Instructions Ursofalk oral suspension 250 mg/5 ml bottle 250 ml
Composition
active ingredient: ursodeoxycholic acid;
5 ml of suspension (one measuring cup) contains 250 mg of ursodeoxycholic acid;
excipients: benzoic acid (E 210), avicel RC-591, sodium chloride, sodium citrate, anhydrous citric acid, glycerin, propylene glycol, xylitol, sodium cyclamate, lemon flavoring, purified water.
Dosage form
Oral suspension.
Main physicochemical properties: white homogeneous suspension with small air bubbles and a lemon odor.
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
Ursodeoxycholic acid is found in small amounts 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 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
Symptomatic treatment of primary biliary cirrhosis (PBC) in the absence of decompensated liver cirrhosis.
For the dissolution of radiopaque cholesterol gallstones no larger than 15 mm in diameter in patients with a functioning gallbladder, despite the presence of gallstone(s).
For the treatment of hepatobiliary disorders in cystic fibrosis in children aged 1 month to 18 years.
Contraindication
Hypersensitivity to bile acids or any of the excipients included in the preparation.
Acute cholecystitis or acute cholangitis.
Biliary obstruction (blockage of the common bile duct or cystic duct).
Frequent attacks of biliary (hepatic) colic.
The presence of radiopaque calcified gallstones.
The contractility of the gallbladder is impaired.
Unsuccessful outcome of portoenterostomy or lack of adequate biliary outflow in children with biliary atresia.
Interaction with other medicinal products and other types of interactions
Ursofalk oral suspension may affect the absorption of cyclosporine from the intestine. In this regard, patients taking cyclosporine should check the concentration of this substance in the blood and, if necessary, adjust the dose.
In some cases, Ursofalk, oral suspension 250 mg/5 ml, may reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers, co-administration of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in a slight increase in plasma concentrations of rosuvastatin. The clinical significance of this interaction, as well as its relevance to other statins, has not been established.
Ursodeoxycholic acid has been shown to reduce the peak plasma concentration (Cmax) and area under the curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Careful monitoring of the outcome of the concomitant use of nifedipine and ursodeoxycholic acid is recommended. An increase in the dose of nifedipine may be required. In addition, a weakening of the therapeutic effect of dapsone has been reported.
These data, as well as in vitro data, suggest that ursodeoxycholic acid has the potential to induce cytochrome P450 3A enzymes. However, in a well-designed interaction study with budesonide, a proven substrate of cytochrome P450 3A, no such effect was observed.
Estrogen hormones, as well as drugs to reduce blood cholesterol concentrations, can increase the secretion of cholesterol by the liver and, thus, contribute to the formation of gallstones, which is the opposite effect of ursodeoxycholic acid, used to dissolve them.
Application features
Ursofalk suspension should be taken under the supervision of a doctor.
During the first three months of treatment, liver function parameters AST (SGOT), ALT (SGPT) and g-GT should be checked every 4 weeks, and then every 3 months. This also allows to determine the presence or absence of 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
To assess the effectiveness of treatment and detect any calcification of gallstones in advance, depending on the size of the stone, it is necessary to conduct an examination of the general appearance of the gallbladder (oral cholecystography) and possible obstruction in the patient's standing and supine positions (ultrasound control) 6–10 months after the start of treatment.
It is not recommended to use Ursofalk, oral suspension 250 mg/5 ml, if the gallbladder is not visualized on X-rays or in the presence of radiopaque calcified gallstones, in case of impaired gallbladder contractility or frequent attacks of biliary (hepatic) colic.
Women taking Ursofalk, oral suspension 250 mg/5 ml, for the dissolution of gallstones should use an effective non-hormonal method of contraception, as hormonal contraceptives may increase the formation of gallstones.
Treatment of patients with advanced stage PBC
Cases of decompensated liver cirrhosis have been reported extremely rarely, which may partially regress after discontinuation of therapy.
In patients with PBC, it is extremely rare for symptoms to worsen at the beginning of treatment, for example, itching may increase. In such cases, the dose of Ursofalk oral suspension should be reduced to 250 mg/5 ml per day; then the dose should be gradually increased as described in the section "Method of administration and dosage".
In case of diarrhea, it is recommended to reduce the dose of the drug, and in case of persistent diarrhea, treatment should be discontinued.
One measuring cup (equivalent to 5 ml) of Ursofalk oral suspension 250 mg/5 ml contains 0.50 mmol (11.39 mg) sodium. Patients on a controlled sodium diet should take this into consideration.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effect on the ability to drive or use other mechanisms was observed.
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 fertility in humans.
There are insufficient data on the use of ursodeoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy. Ursofalk oral suspension 250 mg/5 ml should not be used during pregnancy unless clearly necessary. Women of childbearing potential should only take the drug if they are using reliable contraception.
According to several recorded cases of use of the drug in breastfeeding women, the content of ursodeoxycholic acid in breast milk was extremely low, so no adverse effects should be expected in children receiving such milk.
Method of administration and doses
Opening a bottle with a child-resistant cap
To open the bottle, press the cap down firmly and twist to the left.
The following daily doses are recommended for various indications.
To dissolve cholesterol gallstones
Approximately 10 mg ursodeoxycholic acid/kg body weight per day
| Body weight | Measuring cup * | Equivalent in ml |
| From 5 to 7 kg | ¼ | 1.25 |
| From 8 to 12 kg | ½ | 2.50 |
| From 13 to 18 kg | ¾ (= ¼ + ½) | 3.75 |
| From 19 to 25 kg | 1 | 5.00 |
| From 26 to 35 kg | 1 ½ | 7.50 |
| From 36 to 50 kg | 2 | 10.00 |
| From 51 to 65 kg | 2 ½ | 12.50 |
| From 66 to 80 kg | 3 | 15.00 |
| From 81 to 100 kg | 4 | 20.00 |
| Over 100 kg | 5 | 25.00 |
* 1 measuring cup (= 5 ml of suspension) contains 250 mg of ursodeoxycholic acid.
