SENEASE EIGHTEEN YEARS PLUS 7.5 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Senease Eighteen Years Plus 7.5mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each uncoated tablet contains sennosides (as calcium salts) equivalent to 7.5mg hydroxyanthracene glycosides, calculated as Sennoside B.

Each tablet also contains 16 mg lactose monohydrate

For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablets

Light green to brown colour, round convex shaped uncoated tablet approx. 8.00 mm, plain on both sides.

4.1 Therapeutic indications

For the short-term relief of occasional constipation.

4.2 Posology and method of administration

For oral administration.

Posology:

The correct individual dose is the smallest required to produce a comfortable soft-formed motion.

Should not be used in children or adolescents under the age of 18 years.

Adults and the elderly: Swallow one to two tablets at night.

The maximum daily dose must not exceed 15mg sennosides.

New users should start with the lowest dose and increase it to the maximum dose if necessary. Once regularity has been regained dosage should be reduced and can usually be stopped.

If no bowel action has occurred after three days of progressively increased dosage, a medical examination should be considered.

Duration of use

Not to be used for more than 1 week. Usually it is sufficient to take this medicinal product up to two to three times during that week.

Use for more than 1–2 weeks requires medical supervision.

If the symptoms persist or worsen 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

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Cases of intestinal obstructions and stenosis, atony, appendicitis, inflammatory bowel diseases (e.g Crohn’s disease, ulcerative colitis), abdominal pain of unknown origin, severe dehydration state with water and electrolyte depletion.

Not to be used at the same time as other laxative agen

5.1 Special warnings and precautions for use

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 laxatives are needed every day the cause of the constipation should be investigated. Long-term use of laxatives should be avoided.

Do not exceed the stated dose.

Should not be used in children or adolescents under the age of 18 years

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).

Long-term use of stimulant laxatives should be avoided, as use for more thana brief period of treatment may lead to impaired function of the intestine and dependence on laxatives. If laxatives are needed every day the cause of the constipation should be investigated. 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.

Patients taking cardiac glycosides, antiarrhythmic medicinal products, medicinal products inducing QT-prolongation, diuretics, adrenocorticos­teroids or liquorice root, have to consult a doctor before takingthis product concomitantly.

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. Patients with kidney disorders should be aware of possible electrolyte imbalance.

Intestinal loss of fluids may promote dehydration. Symptoms may include thirst and oliguria. In patients suffering from fluid loss where dehydration may be harmful (e.g. renal insufficiency, elderly patients) this product shouldbe discontinued and only be restarted under medical supervision.

When products containing senna/sennoside preparations are administered to incontinent adults, pads should be changed more frequently to prevent extended skin contact with faeces.

Stimulant laxatives (including this product) do not help with weight loss.

If the symptoms worsen during the use of the medicinal product, or there isno bowel movement after three days, a doctor or pharmacist should be consulted.

The leaflet will state:

“Before you take this medicine” section

Does this help with weight loss?

Stimulant laxatives (including Senease Eighteen Years Plus 7.5mg Tablets) do not help with weight loss. They do not reduce the absorption of calories or nutrients. They cancause watery stools (diarrhoea), abdominal cramps and dehydration. Dehydration canseem like weight loss.

Overuse of laxatives may damage your health by:

Causing disturbances of electrolyte and mineral balances. Sodium, potassium, magnesium, and phosphorus are electrolytes and minerals that are present in very specific amounts necessary for proper functioning of the nerves and muscles, including those of the colon and heart. Upsetting this delicate balance can cause incorrect functioning of these vital organs.

Severe dehydration may cause tremors, weakness, blurry vision, fainting, kidney damage, and, in extreme cases, death. Dehydration often requires medical treatment.

Overuse of laxatives can cause the colon to stop reacting to usual doses of laxatives so that larger and larger amounts of laxatives may be needed to produce bowel movements.

Laxative dependency occurs from overuse.

The label will state:

Front of pack:

Does not help with weight loss.

Overuse can be harmful.

Excipient Warning:

This product contains lactose monohydrate. One tablet contains 16 mg lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, theLapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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 antiarrhythmic medicinal products, with 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 schedule.

However, as a consequence of experimental data concerning a genotoxic risk of several anthranoids, e.g emodin and aloe-emodin, use is not recommended during pregnancy.

Lactation

Use during breastfeeding is not recommended as there are insufficient data on the excretion of metabolites in breast milk.

Small amounts of active metabolites (rhein) are excreted in breast milk. A laxative effect in breast fed babies has not been reported.

Fertility

There are no data on the effects of the product on fertility.

4.7 Effects on ability to drive and use machines

None known

4.8 Undesirable effects

Hypersensitivity reactions (pruritus, urticaria, local or generalized exanthema) may occur.

Abdominal pain and spasm and passage of liquid stools have been reported, 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.

The frequency is not known (cannot be estimated from the available data).

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 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 or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9 Overdose

Symptoms

Where diarrhoea is severe, conservative measures are usually sufficient; generous amounts of fluid, especially fruit drinks, should be given.

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

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

Pharmaco-therapeutic group: contact laxatives

ATC-code: A06 AB06

The sugar moiety of the sennosides is removed by bacteria in the large intestine releasing the active anthrone fraction. This stimulates peristalsis via the submucosal and myenteric nerve plexuses.

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 intestine into 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.

Defaecation takes place after a delay of 8 – 12 hours due to the time taken for transport to the colon and metabolism into the active compound.

5.2 Pharmacokinetic properties

The action of the sennosides is colon specific and does not depend upon systemic absorption.

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. 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. Active metabolites, e.g. rhein, pass in small amounts into breast milk. Animal experiments demonstrated that placental passage of rhein is low.

5.3 Preclinical safety data

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. Dosedependent 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.

Chronic 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

Lactose monohydrate

Maize starch

Calcium hydrogen phosphate

Magnesium stearate

6.2 Incompatibilities

None known

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

Store in the original container.

6.5 Nature and contents of container

6.6    Special precautions for disposal

7 MARKETING AUTHORISATION HOLDER

Special Concept Development (UK) Limited T/A RxFarma,

Colonial Way,

Watford, Hertfordshire,

WD24 4YR, United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 36722/0124