VENAFORCE HORSE CHESTNUT GR* TABLETS … seeds are 20-40 mm in diameter and are spherical-oval,...

MHRA PAR; VENAFORCE HORSE CHESTNUT GR* TABLETS, THR 13668/0010

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VENAFORCE HORSE CHESTNUT GR* TABLETS

THR 13668/0010

UKPAR

TABLE OF CONTENTS

Lay summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

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Summary of product characteristics

Page 14

Product information leaflet

Page 18

Labelling Page 21

Steps taken after THR grant Page 24


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THR 13668/0010

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Bioforce (UK) Limited a Traditional Herbal Registration certificate for the traditional herbal medicinal product Venaforce Horse Chestnut GR* tablets (Traditional Herbal Registration number: THR 13668/0010). This product is available without prescription and can be bought from pharmacies and other outlets. The active ingredient of Venaforce Horse Chestnut GR* tablets comes from the seeds of the horse chestnut tree, also known as Aesculus hippocastanum L. Horse chestnut seeds are a traditional herbal medicine used for the relief of symptoms associated with varicose veins, such as tired heavy legs, aching painful legs, leg cramps and swollen ankles. This registration is based exclusively upon the longstanding use of horse chestnut seeds as a traditional herbal medicine and not upon data generated from clinical trials. There is no requirement under the Traditional Herbal Registration scheme to prove scientifically that the product works. No new or unexpected safety concerns arose from this application and it was, therefore, decided that a Traditional Herbal Registration Certificate could be granted.


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THR 13668/0010

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS Introduction

Page 4

Pharmaceutical assessment

Page 5

Preclinical assessment

Page 9

Clinical assessment

Page 10

Overall conclusions and risk assessment Page 12


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INTRODUCTION

The MHRA granted a Traditional Herbal Registration Certificate for the traditional herbal remedy Venaforce Horse Chestnut GR* tablets (THR 13668/0010) to Bioforce (UK) Limited on 20 February 2008. This product is on the general sales list (GSL). This application was submitted as a standard application according to Article 16.c of Directive 2001/83 EC, as amended, as part of the Traditional Herbal Medicines Registration Scheme. The data supplied by the applicant demonstrate 30 years of traditional use of horse chestnut (Aesculus hippocastanum L.) seeds in the European Community. A satisfactory review of the available safety data on horse chestnut seeds has also been provided, together with an expert report supporting the proposed product.


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PHARMACEUTICAL ASSESSMENT

HERBAL SUBSTANCE General information

Scientific name of plant: Aesculus hippocastanum L. Synonyms: Aesculus castanea Gilib., A. procera Salisb., Castanea equina, Hippocastanum vulgare Gaertner English name: Horse Chestnut Part of the plant used: Fresh horse chestnut seeds (Aesculus hippocastanum: Semen rec.)

The seeds are 20-40 mm in diameter and are spherical-oval, somehow flattened and covered by a brown seed shell with a large, spherical, light-brown scar (nilum). The area beyond the seed shell is totally filled by the embryo with big, slightly yellowish cotyledons.

Manufacture The plants are not cultivated. Freshly fallen horse chestnut seeds are collected by hand at the end of September-October from ornamental trees in Switzerland, Austria and Germany. The trees are located in parks or line avenues. It is stated that seeds from trees in streets with heavy traffic are not collected. Following harvest neither treatment with fumigation agents nor ionising radiation occurs. There is no drying stage as only fresh fruits are used. The storage conditions and maximum storage time have been defined from process validation studies. A satisfactory flow diagram of the process has been provided. The information provided on the collection of the plant starting material is considered to be acceptable and assurance has been given that cultivation and harvesting are performed according to Good Agricultural and Collection Practice (GACP).

Control of Herbal Substance An appropriate specification based on the Ph Eur monograph for horse chestnut seeds is used and is

acceptable. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specification. The specification is supported by the batch data provided.

Stability The storage time after delivery to the production plant has been identified as one of the critical production steps and, consequently, has been validated. The maximum storage time is 48 hours, if


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the delivered fresh seeds are dry and 24 hours if the delivered fresh seeds are moist. Storage will occur at room temperature.

