Neuropret Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Neuropret® Coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each coated tablet contains 425 mg of extract (as dry extract) from St. John's wort aerial parts (Hypericumperforatum L.) (3.5-6:1) (equivalent to 1490-2550 mg of St. John’s wort).
Extraction solvent: Ethanol 60% m/m.
Excipients: 1 tablet contains 234 mg sucrose and 6 mg glucose.
For a full list of excipients see section 6.1.
3 PHARMACEUTICAL FORM
Coated tablet
Yellow coated tablet, shape like lenses, 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 one tablet daily.
The tablets should be swallowed whole with a little water or other liquid. The tablets should not be chewed.
The patient should consult a doctor or a qualified healthcare practitioner if symptoms worsen or do not improve after 6 weeks.
Neuropret® Coated Tablets are not recommended for children or adolescents under 18 years of age. (See Section 4.4 Special warnings and precautions for use)
4.3 Contraindications
Patients with known hypersensitivity to St. John's wort or any other ingredient should not use Neuropret®.
Neuropret® should not be used in patients with known dermal photosensitivity or those undergoing phototherapy or any photodiagnostic procedures.
Neuropret® should not be taken concomitantly with any of the medicines specified in section 4.5. This is because St John’s wort (Hypericumperforatum) 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.
If the condition worsens or if symptoms persist for more than 6 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.
Neuropret® 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 Neuropret® should avoid excessive sunbathing or the use of sunbeds or solariums.
Neuropret® 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 (see section 4.5).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This medicine contains glucose and sucrose.
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, 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 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 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-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, |
Increased serotonergic effects with increased incidence of adverse reactions. |
Do not take with this product. |
|
clomipramine | ||
|
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. |
|
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 |
Do not take with this product. |
|
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: 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 , 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 Pregnancy and lactation
Safety of the product during pregnancy and lactation has not been established. In the absence of sufficient data, 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 other adverse reactions not mentioned above occur, a doctor, pharmacist or a qualified healthcare practitioner should be consulted.
4.9 Overdose
There are no data on human overdose with St. John’s wort.
After the intake of up to 4.5 g dry extract per day for 2 weeks and additionally 15 g 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
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 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 degraded by the same pathway. This leads to a reduction in the plasma concentration and effectiveness of these other substances. Secondly, active ingredients in St John’s wort, like other SRI or SSRI-type 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. This is particularly the case when drugs containing St John’s wort are combined with other antidepressants.
5.3
Preclinical safety data
Acute toxicity
The toxicity of Neuropret® after single dose can be classified as low. When given to rats and mice, the following LD50 values were established:
|
Species |
Method of Administration |
LD50 (mg/kg body weight) |
|
rat |
oral |
> 2000 |
|
rat |
intraperitoneal |
571 |
|
mouse |
oral |
> 2000 |
|
mouse |
intraperitoneal |
631 |
Subacute toxicity
The oral application of Neuropret® to rats for a period of four weeks up to a maximum dose of 1000 mg/kg body weight revealed no substance-related changes.
Reproductive toxicity, carcinogenicity and genotoxicity
Tests on reproductive toxicity and carcinogenicity have not been performed.
Three different genotoxicity tests (UDS-test, thymidine kinase mutation assay in mouse lymphoma cells and in vivo micronucleus assay in the mouse) showed no evidence for a mutagenic potential of Hypericum extract.
Phototoxicity
After oral application of dosages of 1800 mg 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 phototoxicity are reported.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Extract excipients:
Maltodextrin
Silica, colloidal anhydrous
Tablet core:
Silica, colloidal anhydrous Cellulose, microcrystalline Croscarmellose sodium Sodium starch glycolate-(type A)
Magnesium stearate
Coating:
Hypromellose
Sucrose
Talc
Calcium carbonate E 170
Tragacanth
Acacia
Liquid glucose (dry substance)
Titanium dioxide E 171
Iron oxide hydrate E 172 (=yellow iron oxide)
Vanillin
Beeswax, white
Carnauba wax
Shellac
6.2 Incompatibilities
Not applicable.
6.3
Shelf life
3 years.
Special precautions for storage
6.4
Do not store at temperatures above 25°C.
6.5 Nature and contents of container
Tablets are sealed in PVC/PVDC aluminium blisters which are packaged into a cardboard carton.
Package with 30 or 60 coated tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
BIONORICA SE KerschensteinerstraBe 11-15 92318 Neumarkt Phone: ++49 9181 231-90 Fax: ++49 9181 231-265 E-Mail: info@bionorica.de
8 MARKETING AUTHORISATION NUMBER(S)
THR 26411/0004
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26/05/2010
10 DATE OF REVISION OF THE TEXT
26/05/2010