PROSTASAN SAW PALMETTO CAPSULES THR 13668/ · PDF filemhra par; prostasan saw palmetto capsules, thr 13668/0011 3 prostasan saw palmetto capsules thr 13668/0011 scientific discussion

MHRA PAR; PROSTASAN SAW PALMETTO CAPSULES, THR 13668/0011

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PROSTASAN SAW PALMETTO CAPSULES

THR 13668/0011

UKPAR

TABLE OF CONTENTS

Lay summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 14

Summary of Product Characteristics

Page 15

Product Information Leaflet

Page 19

Labelling Page 24

Steps taken after THR grant Page 27


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THR 13668/0011

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Bioforce (UK) Limited a Traditional Herbal Registration (THR) Certificate for the traditional herbal medicinal product Prostasan Saw Palmetto Capsules (THR 13668/0011). This product is available without prescription and can be bought from pharmacies and other outlets. The active ingredient of Prostasan Saw Palmetto Capsules is the extract from the saw palmetto fruit. Prostasan Saw Palmetto Capsules is a traditional herbal medicinal product used to relieve of symptoms of an enlarged prostate in men, such as the need to urinate frequently (especially at night), weak or interrupted urinary flow, or the feeling of not being able to empty the bladder completely. This registration is based exclusively upon evidence of traditional use of saw palmetto fruit as a herbal medicine and not upon data generated from clinical trials. There is no requirement under the THR 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 THR Certificate could be granted.


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THR 13668/0011

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 10

Clinical assessment

Page 11

Overall conclusions and risk assessment Page 13


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INTRODUCTION

The MHRA granted a THR Certificate for the traditional herbal medicinal product Prostasan Saw Palmetto Capsules to Bioforce (UK) Limited on 10 September 2007. This product is on the general sales list (GSL). This application was submitted according to Article 16.c of Directive 2001/83 EC, as amended, as part of the THR Scheme. This product consists of soft gelatin capsules containing 320 mg of extract from saw palmetto fruit. The product is used for the relief of lower urinary tract symptoms in men who have a confirmed diagnosis of benign prostatic hypertrophy (BPH). This THR is based exclusively on evidence of traditional use of saw palmetto fruit. The recommended dose is one capsule daily to be taken with food. The data supplied by the applicant demonstrate 30 years of traditional use of saw palmetto fruit in the European Community. A satisfactory review of the available safety data on saw palmetto fruit has also been provided, together with an expert safety report supporting the proposed product.


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PHARMACEUTICAL ASSESSMENT REPORT

HERBAL SUBSTANCE

Scientific name of the plant: Serenoa repens (Bartrum) Small Family: Arecaceae Synonyms of the herbal substance: Saw palmetto, sabal Parts of the plant used: Fruit Name of the herbal substance: Saw palmetto fruit

Constituents The phytochemical composition of saw palmetto fruits has been studied extensively. The fruits are reported to contain fixed oil, sterols and carbohydrates. Fixed oil containing many free fatty acids, e.g. capric, caproic, caprylic, lauric, linoleic, myristic, oleic, palmitic and stearic, as well as their triglycerides and fatty alcohols. Sterols including campesterol, stigmasterol, β-sitosterol and β-sitosterol glucopyranoside. Carbohydrates e.g. invert sugar, mannitol, high molecular weight polysaccharides (eg. MW 100,000) with galactose, arabinose, and uronic acid as the main sugar components. Other constituents include flavonoids, carotene, resin, tannin, volatile oil.

Manufacture The plant is a small fan palm with dark red fruits the size of olives. The plant is indigenous to the coastal areas of the southern states of the USA (South Carolina, Florida) and tropical Central and South America. The saw palmetto fruits used by Bioforce are grown in Florida in a certified organic program. The information provided on the collection of the plant starting material is considered to be acceptable and assurance has been given that cultivation, harvesting and documentation are performed according to Good Agricultural and Collection Practice (GACP).

Control of Herbal Substance Specification

The proposed specification for the herbal drug is largely based on the Ph Eur monograph and is considered acceptable.