HERBAL PREPARATION General information

Native drug-extract ratio, referred to the dried drug 4-6:1 Native drug-extract ratio, referred to the fresh drug 7.1-11.2:1 Extraction solvent: Ethanol 60.0 % (m/m)

Manufacture A satisfactory description of the manufacturing process of the herbal substance and flow diagram has been provided. Certificates of analysis for all materials used in the manufacture of the herbal preparation are provided. All excipients are tested and released according to their Ph. Eur. monograph or, in the absence of a Ph. Eur. monograph, a satisfactory in-house specification.

Satisfactory in-process controls are in place during manufacture to ensure the quality of the herbal preparation.

Control of Herbal Preparation A satisfactory specification with appropriate tests and limits has been provided for the herbal

preparation

Appriopriate analytical procedures are used to control the quality of the herbal preparation. Analytical procedures have been validated, as appropriate.

Certificates of analysis have been provided for production batches of the herbal preparation, demonstrating satisfactory compliance with the proposed specification.

The proposed specification has been justified satisfactorily.

Container Closure System

Specifications have been provided by the supplier of the container closure system together with a declaration of compliance with Directive 90/128 EC, as amended. Assurances have also been provided from the suppliers that the packs and their contents/labels etc are suitable for food use.

Stability Batches were packed in the container closure system and stored in ICH conditions. The data support the proposed retest period of 24 months.

HERBAL PRODUCT Description and Composition of the Herbal Product

The herbal products are gastro-resistant tablets that contain a dry extract preparation of horse chestnut seeds. The tablets comprise microcrystalline cellulose, maize starch, colloidal silica (anhydrous) and soya polysaccharide. The tablets are coated in a mixture of methacrylic acid (ethyl acrylate copolymer (1:1) and methyl methacrylate copolymer (1:1)), talc and triethyl citrate.


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The choice of excipients is based on experience and compatibility of the chosen excipients with the herbal preparation is confirmed by stability testing. Interaction of the herbal product with the container is not expected based on the results of stability testing.

Control of Excipients All of the excipients and analytical procedures are as specified by their respective Ph Eur monographs. Certificates of analysis (CoA) for the excipients have been provided by the suppliers. All of the excipients are produced from non-animal and non-human sources.

Manufacture The manufacturing process is a standard procedure and a satisfactory flow diagram outlining the various stages of the manufacturing process and the in-process controls is provided.

A number of in-process control tests are performed during the manufacturing process to ensure the quality of the product. All are considered adequate.

Control of Herbal Product

The finished product specifications at release and end of shelf life are detailed and the tests and limits applied were found to be satisfactory for a product of this nature.

Satisfactory details have been provided on all analytical procedures and these analytical procedures are valid. Certificates of Analysis have been presented for batches of the drug product demonstrating little inter-batch variation.

Reference Standards or Materials Certificates of Analysis for the reference substance have been provided by the finished product manufacturer.

Container Closure System The product is presented in an amber glass bottle (type III glass) containing 30 or 60 tablets. The container is sealed with an aluminium pilfer proof screw cap fitted with a polyseal expanded polyethylene liner. Suitable specifications have been provided by the packaging suppliers and the supplier declares that the glass containers comply with the Ph Eur monograph for Type III glass containers. A declaration of compliance with the Directive for food contact has also been provided.

Stability Stability studies were conducted under ICH conditions on product batches in the container proposed

for marketing. Based on the results, a proposed shelf life of 4 years with no special storage conditions is justified. Product literature The product literature (Summary of Product Characteristics, Patient Information Leaflet and labelling) for this product are pharmaceutically satisfactory. A package leaflet has been submitted to the MHRA along with results of consultations with target patient groups ("user testing"), in accordance with Article 59 of Council Directive 2001/83/EC. The results indicate that the package leaflet is well-structured and organised, easy to understand and


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written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that it contains.

ASSESSOR’S OVERALL CONCLUSIONS ON QUALITY This product is satisfactory and a Traditional Herbal Registration can be granted.


