SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Karmamood Maximum Strength St John’s Wort Tablets

Boots Max Strength Mood Lift St John’s Wort Tablets

Higher Nature St John’s Wort Mood Uplift Tablets

Simply Supplements Mood Boost Max Strength St John’s Wort Tablets

Holland & Barrett Moodease St John’s Wort One-a-Day tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each coated tablet contains:

425 mg of extract (as dry extract) from St John’s wort aerial parts (Hypericum perforatum L.)(3.5-6:1)(equivalent to 1490 - 2550 mg of St John’s wort).

Extraction solvent: Ethanol 60% v/v.

Excipients: 1 tablet contains 234 mg of sucrose and 6 mg of glucose.

For full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Coated tablet.

Round, yellow, coated tablets, free from ruptures.

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.

For adults and the elderly, take 1 tablet daily. The tablets should be swallowed whole with a little liquid. The tablets should not be chewed.

The patient should consult a doctor if symptoms worsen or do not improve after 6 weeks.

Not for children or adolescents under 18 years.

4.3 Contraindications

Hypersensitivity to the active ingredient or any of the excipients.

The product should not be used in children or adolescents under 18 years of age.

Pregnancy and lactation (see Section 4.6)

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

This product should not be taken concomitantly with the medicines included in Section 4.5. This is because St John’s wort (Hypericum perforatum) has been shown to induce the cytochrome P450 isoenzymes CYP1A2, CYP2C9 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, or if symptoms persist for more than six weeks medical advice should be sought.

The dosing and safety of St John’s Wort have not been studied in children/ adolescents below 18 years and safety is not established.

This product is intended for relief of symptoms of slightly low mood and mild anxiety. Patients with signs and symptoms of depression should seek medical advice for appropriate treatment.

In very rare cases, particularly in light-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 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. Clinically significant interactions have been reported with for example: warfarin, ciclosporin, HIV protease inhibitors, theophylline, digoxin, oral contraceptives, and anticonvulsants.

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.

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 halflives 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. citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, Others eg. duloxetine, venlafaxine	Increased serotonergic effects with increased incidence of adverse reactions.	Do not take with this product.
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	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.

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: 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 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
cyclosporin, 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 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
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 Pregnancy and lactation

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.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

A drug-monitoring study of 3,250 patients receiving St John’s wort included an overall rate of adverse reactions of 2.4%. All patients were treated with St John’s wort extract (300 mg three times daily). Adverse events were spontaneously reported by 79 (2.4%) patients during 4 weeks of treatment. Gastrointestinal symptoms were the most frequently reported adverse events (n=18, 0.6%) followed by allergic reactions (n=17, 0.5%) and fatigue (n=13, 0.4%). Gastrointestinal adverse events reported include dyspepsia, anorexia, nausea, diarrhoea and constipation. Other ADRs reported in the literature include headaches, neuropathy, anxiety, dizziness, mania and allergic reactions.

When St John’s wort is used, sunburn-like reactions in the parts of skin exposed to strong UV irradiation (sun, solarium) can rarely occur, particularly in fair-skinned individuals, due to the increased sensitivity of the skin to sunlight (photosensitisation).

4.9 Overdose

There are no data on human overdose with St John’s wort. Where a large overdose has occurred, phototoxic reactions may occur. The skin of the patient should be protected for one week from UV irradiation. 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

Pharmacotherapeutic group: Herbal medicinal product for the treatment of depressive disorders.

ATC code: N06AP01

The active constituents of St John’s wort have not been definitively established. However, the phloroglucinol constituent, hyperforin, and the hypericin group of constituents, are thought to play an important 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

Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed.

6    PHARMACEUTICAL    PARTICULARS

6.1    List of excipients

Tablet core:

Maltodextrin

Silica, colloidal anhydrous Cellulose, microcrystalline Croscarmellose sodium Sodium starch glycolate (Type A)

Magnesium stearate

Coating:

Hypromellose

Sucrose

Talc

Calcium carbonate E170

Tragacanth

Acacia

Liquid glucose (dry substance)

Titanium dioxide E171

Iron oxide hydrate E172 (=yellow iron oxide)

Vanillin Beeswax white Carnauba wax Shellac

6.2 Incompatibilities

Not applicable

6.3 Shelf life

The shelf life is 3 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Original packages contain 30, 60 or 90 Karmamood Maximum Strength St John’s Wort coated tablets.

Original packages containing 30 coated tablets (Boots Max Strength Mood Lift St John’s Wort Tablets,Higher Nature St John’s Wort Mood Uplift Tablets, Simply Supplements Mood Boost Max Strength St John’s Wort Tablets, Holland & Barrett Moodease St John’s Wort One-a-Day tablets ) or 90 coated tablets (Boots Max Strength Mood Lift St John’s Wort Tablets).

The coated tablets are packed in PVC/ PVDC aluminium blisters and inserted into a carton together with the package leaflet.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements

7. REGISTRATION HOLDER

Schwabe Pharma (UK) Ltd