Simvastatin 20mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Simvastatin
Available from:
Mawdsley-Brooks & Company Ltd
ATC code:
C10AA01
INN (International Name):
Simvastatin
Dosage:
20mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 02120000

Public Assessment Report

UKPAR

Simvastatin 10mg tablets

Simvastatin 20mg tablets

Simvastatin 40mg tablets

(Simvastatin)

UK Licence No: PL 36722/0060-62

Special Concept Development (UK) Limited (trading as Rx

Farma).

PAR Simvastatin 10mg, 20mg and 40mg tablets

PL 36722/0060-62

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LAY SUMMARY

Simvastatin 10mg tablets

Simvastatin 20mg tablets

Simvastatin 40mg tablets

(simvastatin, tablet, 10mg, 20mg or 40mg)

This is a summary of the Public Assessment Report (PAR) for Simvastatin 10mg tablets

(PL 36722/0060), Simvastatin 20mg tablets (PL 36722/0061) and Simvastatin 40mg tablets (PL

36722/0062). It explains how Simvastatin 10mg, 20mg and 40mg 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 Simvastatin 10mg, 20mg and 40mg tablets.

The products will be collectively referred to as Simvastatin throughout the remainder of this public

assessment report.

For practical information about using Simvastatin patients should read the package leaflet or contact

their doctor or pharmacist.

What is Simvastatin and what is it used for?

Simvastatin is used to:

- lower levels of cholestrerol and fatty substances (triglycerides) in the blood, thereby reducing the risk

of heart disease.

- slow or reduce the progression of:

atherosclerosis (clogging of blood vessels by cholesterol) which can lead to angina (chest pain)

and heart attack

coronary heart disease (CHD)- this medicine can help to lessen the risk of a heart attack.

These applications are the same as Simvastatin 10mg, 20mg and 40mg tablets (PL 43870/0015-0017)

which are already authorised.

The company (Medley Pharma Limited) that makes Simvastatin (PL 43870/0015-0017) has agreed that

its scientific data can be used as a basis for the grant of identical licences for Simvastatin (informed

consent).

How does Simvastatin work?

This medicine contains the active ingredient simvastatin, which belongs to a group of medicines known

as HMG-CoA reductase inhibitors.

If levels of cholesterol are too high in the bloodstream, it can be deposited on the walls of the arteries

and build up to form plaques. These plaques will eventually block the blood vessels. This medicine

works by reducing the amount of cholesterol and fatty substances (triglycerides) in the blood.

How is Simvastatin used?

The pharmaceutical form of this medicine is a tablet and the route of administration is oral (by mouth).

The patient should always take this medicine exactly as their doctor or pharmacist has told them. The

patient should check with their doctor or pharmacist if they are not sure. It is important the patient stays

on a low-fat diet as well as taking this medicine.

Your doctor may prescribe a dose of 5mg, 10mg, 20mg, 40mg or 80mg once a day by mouth

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For children aged 10-17 years of age, the recommended usual starting dose is 10mg a day in the evening.

The maximum recommended dose is 40mg a day.

For high cholesterol levels, the usual starting dose in 10-20mg per day.

For coronary heart disease, the usual starting dose is 20-40mg per day, given as a single dose in the

evening.

The doctor may adjust the patient’s dose to a maximum dose of 80mg to have the best effect. The 80mg

dose is only recommended for adult patients with very high cholesterol levels and at high risk of heart

disease problems.

This medicine should be taken for as long as the patient’s doctor has recommended.

Please refer to section 3 of the package leaflet for information on how to use this medicine.

This medicine can only be obtained with a prescription.

For further information on how Simvastatin is used, refer to the package leaflet and Summary of Product

Characteristics available on the Medicines and Healthcare products Regulatory Agency (MHRA)

website.

What benefits of Simvastatin have been shown in studies?

Simvastatin is considered identical to previously authorised Simvastatin 10mg, 20mg and 40mg tablets

(PL 43870/0015-0017), with the same benefits and risks. Therefore no new studies have been provided

for Simvastatin but reference is made to the studies for Simvastatin 10mg, 20mg and 40mg tablets (PL

43870/0015-0017).

What are the possible side effects from Simvastatin?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Simvastatin is considered identical to previously authorised Simvastatin 10mg, 20mg and 40mg tablets

(PL 43870/0015-0017)

with the same benefits and risks.

