Pharmacological activity

Anti-inflammatory Activity

Glucocorticoids (GCs) inhibit pro-inflammatory signalling pathways in the endothelium and reduce the loss of adhesion molecule that maintain the endothelial function.1

Anti-inflammatory mechanism of action of aescin is correlated with the glucocorticoid receptor pathways.2

Glucocorticoid receptor pathway
Adapted from Zielińska KA, et al. Front Immunol. 2016.

AP-1: Activator protein 1; eNOS: Endothelial nitric oxide synthase-3; GCs: Glucocorticoids; GR: Glucocorticoid receptor; ICAM-1: Intercellular cell adhesion molecule-1; NF-kB: Nuclear factor kappa B; MKP-1: Mitogen-activated protein kinase (MAPK) phosphatase 1; ROS: Reactive oxygen species; TTP: Tristetraprolin; VCAM-1: Vascular cell adhesion molecule-1.


  1. Zielińska KA, et al. Endothelial Response to Glucocorticoids in Inflammatory Diseases. Front Immunol. 2016;7:592.
  2. Wang H, et al. Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway. Exp Ther Med. 2013;6(2):419–422.

Anti-edemetous Activity

Anti-inflammatory and anti-oedema effects of aescin may at least partially be mediated by the GR/NF-kB signalling pathway and PGF2α pathway respectively.1

Aescin achieves GC-like anti-inflammatory effects, reducing carrageenan-induced paw oedema.1
Time-effect curves of Aescin and Dexamethasone in carrageenan-induced paw oedema1

Anti-edemetous Activity

GR: Glucocorticoids receptor; NF-kB: Nuclear factor kB.


  1. Wang H, et al. Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway. Exp Ther Med. 2013;6(2):419–422.

Role of aescin in anti-edemotous activity

Anti-oedematous Activity

Aescin plays a role within the classical inflammatory cascade by inhibiting the effect of bradykinin and other catabolic enzymes.1,2

Reparil tablet anti-oedematous role within classical inflammatory cascade


  1. Gallelli L. Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug Des DevelTher. 2019;13:3425–3437.
  2. Dudek-Makuch M, et al.Horse chestnut – efficacy and safety in chronic venous insufficiency: an overview. Revista Brasileira de Farmacognosia. 2015;25(5):533–541.


A placebo-controlled, parallel-group, 4-arm study assessed the efficacy of amorphous aescin in 50 patients with post-plaster oedema and 50 patients with post-traumatic oedema.1

Post plastering Oedema reduction with Reparil Tablet

Adapted from Gallelli L, et al. Drug Des DevelTher.2019.

Post traumatic Odemea reduction with Reparil Tablet

A significant improvement in both types of oedema, particularly in the first 3 weeks of treatment with aescin, was observed in both the groups: 92% Patients of post-plastering oedema and 95% Patients of post-traumatic oedema.1


  1. Gallelli L. Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug Des DevelTher. 2019;13:3425–3437.

Safety profile

A meta-analysis of studies using a range of oral escin preparations demonstrated that these products were well tolerated, with no severe adverse events reported1

Safety in Preclinical Studiesx`x`

A preclinical study in rabbits and rats investigated the effects of aescin on healing of tibia fracture and abdominal wound after surgery.2

Effect of Reparil Tablet on BMD
Adapted from Zhang L, et al. Exp Ther Med. 2012.

Aescin did not affect the process of fracture.*2

Aescin showed no inhibition of the wound healing process.*2

Adapted from Zhang, et al.* Effect of aescin on bone mineral density (BMD) values of the fracture site at 2, 4 and 6 weeks after osteotomy. A DEXA (Dual-energy X-ray absorptiometry) scanner was used to measure the BMD value of a 15-mm long and 30-mm wide “ROI” centrally between the second and third screws, which included the proximal and distal old bone and the callus. No significant difference was found among groups.2

Effect of Reparil Tablet on immune cell apoptosis in mouse spleen

effect of Reparil Tablet on immune cell apoptosis in mouse thymus

7-day treatment with intravenous injection of dexamethasone induced a significant increase in spleen apoptosis and in thymus apoptosis, whereas with aescin no significant increase in apoptotic cells was observed.3

Safety in Clinical Studies with Horse Chestnut Seed Extracts4

In a criteria-based systematic review reported potential adverse effects of horse chestnut seed extracts are:4

Horse chestnut seed extract adverse events

The frequency of these ranges from 0.9% to 3% across experiments, and several studies have found no more adverse effects with horse chestnut seed extracts that with placebo.4

ROI: region of interest


  1. Gallelli L. Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug Des DevelTher. 2019;13:3425–3437.
  2. Zhang L, et al. Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model. Exp Ther Med. 2012;3(4):735–739.
  3. Zhang L, et al. The potent anti-inflammatory agent escin does not increase corticosterone secretion and immune cell apoptosis in mice. Fitoterapia. 2011;82(6):861–867.
  4. Robert W. Frick, Three Treatments for Chronic Venous Insufficiency:Escin, Hydroxyethylrutoside, and Daflon. Angiology. 2000;51:197..