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NONCLINICAL ASSESSMENT

1 NONCLINICAL ASPECTS The Expert Safety Report submitted by the applicant lists relevant references to published work studying the toxicology of horse chestnut seed. 2 NONCLINCIAL OVERVIEW The applicant has submitted a good literature review with this application. An Expert Report on Safety was provided, which included reviews of some non-clinical data. The Expert Safety Report was written by a pharmacist with expertise in herbal medicines and is dated January 2006. The overview submitted in support of this application is satisfactory. Due to a shortage of published data on horse chestnut seed, it is not possible to assess if the safety package for the phytochemical constituents is acceptable to the standards of today’s GLP and safety testing requirements. However, the information supplied demonstrating traditional use is acceptable and thus the lack of provision of a complete standard safety package is acceptable and in compliance with guideline EMEA/HMPC/32116/05. 3 SUMMARY OF PRODUCT CHARACTERISTICS (SPC) The SPC for this product is satisfactory from a preclinical point of view. 4 ENVIRONMENTAL RISK ASSESSMENT

An environmental risk assessment is not required for herbal medicinal products according to guidance CPMP/SWP/4447/00.

5 CONCLUSION The information supplied demonstrates the traditional use of horse chestnut seed. An adequate literature review of horse chestnutseed has been carried out by the applicant and no new non-clinical data was submitted for assessment with this application. Granting of a THR is acceptable.


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CLINICAL ASSESSMENT

PROPOSED INDICATION The applicant has proposed the following: “A traditional herbal medicinal product that has been used for the relief of symptoms associated with chronic venous insufficiency and varicose veins, such as tired heavy legs, pain, cramps and swelling, based on traditional use only.” The proposed indications are considered to be in agreement with the traditional uses of horse chestnut seed extract. The product is considered suitable for use without the supervision of a medical practitioner. EVIDENCE OF TRADITIONAL USE Article 16 c 1 (c) requires the applicant to provide bibliographic or expert evidence to show that the medicinal product in question, or a corresponding product, has been in medicinal use throughout a period of at least 30 years, including at least 15 years within the European Community. The applicant has provided a bibliographic review of the evidence for the use of horse chestnut seed within the EU for a period exceeding 30 years. The principal points of this review are as follows:

• Bioforce has marketed a product containing 100 % horse chestnut seed aqeous ethanolic extract in Switzerland since 1974 and the same product has been available in the United Kingdom since 1985. Aesculaforce Tablets 20mg, the concentrated aqueous ethanolic extract of horse chestnut seed, has been available in the EU since 1998 and Aesculaforce Tablets 50mg have been available in the United Kingdom since 2002.

• Products containing horse chestnut seed extract standardised to provide a dosage of 100mg

aescin per day have been available within the EU since before 1978.

• The bibliographic review has found that a large number of monographs and authoritative publications are in agreement regarding the traditional indication of horse chestnut seed extracts. The indications proposed for Venaforce Horse Chestnut GR* tablets are consistent with these traditional indications and, hence, compatible with the requirements of Directive 2004/24/EC.

Assessor’s comment: The information provided satisfactorily demonstrates that horse chestnut seed extract has been in use for at least 30 years (of which at least 15 have been in an EU member state), and that its use covers the indications sought. The requirements of Directive 2004/24/EC are therefore satisfied. SAFETY REVIEW Article 16 c 1 (D) requires the applicant to provide a bibliographic review of safety data together with an expert report. A safety review has been provided, along with an expert report written by an expert with a medical degree and expertise in herbal medicines. The clinical review of safety submitted in the dossier outlined adverse events from controlled and uncontrolled studies relevant to the safety of horse chestnut seed.


