This information is intended for use by health professionals

1. Name of the medicinal product

Senokot 7.5 mg/5 ml Syrup.

2. Qualitative and quantitative composition

Each 5 ml of Senokot Syrup contains calcium sennosides equivalent to 7.5 mg per 5 ml total sennosides (calculated as sennoside B).

Also contains maltitol syrup (E965), methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) and ethanol.

For full list of excipients, see Section 6.1.

3. Pharmaceutical form

Syrup.

Amber, slightly viscous liquid.

4. Clinical particulars
4.1 Therapeutic indications

As a laxative for the relief of occasional or non-persistent constipation.

4.2 Posology and method of administration

Senokot 7.5 mg/5 ml Syrup is for oral administration.

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

Adults, including the elderly and children over 12: One to two 5 ml spoonfuls at night.

A higher dose may be prescribed under medical guidance. The maximum recommended daily dose of hydroxyanthracene glycosides is 30 mg (20ml).

Children over 6 years: One to two 5 ml spoonfuls at night, under the guidance of a medical professional.

Children aged 2 to 6 years: Half to one 5 ml spoonful at night under the guidance of a medical professional.

New users should start with the lowest dose and increase it, if necessary, by one half of the initial dose each day. Once regularity has been regained the dosage should be gradually reduced and stopped.

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

Duration of use

Normally 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 the medicinal product, a doctor or a pharmacist should be consulted.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

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

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

Children under 2 years of age.

4.4 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.

Contains maltitol liquid. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Each 5 ml of syrup can provide up to 3.2 kcal and this should be taken into account in patients with diabetes mellitus.

Methyl and propyl parahydroxybenzoate may cause allergic reactions (possibly delayed)

This medicinal product contains small amounts of ethanol (alcohol), less than 100mg per dose

Do not exceed the stated dose.

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 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.

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.

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 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 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.

However, as a consequence of experimental data concerning a genotoxic risk of several anthranoids, e.g emodin and aloe-emodin, use is not recommended in 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, such as rhein, are excreted in breast milk in small amounts. 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

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 sennosides 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

System Organ Class

Frequency

Adverse Events

Immune System Disorders

Not known

Hypersensitivity, urticaria, asthma, hypogammaglobulinaemia

Metabolism and Nutrition Disorders

Not known

Hypokalaemia1, cachexia

Gastrointestinal Disorders

Not known

Abdominal pain, abdominal spasm, diarrhoea2, gastrointestinal tract mucosal pigmentation3

Skin and Subcutaneous Tissue Disorders

Not known

Pruritus, local or generalised exanthema

Musculoskeletal and Connective Tissue Disorders

Not known

Finger clubbing, tetany and hypertrophic osteoarthropathy

Renal and Urinary Disorders

Not known

Chromaturia4

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 patient stops taking the preparation.

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

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: A 06 AB

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 β-Ο-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 metabolisation into the active compound.

5.2 Pharmacokinetic properties

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

The β-Ο-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

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.

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

Potassium sorbate E202

Methyl parahydroxybenzoate E218

Propyl parahydroxybenzoate E216

Maltitol liquid E965

Xanthan gum

Anti-foam (Medical C) emulsion

Prune flavour

Citric acid anhydrous

Purified water

6.2 Incompatibilities

None known.

6.3 Shelf life

13 months

6.4 Special precautions for storage

Do not store above 25°C. Do not freeze.

6.5 Nature and contents of container

Glass bottle with a polypropylene cap with a polyethylene tamper-evident band with an expanded polyethylene wad containing 100, 150 or 200 ml syrup.

6.6 Special precautions for disposal and other handling

No special instructions.

6.6. Special precaution for disposal

No special requirements.

7. Marketing authorisation holder

Reckitt Benckiser Healthcare (UK) Limited,

Dansom Lane,

Hull,

HU8 7DS.

United Kingdom

8. Marketing authorisation number(s)

PL 00063/0123.

9. Date of first authorisation/renewal of the authorisation

8th April 2005

10. Date of revision of the text

11/07/2018