/12.5 mg tablets, 80 mg/12.5 mg tablets and 80 mg/25 mg tablets, which were initially granted

Marketing Authorisations to Boehringer Ingelheim International GmbH in the EU, via the Centralised

Procedure, on 23 April 2002.

These products are indicated for the treatment of essential hypertension.

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg and 80 mg/12.5 mg tablets are indicated in adults

whose blood pressure is not adequately controlled on telmisartan alone.

Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets are indicated in adults whose blood pressure is

not adequately controlled on Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets or adults who

have been previously stabilised on telmisartan and hydrochlorothiazide given separately.

These products contain a combination of the active substances telmisartan and hydrochlorothiazide. The

combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a

greater degree than either component alone.

Telmisartan is a specific angiotensin II receptor subtype 1 (AT1) antagonist. It displaces angiotensin II

with very high affinity from its binding site at the AT1 receptor subtype and does not exhibit any partial

agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is

long-lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less

characterised AT receptors. The functional role of these receptors is not known, nor is the effect of their

possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma

aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or

block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the

enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated

adverse effects.

Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide

diuretics is not fully known. Thiazides have an effect on the renal tubular mechanisms of electrolyte

reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.

The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity,

increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss,

and decreases in serum potassium. Presumably through blockade of the renin-angiotensin-aldosterone

system, co-administration of telmisartan tends to reverse the potassium loss associated with these

diuretics. With hydrochlorothiazide, onset of diuresis occurs in 2 hours, and peak effect occurs at about

4 hours, while the action persists for approximately 6-12 hours. Epidemiological studies have shown that


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long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and

morbidity.

With the exception of the bioequivalence studies, no new clinical or non-clinical studies were

conducted, which is acceptable given that the applications were based on being generic medicinal

products of originator product that have been licensed for over 10 years.

Two bioequivalence studies were performed. The first compared the pharmacokinetics of

Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets to those of the reference product Micardis Plus

80 mg/25 mg tablets (Boehringer Ingelheim International GmbH). The second compared the

pharmacokinetics of Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets to those of the reference

product Micardis Plus 80 mg/12.5 mg tablets (Boehringer Ingelheim International GmbH). The

bioequivalence studies were carried out in accordance with Good Clinical Practice (GCP).

The RMS has been assured that acceptable standards of Good Manufacturing Practice are in place for

this product type at all sites responsible for the manufacture, assembly and batch release of these

products.

The RMS and CMS considered that the applications could be approved at the end of procedure on 10

February 2016. After a subsequent national phase, licences were granted in the UK on 03 March 2016.


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II QUALITY ASPECTS

II.1 Introduction

Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg tablets are white to off-white on one side and red,

possibly mottled, on the other side. They are biconvex, bilayer, oblong shaped, uncoated tablets,

approximately 13 mm in length and 6.2 mm in width, debossed with “T1” on the red side and plain on

the other side. Each tablet contains 40 mg telmisartan and 12.5 mg hydrochlorothiazide.

Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets are white to off-white on one side and red,


approximately 16.2 mm in length and 7.9 mm in width, debossed with “T2” on the red side and plain on

the other side. Each tablet contains 80 mg telmisartan and 12.5 mg hydrochlorothiazide.

Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets are white to off white on one side and yellow,


approximately 16.2 mm in length and 7.9 mm in width, debossed with “T2” on the yellow side and plain

on the other side.

Other ingredients consist of the pharmaceutical excipients, namely microcrystalline cellulose, lactose

monohydrate, mannitol, sodium hydroxide, meglumine, povidone (K30), magnesium stearate, sodium

stearyl fumarate. In addition Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg and 80 mg/12.5 mg

tablets contain red ferric oxide (E172) and Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets

contain Yellow ferric oxide (E172).

The finished product is packaged in aluminium blisters packed into cartons, in pack sizes of 14, 28, 30,

56, 60, 84, 90, 98 or 100 tablets.

Not all pack sizes may be marketed.

Satisfactory specifications and Certificates of Analysis have been provided for all packaging

components. All primary packaging complies with the current European regulations concerning

materials in contact with food.

II.2 Drug substance rINN: Telmisartan

Chemical name(s): 4'-[[4-Methyl-6-(1-methyl-1Hbenzimidazol- 2yl)-2- propyl-1Hbenzimidazol-1-yl]

methyl] biphenyl-2-carboxylic acid

Structure:

Molecular formula: C33H30N4O2

Molecular weight: 514.6

Appearance: White or slightly yellowish, crystalline powder

Solubility: Soluble in 1M sodium hydroxide, sparingly soluble in methylene chloride,

slightly soluble in methanol, practically insoluble in water


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rINN: Hydrochlorothiazide

Chemical name(s): 6-Chloro-3,4-dihydro-2H-1,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide.

Structure:

Molecular formula: C7H8ClN3O4S2

Molecular weight: 297.7

Appearance: White or almost white, crystalline powder.