Analytical Procedures/Validation of Analytical Procedures Analytical procedures are generally carried out according to the Ph Eur monograph. Further validation is therefore not required Batch Analyses

Satisfactory batch data have been provided to support the specifications.


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Justification of Specification The proposed specification for the herbal drug is largely based on the Ph Eur monograph and is considered acceptable. The specification is supported by the batch data provided.

Reference Standards or Materials Suitable details of the reference standard have been provided. A satisfactory certificate of analysis has also been provided.

Stability Confirmation is given that the herbal substance is completely analysed prior to being used to make the herbal preparation, providing assurance that it complies with Ph.Eur. requirements and, therefore, also with the specification.

HERBAL PREPARATION General information Nomenclature

Name: Saw palmetto concentrated extract Part of plant: Fruit Drug to Extract Ratio (DER crude): 9.0-12.0: 1 (defined with reference to dried mass) Extractant (Extraction solvent): Ethanol 94.0% m/m

Manufacture

Manufacturers

A qualified person has provided a good manufacturing practice (GMP) declaration confirming that the manufacturer of the herbal preparation is subject to regular GMP inspections by their national authority and are operating in compliance with GMP for starting materials.

Description of Manufacturing Process and Process Controls A flow diagram of the manufacturing process of the herbal preparation has been provided and is satisfactory.

Control of Materials The ethanol used for extraction complies with the Ph Eur monograph.

Controls of Critical Steps and Intermediates Satisfactory in-process controls are performed during manufacture of the herbal preparation.

Process Validation and/or Evaluation The applicant has provided data to support the choice of extraction solvent.

Characterisation Suitable tests are performed to elucidate the structure and other characteristics of the

herbal preparation.


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

the herbal preparation Analytical Procedures

Analytical methods are either those of the Ph Eur or have been fully validated.

Batch Analyses Batch analysis data are provided and these comply with the proposed specification.

Justification of Specification In general, the proposed specification has been justified satisfactorily.

Reference Standards or Materials Suitable details have been provided for the reference standard. A satisfactory certificate of analysis has been provided.

Container Closure System The extract is stored in suitable containers.

Stability Batches were packed in the final container closure system and stored under ICH real time, intermediate and accelerated conditions. The data support the storage conditions and shelf life.

HERBAL PRODUCT Description and Composition of the Herbal Product

Prostasan capsules are dark brown, soft gelatin capsules, measuring 13.0±0.5 mm in length and 8.0±0.5 mm in thickness, with yellow-brown contents and a characteristic odour and a soapy taste. The capsules contain 320 mg saw palmetto extract. The extract is encapsulated without the addition of excipients. The capsule shell is composed of gelatin, and glycerol and sorbitol are added as softeners to prevent brittleness. A combination of iron oxide pigments is used as colouring matter. All excipients are described in either the Ph. Eur or USP/NF.

Manufacture

GMP Certificates have been provided by all manufacturers. Production of the filling mass, encapsulation, the drying process and packaging are standard procedures ensuring a consistent quality of drug product. The finished product manufacturer produces many different soft capsules with plant extracts as the active substance well dispersed in a matrix of fats and oils. The manufacturing process is straightforward and the manufacturer has provided justification that a process development program is not necessary. There are no overages in this product.


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Description of Manufacturing Process and Process Controls A flow diagram summarising the manufacturing process and in-process controls has been provided. The extract is filtered and encapsulated in the gelatin shell and then dried. The resulting capsules are filled into polyethylene bags of pharmaceutical quality and then filled into bottles.

Control of Critical Steps and Intermediates A number of in-process control tests are performed during the manufacturing process. All are considered adequate.

Process Validation and/or Evaluation The manufacturing procedure is a standard procedure and has been used for over 50 years. Process validation results for production scale batches show that the production process provides a reproducible product of satisfactory quality and consistency. All results were within the release specification.

Control of Excipients

Most of the excipients comply with the Ph. Eur. Where the Ph. Eur is used, confirmation is provided that the most current version is applied. The colouring agents, ferric oxides red, yellow and black, comply with the USP. Representative certificates of analysis have been provided from the suppliers of all the excipients. The gelatin is of animal origin. It is the main component of the capsule shell and is exclusively derived from pig skin. The gelatin is tested according to the Ph. Eur monograph for gelatin. A suitable declaration in relation to the TSE status of glycerol is provided.

