BOLDOFLORINE Herbal tea blend in sachet-dose 48 Sachets

Senna (Cassia senna L. (C. acutifolia Delile) and/or Cassia angustifolia Vahl) (leaf) …0,400 g to 0,551g

Quantity corresponding to 12,5 mg of hydroxyanthracene glycosides, expressed as sennoside B.

For 1 sachet-dose.

BOLDOFLORINE, herbal mixture for infusion in sachet-dose is a herbal medicine used for the short-term treatment of occasional constipation.

This medicine is indicated in adults and adolescents aged 12 years and older.

Dosage

Adults and adolescents aged 12 years and older.

1 to 2 sachets per day, to be taken in a single evening dose as an infusion.

The recommended dosage is the lowest dose allowing a satisfactory transit and soft stools.

Usually the bowel movement occurs within 8 to 12 hours.

Taking this medicine up to two to three times during the treatment week is generally sufficient.

Paediatric population

BOLDOFLORINE, herbal mixture for infusion in sachet-dose is contraindicated in children aged under 12 years (see section Contraindications).

Method of administration

Oral use.

Bring water to the boil and pour it over the sachet, cover and leave to infuse for 5 minutes, then remove the sachet.

The infusion must be prepared at the time of use.

Duration of treatment

The duration of treatment must not exceed 1 week.

If symptoms persist beyond one week of use of this medicine, a doctor or pharmacist must be consulted.

This medicine is contraindicated in the following situations:

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

• Inflammatory bowel diseases (hemorrhagic rectocolitis, Crohn's disease…).

• Intestinal obstructions and strictures, atony, appendicitis.

• Abdominal pain syndromes of undetermined cause.

• States of severe dehydration with electrolyte depletion.

• Pregnant and breast-feeding women (see sections Fertility, pregnancy and breastfeeding and Preclinical safety).

• Children under 12 years.

Drug treatment of constipation is only an adjunct to dietary and lifestyle measures:

• enrichment of the diet with vegetable fibres and water,

• advice on physical activity and re-education of defecation.

Prolonged use of stimulant laxatives should be avoided, as use for more than a brief treatment period may lead to impaired bowel function and laxative dependence. If daily laxative intake is necessary, the cause of constipation should be investigated. Senna leaf preparations should only be used if a therapeutic effect could not be obtained after a change in diet or administration of a bulk-forming laxative.

Patients taking cardiac glycosides, anti-arrhythmic medicinal products, medicinal products inducing QT interval prolongation, diuretics, adrenocorticoids or liquorice root, should consult a doctor before taking senna leaf preparations concomitantly.

Like all laxatives, senna leaf preparations should not be taken by patients suffering from faecal impaction and undiagnosed acute or persistent gastrointestinal disorders, e.g. abdominal pain, nausea and vomiting, unless advised otherwise by a doctor, as these symptoms may be a sign of a latent or established intestinal obstruction (ileus).

When preparations containing senna leaves are administered to incontinent adults, pads should be changed more frequently to avoid prolonged skin contact with stools.

Patients suffering from renal pathologies must be warned of a risk of electrolyte imbalance.

If symptoms worsen during use of the medicine, a doctor or pharmacist must be consulted.

Paediatric population

This medicinal product is contraindicated in children under 12 years of age.

In adolescents aged 12 years and over, the prescription of stimulant laxatives should be exceptional; the risk of interfering with the normal functioning of the defecation reflex must be taken into account.

• Cardiac glycosides : hypokalaemia (resulting from long-term laxative abuse) promotes the toxic effects of cardiac glycosides and interacts with anti-arrhythmic medicinal products.

• Monitoring of kalaemia and, if necessary, ECG. Use a non-stimulant laxative.

• Other potassium-lowering agents : potassium-depleting diuretics (alone or in combination), amphotericin B (IV route), glucocorticoids and mineralocorticoids (systemic route), tetracosactide, liquorice root. Increased risk of hypokalaemia (additive effect).

• Monitor serum potassium and correct if necessary. Use a non-stimulant laxative.

Pregnancy

The use of BOLDOFORINE, a herbal tea mixture in sachet-dose, is contraindicated during pregnancy because experimental data exist concerning a genotoxic risk of several anthracene derivatives, including emodin and aloe-emodin.

Breast-feeding

Use during breast-feeding is contraindicated because after administration of anthracene derivatives, active metabolites such as rhein have been excreted into breast milk in small quantities.

Fertility

No data on fertility is available (see section Preclinical safety).

The effects on the ability to drive vehicles and use machines have not been studied.

