Ursaklin

Ursodeoxycholic acid

Capsules 250 mg

White hard gelatin capsules. Capsules contain a mixture of powder and granules of white or almost white color, odorless or with a slight specific odor.

Each capsule contains:
Active substance: ursodeoxycholic acid 250 mg.
Excipients: corn starch, pregelatinized corn starch, anhydrous colloidal silicon dioxide, and magnesium stearate.
Shell composition: gelatin, and titanium dioxide (E 171).

Bile and liver therapy. Bile acids and derivatives.

A05AA02

Pharmacodynamics
A negligible quantity of ursodeoxycholic acid is present in human bile. After oral administration, it reduces saturation of bile with cholesterol, inhibiting its absorption in the intestine and reducing secretion into bile. Presumably, gradual dissolution of gallstones occurs due to dispersion of cholesterol and formation of liquid crystals.

According to modern concepts it is believed that the effect of ursodeoxycholic acid in liver diseases and cholestasis is due to relative replacement of lipophilic, toxic bile acids with hydrophilic cytoprotective non-toxic ursodeoxycholic acid. This replacement improves secretory capacity of hepatocytes and immunoregulatory processes.

• Dissolution of x-ray negative cholesterol gallstones not larger than 15 mm in diameter in patients with a functioning gallbladder despite the presence of gallstone(s).
• Treatment of gastritis with bile reflux.
• Symptomatic treatment of primary biliary cirrhosis in the absence of decompensated liver cirrhosis.
• Treatment of hepatobiliary disorders in cystic fibrosis in children aged 6 to 18 years.

There are no age restrictions for taking Ursaklin. Patients who weigh less than 47 kg or who have difficulty swallowing capsules should take ursodeoxycholic acid in the form of a suspension.

• Dissolution of cholesterol gallstones
Approximately 10 mg ursodeoxycholic acid per 1 kg of body weight:
Up to 60 kg = 500 mg
61-80 kg = 750 mg
81-100 kg = 1000 mg
More than 100 kg = 1250 mg
Capsules should be swallowed whole with water. Capsules should be taken regularly, once daily in the evening before bedtime.
The time required for gallstones to dissolve is usually 6-24 months. If a decrease in the size of gallstones is not observed after 12 months of administration, the therapy should be discontinued.
The success of the treatment should be checked every 6 months by ultrasound or X-ray. Additional studies are required to check that stones do not calcify over time. If this happens, the treatment should be discontinued.

• Treatment of gastritis with bile reflux
250 mg once daily with some liquid in the evening before bedtime. Normally Ursaklin is taken during 10-14 days for treatment of gastritis with bile reflux. Duration depends on a patient’s condition. A healthcare provider should decide on the duration of treatment in each case individually.

• Symptomatic treatment of primary biliary cirrhosis (PBC)
The daily dose depends on body weight and varies from 750 mg to 1750 mg (14±2 mg per 1 kg of body weight).
In the first 3 months of treatment Ursaklin should be taken by distributing the daily dose into 3 portions during the day. With improvement in liver function, the daily dose can be taken once daily in the evening.

The capsules should be swallowed whole with a liquid. It is necessary to observe regular administration.
The use of Ursaklin in primary biliary cirrhosis can be unlimited in time.
In rare cases clinical symptoms may worsen in patients with primary biliary cirrhosis at the beginning of treatment. For example, itching may increase. If it happens, the therapy should be continued taking 250 mg per day. Then the daily dose should be increased gradually (by 250 mg weekly) until the prescribed dosing regimen is reached.

Children
Cholesterol gallstones and primary biliary cirrhosis are very rare in children. Efficacy and safety data are not available in this population. If necessary, the dose should be adjusted according to the body weight.
For children with cystic fibrosis aged 6 to 18 years old, the dosage is 20 mg/kg/day. It is divided into 2-3 doses, followed by an increase in dose to 30 mg/kg/day when needed.

Ursaklin is well tolerated by patients.
Frequency of side effects: very common (>1/10); common (>1/100, but <1/10); uncommon (>1/1000, but <1/100); rare (>1/10000, but <1/1000); very rare (<1/10000). When taking ursodeoxycholic acid, the following side effects are possible:

Gastrointestinal disorders
Common: diarrhea, dyspepsia.
Rare: pain in the epigastric region and right hypochondrium.

Hepatobiliary disorders
Very rare: calcification of stones, decompensation of cirrhosis of the liver, which disappears after discontinuation of Ursaklin.

Hypersensitivity reactions
Very rare: itching, and allergic rash (urticaria).
In the treatment of primary biliary cirrhosis, decompensation of liver cirrhosis was very rarely observed, which partially regressed after discontinuation of treatment.

In case of any unusual reactions, you should stop taking Ursaklin and consult your healthcare provider.

• hypersensitivity to the active substance or other ingredients of Ursaklin;
• X-ray positive (high in calcium) gallstones;
• obstruction of the bile tract (occlusion of the common bile duct or cystic duct)
• reduced contractility of the gallbladder;
• frequent episodes of biliary colic;
• acute inflammatory diseases of the gallbladder or bile ducts;
• children under 6 years of age;
• unsuccessful portoenterostomy or unrecovered bile flow in children with biliary atresia.

