Instructions for Ursosan forte tablets 500 mg No. 30
Composition
active ingredient: ursodeoxycholic acid;
1 film-coated tablet contains 500 mg of ursodeoxycholic acid;
excipients: corn starch, pregelatinized corn starch, sodium starch glycolate (type A), colloidal anhydrous silica, magnesium stearate, white coating 03B28796 (hypromellose 6, titanium dioxide (E 171), macrogol 400).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white or almost white in color, oblong in shape, with a transverse dividing line on one side and a transverse notch on the other side, length 17 mm.
Pharmacotherapeutic group
Drugs used to treat the liver and biliary tract. Drugs used in biliary pathology.
ATX code A05A A02.
Drugs used in cases of liver disease are lipotropic substances.
ATX code A05B.
Pharmacological properties
Pharmacodynamics.
Small amounts of ursodeoxycholic acid have been found in human bile. After oral administration, ursodeoxycholic acid reduces the cholesterol saturation of bile by inhibiting its absorption in the intestine and reducing cholesterol secretion into the bile. It is possible that due to the dispersion of cholesterol and the formation of liquid crystals, the gradual dissolution of gallstones occurs.
According to current knowledge, it is believed that the effect of ursodeoxycholic acid in liver diseases and cholestasis is due to the relative replacement of lipophilic, detergent-like toxic bile acids with hydrophilic cytoprotective non-toxic ursodeoxycholic acid, improvement of the secretory capacity of hepatocytes, and immunoregulatory processes.
Use in children
Cystic fibrosis
There is information available from clinical reports regarding the long-term use of ursodeoxycholic acid (up to 10 years) in the treatment of children with hepatobiliary disorders associated with cystic fibrosis. There is evidence that the use of ursodeoxycholic acid can reduce proliferation in the bile ducts, stop the progression of histological changes, and even eliminate hepatobiliary changes, provided that therapy is started in the early stages of cystic fibrosis. For best effectiveness, treatment with ursodeoxycholic acid should be started immediately after the diagnosis of cystic fibrosis is clarified.
Pharmacokinetics.
When administered orally, ursodeoxycholic acid is rapidly absorbed in the jejunum and upper ileum by passive transport, and in the terminal ileum by active transport. The absorption rate is usually 60-80%. After absorption, the bile acid undergoes almost complete conjugation in the liver with the amino acids glycine and taurine and is then excreted in the bile. The first-pass clearance through the liver is up to 60%.
Depending on the daily dose and the underlying liver disorder or condition, the more hydrophilic ursodeoxycholic acid accumulates in the bile. At the same time, there is a relative decrease in the other more lipophilic bile acids.
Under the influence of intestinal bacteria, partial degradation occurs to 7-ketolithocholic and lithocholic acids. Lithocholic acid is hepatotoxic and causes damage to the liver parenchyma in some animal species. In humans, only a small amount is absorbed, which is sulfated in the liver and thus detoxified before being excreted in the bile and then in the feces.
The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.
Indication
For the dissolution of radiopaque cholesterol gallstones no larger than 15 mm in patients with a functioning gallbladder, despite the presence of gallstone(s) in it.
For the symptomatic treatment of primary biliary cirrhosis (PBC) in the absence of decompensated liver cirrhosis.
For the treatment of hepatobiliary disorders in cystic fibrosis in children aged 6 to 18 years.
Contraindication
Hypersensitivity to any substance included in the medicinal product.
Acute inflammation of the gallbladder or bile ducts.
Bile duct obstruction (occlusion of the common bile duct or cystic duct).
Frequent episodes of hepatic colic.
Radiopaque calcified gallbladder stones.
Violation of gallbladder contractility.
Liver cirrhosis in the decompensation stage.
Unsuccessful outcome of portoenterostomy or lack of adequate biliary outflow in children with bile duct atresia.
Interaction with other medicinal products and other types of interactions
Ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine. In patients taking cyclosporine, the doctor should check the concentration of this substance in the blood and, if necessary, adjust the dose of cyclosporine.
In some cases, the drug may reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers, concomitant administration of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in a slight increase in plasma levels of rosuvastatin. The clinical significance of this interaction for other statins is unknown. Ursodeoxycholic acid reduces the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of the calcium antagonist nitrendipine.
