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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Holland & Barrett Max Strength St. John’s Wort Capsules GNC Live Well Max Strength St. John’s Wort Capsules Lifecycle Max Strength St. John’s Wort Capsules Nature’s Garden Max Strength St. John’s Wort Capsules

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each hard capsule contains 284mg of extract (as dry extract) from St. John’s Wort aerial parts (Hypericumperforatum L.) (equivalent to 1422mg - 1991mg of St. John’s Wort)

Extraction solvent: ethanol 60% v/v.

For full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Capsule, hard

Clear, hard, two piece capsules with green brown powder fill.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

A traditional herbal medicinal product used    to    relieve    the symptoms of slightly low

mood and mild anxiety, based on traditional use only.

4.2 Posology and method of administration

For oral use only.

Adults and the elderly - Take 1 capsule 2 times daily. Swallow the whole capsule with water.

Not for use in children or adolescents under 18 years (see section 4.4 ‘Special Warnings and Precautions for use’).

Duration of use:

If symptoms worsen or persist after 6 weeks of using the medicinal product, a doctor or a qualified healthcare practitioner should be consulted.

4.3 Contraindications

Hypersensitivity to St. John’s Wort or any of the excipients in this product

This product should not be used in patients with known dermal photosensitivity or those undergoing phototherapy or any photodiagnostic procedures.

This product should not be taken concomitantly with any of the medicines specified in section 4.5. This is because St. John’s wort (Hypericum perforatum) has been shown to induce the cytochrom P450 isoenzymes CYP1A2, CYP2C19, CYP2C9 and CYP3A4 as well as the transport protein

P-gycoprotein. This results in pharmacokinetic interaction with a large number of medicines including a possible decrease in the effectiveness of those medicines.

Pharmacodynamic interactions have also been identified with antidepressants, particularly the SSRI antidepressants and the triptan group of medicines.

4.4 Special warnings and precautions for use

If the condition worsens or if symptoms persist for more than 6 weeks a doctor or qualified healthcare practitioner should be consulted.

This product is intended for the relief of symptoms of slightly low mood and mild anxiety. Patients with signs and symptoms of depression should consult a doctor for appropriate treatment.

In very rare cases, particularly in fair-skinned individuals, sunburn type reactions may occur on skin areas exposed to strong sunlight due to photosensitisation by St. John’s wort. Patients taking this product should avoid excessive sunbathing or the use of sunbeds or solariums.

The product should be discontinued at least 10 days prior to elective surgery due to the potential for interactions with medicinal products used during general and regional anaesthesia

The use of this product is not recommended in children and adolescents below the age of 18 years because data are not sufficient and medical advice should be sought.

Do not exceed the stated dose.

4.5 Interaction with other medicinal products and other forms of interaction

Substances in St. John’s wort (Hypericum perforatum) have been shown to induce the cytochrome P450 isoenzymes CYP1A2, CYP2C19, CYP2C9 and CYP3A4 as well as the transport protein P-glycoprotein. This results in pharmacokinetic interactions with a large number of medicines leading to a potential decrease in the effectiveness of those medicines.

The concomitant use of ciclosporin, tacrolimus for systemic use, amprenavir, indinavir and other protease-inhibitors, irinotecan and warfarin is contraindicated.

Special care should be taken in case of concomitant use of all drug substances the metabolism of which is influenced by CYP1A2, CYP3A4, CYP2C9, CYP2C19 or P-gly coprotein (e.g. amitriptyline, fexofenadine, benzodiazepines, methadone, simvastatin, digoxin, finasteride), because a reduction of plasma concentrations is possible

Users of oral contraceptives taking St. John’s wort (Hypericum perforatum) may experience intracyclic menstrual bleeding and the risk of contraception failure is increased.

Clinically significant pharmacodynamic interactions have also been identified with SSRI antidepressants, and the triptan group of medicines used to treat migraine. Due to the increased risk of undesirable effects associated with these interactions this product should not be used concomitantly with these types of medicines.

This product should not be taken concomitantly with the medicines included in the Table below

Co-administered drug	Interaction	Recommendations concerning co-administration
Anaesthetics/pre-operative medicines
Fentanyl, propofol, sevoflurane, midazolam	Reduced blood levels with risk of therapeutic failure	Based on the elimination half -life of hypericin and hyperforin this product should

		be discontinued at least 10days prior to elective surgery
Analgesics
Tramadol	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Antianginals
Ivabradine	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Anti-arrhythmics
Amiodarone	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Antibacterials
Erythromycin Clarithromycin telithromycin	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Anticoagulants (blood thinning medicines)
Warfarin, acenocoumarol	Reduced anticoagulant effect and need for increased dose	Do not take with this product
Antidepressants

Tricyclics eg	Increased serotonergic	Do not take with this
Amitiptyline	effects with increased incidence of adverse	product
Clomipramine	reactions
MAOIs eg
Moclobemide
SSRIs eg Citalopram, escitalopram Fluoxetin Fluvoxamine Paroxetin, sertraline
Others eg
Duloxetin
Venlafaxine

Co-administered drug	Interaction	Recommendations concerning co-administration
Antiepileptics
All drugs in this class including: Carbamazepine Phenobarbitone Phenytoin Primidone Sodium valproate	Reduced blood levels with increased risk of frequency and severity of seizures.	Do not take with this product
Antifungals
Itraconazole, voriconazole	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Antimalarials
Artemether	Reduced blood levels with	Do not take with this product

lumefantrine	risk of therapeutic failure
Anti-parkinsons
Rasagiline	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Antipsychotics
aripiprazole	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Antivirals
HIV protease inhibitors: Amprenavir, atazanavir, Darunavir, fosamprenavir Indinavir, lopinavir, Nelfinavir, ritonavir, Saquinavir, tipranavir,	Reduced blood levels with possible loss of HIV suppression	Do not take with this product
HIV nonnucleoside reverse transcriptase inhibitors: efavirenz, nevirapine, delavirdine	Reduced blood levels with possible loss of HIV suppression	Do not take with this product
Anxiolytics
buspirone	Increased serotonergic effects with increased incidence of adverse reactions	Do not take with this product
Aprepitant	Reduced blood levels with risk of therapeutic failure	Do not take with this product