Reparil prescribing information

    Reparil ®-Dragees (coated tablets)
    20 mg, gastro-resistant coated tablet
    For use in adults and children over 7 years of age
    Active substance: aescin
    Active substance:
    Each gastro-resistant coated tablet contains:
    Aescin 20 mg
    For the full list of excipients, see section 6.1.
    Gastro-resistant coated tablet
    4.1Therapeutic indications
    Localized swelling following injury
    4.2 Posology and method of administration
    Adults and adolescents aged 14 years and above initially take 2 tablets 3 times daily, as maintenance dose and in milder cases 1 tablet unchewed with some liquid after meals
    3 times daily.
    Paediatric population
    Children aged 7 to 14 years take 1 tablet unchewed with some liquid after meals 2 to 3 times daily.
    Reparil coated tablets are not indicated in children under the age of 7 years.
    Method of administration
    The tablets are taken unchewed with some liquid after meals.
    4.3 Contraindications
    Reparil coated tablets must not be taken by patients with
    - hypersensitivity to the active substance or to any of the excipients listed in section 6.1,
    - renal insufficiency or renal diseases,
    - pregnancy and breast-feeding.
    4.4 Special warnings and precautions for use
    Patients with rare hereditary (deficiency) problems of galactose intolerance, lactase deficiency, glucose-galactose malabsorption, fructose intolerance or sucrase isomaltase
    deficiency should not use Reparil coated tablets.
    Information on some of the excipients
    This medicine contains less than 1 mmol sodium (23 mg) per coated tablet, that is to say essentially 'sodium-free'.
    Paediatric population
    Reparil coated tablets are not indicated in children under the age of 7 years.
    4.5 Interaction with other medicinal products and other forms of interaction
    Administration of aescin can enhance the effect of anticoagulant medicinal products.
    Concurrent use of aminoglycosides (e.g. gentamicin) should be avoided because an increase in the nephrotoxicity of aminoglycosides cannot be completely excluded.
    The plasma protein binding of aescin can be inhibited by antibiotics. Cephalotin and ampicillin, for instance, raise the concentration of free aescin in the serum.
    Therefore, concurrent administration of these medicinal products with Reparil coated tablets is not recommended.
    4.6 Pregnancy and lactation
    Reparil coated tablets should not be used during pregnancy because the product has only inadequately been tested in animal studies and no experience with pregnant women
    has been documented. Breast-feeding during treatment is not recommended, because it is not known to which extent the active substance passes into breast milk.
    4.7 Effects on ability to drive and use machines
    Not applicable.
    4.8 Undesirable effects
    The following convention has been used for the classification of side effects in terms of frequency:
    Very common: ≥ 1/10
    Common: ≥ 1/100 to < 1/10
    Uncommon: ≥ 1/1,000 to < 1/100
    Rare: ≥ 1/10,000 to < 1/1,000
    Very rare: < 1/10,000
    Not known: Frequency cannot be estimated from the available data.
    The following side effects are known for Reparil coated tablets:
    Immune system disorders :
    Very rare: hypersensitivity reactions (e.g. urticaria)
    Gastro-intestinal disorders:
    Uncommon: gastro-intestinal tract disorders
    If hypersensitivity reactions occur, use of Reparil coated tablets should be discontinued.
    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 following:
    To report side effect(s):
    Saudi Arabia:
    The National Pharmacovigilance Centre (NPC):
    Fax: +966-11-205-7662
    SFDA Call Center: 19999
    Other Countries:
    Please contact the relevant competent authority.
    4.9 Overdose
    No cases of overdose have been reported.
    5.1 Pharmacodynamic properties
    Pharmacotherapeutic group: Capillary stabilizing agents ATC Code: C05CA07
    The site of action of aescin is the vascular wall. In case of abnormally raised permeability, aescin inhibits exsudation by reducing extravasation of fluid into the tissue and
    accelerating re-absorption of the existing oedema. The mechanism of action is based on a change in the permeability of the capillary openings involved. Furthermore, aescin
    promotes capillary resistance, inhibits inflammatory processes and improves microcirculation.
    5.2 Pharmacokinetic properties
    After oral administration of tritium-labelled aescin , a mean 12 – 16% of the applied activity was absorbed from the intestinal tract in mice and rats. Excretion occurs via the bile
    as well as the urine. The metabolisation rate is higher after oral administration than after intravenous injection. Organ distribution is negligibly low in the excretory organs liver and kidneys in comparison to the higher values in the blood.
    5.3 Preclinical safety data
    Aescin was only inadequately tested in animal experiments. In these experiments it proved to be moderately to highly toxic. Nephrotoxic changes were particularly significant.
    Complete testing for mutagenicity produced no evidence of mutagenic effects. No carcinogenicity studies have been carried out.
    Aescin was inadequately tested for reproductive toxicity. After oral administration of aescin in mice and rabbits during organogenesis embryotoxic effects occurred (reduced
    foetal weights, delayed skeleton ossification, in higher doses embryo lethality). No effects on the viability of offspring with prenatal exposure were found.
    6.1 List of excipients
    Lactose monohydrate, Povidone (K29-32), Magnesium stearate (Ph. Eur.), Sucrose (sugar), Talc, Gum arabic , Titanium dioxide E 171, Colloidal anhydrous silica, Poly(ethyl
    acrylate, methacyrylic acid), Macrogol 8000, Sodium hydroxide, Carmellose sodium, Triethyl citrate, Simeticone emulsion, Bleached wax, Carnauba wax.
    6.2 Incompatibilities
    Not applicable.
    6.3 Shelf life
    36 months
    6.4 Special precautions for storage
    Store below 30°C, in a dry place.
    6.5 Nature and contents of container
    PVC and printed aluminium blister packs in strips of 10 coated tablets Packs of 40 coated tablets
    6.6 Special precautions for disposal
    No special requirements.
    MEDA Pharma GmbH & Co. KG Benzstrasse 1,
    61352 Bad Homburg, Germany
    1983 / 05-Sep-2020
    September 2020
    Medicinal product subject to medical prescription


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