Control of Herbal Product

Specification The finished product specifications at release and end of shelf life are detailed and the tests and limits used were found to be satisfactory for a product of this nature. Analytical Procedures / Validation of Analytical Procedures Satisfactory details have been provided on all analytical procedures and these analytical procedures are valid. Batch Analyses Satisfactory batch data have been provided to support the specifications.

Characterisation of Impurities Satisfactory tests are used to ensure that there is good comparison between the raw material and the finished product. Justification of Specification(s) The proposed release and shelf-life specifications have been adequately justified with respect to the parameters controlled and the limits applied.


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Reference Standards or Materials Suitable details have been provided for the reference standard. A satisfactory certificate of analysis has been provided.

Container Closure System The capsules are packed in brown glass bottles, Type III (Ph Eur).

Stability Studies have been conducted under ICH conditions (longterm and accelerated) on production scale batches in the container type proposed for marketing. Based on the data provided, a shelf- life of 60 months when unopened is accepteble.

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


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NON-CLINICAL ASSESSMENT Non-clinical aspects The Expert Safety Report submitted by the applicant lists relevant references to published work studying the toxicology of saw palmetto. Non-clincial overview The applicant has submitted a good literature review with this application. An Expert Safety Report was also provided, which included reviews of some non-clinical data. The Expert Safety Report was written by a registration pharmacist and a medical director and is dated December 2005. The overview contains a review of some non-clinical data for saw palmetto. Some of the studies in the literature review were conducted and published before GLP was a regulatory requirement. Moreover, it is not possible to ascertain if the data assessed in the review would comply with today’s regulatory safety testing requirements with regards to design, conduct and analysis. Due to a shortage of published data on saw palmetto, it is not possible to assess if the safety package for the phytochemical constituents of saw palmetto 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 may be acceptable and in compliance with guideline EMEA/HMPC/32116/05. The company has identified that data in the literature for genotoxicity studies of the product’s active components is deficient. They have conducted an Ames test with their product and have sufficiently justified not conducting further additional genotoxicity tests, thus, points on genotoxicity are resolved. Summary of product characteristics The Summary of Product Characteristics for this product is satisfactory. Environmental risk assessment An environmental risk assessment is not required for herbal medicinal products according to guidance CPMP/SWP/4447/00. Conclusion The information supplied demonstrating traditional use of saw palmetto is acceptable. An adequate literature review of saw palmetto has been carried out by the applicant and no new nonclinical data were submitted for assessment with this application. Granting of a THR is acceptable.


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CLINICAL ASSESSMENT

LEGAL STATUS Saw palmetto is currently on the General Sales List for internal use. PROPOSED INDICATION The applicant has proposed the following: ‘Traditional herbal medicinal product used for the relief of lower urinary tract symptoms in men who have a confirmed diagnosis of benign prostatic hypertrophy (BPH), based on traditional use only. Prior to treatment other serious conditions should have been ruled out by a doctor.’ Assessor’s comments This indication is acceptable. EVIDENCE OF TRADITIONAL USE Article 16 c 1 (c) requires the applicant to provide bibliographic or expert evidence showing 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 Community. The applicant has provided evidence of use of saw palmetto within the EU for a period exceeding 30 years. Bioforce have marketed a product named Prostasan in Holland since 1964 and in Switzerland and Finland since 1969. The original Prostasan formulation consisted of saw palmetto extract in combination with solidago virgaurea, echinacea purpurea and populus tremula. Assessor’s comments The information provided is adequate to demonstrate that saw palmetto fruit has been in use for at least 30 years, of which at least 15 years have been in an EU Member State. The requirements of the Directive are therefore satisfied. SAFETY REVIEW Article 16 c 1 (d) requires the applicant to provide a bibliography of the safety data together with an expert report. A safety review has been provided, as well as an expert report written by a registration pharmacist and medical director. Their CVs are provided. Assessor’s comments The safety review is comprehensive and reveals the main safety issues associated with treatment with saw palmetto. The SPC includes information taking account of the known safety profile of saw palmetto. SUMMARY OF PRODUCT CHARACTERISTICS The SPC for this product is satisfactory. PATIENT INFORMATION LEAFLET The PIL for this product is satisfactory.