Barbiturates
Butobarbital phenobarbital	Reduced blood levels with risk of therapeutic failure	Do not take with this product

Co administered drug	Interaction	Recommendations concerning co-administration
Calcium channel	jlockers
Amlodipine, nifedipine Verapamil, felodipine	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Cardiac glycosides
Digoxin	Reduced blood levels and loss of control of heart rhythms or heart failure	Do not take with this product
CNS Stimulants
Methyl phenidate	Reduced blood levels and loss of control of heart rhythms or heart failure	Do not take with this product
Cytotoxics
Irinotecan, dasatinib, erlotinib, imatinib, Sorafenib, sunitinib, Etoposide, mitotane	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Hormonal contraceptives

Oral contraceptives Emergency hormonal contraception Hormonal implants injections Transdermal patches creams etc. Intra-uterine devices with hormones	Reduced blood levels with risk of unintended pregnancy and breakthrough bleeding.	Do not take with this product
Hormone Replacement Therapy
Oral Trandermal patches, Gels Vaginal rings	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Hormone antagonists
Exemestane	Reduced blood levels with riskof therapeutic failure	Do not take with this product
Diuretics
eplerenone	Reduced blood levels with risk of therapeutic failure	Do not take with this product

Co-administered drug	Interaction	Recommendations concerning co-administration
5HT agonists

Almotriptan, eletriptan, Frovatriptan, naratriptan, Rizatriptan, sumatriptan, And zolmitriptan	Increased serotonergic effects with increased incidence of adverse reactions	Do not take with this product
Immunosuppressants
Cyclosporine tacrolimus	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Lipid regulating drugs
Simvastatin atorvastatin	Reduced blood levels with risk of transplant rejection.	Do not take with this product
Lithium	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Proton pump inhibitors
Lansoprazole, omeprazole	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Theophylline	Reduced blood levels and loss of control of asthma or chronic airflow limitation	Do not take with this product
Thyroid hormones
throxine	Reduced blood levels with risk of therapeutic failure	Do not take with this product
Oral hypoglycaemic drugs
gliclazide	Reduced blood levels with	Do not take with this product

4.6 Pregnancy and lactation

Safety during pregnancy and lactation has not been established. Due to the lack of data, use during pregnancy and lactation is not recommended.

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

Gastrointestinal disorders (e.g. dyspepsia, anorexia, nausea, diarrhoea, constipation), allergic skin reactions (e.g. rash, urticaria, pruritus) fatigue and restlessness may occur. The frequency is not known

Fair-skinned individuals may react with intensified sunburn-like symptoms under intense sunlight or strong ultra-violet (UV) irradiation

If other adverse reactions not mentioned above occur, a doctor, pharmacist or a qualified health care practitioner should be consulted

4.9 Overdose

There is no data on human overdose with St. John’s Wort.

After the intake of up to 4.5g dry extract per day for 2 weeks and additionally 15g dry extract just before hospitalisation seizures and confusion have been reported.

Where a large overdose has occurred, phototoxic reactions may occur. The skin of the patient should be protected for 1-2 weeks from UV irradiation and sunlight. Outdoor activities should be restricted and clothes and/or sun block preparations used to protect the skin from sunlight. Symptomatic and supportive measures should be taken as appropriate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.

5.2 Pharmacokinetic properties

Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.

5.3 Preclinical safety data

Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC amended.

Studies on acute toxicity and repeated dose toxicity did not show signs of toxic effects.

The weak positive results of an ethanolic extract in the AMES-test (salmonella typhimurium TA 98 and TA 100, with and without metabolic activation) could be assigned to quercetin and are irrelevant to human safety

No signs of mutagenicity have been detected in further in vitro and in vivo test systems.

Tests on reproductive toxicity revealed equivocal results.

Test on the carcinogenic potential have not been performed.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Microcrystalline cellulose Magnesium stearate Silica colloidal hydrated Excipients in the extract:

Maltodextrin

Silica colloidal anhydrous

Capsule Shell: Hypromellose

6.2    Incompatibilities

Not applicable

6.3    Shelf life

Dark amber PET bottles - Two years

Green Polyethylene terephthalate (PET) bottles - Three years

6.4    Special precautions    for storage

Do not store the capsules above 25°C.

Store in the original packaging.

6.5    Nature and contents    of container

Container:

1.    Dark amber Polyethylene terephthalate (PET) bottles with a chiffon black hinge cap (low density Polyethylene) with a paper backed aluminium foil liner which acts as a tamper evident seal under the cap.

2.    Green Polyethylene terephthalate (PET) bottles with a chiffon green hinge cap

(Polypropylene), with an inner seal liner designed to lift ‘n’ peel. The inner seal acts as a tamper evident seal under the cap. The Inner seal liner is made up of polyester film, polymer adhesive layer, polyester tab, polyolefin foam, aluminium foil and sealable polyester film

Pack size: 50 capsules and 100 capsules

6.6 Special precautions for disposal

No special requirements

7    MARKETING AUTHORISATION HOLDER

NBTY Europe Limited Samuel Ryder House,

Barling Way,

Nuneaton,

Warwickshire,

CV10 7RH United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

THR 21710/0003

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

09/11/2010

DATE OF REVISION OF THE TEXT

10/01/2013

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