Active ingredients: Ursodeoxycholic acid
Deursil Hard capsules
Deursil Prolonged-release hard capsules
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
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01.0 NAME OF THE MEDICINAL PRODUCT
DEURSIL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One hard capsule contains:
Active principle:
Ursodeoxycholic acid (UDCA) 50 mg 150 mg 300 mg
One prolonged-release capsule, hard contains:
Active principle
Ursodeoxycholic acid (UDCA) 450.00 mg 225.00 mg
03.0 PHARMACEUTICAL FORM
DEURSIL hard capsules: hard gelatin capsules for oral use
DEURSIL prolonged-release hard capsules: hard gelatin capsules containing 3 differentiated release tablets, for oral use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Qualitative or quantitative alterations of the biligenetic function, including forms of supersaturated bile in cholesterol, to oppose the formation of cholesterol stones or to create suitable conditions for dissolution if radiolucent stones are already present: in particular gallstones in functioning gallbladder and stones in the choledochus residual and recurrent after biliary tract operations.
Biliary dyspepsia.
04.2 Posology and method of administration
DEURSIL hard capsules: In prolonged use to reduce the lithogenic characteristics of bile, the average daily dosage is 5-10 mg / kg; in most cases, the daily dosage is between 300 and 600 mg per day (after or during meals and in the evening); to maintain the conditions suitable for the dissolution of the stones already present, the duration of treatment must be at least 4-6 months, up to 12 or more, continuously and must be continued for 3-4 months after the disappearance In any case, treatment should not exceed 2 years In dyspetic syndromes and maintenance therapy, doses of 300 mg per day, divided into 2-3 administrations, are sufficient.
Doses can be changed at the doctor's discretion.
DEURSIL prolonged-release hard capsules: In prolonged use to reduce the lithogenic characteristics of bile, the dosage is 450 mg per day, while in obese patients, or in any case in the presence of other important lithogenic factors, it is advisable to increase the daily dosage to 675 mg; a more high is also advisable in cases with stones larger than 2 cm.
To maintain the conditions suitable for the dissolution of stones already present, the duration of treatment must be at least 4-6 months, up to 9 months or more, continuously and must be continued for 3-4 months after the radiological or ultrasound disappearance of the calculations themselves. However, treatment must not exceed 2 years.
In dyspetic syndromes and maintenance therapies, smaller doses are sufficient: 225 mg per day.
Doses can be changed according to the doctor's judgment; in particular, the excellent tolerability of the preparation allows to adopt significantly higher doses.
The administration of DEURSIL RR should be carried out in a single evening intake, preferably at bedtime.
There is no treatment for pediatric patients.
04.3 Contraindications
DEURSIL hard capsules and DEURSIL prolonged-release hard capsules they are contraindicated in cases of ascertained individual hypersensitivity to the substance. The substance is also contraindicated in pregnant patients and in the presence of gastric or duodenal ulcer in an active phase.
04.4 Special warnings and appropriate precautions for use
In patients with frequent biliary colic, with biliary infections, with severe pancreatic alterations or with intestinal affections that can alter the enterohepatic circulation of bile acids (resection and ostomy of the ileum, regional ileitis, etc.) it is advisable to avoid the use of the substance.
When starting long-term dissolving treatments it is advisable to carry out a preliminary check of the transaminases and alkaline phosphatase.
The prerequisite for establishing a calculolytic treatment with ursodeoxycholic acid is represented by the cholesterol nature of the stones themselves; a reliable index in this sense is represented by their radiolucency.
The gallstones that have the highest probability of dissolution are those of small size in a functioning gallbladder; the desaturation of the bile in cholesterol is a useful predictor for a good outcome of the treatment, but it is not decisive, since the dissolution can also occur due to a physical process of formation of liquid crystals independent of the state of saturation.
In patients undergoing treatment for the dissolution of gallstones, it is advisable to verify the efficacy of the drug by means of cholecystographic or ultrasound examinations every 6 months.
Keep this medicine out of the reach of children.
04.5 Interactions with other medicinal products and other forms of interaction
Avoid the association with substances that inhibit intestinal absorption of bile acids, such as cholestyramine, and with drugs that increase the biliary elimination of cholesterol (estrogens, hormonal contraceptives, some lipid-lowering agents).
Avoid association with potentially hepatologic drugs.
04.6 Pregnancy and lactation
Treatment is contraindicated in pregnant women. Treatment in women of childbearing age can be undertaken bearing in mind the need to interrupt it in the event of pregnancy.
There are no data that ursodeoxycholic acid is excreted in human milk, however it should be administered with caution during lactation.
04.7 Effects on ability to drive and use machines
There are no assumptions or evidence that the substance can change the attention span and reaction times.
04.8 Undesirable effects
The tolerability of the substance at the recommended doses is generally good. Irregularities of the alvus have been found only occasionally, which generally disappear with continued treatment.
04.9 Overdose
There are no known cases of overdose over 4 g per day (this dose was well tolerated).