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LABELLING All labelling is satisfactory. 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 of corresponding products and satisfactory safety data have been provided supporting the proposed product. RECOMMENDATIONS A Traditional Registration may be granted.


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OVERALL CONCLUSION AND RISK ASSESSMENT

QUALITY The quality data submitted with this application are satisfactory. PRECLINICAL No new 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 saw palmetto within the EU for a period exceeding 30 years. A satisfactory review of the safety data has been provided. The SmPC, 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 13668/0011

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Traditional Herbal Registration application on 3 March 2006

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 22 June 2006

3 The Herbal Medicines Advisory Committee considered this application in January 2007 and requested further information relating to the dossier on 6 February 2007

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

5 Following assessment of the response the MHRA requested further information relating to the dossier on 5 July 2007

6 The applicant responded to the MHRA’s requests, providing further information on the dossier on 1 August 2007

7 Following assessment of the response the MHRA requested further information relating to the dossier on 16 August 2007

8 The applicant responded to the MHRA’s requests, providing further information on the quality dossier on 16 August 2007

9 A THR was granted on 10 September 2007


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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Prostasan Saw Palmetto Capsules 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 capsule contains 320mg of extract (as soft extract) from Saw palmetto fruit (Serenoa repens (Bartram) Small fructus (Sabal serrulata (Michaux) Nichols fructus)) (9-12 :1). Extraction solvent: Ethanol 96% V/V. For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Soft capsule. It is an oval-shaped, dark brown coloured soft capsule containing a clear, yellow-brown coloured oil.

4 CLINICAL PARTICULARS

4.1 THERAPEUTIC INDICATIONS

Traditional herbal medicinal product used for the relief of lower urinary tract symptoms in men who have a confirmed diagnosis of benign prostatic hypertrophy (BPH), based on traditional use only. Prior to treatment other serious conditions should have been ruled out by a doctor.

4.2 POSOLOGY AND METHOD OF ADMINISTRATION

Adults and the elderly: One capsule daily to be taken with food. Children and adolescents less than 18 years old: This product is not indicated in patients less than 18 years. Hepatic and renal impairment: The safety of Saw palmetto has not been studied in patients with hepatic and/or renal impairment.

4.3 CONTRAINDICATIONS

This product should not be used: • In patients who have a known hypersensitivity to Saw palmetto or any of the other

ingredients used in this product. • By patients who are under 18 years of age. • By women who are pregnant or breastfeeding.

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Do not exceed stated dose. This product is intended for use in men who have had benign prostatic hypertrophy already diagnosed by a medical practitioner. If symptoms worsen consult a healthcare practitioner.


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If symptoms include haematuria or pyrexia medical advice must be sought immediately. Saw palmetto is unlikely to have an effect on levels of serum prostate specific antigen (PSA). There has been a case report of intra-operative haemorrhage associated with the use of Saw palmetto. The prolonged bleeding time may have been a result of platelet dysfunction caused by cyclooxygenase inhibition by Saw palmetto. As a precaution Saw palmetto should be discontinued and the platelet function assessed prior to patients undergoing surgery. Patients taking medication for Benign Prostatic Hypertrophy should consult their doctor before using Prostasan Capsules.

4.5 INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION

Limited interaction studies have identified no clinically important drug interactions. Saw palmetto does not appear to significantly affect the cytochrome P450 linked enzyme system.

4.6 PREGNANCY AND LACTATION

The safety of this product during pregnancy and lactation has not been established, therefore the use of this product during pregnancy and lactation should be avoided. Fertility: Non-clinical data on constituents of Saw palmetto indicate a potential effect of reduced sperm motility, viability and sperm concentration. The relevance of these findings to humans is not known. (See Section 5.3).

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES No studies on the effects on the ability to drive and use machines have been performed.