Careful monitoring of the results of concomitant administration of nitrendipine and ursodeoxycholic acid is recommended. An increase in the dose of nitrendipine may be necessary. In view of this, as well as the one reported case of interaction with dapsone (reduced therapeutic effect) and in vitro studies, it can be concluded that ursodeoxycholic acid induces the drug-metabolizing enzyme cytochrome P450 3A. However, induction was not observed in a well-designed interaction study with budesonide, a known substrate of cytochrome P450 3A.
Estrogen hormones and cholesterol-lowering drugs such as clofibrate increase hepatic cholesterol secretion and may therefore promote biliary lithiasis, which counteracts ursodeoxycholic acid, which is used to dissolve gallstones. Therefore, in the case of concomitant use of drugs metabolized by the P450 3A enzyme, special caution should be exercised and it should be borne in mind that dose adjustment may be necessary.
Application features
Ursosan® forte tablets should be taken under the supervision of a doctor.
During the first 3 months of therapy, the physician should monitor liver function parameters - AST (SGOT), ALT (SGPT) and γ-GT - every 4 weeks, and then every 3 months. This allows to determine the presence or absence of an appropriate response to treatment in patients with PBC, as well as to timely identify potential liver dysfunction, especially in patients with PBC in the late stages.
Uses for dissolving cholesterol gallstones
6-10 months after the start of treatment, oral cholecystography should be performed to determine the general appearance of the stone and the appearance of gallbladder obstruction in the standing and supine positions (ultrasound). This is necessary to assess therapeutic progress and to promptly detect possible calcification of gallstones.
The drug should not be taken by patients with a gallbladder that is not visualized by X-ray methods, with calcified stones, impaired gallbladder contractility, or those who have frequent biliary colic.
Patients taking a drug to dissolve gallstones should use an effective non-hormonal method of contraception, as hormonal contraceptives may increase the formation of gallstones (see sections “Interaction with other medicinal products and other types of interactions” and “Use during pregnancy or breastfeeding”).
Treatment of patients with advanced stage PBC
Cases of decompensated liver cirrhosis, which partially regressed after discontinuation of therapy, have been reported extremely rarely.
In patients with PBC, very rarely, symptoms may worsen at the beginning of treatment, for example, itching may increase. In such cases, the dose should be reduced to half a tablet per day, then the dose should be gradually increased as described in the section "Method of administration and dosage".
If diarrhea develops, the dosage should be reduced; if diarrhea becomes persistent, treatment should be discontinued.
Use during pregnancy or breastfeeding
Animal studies have not shown any effect of ursodeoxycholic acid on fertility. There are no data on the effect on human fertility.
There are insufficient data on the use of ursodeoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy. The drug should not be used in pregnancy unless clearly necessary. Women of childbearing potential should only use the drug if reliable contraception is used.
It is recommended to use non-hormonal contraceptives or oral contraceptives with a low estrogen content. Patients receiving Ursosan® forte, film-coated tablets, 500 mg, for the dissolution of gallstones should use effective non-hormonal contraceptives, since hormonal oral contraceptives may increase the formation of gallstones. Before starting treatment, the possibility of pregnancy should be excluded.
According to several recorded cases of use of the drug in breastfeeding women, the content of ursodeoxycholic acid in milk was extremely low, so no adverse effects should be expected in infants.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effect on the ability to drive or use machines was observed.
Method of administration and doses
There are no age restrictions on the use of the drug.
Patients weighing less than 47 kg or those who have difficulty swallowing tablets may be given ursodeoxycholic acid in a different dosage form.
To dissolve cholesterol gallstones
Approximately 10 mg of ursodeoxycholic acid per 1 kilogram of body weight per day (see Table 1)
Table 1
Body weight (kg) | Number of tablets |
up to 60 61-80 81-100 more than 100 | 1 1 ½ 2 2 ½ |
The tablets should be swallowed without chewing, with a small amount of liquid, in the evening before bedtime.
The tablets must be taken regularly.
The time required for gallstones to dissolve is usually 6-24 months. If a reduction in the size of the gallstones is not observed after 12 months of treatment, therapy should not be continued.
The success of the treatment should be checked every 6 months by ultrasound or X-ray. Additional tests should be performed to check whether calcification of the stones has occurred over time. If this occurs, treatment should be discontinued.
For the symptomatic treatment of primary biliary cirrhosis (PBC)
The daily dose depends on body weight and varies from 1½ to 3½ tablets (14 ± 2 mg ursodeoxycholic acid per kilogram of body weight), see Table 2.
