Potters Cleansing Herb Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Potter’s Cleansing Herb Tablets Senokot Dual Relief Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains: -
100 mg Senna Leaf Tinnevelly (Cassia angustifolia Vahl)
45 mg Cape Aloes (Aloe ferox Mill)
30 mg Cascara Bark (Rhamnus purshianus D.C.)
30 mg Dandelion Root (Taraxacum officinale F.H. Wigg)
15 mg Fennel Fruit (Foeniculum vulgare var. dulce Miller)
Excipient(s):
Each tablet contains 100 mg of sucrose.(See section 4.4 Special warnings and precautions for use.)
For full list of excipients see Section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
A brownish olive-green round biconvex tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
A traditional herbal medicinal product used for the short-term relief of occasional constipation and bloating, based on traditional use only.
4.2 Posology and method of administration
For oral use.
Adults, the elderly: Take one or two tablets at bedtime when necessary.
Normally it is sufficient to take this medicinal product up to 2 to 3 times per week.
Not recommended for use in children and adolescents underr 18 years of age (see section 4.3 Contraindications).
Duration of use:
Use for more than 1 - 2 weeks requires medical supervision.
If there is no bowel movement after three days a doctor should be consulted.
If laxatives are needed every day, or abdominal pain persists a doctor should be consulted.
If the symptoms persist during the use of the medicinal product, a doctor or a pharmacist should be consulted.
See also section 4.4 Special warnings and precautions for use.
4.3 Contraindications
Known hypersensitivity to any of the active substances or to Apiaceae (Umbelliferae) (aniseed, caraway, celery, coriander and dill), anethole or to plants of the Asteraceae (Compositae) family.
Cases of intestinal obstructions and stenosis, atony, appendicitis, inflammatory colon diseases (e.g. Crohn’s disease, ulcerative colitis), abdominal pain of unknown origin, severe dehydration state with water and electrolyte depletion.
Obstructions of bile ducts, cholangitis, liver diseases, gallstones, active peptic ulcer and any other biliary diseases.
Children and adolescents under 18 years.
4.4 Special warnings and precautions for use
Do not exceed the stated dose.
This product contains sucrose. One tablet contains 100 mg of sucrose.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
Patients taking cardiac glycosides, antiarrhythmic medicinal products, medicinal products inducing QT-prolongation, diuretics, adrenocorticosteroids or liquorice root, have to consult a doctor before taking this product concomitantly.
Like all laxatives, this product should not be taken by patients suffering from faecal impaction and undiagnosed, acute or persistent gastro-intestinal complaints, e.g.
abdominal pain, nausea and vomiting, unless advised by a doctor, because these symptoms can be signs of potential or existing intestinal blockage (ileus).
If laxatives are needed every day the cause of the constipation should be investigated Long-term use of laxatives should be avoided.
If stimulant laxatives are taken for longer than a brief period of treatment, this may lead to impaired function of the intestine and dependence on laxatives.
This product should only be used if a therapeutic effect cannot be achieved by a change of diet or the administration of bulk forming agents.
When administering this product to incontinent adults, pads should be changed more frequently to prevent extended skin contact with faeces.
Patients with kidney disorders should be aware of possible electrolyte imbalance.
The use in patients with renal failure and/or diabetes, and/or heart failure should be avoided because of possible risks due to hyperkalaemia.
The use in children and adolescents under 18 years of age is not recommended due to lack of adequate data.
Prolonged use may precipitate the onset of an atonic, non-functioning colon. Prolonged and excessive use may lead to fluid and electrolyte imbalance and hypokalaemia.
Intestinal loss of fluids may promote dehydration. Symptoms may include thirst and oliguria.
Laxatives do not help in long-term weight loss.
4.5 Interaction with other medicinal products and other forms of interaction
Hypokalaemia (resulting from long-term laxative abuse) potentiates the action of cardiac glycosides and interacts with anti arrhythmic medicinal products which induce reversion to sinus rhythm (e.g. quinidine) and with medicinal products inducing QT-prolongation. Concomitant use with other medicinal products inducing hypokalaemia (e.g. diuretics, adrenocorticosteroids and liquorice root) may enhance electrolyte imbalance.
4.6 Fertility, Pregnancy and lactation
Pregnancy
There are no reports of undesirable or damaging effects during pregnancy and on the foetus when used at the recommended dosage.
Experimental data show a genotoxic risk of several anthranoids, e.g. aloe-emodin, emodin, frangulin, chrysophanol and physcion, use is not recommended during pregnancy.
Lactation
There are no data on the use of the product during lactation.
Use during breastfeeding is not recommended as there are insufficient data on the excretion of metabolites in breast milk.
After administration of other anthranoids, active metabolites, such as rhein, are excreted in breast milk in small amounts. A laxative effect in breast fed babies has not been reported.