Solubility: Very slightly soluble in water, soluble in acetone, sparingly soluble in ethanol (96

%). It dissolves in dilute solutions of alkali hydroxides.

All aspects of the manufacture and control of the active substances telmisartan and hydrochlorothiazide

from their starting materials are covered by European Directorate for the Quality of Medicines and

Healthcare (EDQM) Certificates of Suitability (CEPs).

Suitable specifications have been provided for all packaging used. The primary packaging has been

shown to comply with current guidelines concerning contact with food.

Appropriate stability data have been generated to support a suitable retest period when stored in the

proposed packaging.

II.3 Medicinal Product

Pharmaceutical Development

The objective of the development programme was to formulate globally acceptable and stable products

that could be considered generic medicinal products of the currently licensed products, Micardis Plus 40

mg/12.5 mg tablets, 80 mg/12.5 mg tablets and 80 mg/25 mg tablets (Boehringer Ingelheim

International GmbH).

A satisfactory account of the pharmaceutical development has been provided.

Comparative in vitro dissolution and impurity profiles have been provided for the applicant’s product

versus the reference product.

With the exception of the red and yellow iron oxides (E172), all excipients comply with their respective

European Pharmacopoeia monographs. Red iron oxide (E172) and yellow iron oxide (E172) comply

with the United State Pharmacopoeia and are authorised colourants in the EU, meeting the criteria

specified by the European legislation.

With the exception of lactose monohydrate, none of the excipients are sourced from animal or human

origin. The milk used in the production of lactose monohydrate is sourced from healthy animals under

the same conditions as that for human consumption. The magnesium stearate is of vegetable origin. No

genetically modified organisms (GMO) have been used in the preparation of these products.

Manufacturing Process

Satisfactory batch formulae have been provided for the manufacture of the products, along with an

appropriate description of the manufacturing process. Suitable in-process controls are in place to ensure


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the quality of the finished products. Process validation has been carried out on three batches of each

strength of finished product. The results are satisfactory.

Finished Product Specification

The finished product specifications proposed are acceptable. Test methods have been described and have

been adequately validated. Batch data have been provided and comply with the release specification.

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 batches of finished product

in the packaging proposed for marketing.

The results from these studies support a shelf-life of 30 months with no special storage precautions. The

products should be stored in the original packaging in order to protect them from moisture.

II.4 Discussion on chemical, pharmaceutical and biological aspects

It is recommended that Marketing Authorisations are granted for Telmisartan/Hydrochlorothiazide 40

mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg tablets.

II.5 Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and

Labels

The SmPCs, PIL and labels are satisfactory and, where appropriate, in line with current guidance.

In accordance with Directive 2010/84/EU, the current version of the SmPCs and PIL are available on the

MHRA website.

The approved labels are shown below:


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III NON-CLINICAL ASPECTS

III.1 Introduction

The pharmacodynamic, pharmacokinetic and toxicological properties of telmisartan and

hydrochlorothiazide are well known. No new non-clinical data have been submitted for these

applications and none are required.

The applicant has provided an overview based on published literature. The non-clinical overview has

been written by an appropriately qualified person and is satisfactory, providing an appropriate review of

the product’s pharmacology and toxicology.

III.2 Pharmacology

No new pharmacology data are required for these applications and none have been submitted.


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III.3 Pharmacokinetics No new pharmacokinetic data are required for these applications and none have been submitted.

III.4 Toxicology

No new toxicology data are required for these applications and none have been submitted.

III.5 Ecotoxicity/Environmental risk Assessment (ERA)

As these products are intended for generic substitution of products that are already marketed, no increase

in environmental exposure to of telmisartan and hydrochlorothiazide is anticipated. Thus the absence of

an ERA is accepted.

III.6 Discussion of the non-clinical aspects



IV. CLINICAL ASPECTS

IV.1 Introduction

With the exception of the bioequivalence studies detailed below, no new clinical studies have been

performed and none are required for this type of application. The applicant’s clinical overview has been

written by an appropriately qualified person and is considered acceptable.

IV.2 Pharmacokinetics

In support of this application, the applicant submitted the following bioequivalence studies:

Study 1:

A single dose, open label, replicated crossover bioequivalence study comparing the

pharmacokinetics of the test product, Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets to

those of the reference product, Micardis Plus 80 mg/25 mg tablets (Boehringer Ingelheim

International GmbH), in healthy, adult, human volunteers, under fasting conditions.

Volunteers were given each treatment after an overnight fast. Blood samples were collected for the

measurement of pharmacokinetic parameters pre-dose and up to 96 hours post dose. Each treatment was

separated by a washout period of 14 days.

A summary of the main pharmacokinetic results is presented in the tables below:


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Telmisartan

Hydrochlorothiazide


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Telmisartan

The Intra-subject CV of the reference product for the ln-transformed pharmacokinetic parameter Cmax was

found to be > 30%; hence the acceptance limit for Cmax was widened up to 72.25 - 138.41.