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Assessor’s comment: The safety review is acceptable and includes most major studies. In terms of interactions, there have been no conclusive drug-drug interactions reported, however there is a suggestion that bleeding time may be prolonged in patients already receiving oral anticoagulants. Based on the supplied literature, there is a minimal risk that this product will interact with drugs metabolised by the cytochrome P450 enzyme system. Adverse events associated with this product appear to be generally mild. The most frequently reported adverse events, based on the results of clinical and post-marketting surveillance studies are gastrointestinal conditions including, flatulence, nausea and diahorrea., pruritis, headache and dizziness. As there are inadequate reproductive toxicity data and the data in humans are limited, the product should not be used by women who are pregnant or breast-feeding. PRODUCT LITERATURE The product literature (Summary of Product Characteristics, Patient Information Leaflet and labelling) for this product are medically satisfactory. A package leaflet has been submitted to the MHRA along with results of consultations with target patient groups ("user testing"), in accordance with Article 59 of Council Directive 2001/83/EC. 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 the patients/users are able to act upon the information that it contains. DISCUSSION This is an application for registration under the Traditional Herbal Medicinal Products Directive. The data supplied by the applicant are sufficient to demonstrate 30 years of traditional use within the European Community for corresponding products. An acceptable review of the available safety data on horse chestnut seed extract has been provided, together with an expert report supporting the proposed product. RECOMMENDATIONS A Traditional Registration may be granted.


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OVERALL CONCLUSION AND RISK ASSESSMENT

QUALITY Bioforce AG has over 30 years of experience in manufacturing herbal medicinal products. The quality data submitted with this application are satisfactory. PRECLINICAL No preclinical data were submitted and none are required for an application of this type. EFFICACY AND SAFETY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products (THMP). The Applicant has provided a bibliographic review which shows ample evidence for the use of horse chestnut seed within the EU for a period exceeding 30 years. The SPC, PIL and labelling are satisfactory. RISK ASSESSMENT The quality of the product is acceptable and no new preclinical or clinical safety concerns have been identified.


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THR 13668/0010

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Traditional Herbal Registration application on 18 May 2006

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 28 December 2006

3 Following assessment of the application the MHRA requested further information relating to the clinical dossier on 16 May 2007 and the quality dossier on 24 May 2007

4 The applicant responded to the MHRA’s requests, providing further information on the dossiers on 30 September 2007

5 Following assessment of the response the MHRA requested further information relating to the quality dossier on 1 October 2007

6 The applicant responded to the MHRA’s requests, providing further information on the quality dossier on 19 December 2007

7 Following assessment of the response the MHRA requested further information relating to the quality dossier on 14 January 2008

7 The applicant responded to the MHRA’s requests, providing further information on the quality dossier on 15 February 2008

8 A THR was granted on 20 February 2008


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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Venaforce Horse Chestnut GR* tablets 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One gastro-resistant tablet contains 157.5–225.0 mg of extract (as dry extract) from fresh Horse chestnut seeds (Aesculus hippocastanum L., semen) corresponding to 50 mg triterpene glycosides, calculated as anhydrous β-aescin. Extraction solvent: ethanol (60% m/m) For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Gastro-resistant, tablet for oral use. It is a biconvex, oval-shaped, yellowish-beige coated tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

A traditional herbal medicinal product that has been used for the relief of symptoms associated with chronic venous insufficiency and varicose veins, such as tired heavy legs, pain, cramps and swelling, based on traditional use only.

4.2 Posology and method of administration

Adults: one tablet twice daily taken immediately after food. Tablet should be swallowed whole. Do not exceed the recommended dose. Tablets are for oral use only. This product should not be given to children and adolescents under the age of 18 years.

4.3 Contraindications

This product should not be used by patients who: Have an allergy or are hypersensitive to horse chestnut seed or any of the other ingredients.

4.4 Special warnings and precautions for use

If symptoms worsen or persist for more than two weeks medical advice should be sought. Patients who have developed ulcers on their lower limbs due to chronic venous insufficiency should not use this product if they are not receiving medical care for their venous ulcers. If a patient develops a venous ulcer while using this product they should immediately seek medical treatment for the ulceration. This product contains soya oil polysaccharide and should not be used by patients who are allergic to peanut or soya.


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4.5 Interaction with other medicinal products and other forms of interaction There are limited data available on drug interactions with extracts of horse chestnut seed. The data indicates that horse chestnut seed extracts are unlikely to interact with other medicinal products.