There are no data on the effects of the product on fertility.
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
Hypersensitivity reactions (pruritis, urticaria, local or generalized exanthema) may occur. Allergic reactions to fennel, affecting the skin or the respiratory system, may occur.
This product may produce abdominal pain and spasm and passage of liquid stools, in particular in patients with irritable colon. However, these symptoms may also occur generally as a consequence of individual overdose. In such cases dose reduction is necessary.
Chronic use may lead to disorders in water equilibrium and electrolyte metabolism and may result in albuminuria and haematuria.
Furthermore, chronic use may cause pigmentation of the intestinal mucosa (pseudomelanosis coli) which usually recedes when the patient stops taking the preparation.
Yellow or red-brown (pH dependent) discolouration of urine by metabolites, which is not clinically significant, may occur during the treatment.
Epigastric pain and hyperacidity may occur.
The frequency of the undesirable effects is not known.
If other adverse reactions not mentioned above occur, a doctor 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 continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
The major symptoms of overdose/abuse are griping pain and severe diarrhoea with consequent losses of fluid and electrolytes, which should be replaced. Diarrhoea may especially cause potassium depletion, which may lead to cardiac disorders and muscular asthenia, particularly where cardiac glycosides, diuretics, adrenocorticosteroids or liquorice root are being taken at the same time.
Treatment should be supportive with generous amounts of fluid. Electrolytes, especially potassium, should be monitored. This is especially important in the elderly. Chronic ingested overdoses of anthranoid containing medicinal products may lead to toxic hepatitis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.
Pharmaco-therapeutic group: contact laxatives ATC-code: A 06 AB
1,8-dihydroxyanthracene derivatives possess a laxative effect.
Cascara
Cascarosides A and B are mixed anthrone-C- and O-glycosides, Cascarosides C, D, E and F are 8-O-P-D-glucosides, which are largely not split by human digestive enzymes in the upper gut and therefore not absorbed to a large extent. They are converted by the bacteria of the large intestine into the active metabolite (mainly -emodin-9-anthrone
Aloes
Aloinosides and aloins are respectively C,0-diglycosides and C-glycosides, which are not absorbed in the upper gut, but are converted by bacteria of the large intestine into the active metabolite (aloe-emodin-9-anthrone).
Systemic metabolism of free anthranoids depends on their ring constituents. In the case of aloe-emodin, it has been shown in animal experiments that at least 20-25% of an oral dose is absorbed. The bioavailability of aloe-emodin is much lower than the absorption, because it is quickly oxidised to rhein and unknown metabolite, or conjugated
Senna Leaf
1,8-dihydroxyanthracene derivatives possess a laxative effect. The p-O-linked glycosides (sennosides) are not absorbed in the upper gut; they are converted by bacteria of the large intestineinto the active metabolite (rhein anthrone).
There are two different mechanisms of action:
1. stimulation of the motility of the large intestine resulting in accelerated colonic transit
2. influence on secretion processes by two concomitant mechanisms viz. inhibition of
+ -
absorption of water and electrolytes (Na , Cl) into the colonic epithelial cells (antiabsorptive effect) and increase of the leakiness of the tight junctions and stimulation of secretion of water and electrolytes into the lumen of the colon (secretagogue effect) resulting in enhanced concentrations of fluid and electrolytes in the lumen of the colon. The motility effects are mediated by direct stimulation of colonic neurons and possibly by prostaglandins.
Defaecation takes place after a delay of 8 - 12 hours (6 - 12 hours for Aloes and Cascara) due to the time taken for transport to the colon and metabolisation into the active compound
5.2 Pharmacokinetic properties
Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.
Aloes
Aloinosides, aloins and hydroxyaloins pass directly into the large intestine where they are metabolised by bacterial enzymes (viz. Eubacterium sp. strain BAR) into the active anthrone compounds mainly aloe-emodin-9-anthrone.
It is not known to what extent aloe-emodin-9-anthrone is absorbed. However, in the case of senna, animal experiments with radio-labeled rhein-anthrone administered directly into the caecum show that only a very small proportion (less than 10%) of rhein-anthrone is absorbed.
Systemic metabolism of free anthranoids depends on their ring constituents. In the case of aloe-emodin, it has been shown in animal experiments that at least 20-25% of an oral dose is absorbed. The bioavailability of aloe-emodin is much lower than the absorption, because it is quickly oxidised to rhein and unknown metabolite, or conjugated.
Cascara
The P-0-linked glycosides are not split by human digestive enzymes and therefore not absorbed in the upper gut to a large extent. They are converted by the bacteria of the large intestine into the active metabolite (emodin-9-anthrone). Mainly anthraquinone aglycones are absorbed and transformed into their corresponding glucuronides and sulphate derivatives.