Hydrochlorothiazide

Compared with the reference product, the 90 % confidence intervals for telmisartan and

hydrochlorothiazide for the test product are within 80.00-125.00 % for AUC. For telmisartan the 90 %

confidence intervals for Cmax are within the protocol-defined widened range, based on the observed

intra-subject variability. For hydrochlorothiazide the 90 % confidence intervals for Cmax are within the

bioequivalence acceptance limits of 80 - 125 %.

However, bioequivalence could not be accepted as the applicant's pre-specified approach to only include

data in the analysis from subjects fully completing all the treatment periods was incorrect. The applicant

was, therefore, asked to re-analyse the data.

The recalculated data is presented below:

Telmisartan


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Hydrochlorothiazide

The recalculated bioequivalence acceptance limits for Cmax were 72.58-137.77, based on the

recalculated observed intra-subject variability.

For both telmisartan and hydrochlorothiazide, compared with the reference product, the 90 %

confidence intervals for the test product for AUC remained within the bioequivalence acceptance limits

of 80 - 125 %. For telmisartan, compared with the reference product the 90 % confidence intervals for

Cmax for the test product remained within the protocol defined widened range. For hydrochlorothiazide,

compared with the reference product, the 90 % confidence intervals for Cmax for the test product

remained within the bioequivalence acceptance limits of 80 - 125 %.

Telmisartan/Hydrochlorothiazide 80 mg/25 mg tablets are, therefore, considered bioequivalent to

Micardis Plus 80 mg/25 mg tablets (Boehringer Ingelheim International GmbH),

As these products meet the bio-waiver criteria specified in the Guideline on the Investigation of

Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1/Corr**), the results and conclusions of the

bioequivalence study on the 80 mg/25 mg strength can be extrapolated to the 40mg/12.5mg strength.

These products are bilayer tablets and, in line with the above Guideline on the Investigation of

Bioequivalence, each layer can be treated independently. As such, the results and conclusions of the

bioequivalence study on the 80 mg/25 mg strength can be extrapolated to the telmisartan component of

the 80 mg/12.5mg strength.

A further study was conducted to establish bioequivalence for the hydrochlorothiazide component of the

80 mg/12.5 mg strength, as follows:

Study 2:

An open-label, balanced, randomised, two-treatment, two-period, two-sequence, single oral dose,

crossover, bioequivalence study comparing the pharmacokinetics of the test product,

Telmisartan/Hydrochlorothiazide 80 mg/12.5 mg tablets to those of the reference product,

Micardis Plus 80 mg/12.5 mg tablets (Boehringer Ingelheim International GmbH), in healthy,

adult, human volunteers, under fasting conditions.

Volunteers were given each treatment after an overnight fast of at least 10 hours. Blood samples were

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

Each treatment was separated by a washout period of 28 days.

A summary of the main pharmacokinetic results is presented in the tables below:


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Compared with the reference product, the 90 % confidence intervals for hydrochlorothiazide for the test

product are within 80.00-125.00 % for Cmax and AUC. Telmisartan/Hydrochlorothiazide 80 mg/12.5

mg tablets are, therefore, considered bioequivalent to Micardis Plus 80 mg/12.5 mg tablets (Boehringer

Ingelheim International GmbH) for the hydrochlorothiazide component.

IV.3 Pharmacodynamics

No new pharmacodynamic data were submitted and none are required for applications of this type.

IV.4 Clinical efficacy

No new data on efficacy have been submitted and none are required for applications of this type.

IV.5 Clinical Safety

No new data on safety have been submitted and none are required for applications of this type.

IV.6 Risk Management Plan (RMP) and Pharmacovigilance System

The Pharmacovigilance System, as described by the applicant, fulfils the requirements and provides

adequate evidence that the applicant has the services of a qualified person responsible for

pharmacovigilance, and has the necessary means for the notification of any adverse reaction suspected

of occurring either in the Community or in a third country.

The MAH has submitted a 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 Telmisartan/Hydrochlorothiazide 40 mg/12.5 mg, 80

mg/12.5 mg and 80 mg/25 mg tablets


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

listed below:


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IV.7 Discussion of the clinical aspects



V. USER CONSULTATION The package leaflet has been evaluated in accordance with the requirements of Articles 59(3) and 61(1)

of Directive 2001/83/EC, as amended. The results indicate that the package leaflet is well-structured and

organised, easy to understand and written in a comprehensive manner. The test shows that patients/users

are able to act upon the information that it contains.

VI OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT

The quality of the product is acceptable, and no new non-clinical or clinical safety concerns have been

identified. The data supplied support the claim that the applicant’s products and the reference products

are interchangeable. Extensive clinical experience with telmisartan and hydrochlorothiazide is

considered to have demonstrated the therapeutic value of the compounds. The benefit-risk assessment is

therefore considered to be positive.


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Annex 1 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

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)

public assessment report decentralised procedure assessment report decentralised procedure...

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