4.8 UNDESIRABLE EFFECTS

There has been one case report of intraoperative haemorrhage associated with the use of Saw palmetto. Based on post-marketing data other adverse events that have been reported are: Rare (>1/10,000 to <1/1,000):

• Eructation and gastrointestinal discomfort • Allergic reactions

4.9 OVERDOSE

There are no data on human overdose with Saw palmetto. Appropriate symptomatic and supportive treatment should be administered as clinically indicated.

5 PHARMACOLOGICAL PROPERTIES

5.1 PHARMACODYNAMIC PROPERTIES

The active constituents of Saw palmetto have not been established definitively, however the fatty acid and phytosterol (such as β-sitosterol) components are considered to play a role in its activity.


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5.2 PHARMACOKINETIC PROPERTIES No definitive pharmacokinetic data are available.

5.3 PRECLINICAL SAFETY DATA

Data on reproductive toxicity are limited. Carcinogenicity studies have not been performed. An Ames test conducted with the extract to investigate genotoxic potential was negative. β-sitosterol (5mg/kg) given subcutaneously for 32 or 48 days had an antifertility effect on male rats by reducing sperm motility, viability and sperm concentration. The relevance of these findings to humans is not known, but it is considered that the low levels of β-sitosterol in this product are unlikely to have an effect on human fertility.

6 PHARMACEUTICAL PARTICULARS

6.1 LIST OF EXCIPIENTS

Gelatin Glycerol Sorbitol Ferric oxide red

Ferric oxide black Ferric oxide yellow Purified water

6.2 INCOMPATIBILITIES

Not applicable. 6.3 SHELF LIFE

Unopened 60 months. 6.4 SPECIAL PRECAUTIONS FOR STORAGE

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

6.5 NATURE AND CONTENTS OF CONTAINER

Amber glass bottles (Type III glass) with aluminium pilfer proof closure with a polyethylene liner. Pack sizes: 30 capsules 60 capsules 90 capsules 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, Ayrshire KA11 5DD, United Kingdom


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Tel: 01294 277 344 [email protected]

8 MARKETING AUTHORISATION NUMBER(S)

THR 13668/0011

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10/09/2007 10 DATE OF REVISION OF THE TEXT

10/09/2007


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PATIENT INFORMATION LEAFLET


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LABELLING


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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

26/11/2010 Label and leaflet update

To update labels and leaflet - addition of the THR certification mark, front panel of

product label upadted with new style and addition of yellow card scheme information

to the leaflet.

Approved 21/02/2011

21/12/2011 Type II variation

To update section 4.8 (Undesirable effects) of the SmPC. As a consequence, the product

labels and PIL have been updated.

Approved 27/09/2012

21/12/2011 Type II variation

To amend sections 4.2 (Posology and method of administation) and 4.4 (Special warnings and precautions) of the SmPC to

provide information on an appropriate duration of use for the product. As a

consequence, the product labels and PIL have been updated.

Approved 27/09/2012

21/12/2011 Type IB variation

To update sections 2 (Qualitative and quantitative composition) and 4.4 (Special warnings and precautions for use) of the

SmPC in line with the guideline 'Excipients in the label and package leaflet of medicinal products for human use' (July 2003). As a consequence, the product labels and PIL

have been updated.

Approved 27/09/2012


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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 Prostasan Saw Palmetto Capsules:


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SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Prostasan Saw palmetto Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION 1 capsule contains 320mg of extract (as soft extract) from Saw palmetto fruit (Serenoa repens (Bartram) Small fructus (Sabal serrulata (Michaux) Nichols fructus)) (9-12 :1). Extraction solvent : Ethanol 96% V/V.

One capsule contains 6.93 – 8.47 mg sorbitol.

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Soft capsule. It is an oval-shaped, dark brown coloured soft capsule containing a clear, yellow-brown coloured oil.

4 CLINICAL PARTICULARS 4.1 Therapeutic indications

Traditional herbal medicinal product used for the relief of lower urinary tract symptoms in men who have a confirmed diagnosis of benign prostatic hypertrophy (BPH), based on traditional use only. Prior to treatment other serious conditions should have been ruled out by a doctor.

