SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Vitabiotics St John’s Wort Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film coated tablet contains 425 mg of extract (as dry extract) from St John’s Wort aerial parts (Hypericum perforatum L.) (5-7:1) (equivalent to 2125mg - 2975mg of St John’s Wort.)

Extraction solvent: Ethanol 60% V/V

For fUll list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablets

Coated Red Oval Shaped Tablet.

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 short term use only

Adults and the elderly: The recommended dosage is 1 tablet daily.

The tablet should be swallowed whole with a little water or other liquid. The tablets should not be chewed.

This product is not recommended for children or adolescents under 18 years of age (See Section 4.4. Special Warnings and precautions for use)

If symptoms worsen during the use of the product or persist for more than 6 weeks, a doctor or a qualified healthcare practitioner should be consulted.

4.3 Contraindications

Hypersensitivity to the active substance or any of the excipients.

Patients with known dermal photosensitivity or patients undergoing phototherapy or other photodiagnostic procedures.

This product should not be taken concomitantly with the medicines included in Section 4.5. This is because St John’s wort (Hypericumperforatum) has been shown to induce the cytochrome P450 isoenzymes CYP1A2, CYP2C9, CYP2C19 and CYP3A4 as well as transport protein P-glycoprotein. This results in pharmacokinetic interactions with a large number of medicines including leading to a possible decrease in the effectiveness of those medicines.

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

4.4 Special warnings and precautions for use

Do not exceed the stated dose.

If the condition worsens during the use of the product or if symptoms persist for more than 6 weeks, consult a doctor or qualified healthcare practitioner.

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

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 persons, sun burn type reactions on skin areas exposed to strong sunlight may occur due to photosensitisation by St John’s wort. Persons using this product should avoid excessive sunbathing or the use of sunbeds or solariums.

This 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 (see Section 4.5).

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, CYP2C9, CYP2C19 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.

Substances in St John’s Wort (Hypericum perforatum) have been shown to induce the cytochrome P450 isoenzymes CYP1A2, CYP2C9, CYP2C19 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-glycopprotein (e.g. amitriptyline, fexofenadine, benzodiazepines, methadone, simvastatin, digoxin, finasteride), because a reduction of plasma concentration is possible.

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

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

		Recommendations
Co-Administered Drug	Interaction	concerning coadministration

Anaesthetics/pre-operative medicines
Fentanyl, Propofol, Sevoflurane, Midazolam	Reduced blood levels with risk of therapeutic failure.	Based on the elimination half-lives of hypericin and hyperforin this product should be discontinued at least 10 days 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
Warfarin, Acenocoumarol	Reduced anticoagulant effect and need for increased dose.	Do not take with this product.
Antidepressants
Tricyclics eg. Amitriptyline, Clomipramine MAOIs eg. Moclobemide SSRIs eg.	Increased serotonergic effects with increased incidence of adverse reactions.	Do not take with this product.

Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline Others eg. Duloxetine, Venlafaxine
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, Lumefantrine	Reduced blood levels with risk of therapeutic failure	Do not take with this product.
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 non-nucleoside reverse transcriptase inhibitors: Efavirenz, Nevirapine, Delavirdine
Anxiolytics
Buspirone Aprepitant	Increased serotonergic effects with increased incidence of adverse reactions.	Do not take with this product.
	Reduced blood levels with risk of therapeutic failure.
Barbiturates
Butobarbital, Phenobarbital	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.
Calcium channel blockers

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 rhythm or heart failure.	Do not take with this product.
CNS Stimulants
Methyl phenidate	Reduced blood levels with risk of therapeutic 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
Hormone Replacement Therapy:	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.

Oral Transdermal patches, gels, vaginal rings
Hormone antagonists
Exemestane	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.
Diuretics
Eplerenone	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.
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
Ciclosporin, Tacrolimus	Reduced blood levels with risk of transplant rejection.	Do not take with this product.
Lipid regulating drugs
Simvastatin, Atorvastatin	Reduced blood levels with risk of therapeutic failure.	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	Do not take with this product.

	failure.
Theophylline	Reduced blood levels and loss of control of asthma or chronic airflow limitation.	Do not take with this product.
Thyroid hormones
Thyroxine	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.
Oral hypoglycaemic drugs
Gliclazide	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.

4.6 Fertility, pregnancy and lactation

Safety of the product during pregnancy and lactation has not been established. In the absence of sufficient data the use in pregnancy and lactation is not recommended.

No studies on the effects on fertility have been performed.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Gastrointestinal disorders including dyspepsia, anorexia, nausea, diarrhoea or constipation; allergic skin reactions such as rash, urticaria, pruritis;. fatigue and restlessness have been reported. The frequency is not known.

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

Other adverse reactions that have been reported include headaches, neuropathy, anxiety, dizziness and mania.

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

4.9 Overdose

No case of overdose has been reported.

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.

When 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

The active constituents of St. John’s wort have not been definitively established.

However, hypericin, pseudohypericin, hyperforin and the flavonoids are considered to play a role in its activity.

5.2 Pharmacokinetic properties

The active ingredients of St John’s wort can interact with other medicinal agents in two ways. Firstly, active ingredients in St John’s wort that themselves are metabolised in the liver by the CYP3A4 isoenzyme, increase (induce) the activity of this enzyme so that it accelerates the elimination of other medicinal agents which are degraded by the same pathway. This leads to a consequent reduction in the plasma concentration and effectiveness of these other substances. Secondly, the active ingredients in St John’s wort, like other type SRI or SSRI medicinal agents with an antidepressant action, can raise the concentration of serotonin in certain parts of the central nervous system so that this neurotransmitter can sometimes reach toxic levels,

particularly when drugs containing St John’s wort are combined with other antidepressants.

5.3 Preclinical safety data

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

Reverse mutation assays (Ames test) on bacteria indicated that the product was mutagenic in Salmonella typhimurium (strains TA 98, TA 100, TA 102, TA 1535 and TA 1537) mutation assays with or without metabolic activation. However this could be attributed to quercetin/kaempferol and is therefore not considered relevant to human safety.

Adequate tests on reproductive toxicity and carcinogenicity have not been performed. Phototoxicity:

After oral application of dosages of 1800mg of an extract per day for 15 days the skin sensitivity against UVA was increased, and the minimum dose for pigmentations was significantly reduced. In the recommended dosage, no signs of phototoxicity are reported

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Excipients in the extract

Maltodextrin

Silica colloidal anhydrous

Tablet Core Maltodextrin Microcrystalline cellulose Croscarmellose Sodium Stearic Acid Magnesium Stearate Silica Colloidal Anhydrous

Tablet Coating

Hypromellose

Glycerol

Red iron oxide (E172)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

6.4    Special precautions for    storage

Do not store above 25 °C. Store in the original package.

6.5 Nature and contents of container

Tablets are packed into PVC/PVDC aluminium foil blister strips of 15 tablets in the following pack size; 30, 60, 90 Tablets and packed into a Carton.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Vitabiotics Limited,

1 Apsley Way,

London,

NW2 7HF,

UK

8    MARKETING AUTHORISATION NUMBER(S)

THR 00387/0055

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/11/2016

10    DATE OF REVISION OF THE TEXT

01/11/2016