It is not known to what extent aloe-emodin-9-anthrone is absorbed. However, in the case of senna, animal experiments with radio-labeled rhein-anthrone administered directly into the caecum show that only a very small proportion (less than 10%) of rhein-anthrone is absorbed.
Senna Leaf
The P-O-linked glycosides (sennosides) are neither absorbed in the upper gut nor split by human digestive enzymes. They are converted by the bacteria of the large intestine into the active metabolite (rhein anthrone). Aglyca are absorbed in the upper gut.
It is not known to what extent aloe-emodin-9-anthrone is absorbed.
Animal experiments with radio-labeled rhein anthrone administered directly into the caecum demonstrated absorption < 10%. In contact with oxygen, rhein anthrone is oxidised into rhein and sennidins, which can be found in the blood, mainly in the form of glucuronides and sulphates. After oral administration of sennosides, 3 - 6% of the metabolites are excreted in urine; some are excreted in bile.
Most of the sennosides (ca. 90%) are excreted in faeces as polymers (polyquinones) together with 2 - 6% of unchanged sennosides, sennidins, rhein anthrone and rhein. In human pharmacokinetic studies with senna pods powder (20 mg sennosides), administered orally for 7 days, a maximum concentration of 100 ng rhein/ml was found in the blood.. An accumulation of rhein was not observed.
After administration of anthranoids, active metabolites, such as rhein, pass in small amounts into breast milk. Animal experiments demonstrated that placental-passage of rhein is low.
5.3 Preclinical safety data
Tests on reproductive toxicity, genotoxicity and on carcinogenicity have not been performed.
Senna Leaf
There are no new, systematic preclinical tests for senna leaves or preparations thereof. Data derive from investigations with senna pods. Since the spectrum of constituents of senna leaf and fruit is comparable these data can be transferred to senna leaves. Most data refer to extracts of senna pods containing 1.4 to 3.5% of anthranoids, corresponding to 0.9 to 2.3% of potential rhein, 0.05 to 0.15% of potential aloe-emodin and 0.001 to 0.006% of potential emodin or isolated active constituents, e.g. rhein or sennosides A and B. The acute toxicity of senna pods, specified extracts thereof, as well as of sennosides in rats and mice was low after oral treatment.
As a result of investigations with parenteral application in mice, extracts are supposed to possess a higher toxicity than purified glycosides, possibly due to the content of aglyca.
In a 90-day rat study, senna pods were administered at dose levels from 100 mg/kg up to 1,500 mg/kg. The tested drug contained 1.83 % sennosides A-D, 1.6 % potential rhein, 0.11 % potential aloe-emodin and 0.014 % potential emodin. In all groups epithelial hyperplasia of the large intestine of minor degree was found and was reversible within the 8-week recovery period. The hyperplastic lesions of the forestomach epithelium were reversible as well. Dose-dependent tubular basophilia and epithelial hypertrophy of the kidneys were seen at a dose of, or greater than 300 mg/kg per day without functional affection. These changes were also reversible. Storage of a brown tubular pigment led to a dark discoloration of the renal surface and still remained to a lesser degree after the recovery period. No alterations were seen in the colonic nervous plexus. A no-observable-effect-level (NOEL) could not be obtained in this study.
A 104 week study on rats of both genders did not reveal any carcinogenic effects with the same senna pods preparation at oral dosages of up to 300 mg/kg.
In addition a specified senna extract given orally for 2 years was not carcinogenic in male or female rats. The extract investigated contained approximately 40.8% of anthranoids from which 35% were sennosides, corresponding to about 25.2% of potential rhein, 2.3% of potential aloe-emodin and 0.007% of potential emodin and 142 ppm free aloe-emodin and 9 ppm free emodin.
Further 2-year studies on male and female rats and mice with emodin gave no evidence of carcinogenic activity for male rats and female mice, and equivocal evidence for female rats and male mice.
Sennosides displayed no specific toxicity when tested at doses up to 500 mg/kg in dogs for 4 weeks and up to 100 mg/kg in rats for 6 months.
There was no evidence of any embryolethal, teratogenic or foetotoxic actions in rats or rabbits after oral treatment with sennosides. Furthermore, there was no effect on the postnatal development of young rats, on rearing behaviour of dams or on male and female fertility in rats. Data for herbal preparations are not available.
An extract and aloe-emodin were mutagenic in in vitro tests, sennoside A, B and rhein gave negative results. Comprehensive in vivo examinations of a defined extract of senna pods were negative
Aloes
There are no new, systematic preclinical tests for aloes or preparations thereof.
No teratogenic or foetotoxic effects were seen in rats after oral treatment with aloes extract (up to 1,000 mg/kg) or aloin A (up to 200 mg/kg).