Symptoms of an overdose with ursodeoxycholic acid are not known. Absorption of ursodeoxycholic acid decreases with increasing dose. If diarrhea occurs, the dose should be reduced. If diarrhea persists, the treatment should be discontinued. Treatment of diarrhea is symptomatic with restoration of fluid volume and electrolyte balance. When taking more capsules than required, gastric lavage is recommended. Symptomatic therapy is initiated if necessary.
Long-term use of high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with primary sclerosing cholangitis (off-label use) was associated with an increased incidence of serious side effects.

Colestyramine, colestipol, and antacids containing aluminum hydroxide and/or smectite (aluminum oxide) bind ursodeoxycholic acid in the intestine, reduce its absorption and impair efficacy. If necessary, simultaneous treatment with the above medicines is recommended 2 hours before or 2 hours after taking Ursaklin.
Lipid-lowering medicines (especially clofibrate), estrogens, neomycin, and progestins can increase saturation of bile with cholesterol and reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

In a clinical study with healthy volunteers, the combined use of UDCA (500 mg/day) and rosuvastatin (20 mg/day) resulted in a slight increase in plasma concentrations of rosuvastatin. The clinical significance of this interaction and interactions with other statins is unknown.
In some cases Ursaklin may reduce absorption of ciprofloxacin.

In some cases Ursaklin can reduce peak plasma concentrations (C_max) and the area under the concentration-time pharmacokinetic curve (AUC) of nitrendipine, a calcium antagonist. An increase in the dose of nitrendipine may be required. UDCA influences the metabolism of dapsone by cytochrome P450 3A enzymes. These observations are consistent with the results obtained in vitro, and may indicate the ability of ursodeoxycholic acid to induce enzymes of the cytochrome P450 3A system. However, induction has not been observed in well-designed interaction studies with budesonide, which is a well-known cytochrome P450 3A substrate. Therefore, precautions should be taken when co-administering medicines metabolized by this enzyme. Dosage adjustments may be required.

Ursaklin can affect absorption of cyclosporine in the intestine. Therefore it is necessary to monitor the level of cyclosporine and adjust its dose in patients taking this medicine at the same time.

Your healthcare provider must be informed about all medicines you are taking. Talk to your doctor before taking any medicine during treatment with Ursaklin.

Ursaklin capsules should only be taken under medical supervision.
With long-term (more than 1 month) administration of Ursaklin, every 4 weeks in the first 3 months of treatment, and once in 3 months at a later stage, a biochemical blood test should be performed to determine the activity of hepatic transaminases and gamma-glutamyl transferase. If elevated levels persist, Ursaklin should be discontinued.
After complete dissolution of the gallstones it is recommended to continue treatment for at least 3 months to dissolve the remnants of the gallstones that are too small to be detected.

Monitoring of the treatment effectiveness should be carried out every 6 months by conducting X-ray and ultrasound examination of the biliary tract in order to prevent recurrence of cholelithiasis.

Ursaklin is not recommended in cases where the gallbladder cannot be visualized on x-rays or in cases of calcification of stones, weak contractility of the gallbladder or frequent attacks of biliary colic.

In patients with primary biliary cirrhosis, in rare cases, after the start of treatment, the condition may worsen, which is associated with increased itching. In this case, the dose should be reduced to 250 mg per day and then gradually increased to the recommended dose.
Cases of decompensated liver cirrhosis have been reported extremely rare. After discontinuation of therapy, a partial regression of decompensation manifestations was noted.

In case of diarrhea the dose should be reduced. In case of persistent diarrhea, treatment should be discontinued.
Despite the fact that Ursaklin has no age restrictions for use, it is not prescribed for children under the age of 6 years old due to possible difficulties in swallowing the capsules.
During treatment, women of childbearing age should use effective non-hormonal methods of contraception.

Women of reproductive age can be treated only with reliable contraception. Patients of childbearing age taking Ursaklin to dissolve gallstones should use effective non-hormonal methods of contraception. Hormonal oral contraceptives can initiate formation of gallstones. Before starting treatment the possibility of pregnancy should be excluded.

There are no or limited data on the use of ursodeoxycholic acid during pregnancy. Animal studies have demonstrated reproductive toxicity with high doses of ursodeoxycholic acid administered early in gestation. The use of Ursaklin by women during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. The decision to use Ursaklin should be made by the healthcare provider.

According to the latest data, the level of ursodeoxycholic acid that enters breast milk is very low. So the development of adverse reactions in breastfed infants is unlikely. If it is necessary to prescribe Ursaklin during lactation, the final decision can only be made by a healthcare provider.

Ursaklin does not affect the ability to drive vehicles or use mechanisms.

Hard gelatin capsules 250 mg. 10 or 14 capsules in a blister pack made of PVC film and aluminum foil. 2 or 4 blister packs No. 14 or 6 blister packs No. 10 with a patient information leaflet in an outer carton.

Protect from light and moisture. Store at a temperature not exceeding 25°C. Keep out of the reach of children.

2 years. Do not use after the expiry date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en