УРСОФЛОР 200мг

Ursoflor


International nonproprietary name

Ursodeoxycholic acid


Dosage form

Gelatin capsules 300 mg


Compound

One tablet contains

active substance – ursodeoxycholic acid 300.00 mg,

Excipients: corn starch, anhydrous colloidal silicon dioxide, magnesium stearate,

gelatin capsule composition: titanium dioxide (E171), iron oxide (III) yellow (E172), gelatin.

Description

Hard gelatin capsules with a white body and a yellow cap, size No. 0, the contents of the capsules are white powder.




Pharmacotherapeutic group

Preparations for the treatment of diseases of the biliary tract. Bile acid preparations. Ursodeoxycholic acid.

ATX code A05AA02

Pharmacological properties

Pharmacokinetics

After oral administration, ursodeoxycholic acid is rapidly absorbed in the small intestine and the beginning 
of the ileum by passive transport and at the end of the ileum by active transport. The absorption rate is
typically 60-80%. After absorption, bile acid undergoes almost complete conjugation in the liver with the 
amino acids taurine and glycine, and is then excreted in the bile. The first clearance through the liver reaches 60%.

Depending on the daily dose and the existing liver disorder or condition, more and more hydrophilic ursodeoxycholic acid a
ccumulates in the bile. At the same time, there is a relative decrease in the content of other, more lipophilic bile acids.

Under the influence of intestinal bacteria, the drug is partially broken down into 7-keto-lithocholic acid and lithocholic acid. 
Lithocholic acid is hepatotoxic and can cause parenchymal liver lesions in some animal species. In humans, a very small amount is absorbed,
 which is sulfated in the liver and thus detoxified before being excreted in the bile or ultimately in the feces.

The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.



Pharmacodynamics

Ursoflor - a hepatoprotector has a choleretic effect. Reduces cholesterol synthesis in the liver, 
its absorption in the intestines and concentration in bile, increases the solubility of cholesterol
in the biliary system, stimulates the formation and excretion of bile.

Possessing high polar properties, UDCA forms non-toxic mixed micelles with apolar (toxic) bile acids, which reduces the ability 
of gastric reflux to damage cell membranes. In addition, UDCA forms double molecules that can be incorporated into cell membranes, 
stabilize them and make them immune to the action of cytotoxic micelles. Reduces the saturation of bile with cholesterol by inhibiting its 
absorption in the intestine, suppressing synthesis in the liver and reducing secretion into bile; increases the solubility of cholesterol in bile,
forming liquid crystals with them; reduces the lithogenic index of bile.

The result is the dissolution of cholesterol gallstones and the prevention of the formation of new stones. 
The immunomodulatory effect is due to inhibition of the expression of HLA antigens on the membranes of hepatocytes 
and cholangiocytes, normalization of the natural killer activity of lymphocytes, etc. Significantly delays the progression
of fibrosis in patients with primary biliary cirrhosis, cystic fibrosis and alcoholic steatohepatitis,
reduces the risk of developing esophageal varices.

Clinical studies have provided experience with the use of ursodeoxycholic acid for 10 years or more in a pediatric
 population of patients with cystic fibrosis-associated hepatobiliary disease (CFAHD). There is evidence that the
 use of ursodeoxycholic acid reduces bile duct proliferation, inhibits damage detected by histological examination, 
and even promotes the reversal of changes in the hepatobiliary system when therapy is started in the early stages of CFAHD. 
Ursodeoxycholic acid therapy should be initiated as soon as possible after the diagnosis of CFAHD to optimize treatment effectiveness.

Indications for use

- treatment of primary biliary cirrhosis

- dissolution of radiolucent gallstones in the gallbladder



Directions for use and doses

The dosage regimen and duration of treatment with Ursoflor are determined individually, depending on the severity of the disease.

Ursoflor capsules are taken orally with food, without chewing, with a sufficient amount of water.

The duration of the process of dissolving gallstones when using the drug ranges from 6 months to 2 years.
 If after 6 months there is no reduction in the size of gallstones, taking the drug is considered inappropriate.

After complete dissolution of the stones, the intake is continued at a daily dose of 600 mg (2 capsules) once a day before bedtime for another 3 months (to prevent relapses).

Primary biliary cirrhosis

- recommended dose 300 mg 2 times a day (including 14 + 2 mg/kg) for 3 months.

Dosages for the treatment of pediatric patients were not reviewed.

Indications for use

- treatment of primary biliary cirrhosis

- dissolution of radiolucent gallstones in the gallbladder



Directions for use and doses

The dosage regimen and duration of treatment with Ursoflor are determined individually, depending on the severity of the disease.

Ursoflor capsules are taken orally with food, without chewing, with a sufficient amount of water.

Contraindications

- acute inflammatory diseases of the gallbladder or bile ducts, empyema of the gallbladder

- obstruction of the bile ducts (common bile ducts or cystic ducts)

- frequent episodes of hepatic colic

- X-ray positive (high calcium) gallstones

- disorders of gallbladder contractility

- hypersensitivity to the components of the drug or bile acids

- children with biliary atresia: unsuccessful portoenterostomy, normal bile flow is not restored

- children and adolescents up to 18 years of age.