4.6 Pregnancy and lactation

The safety of the product during pregnancy and lactation has not been established, therefore it should be avoided during pregnancy or while breastfeeding.

4.7 Effects on ability to drive and use machines

This product has no influence on the ability to drive and use machines. 4.8 Undesirable effects

Undesirable effects associated with the use of horse chestnut seed extracts are generally mild. The following undesirable effects have been reported in clinical studies: Uncommon (≥1/1,000 to <1/100) Gastrointestinal disorders:

• Nausea • Abdominal Pain • Flatulence • Diarrhoea

Skin and subcutaneous tissue disorders: • Pruritis • Rash • Urticaria

4.9 Overdose

No cases of overdose have been reported. In the event of an overdose, patients may expect an increased likelihood of experiencing an undesirable effect. If symptoms develop, medical advice should be sought. Management of an overdose should include appropriate symptomatic and supportive treatment as warranted by the clinical situation.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

No pharmacodynamic studies have been undertaken with horse chestnut seed extracts. The pharmacodynamic properties are unknown.

5.2 Pharmacokinetic properties

No pharmacokinetic studies have been conducted with horse chestnut seed extracts. 5.3 Preclinical safety data

The non-clinical toxicology data available are limited. 6 PHARMACEUTICAL PARTICULARS


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6.1 List of excipients For the tablet: Microcrystalline cellulose Maize starch Colloidal silica, anhydrous Soya polysaccharide For the film coating: Methacrylic acid – ethyl acrylate copolymer (1:1) dispersion 30 per cent Methacrylic acid – methyl methacrylate copolymer (1:1) Talc Triethyl citrate

6.2 Incompatibilities

Not applicable. 6.3 Shelf life

4 years 6.4 Special precautions for storage

This medicinal product does not require any special storage conditions. Keep out of the reach and sight of children.

6.5 Nature and contents of container

Amber glass bottle (type III glass) with aluminium pilfer proof screw cap fitted with a polyseal expanded polyethylene liner. Pack sizes: 30 tablets 60 tablets Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements 7 MARKETING AUTHORISATION HOLDER

Bioforce (UK) Ltd, 2 Brewster Place, Irvine KA11 5DD, UK Telephone: 01294 277344 [email protected]

8 MARKETING AUTHORISATION NUMBER(S)

THR 13668/0010 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 20/02/2008


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10 DATE OF REVISION OF THE TEXT 20/02/2008


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PATIENT INFORMATION LEAFLET


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LABELLING Labels:


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30 tablet carton:


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60 tablet carton:


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Module 6

Steps taken after THR grant

The following table lists the updates made to the Traditional Herbal Registration for this product that have been approved by the MHRA since the product was first granted a THR.

Date submitted

Application type

Scope Outcome

21/12/2010 Label and leaflet update

To update carton labels and leaflet with the addition of the THR certification mark,

front panel of product label update with new style and addition of yellow card scheme

information to the leaflet

Approved 21/02/2011

31/08/2011 Type IB variation

To update sections 4.4 (Special warnings and precautions for use), 4.5 (Interaction with other medicinal products and other

forms of interaction), 4.6 (Pregnancy and lactation) and 4.8 (Undesirable effects) of the SmPC and, consequentially, the label and leaflet, following a Periodic Safety

Update.

Approved 24/02/2012


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Annex 1 Following approval of the updates decribed in the table above, the following SmPC, PIL and labels have been incorporated into the THR for Venaforce Horse Chestnut GR* tablets:


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SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Venaforce Horse Chestnut GR* tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One gastro-resistant tablet contains 157.5–225.0 mg of extract (as dry extract) from fresh Horse chestnut seeds (Aesculus hippocastanum L., semen) corresponding to 50 mg triterpene glycosides, calculated as anhydrous β-aescin. Extraction solvent: ethanol (60% m/m) For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Gastro-resistant, tablet for oral use. It is a biconvex, oval-shaped, yellowish-beige coated tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

A traditional herbal medicinal product that has been used for the relief of symptoms associated with chronic venous insufficiency and varicose veins, such as tired heavy legs, pain, cramps and swelling, based on traditional use only.