During the first 3 months of treatment, the drug should be taken throughout the day, dividing the daily dose into several doses. As liver function improves, the daily dose can be taken once a day, in the evening.
Table 2
| Body weight (kg) | Ursosan® forte, tablets, film-coated, 500 mg |
| first 3 months | in the future |
| morning | day | evening | evening (1 time per day) |
| 47-62 | ½ | ½ | ½ | 1 ½ |
| 63-78 | ½ | ½ | 1 | 2 |
| 79-93 | ½ | 1 | 1 | 2 ½ |
| 94-109 | 1 | 1 | 1 | 3 |
| more than 110 | 1 | 1 | 1 ½ | 3 ½ |
The tablets should be swallowed whole with liquid. The drug should be used regularly.
The use of the drug in primary biliary cirrhosis is possible for a long period.
In patients with primary biliary cirrhosis, a rare worsening of clinical symptoms, for example, increased itching, may occur at the beginning of treatment. In this case, therapy should be continued at half a tablet per day, and then the dose should be gradually increased (increasing the daily dose by half a tablet of Ursosan® forte every week until the indicated dosage regimen is reached).
Use in children
Children with cystic fibrosis aged 6 to 18 years
The dose is 20 mg/kg/day and is divided into 2-3 doses with a subsequent increase in the dose to 30 mg/kg/day if necessary.
Table 3
Body weight (kg) | Daily dose (mg/kg) | Ursosan® forte, film-coated tablets, 500 mg |
| morning | day | evening |
| 20 – 29 | 17-25 | ½ | -- | ½ |
| 30 – 39 | 19-25 | ½ | ½ | ½ |
| 40 – 49 | 20-25 | ½ | ½ | 1 |
| 50 – 59 | 21-25 | ½ | 1 | 1 |
| 60 – 69 | 22-25 | 1 | 1 | 1 |
| 70 – 79 | 22-25 | 1 | 1 | 1½ |
| 80 – 89 | 22-25 | 1 | 1½ | 1½ |
| 90 – 99 | 23-25 | 1½ | 1½ | 1½ |
| 100 – 109 | 23-25 | 1½ | 1½ | 2 |
| >110 | 1½ | 2 | 2 | |
Children.
For the dissolution of cholesterol gallstones and symptomatic treatment of PBC
There are no fundamental age restrictions for the use of Ursosan® forte in children, but for children weighing less than 47 kg and/or children who have difficulty swallowing, it is recommended to use ursodeoxycholic acid in a different dosage form.
For the treatment of hepatobiliary disorders in cystic fibrosis
Used for children aged 6 to 18 years.
Overdose
In case of overdose, diarrhea is possible. Other symptoms of overdose are unlikely, since the absorption of ursodeoxycholic acid decreases with increasing dose and therefore most of the dose taken is excreted in the feces.
If diarrhea occurs, the dose should be reduced, and if diarrhea is persistent, therapy should be discontinued.
Treatment is symptomatic and involves restoring fluid and electrolyte balance.
Additional information regarding special patient groups
Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with primary sclerosing cholangitis (off-label use) was associated with a higher incidence of serious adverse events.
Adverse reactions
The estimation of the frequency of undesirable effects is based on the following data:
very common: more than 1 in 10 treated;
common: more than 1 in 100 treated people to 1 in 10 treated people;
uncommon: more than 1 in 1000 treated to 1 in 100 treated;
rare: more than 1 in 10,000 treated to 1 in 1,000 treated;
very rare/not known: in 1 in 10,000 treated/cannot be estimated from the available data.
During clinical trials, pasty stools or diarrhea were commonly reported during treatment with ursodeoxycholic acid.
Very rarely, severe abdominal pain in the right hypochondrium has been noted during the treatment of PBC.
Liver and gallbladder
Very rarely, calcification of gallstones is possible during treatment with ursodeoxycholic acid.
During the treatment of advanced stages of PBC, decompensation of liver cirrhosis is very rarely observed, which partially decreases after discontinuation of treatment.
Hypersensitivity reactions
Very rarely, allergic reactions are possible, including rash and urticaria.
Expiration date
4 years. Do not use after the expiry date stated on the packaging.
Storage conditions
Does not require any special storage conditions. Keep out of the reach of children.
Packaging
10 tablets in a blister; 1 or 2, or 3, or 5, or 6, or 9, or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
PRO.MED.CS Praha a.s.
Location of the manufacturer and address of its place of business
Telčska 377/1, Michle, Prague 4, 140 00, Czech Republic
