SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

HYPERIDRINE Capsules

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 300mg of St John’s Wort aerial parts (Hypericum perforatum L.)

For full list of excipients see section 6.1.

3    PHARMACEUTICAL FORM

Hard capsules.

Clear size 0 hard capsules.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Hyperidrine is 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 one capsule three times swallowed with water.

A doctor or qualified healthcare practitioner should be consulted if symptoms or do not improve after 6 weeks.

Not recommended for children or adolescents under 18 years (See Section 4.4 warnings and precautions for use).

4.3 Contraindications

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

P atients with known dermal photosensitivity or those undergoing phototherapy or any photodiagnostic procedures.

Concomitant use with any of the medicines specified in section 4.5. This is because St. John’s wort (Hypericum performatum) has 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 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

Do not exceed the stated dose.

Not recommended for children and adolescents under 18 years of age because data are not sufficient and medical advice should be sought.

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

Hyperidrine 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 Hyperidrine should avoid excessive sunbathing or the use of sunbeds or solariums.

Hyperidrine should be discontinued at least 10 days prior to elective surgery due to the potential for St.John’s Wort to interact with drugs used during general and regional anaesthesia.

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 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 -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 (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, Hyperidrine (St John’s Wort) should not be taken concomitantly with the Medicines included in the following table.

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	Increased serotonergic effects with increased incidence of adverse reactions.	Do not take with this product.
MAOIs eg. moclobemide
SSRIs eg. 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.
Anti psychotics
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	Reduced blood levels with risk of unintended pregnancy and breakthrough bleeding.	Do not take with this product.
Hormonal implants, injections
Transdermal patches, creams etc.
Intra-uterine devices with hormones

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
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 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 Fertility, pregnancy and lactation

The safety of Hyperidrine (St John’s Wort) during pregnancy and lactation has not been established. In the absence of sufficient data, use during 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 effect 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 continual monitoring of the benefit/risk of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow card Scheme at www.mhra.gov .uk/yellowcard

4.9 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 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.

5.1 Pharmacodynamic properties

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

ATC Code: N06AX

The active constituents of Hyperidrine (St John’s Wort) have not been definitively established. However, hypericin, pseudohypericin hyperforin and the flavonoids are considered to have synergistic activity.

5.2 Pharmacokinetic properties

No definitive pharmacokinetic data available.

The active ingredients of Hyperidrine (St John’s Wort) can interact with other medicinal agents in two ways. Firstly, active ingredients in Hyperidrine (St John’s Wort) themselves are metabolised in the liver by the CYP3A isoenzymes, 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 Hyperidrine (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

Reverse mutation assays (Ames test) on bacteria indicated that the product was not mutagenic in Salmonella typhimurium (strains TA 98, TA 100, TA 1535 and TA 1537) mutation assays with or without metabolic activation.

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 pigmentation was significantly reduced. In the recommended dosage, no signs of photoxicity are reported.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Hypromellose (Capsule shell).

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/08/2016

10    DATE OF REVISION OF THE TEXT

18/08/2016