4.2 Posology and method of administration Adults and the elderly: One capsule daily to be taken with food. Children and adolescents less than 18 years old: This product is not indicated in patients less than 18 years. Hepatic and renal impairment: The safety of Saw palmetto has not been studied in patients with hepatic and/or renal impairment.

4.3 Contraindications This product should not be used: • In patients who have a known hypersensitivity to Saw palmetto or any of the other

ingredients used in this product. • By patients who are under 18 years of age. • By women who are pregnant or breastfeeding.

4.4 Special warnings and precautions for use Do not exceed stated dose.


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This product is intended for use in men who have had benign prostatic hypertrophy already diagnosed by a medical practitioner.

If symptoms worsen or if haematuria or pyrexia occur, medical advice must be sought immediately. If no improvement in symptoms is seen after 8 weeks of treatment, consult a doctor or qualified health care practitioner.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Saw palmetto is unlikely to have an effect on levels of serum prostate specific antigen (PSA).

There has been a case report of intra-operative haemorrhage associated with the use of Saw palmetto. The prolonged bleeding time may have been a result of platelet dysfunction caused by cyclooxygenase inhibition by Saw palmetto. As a precaution Saw palmetto should be discontinued and the platelet function assessed prior to patients undergoing surgery.

Patients taking medication for Benign Prostatic Hypertrophy should consult their doctor before using Prostasan Capsules.

4.5 Interaction with other medicinal products and other forms of interaction

Limited interaction studies have identified no clinically important drug interactions. Saw palmetto does not appear to significantly affect the cytochrome P450 linked enzyme system.

4.6 Pregnancy and lactation The safety of this product during pregnancy and lactation has not been established, therefore the use of this product during pregnancy and lactation should be avoided. Fertility: Non-clinical data on constituents of Saw palmetto indicate a potential effect of reduced sperm motility, viability and sperm concentration. The relevance of these findings to humans is not known. (See Section 5.3).

4.7 Effects on ability to drive and use machines No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects There has been one case report of intraoperative haemorrhage associated with the use of Saw palmetto.

Based on post-marketing data other adverse events that have been reported are:

Gastrointestinal disorders • Eructation and gastrointestinal discomfort

Skin disorders • Allergic reactions such as rash, pruritis

The frequency is not known.


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

4.9 Overdose

There are no data on human overdose with Saw palmetto. Appropriate symptomatic and supportive treatment should be administered as clinically indicated.

5 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties

The active constituents of Saw palmetto have not been established definitively, however the fatty acid and phytosterol (such as β-sitosterol) components are considered to play a role in its activity.

5.2 Pharmacokinetic properties No definitive pharmacokinetic data are available.

5.3 Preclinical safety data Data on reproductive toxicity are limited. Carcinogenicity studies have not been performed. An Ames test conducted with the extract to investigate genotoxic potential was negative. β-sitosterol (5mg/kg) given subcutaneously for 32 or 48 days had an antifertility effect on male rats by reducing sperm motility, viability and sperm concentration. The relevance of these findings to humans is not known, but it is considered that the low levels of β-sitosterol in this product are unlikely to have an effect on human fertility.

6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients

Gelatin Glycerol Sorbitol Ferric oxide red

Ferric oxide black Ferric oxide yellow Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life Unopened 60 months.

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

6.5 Nature and contents of container Amber glass bottles (Type III glass) with aluminium pilfer proof closure with a polyethylene liner.


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Pack sizes: 30 capsules 60 capsules

90 capsules 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, Ayrshire KA11 5DD, United Kingdom Tel: 01294 277 344 [email protected]

8 MARKETING AUTHORISATION NUMBER(S) THR 13668/0011

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10/09/2007 10 DATE OF REVISION OF THE TEXT

27/09/2012


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PATIENT INFORMATION LEAFLET


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MHRA PAR; PROSTASAN SAW PALMETTO CAPSULES, THR 13668/0011 36

LABELLING

Labels:


Cartons:



Documents

PROSTASAN SAW PALMETTO CAPSULES THR 13668/ · PDF filemhra par; prostasan saw palmetto capsules, thr 13668/0011 3 prostasan saw palmetto capsules thr 13668/0011 scientific discussion