URSOFLOR 200mg

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 accumulates 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.

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

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.

Dissolution of cholesterol gallstones

– всю суточную дозу принимают 1 раз перед сном в дозе от 10 мг/кг массы тела до 15 мг/кг (2-5 капсул).

Длительность процесса растворения желчных камней при применении препарата составляет от 6 месяцев до 2 лет. Если через 6 месяцев не наблюдается уменьшения размеров желчных камней, прием препарата считается нецелесообразным.

После полного растворения камней прием продолжают в суточной дозе 600 мг (2 капсулы) 1 раз в день перед сном еще 3 месяца (для профилактики рецидивов).

Первичный билиарный цирроз

– рекомендуемая доза 300 мг 2 раза в сутки (с учетом 14 + 2 мг/кг) в течение 3 месяцев.

Дозировки для лечения пациентов педиатрического возраста не просматривались.

Side effects

Common (≥1/100, but <1/10 people)

- pasty stool

- diarrhea

Very rare (< 1/10ˈ000 people)

- severe pain in the abdominal area, on the right side, during treatment of primary biliary cirrhosis

- calcification of gallstones

- decompensation of liver cirrhosis, in the treatment of late stages of primary biliary cirrhosis, which partially regresses after discontinuation of the drug.

- urticaria

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 when using Ursoflor capsules to dissolve cholesterol gallstones should use

An effective non-hormonal method of contraception, as hormonal contraceptives can 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, itching may increase.

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 pack.

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