Hypersensitivity:

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

Gastrointestinal disorders:

• Preparations of senna leaves may cause pain, abdominal spasms and the passage of liquid stools, particularly in patients suffering from irritable colon. However, these symptoms may also generally occur following individual overdose. In this case, the dosage should be reduced.

• In addition, chronic use may cause pigmentation of the intestinal mucosa (colonic pseudomelanosis), which usually resolves upon discontinuation of treatment.

Renal and urinary tract symptoms:

• Long-term use may lead to fluid and electrolyte imbalance and may lead to albuminuria and haematuria.

• A yellow or red-brown (pH-dependent) discolouration of the urine due to metabolites, without clinical significance, may occur during treatment.

The frequency of this type of reaction is not known.

Should other undesirable effects not mentioned above occur, a doctor or pharmacist 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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.

The main symptoms in case of overdose or abuse are abdominal pain and severe diarrhoea with possible loss of fluids and electrolytes.

Treatment will include rehydration; electrolytes and particularly serum potassium will be monitored. This is particularly important in elderly people.

Chronic overdose with medicines containing anthracene derivatives may lead to toxic hepatitis.

Pharmacotherapeutic class: stimulant laxatives, ATC code: A06AB06

Derivatives of 1,8-dihydroxyanthracene have a laxative effect. The β-O-glycosides (sennosides) are not absorbed in the upper part of the intestine. They are transformed by colonic bacteria into the active metabolite (rhein anthrone).

There are two different mechanisms of action:

1) Stimulation of colonic motility leading to acceleration of colonic transit.

2) Influence on secretory processes through two concomitant mechanisms, namely:

- inhibition of water and electrolyte (Na+, Cl-) absorption in the colonic epithelial cells (anti-absorptive effect),

- increased leakage through tight junctions and stimulation of water and electrolyte secretion into the colonic lumen (secretagogue effect), resulting in increased concentrations of fluid and electrolytes in the colonic lumen.

Defecation occurs after a delay of 8 to 12 hours due to the time required for transport to the colon and metabolism into the active compound.

The β-O-glycosides (sennosides) are neither absorbed in the upper part of the intestine nor cleaved by human digestive enzymes. They are transformed by colonic bacteria into the active metabolite (rhein anthrone). The aglycones are absorbed in the upper part of the intestine. Animal studies with administration of radiolabelled rhein anthrone directly into the caecum demonstrated absorption of less than 10%.

On contact with oxygen, rhein anthrone is oxidised into rhein and sennidins, which are found in the blood mainly in the form of glucuronides and sulphates. After oral administration of sennosides, 3 to 6% of the metabolites are excreted in the urine; some of them are excreted in the bile.

Most of the sennosides (approximately 90%) are excreted in the faeces in the form of polymers (polyquinones), as well as 2 to 6% of unchanged sennosides, sennidins, rhein anthrone and rhein.

In human pharmacokinetic studies, carried out with powdered senna pods (containing 20 mg of sennosides) administered orally for 7 days, a maximum concentration of 100 ng of rhein/mL was found in the blood. No accumulation of rhein was observed.

The active metabolites, for example rhein, pass into breast milk in small quantities. Animal studies have demonstrated that placental transfer of rhein is low.

No preclinical data are available for senna leaves or their preparations. It may be assumed that the data obtained with senna pods can be transferred to preparations of senna leaves.

In a 90-day study in rats, senna pods were administered at doses ranging from 100 mg/kg to 1500 mg/kg (equivalent human dose of 16 to 242 mg/kg). Minor hyperplasia of the epithelial cells of the large intestine was observed in all groups and was reversible during the 8-week recovery period. The hyperplastic lesions of the pre-stomach epithelium were also reversible. Tubular and epithelial hypertrophy in the kidney was observed from 300 mg/kg, without functional impairment. These effects were also reversible. Storage of a brown tubular pigment caused a dark discolouration of the renal surface, which persisted to a lesser degree after the recovery period. No alterations were observed in the colonic nerve plexus. The no-effect level (NOEL) could not be established in this study.

Senna pods, their extracts and several hydroxylated anthracene derivatives (with the exception of sennosides, rhein and sennidins) were shown to be mutagenic and genotoxic in several tests in vitro. However, for senna and aloe-emodin, genotoxicity has not been proven in studies in vivo.

In long-term carcinogenicity studies with senna pods, effects on the kidneys and colon / caecum have been reported.

3 years.

Store protected from moisture and at a temperature below 25°C.

No special requirements for disposal.