Well-established use

Traditional use

With regard to the marketing authorisation application of Article 10(a) of Directive 2001/83/EC, as amended

Active ingredients

Senna leaf in the crude or processed state in appropriate dosage units

Definition

Senna leaf consists of the dried leaflets of Cassia senna L. (Cassia acutifolia DELILE), known as Alexandrian or Khartoum senna, or Cassia angustifolia VAHL, known as Tinnevelly senna, or a mixture of the two species. It contains not less than 2.5 per cent of hydroxyanthracene glycosides, calculated as sennosides B (Mr 863) with reference to the dried herbal substance.¹

Constituents

The constituents of known therapeutic activity are sennosides A and B which are rhein-dianthrone diglycosides. There are also small quantities of other dianthrone diglycosides, monoanthraquinone glycosides and aglyca.

3. PHARMACEUTICAL FORM

With regard to the registration application of Article 16d(1) of Directive 2001/83/EC, as amended

Well-established use

Standardised crude or processed herbal substance for oral preparation in solid or liquid dosage forms (to be specified for the individual finished product). The pharmaceutical form should be described according to the standard terms by the European Pharmacopoeia.

Traditional use

Well-established use

Traditional use

For short term use in cases of occasional

None

constipation.

Well-established use

Traditional use

Dosage

The maximum daily dose of hydroxyanthracene glycosides is 30 mg. This is equivalent to ....(dose of the preparation).

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

Adolescents over 12 years of age, adults, elderly Herbal substance / preparation equivalent to 15 -30 mg hydroxyanthracene derivatives, calculated as sennoside B, to be taken at night. The dosage refers to one administration.

Not recommended for use in children under 12 years of age.

The pharmaceutical form must allow lower dosages.

Method of administration

For oral administration

Well-established use

Traditional use

Patients with known hypersensitivity to senna should not use senna preparations.

Not to be used in 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 states with water and electrolyte depletion.

Not recommended for use in children under 12 years of age.

Well-established use

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 leaves concomitantly.

Like all laxatives, senna leaves 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 laxatives are needed every day the cause of the constipation should be investigated. Long-term use of laxatives should be avoided.

Use for more than 1 - 2 weeks requires medical supervision. If stimulating laxatives are taken for longer than a brief period of treatment, this may lead to dependence requiring increasing quantities of the medicinal product, an atonic colon with impaired function and aggravation of the constipation. Senna leaf preparations should only be used if a therapeutic effect cannot be achieved by a change of diet or the administration of bulk forming agents.

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

Traditional use

Well-established use

The absorption of orally administered medicinal products may be reduced.

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.

Traditional use

Well-established use Pregnancy

Wording for extracts specified as those investigated (see preclinical safety data):

There are no reports of undesirable or damaging effects during pregnancy and on the foetus when used at the recommended dosage.

As a consequence of experimental data concerning a genotoxic risk of several anthranoids, e.g. emodin and aloe-emodin, the use is to be avoided during the first trimester. Senna leaves should only be used intermittently and if other actions like behavioural modification, dietary changes and use of bulk forming agents fail.

Wording for all other preparations:

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 during pregnancy.

Lactation

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.

4.7. Effects on ability to drive and use machines

Traditional use

Well-established use Not known.

4.8. Undesirable effects

Traditional use

Well-established use

Hypersensitive reactions (pruritus, urticaria, local or generalised exanthema) may occur very rarely.

Very rarely senna leaves 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 overdosage. In such cases dose reduction is necessary.

Traditional use

2. an influence on secretion processes (stimulation of mucus and active chloride secretion) resulting in enhanced fluid secretion.

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

Well-established use

Traditional use

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 (rheinanthrone). Aglyca are absorbed in the upper gut. Animal experiments with radiolabeled rheinanthrone administered directly into the caecum demonstrated absorption < 10%. In contact with oxygen, rheinanthrone 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, rheinanthrone and rhein. In human pharmacokinetic studies with senna pods powder (20 mg sennosides), administered orally for 7 days, a max. 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 small.

5.3. Preclinical safety data

Not applicable as per Article 16 c(1)(a)(iii) of Directive 2001/83/EC as amended

Well-established use

Traditional use

There are no new, systematic preclinical tests for senna leaves or preparations thereof. 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,

Not applicable as per Article 16 c(1)(a)(iii) of Directive 2001/83/EC as amended