Some in vitro assays show genotoxicity of aloe-emodin. Positive results were obtained in the Ames test with Salmonella typhimurium strains TA1537, TA1538, TA98 and TA1978. In the HPRT test, no reproducible induction of mutations was obtained, while unscheduled DNA synthesis (UDS) and cell transformation was induced.
In in vivo studies (micronucleus assay in bone marrow cells of NMRI mice; chromosome aberration assay in bone marrow cells of Wistar rats; mouse spot test [DBA/2J x NMRI]) no indication of a mutagenic activity of aloe-emodin was found. No specific toxicity was observed in mice when aloes extract was orally administered up to 50 mg/kg daily for 12 weeks and aloin was orally administered up to 60 mg/kg daily for 20 weeks.
Further 2-year studies on male and female rats and mice with emodin gave no evidence of carcinogenic activity for male rats and female mice, and equivocal evidence for female rats and male mice.
Cascara
There are no recent studies on single dose toxicity, on repeated dose toxicity, or on reproductive toxicity.
Experimental data, mainly in vitro tests showed a genotoxic risk of several anthranoids in the Salmonella/ microsome assay, aloe-emodin, emodin, chrysophanol and physcion were weakly mutagenic. No mutagenic effects were observed in the V79-HGPRT mutation assay and in the unscheduled DNA synthesis (UDS) assay for chrysophanol and physcion. Emodin was highly mutagenic in the V79-HGPRT mutation assay. In the UDS assay emodin was a string inducer of UDS in primary hepatocytes. Aloe-emodin showed a significant increase in net grains/nucleus. Emodin was also tested with respect to its transforming activity in C3H/M2 mouse fibroblasts in vitro. In the in vitro Salmonella /microsome mutagen test and the deoxyribonucleic acid (DNA) repair test of primary rat hepatocytes emodin and frangulin showed a dose-dependent increase in the mutation rate or the induction of DNA repair.
However, in vivo studies of other anthranoid-containing herbal substance (senna) in rat hepatocytes (chromosome aberration test, mouse spot test, in vivo/in vitro UDS (unscheduled DNA synthesis) showed no evidence of any genetic effects.
In in vivo studies (micronucleus assay in bone marrow cells of NMRI mice; chromosome aberration assay in bone marrow cells of Wistar rats; mouse spot test [DBA/2J x NMRI]) no indication of a mutagenic activity of aloe emodin was found. Further 2-year studies on male and female rats and mice with emodin gave no evidence of carcinogenic activity for male rats and female mice, and equivocal evidence for female rats and male mice.
Dietary exposure of rats to high doses of the anthraquinone glycosides of cascara for 56 successive days did not cause appearance of aberrant crypti foci (ACF) or increase of incidence of ACF induced by 1,2-dimethyl-hydrazine (DMH). However, in rats treated with both DMH and the highest dose of glycosides, the average number of aberrant crypts per focus, considered a consistent predictor of tumour outcome, was higher than in rats given DMH alone.
Rats were treated with azoyxmethane (AOM) and 140 and 420 mg/kg cascara (alone or in combination) for 13 weeks. Cascara did not induce the development of colonic aberrant crypti foci (ACF) and tumours and did not modify the number of AOM-induced ACF and tumours in both doses.
Fennel
A fennel aqueous extract was tested in an Ames test on Salmonella typhimurium strains TA98,
TA100 and turned out as negative. Results from studies carried out in laboratory animals showed
a weak mutagenic activity of anethole. The genotoxic risk4 related to estragole is not considered to be relevant in the specified conditions of use due to the small amount present in herbal infusions prepared from fennel.
Laxative use as a risk factor in colorectal cancer (CRC) was investigated in some clinical trials. Some studies revealed a risk for CRC associated with the use of anthraquinone-containing laxatives, some studies did not. However, a risk was also revealed for constipation itself and underlying dietary habits. Further investigations are needed to assess the carcinogenic risk definitely.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Calcium Hydrogen Phosphate
Sucrose
Talc
Magnesium Stearate Sodium Starch Glycolate type A
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Three years.
6.4 Special precautions for storage
Do not store above 25°C. Keep in the original container.
6.5 Nature and contents of container
Tamper evident polyethylene/polyproylene pot packed in to a cardboard box: 24, 50 and 60 tablets.
Blister packs of PVC/PVDC and aluminium foil packed into a cardboard box: 20, 24, 30, 40 and 60 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Soho Flordis UK Limited 1 Botanic Court,
Martland Park,
Wigan,
WN5 0JZ,
UK.
Trading as: Potters, Wigan WN5 0JZ
8 MARKETING AUTHORISATION NUMBER(S)
THR 44893/ 0001
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17/05/2012
10
DATE OF REVISION OF THE TEXT
28/10/2015