For a full list of all the side effects reported with Simvastatin

see section 4 of the package leaflet,

available on the Medicines and Healthcare products Regulatory Agency (MHRA) website.

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

Why is Simvastatin approved?

The MHRA decided that the benefits of Simvastatin are greater than the risks and recommended that it is

approved for use.

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

A Risk Management Plan has been developed to ensure that Simvastatin

is used as safely as possible.

Based on this plan, safety information has been included in the Summary of Product Characteristics and

the package leaflet for Simvastatin

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/reviewed continuously.

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Other information about Simvastatin

Marketing Authorisations were granted in the UK on 25 July 2017.

The full PAR for Simvastatin

follows this summary.

For more information about treatment with Simvastatin

read the package leaflet, or contact your doctor

or pharmacist.

This summary was last updated in August 2017.

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TABLE OF CONTENTS

Introduction

Page 6

Quality aspects

Page 7

Non-clinical aspects

Page 9

Clinical aspects

Page 9

User consultation

Page 11

Overall conclusion, benefit/risk assessment and

recommendation

Page 11

Table of content of the PAR update

Page 21

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I

INTRODUCTION

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Special Concept

Development (UK) Limited Marketing Authorisations for the medicinal product Simvastatin (PL

36722/0060-62) on 25 July 2017. The product is a prescription only medicine (POM) indicated for the

treatment of:

Hypercholesterolaemia

Treatment of primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet, when

response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is

inadequate.

Treatment of homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering

treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

Cardiovascular prevention

Reduction of cardiovascular mortality and morbidity in patients with manifest atherosclerotic

cardiovascular disease or diabetes mellitus, with either normal or increased cholesterol levels, as an

adjunct to correction of other risk factors and other cardioprotective therapy (see section 5.1 of the

SmPC).

These applications were submitted as simple abridged (informed consent) applications according to

Article 10c of Directive 2001/83/EC, as amended.

The applications cross-refer to the reference products Simvastatin 10 mg, 20 mg and 40 mg tablets (PL

43870/0015-0017) authorised to the marketing authorisation holder (MAH) Medley Pharma Limited.

These licences were originally granted under Article 4.8 a) (iii) of 65/65/EEC (as amended) to the MAH

Milpharm Limited (PL 16363/0166-8) on 18 August 2004 cross-referring to the reference products

Zocor 10mg, 20mg & 40 mg Tablets (Merck Sharp & Dohme BV, Netherlands; PL 00025/0241-0243).

This is acceptable for a national 10(c) application.

Simvastatin is a HMG-CoA reductase inhibitor.

After oral ingestion simvastatin, which is an inactive lactone, is hydrolysed in the liver to the

corresponding active beta-hydroxyacid form which has a potent activity in inhibiting HMG-CoA

reductase (3 hydroxy-3 methylglutaryl CoA reductase). This enzyme catalyses the conversion of HMG-

CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol.

Simvastatin has been shown to reduce both normal and elevated LDL-C concentrations. LDL is formed

from very-low-density protein (VLDL) and is catabolised predominantly by the high affinity LDL

receptor. The mechanism of the LDL-lowering effect of simvastatin may involve both reduction of

VLDL-cholesterol (VLDL-C) concentration and induction of the LDL receptor, leading to reduced

production and increased catabolism of LDL-C. Apolipoprotein B also falls substantially during

treatment with simvastatin. In addition, simvastatin moderately increases HDL-C and reduces plasma

TG. In addition, simvastatin moderately increases HDL-C and reduces plasma TG. As a result of these

changes the ratio of total- to HDL-C and LDL- to HDL-C are reduced.

No new data were submitted nor were necessary to be submitted for the applications, as the data are

identical to the data for the previously granted cross-referenced products.

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II

QUALITY ASPECTS

II.1

Introduction

These are abridged applications for Simvastatin (PL 36722/0060-62) submitted under Article 10c of

Directive 2001/83/EC, as amended.

The applications cross-refer to the reference products Simvastatin 10mg, 20mg and 40mg tablets (PL

43870/0015-0017) authorised to the MAH Medley Pharma Limited. These licences were originally

granted under Article 4.8 a) (iii) of 65/65/EEC (as amended) to the MAH Milpharm Limited (PL

16363/0166-8) on 18 August 2004 cross-referring to the reference products Zocor 10mg, 20mg & 40 mg

Tablets (Merck Sharp & Dohme BV, Netherlands; PL 00025/0241-0243). This is acceptable for a

national 10(c) application. The applications are considered valid.

