SENNA 7.5 MG TABLETS 12 YEARS PLUS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Senna 7.5 mg Tablets 12 Years Plus

Numark Senna 7.5 mg Tablets 12 Years Plus

Careway Senna 7.5 mg Tablets 12 Years Plus

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains powdered Senna Pods (fruit) (Senna alexandrina Mill. (syn. Cassia acutifolia Delile and Cassia angustifolia Vahl)) equivalent to 7.5 mg of hydroxyanthracene glycosides, calculated as sennoside B

Excipient with known effect:

Each tablet contains 153 mg of lactose monohydrate / anhydrous (See section 4.4 Special Warnings and Precautions for Use)

For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablets

Round biconvex uncoated greenish-brown tablets with a diameter of approximately 9 mm

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the short-term relief of occasional constipation.

4.2 Posology and method of administration

Method of administration:

For oral administration only.

Posology:

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

Adults. the elderly and children over 12 years of age: Take one to two tablets at night when required. A higher dose may be prescribed under medical guidance. The maximum daily dose of hydroxyanthracene glycosides is 30mg.

Should not be used in children or adolescents under the age of 12 years (see section 4.3).

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 movement has occurred after 3 days a doctor or a qualified healthcare practitioner should be consulted.

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 a week.

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

If the symptoms persist or worsen during the use of a medicinal product, a doctor should be consulted.

See also section 4.4 Special warnings and precautions for use.

4.3 Contraindications

Hypersensitivity to the active ingredients or any of the excipients.

Not to be used at the same time as other laxative agents.

Children under 12 years of age.

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.

4.4 Special warnings and precautions for use

If there is no bowel movement after 3 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 problem should be investigated. Long term use of laxatives should be avoided, as use for more than a 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.

The product contains lactose monohydrate. Each tablet contains 153 mg of lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-glacatose malabsorption should not take this medicine.

Do not exceed the stated dose.

Patients taking cardiac glycosides, antiarrhythmic medicinal products, medicinal products inducing Q-T 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 gastrointestinal complaints e.g. abdominal pain, nausea and vomiting, unless advised by a doctor, because these symptoms can be signs of a potential or existing intestinal blockage (ileus).

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,

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. In patients suffering from fluid loss where dehydration may be harmful (e.g.

renal insufficiency, elderly patients) this product should be discontinued and only be restarted under medical supervision.

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

When administering this product 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. They do not reduce the absorption of calories or nutrients. They can cause watery stools (diarrhoea), abdominal cramps and dehydration. Dehydration can seem 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.

Patients taking cardiac glycosides, antiarrhythmic medicinal products, medicinal

products inducing QT-prolongation, diuretics, adrenocorticos­teroids or liquorice root, have to consult a doctor before taking senna leaf preparation concomitantly.

If the symptoms worsen during the use of the medicinal product, a doctor or a

pharmacist should be consulted.

Excipients

The product contains lactose monohydrate / anhydrous. Each tablet contains 153 mg of lactose monohydrate / anhydrous Patients with rare hereditary problems of galactose intolerance, the Lapp 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 concerning several anthranoids, eg. emodin and aloe-emodin, use is not recommended during pregnancy.

Lactation

Use during pregnancy 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 new born 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

No studies on the effect on the ability to drive and use machines have been performed.

4.8 Undesirable effects

Adverse events which have been associated with senna at OTC doses in short-term use are given below, tabulated by system Organ Class and frequency.

In the treatment of chronic condition, under long-term treatment additional adverse effects may occur.

Adverse Events Table

Description of selected adverse reactions

1. Prolonged use of laxatives resulting in diarrhoea and subsequently hypokalaemia.

2. In particular, in patients with irritable colon: symptoms may also occur generally as a consequence of individual overdosage. In such cases dose reduction is necessary.

3. Chronic use may cause pigmentation of the intestinal mucosa (pseudomelanosis coli) which usually recedes when the medication is discontinued.

4. Yellow or red-brown (pH dependent) discolouration of urine by metabolites, which is not clinically significant, may occur during treatment.

Chronic use may lead to disorders in water equilibrium and electrolyte metabolism and may result in albuminuria and haematuria. The frequency is not known (and cannot be estimated from the available data),

If other adverse effects, not mentioned above occur, a doctor or 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 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 fluids, 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: A 06AB

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

1,8– dihydroanthracone derivatives possess a laxative effect. The B-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 process by two concomitant mechanisms viz. inhibition of absorption of water and metabolites (Na+, CL-) into the colonic epithelial cells (anti-absorptive effect) and increase of the leakiness of the tight junctions and stimulation of secretion of the water and electroltyes 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 matabolisation into the active compound.

5.2 Pharmacokinetic properties

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

The B-O-linked glycosides (sennosides) are neither absorbed into 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 rheinanthrone administered directly into the caecum demonstrate 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 26% of unchanged sennosides, sennidins, rhein anthrone and rhein. In human pharmacokinetic studies with senna pods powder (20mg sennosides), administered orally for 7 days, a maximum concentration of 100ng 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 – 3.5% of anthranoids, corresponding to 0.9 –2.3% of potential rhein; 0.05 – 0.15% of potential aloe-emodin and 0.001 – 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 low doses from 100 mg/kg up to 1500 mg/kg. The test drug contained 1.83% sennosides A-D; 1.6% rhein; 0.11% 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/day without functional effect. These changes were also reversible. Storage of a brown tubular pigment led to a dark discoluration 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 of 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 exract 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 emgryolethal, 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 preparatons are not available.

An extract and aloe-emodin were mutagenic in invitro tests, sennosides 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 of 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 definitively.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate/ Lactose anhydrous

Sodium starch glycolate (Type A)

Talc

Colloidal anhydrous silica

Magnesium stearate

Bitter Fennel.

6.2 Incompati­bilities

Not known

6.3 Shelf life

24 months (2 years)

6.4 Special precautions for storage

Store below 25°C. Store in the original package

6.5 Nature and contents of container

White opaque PVC/aluminium blister pack.

Pack sizes: 24 or 60 tablets

Not all pack sizes may be marketed

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Aspar Pharmaceuticals Ltd

Albany House, Acrewood way,

St Albans, AL4 0JY,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 08977/0067