4.2 Posology and method of administration

Adults: one tablet twice daily taken immediately after food. Tablet should be swallowed whole. Do not exceed the recommended dose. Tablets are for oral use only. This product should not be given to children and adolescents under the age of 18 years.

4.3 Contraindications

This product should not be used by patients who: Have an allergy or are hypersensitive to horse chestnut seed or any of the other ingredients.

4.4. Special warnings and precautions for use

If symptoms worsen or persist for more than two weeks medical advice should be sought. If there is inflammation of the skin, thrombophlebitis or subcutaneous induration, severe pain, ulcers, sudden swelling of one or both legs, cardiac or renal insufficiency, a doctor should be consulted immediately as this may be a sign of serious disease. Patients who have developed ulcers on their lower limbs due to chronic venous insufficiency should not use this product if they are not receiving medical care for their venous ulcers. If a patient develops a venous ulcer while using this product they should immediately seek medical treatment for the ulceration.


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This product contains soya oil polysaccharide and should not be used by patients who are allergic to peanut or soya.

4.5. Interaction with other medicinal products and other forms of interaction None reported.

4.6 Fertility. pregnancy and lactation

The safety of the product during pregnancy and lactation has not been established.

In the absence of sufficient data, the use during pregnancy and lactation is not recommended. Studies on fertility have not been performed.

4.7 Effects on ability to drive and use machines

This product has no influence on the ability to drive and use machines. 4.8 Undesirable effects

• Gastrointestinal complaints (nausea, vomiting, diarrhoea, abdominal pain and discomfort) • Allergic reactions (hypersensitivity reactions of the skin, itching, rash, erythema, eczema) • Headache and vertigo

The frequency is not known.

If other adverse reactions not mentioned above occur, a doctor or a qualified healthcare practitioner should be consulted.

4.9 Overdose

No cases of overdose have been reported. In the event of an overdose, patients may expect an increased likelihood of experiencing an undesirable effect. If symptoms develop, medical advice should be sought. Management of an overdose should include appropriate symptomatic and supportive treatment as warranted by the clinical situation.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

No pharmacodynamic studies have been undertaken with horse chestnut seed extracts. The pharmacodynamic properties are unknown.

5.2 Pharmacokinetic properties

No pharmacokinetic studies have been conducted with horse chestnut seed extracts. 5.3 Preclinical safety data

The non-clinical toxicology data available are limited.


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6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients For the tablet: Microcrystalline cellulose Maize starch Colloidal silica, anhydrous Soya polysaccharide For the film coating: Methacrylic acid – ethyl acrylate copolymer (1:1) dispersion 30 per cent Methacrylic acid – methyl methacrylate copolymer (1:1) Talc Triethyl citrate

6.2 Incompatibilities

Not applicable. 6.3 Shelf life

4 years 6.4 Special precautions for storage

This medicinal product does not require any special storage conditions. Keep out of the reach and sight of children.

6.5 Nature and contents of container

Amber glass bottle (type III glass) with aluminium pilfer proof screw cap fitted with a polyseal expanded polyethylene liner. Pack sizes: 30 tablets 60 tablets Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements 7 MARKETING AUTHORISATION HOLDER

Bioforce (UK) Ltd, 2 Brewster Place, Irvine KA11 5DD, UK Telephone: 01294 277344 [email protected]

8 MARKETING AUTHORISATION NUMBER(S)

THR 13668/0010 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 20/02/2008


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10 DATE OF REVISION OF THE TEXT

24/02/2012


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PATIENT INFORMATION LEAFLET


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LABELLING

Labels:


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Cartons:


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VENAFORCE HORSE CHESTNUT GR* TABLETS … seeds are 20-40 mm in diameter and are spherical-oval,...

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Transcript of VENAFORCE HORSE CHESTNUT GR* TABLETS … seeds are 20-40 mm in diameter and are spherical-oval,...