SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Hypericon coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One coated tablet contains:

180 mg extract (as dry extract) from St John’s wort (Hypericum perforatum L.) flowering herb (4-6:1).

Extraction solvent: Ethanol 60% (m/m)

One tablet contains 41.2 mg of sucrose.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

Round coated tablet, light green-coloured.

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: Take one tablet daily.

Swallow the tablet whole with a little liquid. Do not chew the tablet.

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

Children and adolescents less than 18 years old: This product is not indicated in patients less than 18 years. See section 4.4. special warnings and precautions for use

4.3 Contraindications

Hypersensitivity to the active ingredient or any of the excipients.

This product should not be taken concomitantly with any of 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 recommended dose.

If symptoms worsen or do not improve after six weeks medical advice should be sought.

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 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 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).

Patients with rare hereditary problems of fructose intolerance, glucosegalactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Substances in St John’s wort (Hypericumperforatum) 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-glycoprotein (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 (Hypericumperforatum) 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 coadministration
Anaesthetics/pre-o	perative 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-arrhytmics
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.	Increased serotonergic effects	Do not take with this product.

amitriptyline, clomipramine MAOIs eg. moclobemide SSRIs eg. citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline Others eg. duloxetine, venlafaxine	with increased incidence of adverse reactions.
Antiepileptics
All drugs in this class including: carbamazepine phenobarbitone phenytoin primidone sodium valporate	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.
Antipsychotic
Aripiprazole	Reduced blood levels with risk of therapeutic failure.	Do not take with this product.

Antivirals
HIV protease inhibitors: amprenavir, atazanavir, darunavir, fosamprenavir, indinavir,	Reduced blood levels with possible loss of HIV suppression.	Do not take with this product.

lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir
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.
Calcium channel b	ockers
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	Reduced blood levels with risk of unintended pregnancy and breakthrough bleeding.	Do not take with this product.

Emergency Hormonal Contraception Hormonal implants, injections Transdermal patches, creams etc. Intra-uterine devices with hormones
Hormone Replace Therapy
Hormone Replacement Therapy: Oral Transdermal 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
ciclosporin, tacrolimus	Reduced blood levels with risk of transplant rejection.	Do not take with this product.
Liquid 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

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

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.

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

If any other adverse reactions not mentioned occur, a doctor or pharmacist should be consulted.

Overdose

No cases of overdose have been reported.

After the intake of up to 4.5g dry extract per day for 2 weeks and additionally 15 g 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 established definitely. However, hypericin, pseudohypericin, hyperforin and the flavonoids are considered to play a role in its activity.

5.2 Pharmacokinetic properties

No definitive pharmacokinetic data are available

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.

6.1 List of excipients

Excipients of the dry extract:

Maltodextrin

Precipitated silicon dioxide Excipients of the tablet core: Crospovidone Croscarmellose sodium Maize starch

Calcium hydrogen phosphate dihydrate Calcium stearate Precipitated silicon dioxide

Excipients of the coated tablet shell:

Shellac

Povidone

Glycerol diacetate alkanoate (C₁₆-C₁₈)

Talc

Sucrose

Spray-dried acacia Titanium dioxide, E 171 Calcium carbonate Heavy kaolin

Macrogol 6000, viscosity 250-390 Emerald green, E 104/E 132 consisting of:

•    Quinoline yellow, E 104

•    Indigotine, E 132 Quinoline yellow, E 104

6.2 Incompatibilities

Not applicable.

Shelf life

3 years

6.4 Special precautions for storage

Do not store above 30°C.

Store in the original packaging.

6.5 Nature and contents of container

The coated tablets are packed in PVC/PVdC-aluminium blisters. Pack sizes:    30 coated tablets

50    coated tablets

60    coated tablets

100    coated tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements

7 MARKETING AUTHORISATION HOLDER

Swiss Caps GmbH GrassingerstraBe 9 D-83043 Bad Aibling Germany

8    MARKETING AUTHORISATION NUMBER(S)

THR 18397/0006

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

21/01/2011

10    DATE OF REVISION OF THE TEXT

21/01/2011