Drug interactions

Cholestyramine, cholestipol and antacids containing aluminum hydroxide or smectite (aluminum oxide) 
reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its absorption and effectiveness.
 If the use of drugs containing at least one of these substances is still necessary, they should be taken at least 2 hours before or after taking Ursoflor.

Ursodeoxycholic acid may affect the absorption of cyclosporine from the intestine. 
Therefore, in patients taking cyclosporine, the physician should check the concentration 
of cyclosporine in the blood and adjust the dose of cyclosporine if necessary.

In a clinical study in healthy volunteers, concomitant use of ursodeoxycholic acid (500 mg/day) and 
rosuvastatin (20 mg/day) resulted in slightly elevated plasma levels of rosuvastatin. The clinical significance of this interaction with other statins is unknown.

In some cases, Ursoflor may reduce the absorption of ciprofloxacin.

Ursodeoxycholic acid has been shown to reduce peak plasma concentrations (Cmax) and the area under
the pharmacokinetic curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers.
Careful monitoring of the results of simultaneous use of nitrendipine and ursodeoxycholic acid is recommended. An increase in the dose of nitrendipine may be necessary.
In addition, a weakening of the therapeutic effect of dapsone has been reported.

Based on the presented data, as well as the results of in vitro studies, it can be assumed that ursodeoxycholic acid induces cytochrome P450 enzymes 3A;
 however, according to an adequate clinical study of drug interactions, ursodes-hydroxycholic acid does not cause a significant induction of budesonide, 
which is a substrate of cytochrome P450 3A.

Estrogen hormones and blood cholesterol-lowering agents such as clofibrate increase hepatic secretion of cholesterol 
and therefore may stimulate the formation of gallstones, a counter-effect of ursodeoxycholic acid, which is used to dissolve gallstones.

Special instructions

During the first three months of treatment, liver function parameters AST (SGOT), ALT (SGPT) 
and gamma-GT should be monitored every 4 weeks and then every 3 months. Monitoring of these parameters 
makes it possible to identify liver dysfunction in the early stages, in particular in patients in the later 
stages of primary biliary cirrhosis; In addition, it can quickly determine whether a patient with primary biliary cirrhosis is responding to treatment.

When used to dissolve cholesterol gallstones:

To assess progress in treatment and timely detection of signs of calcification of stones depending on the size of the stones, 
the gallbladder should be visualized (oral cholecystography) with examination of opacities in the standing position and in 
the supine position (ultrasound) 6-10 months after the start of treatment.

If the gallbladder cannot be visualized on x-rays or in cases of calcified stones, poor contractility of the gallbladder or
 frequent attacks of colic, Ursoflor capsules should not be used.

Women using Ursoflor capsules to dissolve cholesterol gallstones should use an effective non-hormonal method of contraception, 
as hormonal contraceptives may increase the formation of gallstones.

When treating patients in the later stages of primary biliary cirrhosis:

Cases of decompensation of liver cirrhosis, which partially regressed after cessation of treatment, were reported extremely rarely.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may worsen at the start of treatment, for example,
 increased itching. In such cases, the dose of Ursoflor 300 mg capsules should be reduced to one Ursoflor 300 mg capsule per day and then gradually increased again.

In case of diarrhea, the dose should be reduced; in case of persistent diarrhea, treatment should be discontinued.

Pregnancy and lactation

Studies have not shown an effect of UDCA on fertility. There are no studies on the effect on fertility after treatment with UDCA.

There are no or limited data on the use of ursodeoxycholic acid in pregnant patients. 
Studies indicate a teratogenic effect during the early phase of pregnancy. Ursoflor capsules should not be used during pregnancy 
unless clearly necessary. Women of childbearing age should take the drug only while using reliable contraception.

It is recommended to use non-hormonal or low estrogen methods of contraception. In patients receiving Ursoflor capsules 
300 mg for the purpose of destroying gallstones, non-hormonal methods of contraception should be used, since hormonal 
contraceptives may promote the formation of stones. The possibility of pregnancy must be excluded before starting treatment.

According to several confirmed cases, the concentration of ursodeoxycholic acid in the milk of lactating women is low;
the occurrence of adverse reactions in children during breastfeeding is unlikely.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Does not affect

Overdose

In case of overdose, diarrhea may occur. Other symptoms of overdose are unlikely because the absorption of 
ursodeoxycholic acid decreases with increasing dose and is therefore more excreted in the feces.

Treatment: diarrhea is symptomatic with fluid and electrolyte replacement.

Long-term treatment with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients 
with primary sclerosing cholangitis (off-label) is associated with higher rates of serious adverse events.



Release form and packaging

10 capsules are placed in a blister pack made of polyvinyl chloride-polydivinyl chloride film and aluminum foil.

2 blister packs together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard pac

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children!



Shelf life

3 years

Do not use after the expiration date stated on the package.



Conditions for dispensing from pharmacies

On prescription



Manufacturer

Special product line S.P.A.

Via fratta rotunda vado Largo, 1-03012 Anagni (FR), Italy