Diafemin Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
DiaFemin Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each coated tablet contains: 300 mg of extract (as dry extract) from St. John’s Wort aerial parts (Hypericum perforatum L.) (3.5-6:1) (equivalent to 1050 - 1800 mg of St. John’s Wort).
Extraction solvent: Ethanol 60% m/m and 6.4 mg of extract (as dry extract) from Black Cohosh rhizome and root (Cimicifuga racemosa (L.) Nutt.) (4.5-8.5:1) (equivalent to 28.80-54.40 mg of Black Cohosh rhizome).
Extraction solvent: Ethanol 60% v/v
Each coated tablet contains 19 mg of lactose monohydrate, 234 mg of sucrose and 6 mg of glucose.
For full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Coated tablet.
Light yellow, shape like lenses, smooth glossy surface.
4
CLINICAL PARTICULARS
4.1 Therapeutic indications
A traditional herbal medicinal product used for the relief of symptoms of the menopause, including hot flushes, night sweats, slightly low mood and mild anxiety based on traditional use only.
4.2 Posology and method of administration
For oral use only.
For women experiencing menopausal symptoms, take 1 tablet daily. Tablets should be taken at the same time of day if possible (morning or evening) and swallowed whole with plenty of liquid. Do not chew the tablets.
If symptoms worsen or do not improve after 6 weeks a doctor or qualified healthcare practitioner should be consulted.
The use in children or adolescents under 18 years of age is not recommended (see Section 4.4 special warnings and precautions for use).
4.3 Contraindications
Hypersensitivity to the active ingredient(s) or any of the excipients.
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, 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 medicine.
Patients who have hepatic and/or renal impairment since the safety of Black cohosh extract has not been studied in patients with hepatic and/or renal impairment.
In patients who have active liver disease or a history of liver damage.
In patients currently receiving treatment for or has had a history of an oestrogen dependent tumour.
As there is evidence that Black cohosh may have hormone-like actions, it should only be used by women of childbearing potential if contraception is used.
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 a doctor or qualified healthcare practitioner should be consulted.
The use of this product in children and adolescents under 18 years of age is not recommended since there is no relevant use.
This product is intended for relief of menopausal symptoms including 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 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).
There have been rare cases of hepatic reactions associated with the use of Black Cohosh. Patients taking DiaFemin Tablets should be informed to immediately stop the use of the product and consult their doctor if they develop signs and symptoms suggestive of liver dysfunction. (Fatigue, anorexia, yellowing of the skin and eyes or severe upper stomach pain with nausea and vomiting or dark urine).
Advice should be sought from a doctor if the patient has a family history of an oestrogen dependent tumour.
Oestrogens may only be taken simultaneously with DiaFemin Tablets under supervision of a doctor, as their effect may be intensified by Black Cohosh.
If menstrual disorders occur or menstruation re-appears and if the symptoms are persistent, of unknown origin, or have recently occurred, a doctor should be consulted as this may indicate the presence of other conditions which need to be medically diagnosed.
Patients with rare hereditary problems of galactose intolerance and/or fructose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This product contains sucrose, lactose and glucose.
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 the 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 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 bloc |
ters | |
|
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 | ||
|
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 this product during pregnancy and lactation has not been established. Therefore it should be avoided during pregnancy or lactation.
Additionally because of the potential for Black cohosh to have hormone-like actions, the use by women who could become pregnant is not recommended unless contraception is used.
4.7 Effects on ability to drive and use machines
May impair the ability to drive and use machines. If affected, do not drive or operate machines.
4.8 Undesirable effects
Gastrointestinal disorder (e.g. dyspepsia, anorexia, nausea, diarrhoea, constipation); allergic skin reaction (e.g. rash, urticaria, pruritis); 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 ADRs reported in the literature with products containing Black cohosh include facial oedema, peripheral oedema and weight gain.
Other ADRs reported in the literature with products containing St. John’s wort include headaches, neuropathy, anxiety, dizziness and mania.
In rare cases, Black cohosh containing products may cause liver reactions (including hepatitis, jaundice and disturbances in liver function tests).
If other adverse reactions not mentioned above occur, a doctor or qualified healthcare practitioner should be consulted.
4.9 Overdose
There are no data on human overdose with St John’s Wort.
After intake of up to 4.5 g dry extract per day for 2 weeks and additionally 15 g dry extract just before hospitalization, 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 one to two 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.
Older herbal texts state that doses of over 5 g of unprocessed Black Cohosh daily may produce symptoms of nausea, vomiting, dizziness, visual and nervous disturbances, reduced pulse rate and increased perspiration.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended.
5.2 Pharmacokinetic properties
Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended.
5.3 Preclinical safety data
The preclinical toxicology data available are limited. Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Extract excipients:
Maltodextrin
Silica, colloidal anhydrous Cellulose, powdered Lactose monohydrate
Tablet core:
Silica, colloidal anhydrous Croscarmellose sodium Cellulose, microcrystalline Sodium starch glycollate (type A) Magnesium stearate
Excipients of the coating:
Hypromellose
Sucrose
Talcum
Calcium carbonate E 170
Tragacanth
Acacia
Liquid glucose (dry substance)
Titanium dioxide E 171
Iron oxide hydrate E 172
Vanillin
Beeswax, white
Carnauba wax
Shellac
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 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
Original packages contain 30, 60, 90 or 100 coated tablets
DiaFemin Tablets are packed in PVC/ PVDC- aluminium blisters and inserted into a carton.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
Diapharm GmbH & Co. KG Hafenweg 18-20 48155 Munster Germany
8 MARKETING AUTHORISATION NUMBER(S)
THR 42340/0015
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/04/2011
10 DATE OF REVISION OF THE TEXT
07/08/2013