II.2.

Drug Substance

Drug substance specifications

The proposed drug substance specifications are consistent with the details registered for the cross-

reference products.

II.3.

Medicinal Product Name

The proposed product names for these applications are Simvastatin 10mg, 20mg and 40mg tablets. The

product has been named in line with current requirements.

Strength, pharmaceutical form, route of administration, container and pack sizes

Each tablet contains 10mg, 20mg and 40mg of the active substance simvastatin. All strengths of the

finished product are packed in to polyvinyl chloride (PVC)/polyethylene (PE) and polyvinylidene

chloride (PVDc) or polyvinyl chloride (PVC)/aluminium and orientated polyamide foil blisters in

cartons of 28 tablets.

The proposed shelf life of the unopened product is 24 months with no special storage conditions.

The proposed packaging, shelf-life and storage conditions are consistent with the details registered for

the cross-reference product.

Legal status

Prescription only medicine (POM).

Marketing Authorisation Holder/Contact Persons/Company

Special Concept Development (UK) Limited T/A Rx Farma, Units 1-7, Colonial Way, Watford,

Hertfordshire, WD24 4YR, UK.

The Qualified Person (QP) responsible for pharmacovigilance is stated and a satisfactory CV has been

provided.

Manufacturers

The proposed manufacturing sites are consistent with those registered for the cross-reference products

and evidence of Good Manufacturing Practice (GMP) compliance has been provided.

Qualitative and quantitative compositions

The proposed compositions are consistent with the details registered for the cross-reference products.

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Manufacturing process

The proposed manufacturing processes are consistent with the details registered for the cross-reference

products and the maximum batch size is stated.

Finished product/shelf-life specifications

The proposed finished product specifications are in line with the details registered for the cross-reference

products.

TSE Compliance

None of the excipients used contain material of animal or human origin.

No genetically modified organisms (GMO) have been used in the preparation of these products.

Bioequivalence

No bioequivalence data are required to support these simple abridged applications because the proposed

products are manufactured to the same formulae utilising the same processes as the cross-reference

products, Simvastatin is considered identical to previously authorised Simvastatin 10mg, 20mg and

40mg tablets (PL 43870/0015-0017).

Expert Report

The applicant cross-refers to the data for Simvastatin is considered identical to previously authorised

Simvastatin 10mg, 20mg and 40mg tablets (PL 43870/0015-0017)

to which these applications are

claimed to be identical. This is acceptable.

Product Name and Appearance

See Section II.3 ‘Medicinal Product; Name’ for details of the proposed product names. The appearance

of the products is identical to that of the cross-reference products.

II.4

Discussion on chemical, pharmaceutical and biological aspects

The data submitted with the applications is acceptable. The grant of Marketing Authorisations is

recommended.

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III

NON-CLINICAL ASPECTS

Introduction

As these are abridged applications submitted under Article 10c of Directive 2001/83/EC, as amended, no

new non-clinical data have been supplied and none are required.

Ecotoxicity/environmental risk assessment (ERA)

Suitable justification has been provided for non-submission of an Environmental Risk Assessment. As

the applications are identical versions of already authorised products, it is not expected that

environmental exposure will increase following approval of the Marketing Authorisations for the

proposed products.

Discussion on the non-clinical aspects

The grant of Marketing Authorisations is recommended.

IV

CLINICAL ASPECTS

Introduction

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 marketing authorisation holder (MAH) has submitted a risk management plan (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 Simvastatin.

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

listed below:

Summary table of safety concerns:

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Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

Discussion on the clinical aspects

The grant of Marketing Authorisations is recommended.

V

User consultation

The applicant has committed to submit a user testing report in accordance with the requirements of

Articles 59(3) and 61(1) of Directive 2001/83/EC prior to marketing these products. The text version of

the leaflet (PIL) has been approved for these applications. This is acceptable.

VI

Overall conclusion, benefit/risk assessment and recommendation

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

identified. The applicant’s product is identical to the cross-reference product. Extensive clinical

experience with simvastatin is considered to have demonstrated the therapeutic value of the compound.

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

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Summaries of Product Characteristics (SmPC), Patient Information Leaflets (PIL) and Labels

The SmPC and PIL are consistent with the details registered for the cross-reference product.

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) and

Patient Information Leaflets (PILs) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for this medicine is presented below:

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Annex 1

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

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)

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