In case of accidental ingestion of ursodeoxycholic acid in highly higher doses, it is suggested to implement the normal measures recommended in the intoxication pathology and to administer cholestyramine, as it is capable of chelating bile acids.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
ATC code: A05AA02
Ursodeoxycholic acid (UDCA) represents the 7 beta-epimer of chenodeoxycholic acid and is a bile acid physiologically present in human bile, where it represents a small percentage of total bile acids.
UDCA is able to increase the solubilizing capacity of bile against cholesterol in humans by transforming lithogenic bile into non-lithogenic bile. The mechanisms through which this effect is achieved are many: decrease in the secretion of cholesterol in the bile through a reduction in intestinal absorption and in the hepatic synthesis of cholesterol itself; increase in the overall pool of bile acids favoring the micellar solubilization of cholesterol; formation of a liquid-crystalline mesophase that allows a non-micellar solubilization of cholesterol higher than that obtainable in the equilibrium phase. Treatment with DEURSIL therefore determines the formation of unsaturated bile in cholesterol and richer in bile salts suitable for its solubilization, also favoring a regular flow bile and emptying of the gallbladder.
05.2 Pharmacokinetic properties
After oral administration, ursodeoxycholic acid is easily absorbed in the intestine, taken up by the liver and excreted in the bile in a predominantly glyco-conjugated form: thus entering the enterohepatic circulation; it is partially metabolized by the intestinal flora and its metabolites are eliminated. by fecal route.
The new formulation of DEURSIL with repeated release (DEURSIL RR) has the considerable advantage of ensuring, with a single intake, a release in the intestine of the active principle in three successive times, such as to guarantee its bioavailability for about 7-8 hours.
05.3 Preclinical safety data
Ursodeoxycholic acid has the advantages of a reduced formation of lithocolate, considered hepatotoxic in the experimental animal (in humans it engages the sulphation processes), of the absence of increases in serum transaminases, even in the course of long-term treatments in "human. The experimental toxicity of UDCA is generally very low;" the oral LD50 was 10 g / kg in the rat, while in the mouse it was respectively 5740 mg / kg for the male and 6000 mg / kg for the female. Chronic treatments of 28 weeks in rats with doses up to 2000 mg / kg orally did not show any pathological changes in the histological parameters studied. Treatments for 1 year in dogs with doses up to 100 mg / kg orally were also well tolerated without any adverse reactions, in particular, no significant hepatolesive effects, adverse effects on fertility, teratogenic or carcinogenic effects, lesions were highlighted. of the gastric mucosa.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
DEURSIL hard capsules: starch, magnesium stearate, colloidal silica
DEURSIL prolonged-release hard capsules: microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, sorbitol, gelatin, methyl p-hydroxybenzoate, talc, magnesium stearate, titanium dioxide (E171), neutral copolymer of (meth) acrylic acid esters, copolymers methacrylic acid, dibutyl phthalate, red iron oxide (E172), polyethylene glycol 6000.
06.2 Incompatibility
The pharmaceutical form excludes the presence of incompatibility.
06.3 Period of validity
DEURSIL hard capsules: 5 years
DEURSIL prolonged-release hard capsules: 3 years
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Nature of container: blister in cardboard box.
Packs
DEURSIL 50 mg hard capsules 20 - 40 - 60 capsules.
DEURSIL 150 mg hard capsules 20 - 30 - 40 capsules.
DEURSIL 300 mg hard capsules 10 - 20 capsules.
DEURSIL 225 mg prolonged-release hard capsules 10 - 20 - 30 - 40 capsules.
DEURSIL 450 mg prolonged-release hard capsules 10 - 20 capsules.
06.6 Instructions for use and handling
Not applicable.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
DEURSIL 50 mg hard capsules 20 capsules: AIC n ° 023605013
DEURSIL 50 mg hard capsules 40 capsules: AIC n ° 023605025
DEURSIL 50 mg hard capsules 60 capsules: AIC n ° 023605037
DEURSIL 150 mg hard capsules 20 capsules: AIC n ° 023605076
DEURSIL 150 mg hard capsules 30 capsules: AIC n ° 023605088
DEURSIL 150 mg hard capsules 40 capsules: AIC n ° 023605090
DEURSIL 300 mg hard capsules 10 capsules: AIC n ° 023605102
DEURSIL 300 mg hard capsules 20 capsules: AIC n ° 023605114
DEURSIL 450 mg prolonged-release hard capsules 10 capsules: AIC n ° 023605126
DEURSIL 450 mg prolonged-release hard capsules 20 capsules: AIC n ° 023605138
DEURSIL 225 mg prolonged-release hard capsules 10 capsules: AIC n ° 023605140
DEURSIL 225 mg prolonged-release hard capsules 20 capsules: AIC n ° 023605153
DEURSIL 225 mg prolonged-release hard capsules 30 capsules: AIC n ° 023605165
DEURSIL 225 mg prolonged-release hard capsules 40 capsules: AIC n ° 023605177
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: June 1, 2005
10.0 DATE OF REVISION OF THE TEXT
01/06/2007