Ursofalk suspension should be taken in the evening, before bedtime. The suspension should be taken regularly.
The time required for gallstones to dissolve is usually 6–24 months. If a reduction in gallstone size 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 the stones have calcified 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 is approximately 14 ± 2 mg ursodeoxycholic acid/kg body weight.
During the first 3 months of treatment, Ursofalk suspension should be taken throughout the day, dividing the daily dose into several doses. If liver function indicators improve, the daily dose can be taken once a day, in the evening.
| Body weight (kg) | Daily dose (mg/kg body weight) | Measuring cup* of Ursofalk suspension, 250 mg/5 ml | | | |
| first 3 months | in the future | | | | |
| morning | day | evening | evening (once a day) | | |
| 8-11 | 12-16 | | ¼ | ¼ | ½ |
| 12-15 | 12-16 | ¼ | ¼ | ¼ | ¾ |
| 16-19 | 13-16 | ½ | | ½ | 1 |
| 20-23 | 13-15 | ¼ | ½ | ½ | 1 ¼ |
| 24-27 | 13-16 | ½ | ½ | ½ | 1 ½ |
| 28-31 | 14-16 | ¼ | ½ | 1 | 1 ¼ |
| 32-39 | 12-16 | ½ | ½ | 1 | 2 |
| 40-47 | 13-16 | ½ | 1 | 1 | 2 ½ |
| 48-62 | 12-16 | 1 | 1 | 1 | 3 |
| 63-80 | 12-16 | 1 | 1 | 2 | 4 |
| 81-95 | 13-16 | 1 | 2 | 2 | 5 |
| 96-115 | 14-16 | 2 | 2 | 2 | 6 |
| More than 115 | | 2 | 2 | 3 | 7 |
* 1 measuring cup (= 5 ml of suspension) contains 250 mg of ursodeoxycholic acid.
Ursofalk suspension should be taken according to the dosage regimen given in Table 2. It is necessary to adhere to the regularity of administration.
The use of Ursofalk suspension in primary biliary cirrhosis may be unlimited in time.
In patients with primary biliary cirrhosis, a worsening of clinical symptoms, e.g. increased itching, may occur rarely at the beginning of treatment. In such cases, therapy should be continued initially with a reduced daily dose of Ursofalk suspension, and then gradually increased (increase the daily dose weekly) until the indicated dosage regimen is reached.
For the treatment of hepatobiliary disorders in cystic fibrosis
For children with cystic fibrosis aged 1 month to 18 years, the dose is 20 mg/kg/day, divided into 2–3 doses and then increased to 30 mg/kg/day if necessary.
Children weighing less than 10 kg are very rarely affected. In such cases, it is recommended to use disposable syringes, which are available over the counter, for administering the oral suspension.
Single doses for children weighing up to 10 kg should be drawn up with a syringe from the measuring cup provided, up to a volume of 1.25 ml. For this purpose, a 2 ml disposable syringe with a graduation of 0.1 ml is used. Please note that disposable syringes are not included in the package, but are freely sold in pharmacies.
Before opening the glass bottle, it must be shaken. Then you need to pour a small amount of suspension into a measuring cup. Draw a little more suspension than needed into the syringe. Press the syringe plunger with your finger to remove air bubbles from the drawn suspension. Check the volume of suspension in the syringe, adjust if necessary. Carefully introduce the contents of the syringe directly into the child's mouth. Do not draw the suspension into the syringe directly from the bottle. Do not pour unused suspension from the measuring cup or syringe back into the bottle.
Dosage regimen for children weighing less than 10 kg: 20 mg ursodeoxycholic acid/kg/day (volume measuring device – disposable syringe)
| Body weight (kg) | Ursofalk, oral suspension 250 mg/5 ml | |
| Morning | Evening | |
| 4 | 0.8 | 0.8 |
| 4.5 | 0.9 | 0.9 |
| 5 | 1.0 | 1.0 |
| 5.5 | 1.1 | 1.1 |
| 6 | 1.2 | 1.2 |
| 6.5 | 1.3 | 1.3 |
| 7 | 1.4 | 1.4 |
| 7.5 | 1.5 | 1.5 |
| 8 | 1.6 | 1.6 |
| 8.5 | 1.7 | 1.7 |
| 9 | 1.8 | 1.8 |
| 9.5 | 1.9 | 1.9 |
| 10 | 2.0 | 2.0 |
Dosage regimen for children weighing more than 10 kg: 20–25 mg ursodeoxycholic acid/kg/day (volume measuring device – measuring cup)
| Body weight (kg) | Daily dose of ursodeoxycholic acid (mg/kg body weight) | *Measuring cup of Ursofalk 250 mg/5 ml suspension | |
| Morning | Evening | | |
| 11-12 | 21-23 | ½ | ½ |
| 13-15 | 21-24 | ½ | ¾ |
| 16-18 | 21-23 | ¾ | ¾ |
| 19-21 | 21-23 | ¾ | 1 |
| 22-23 | 22-23 | 1 | 1 |
| 24-26 | 22-23 | 1 | 1¼ |
| 27-29 | 22-23 | 1¼ | 1¼ |
| 30-32 | 21-23 | 1¼ | 1½ |
| 33-35 | 21-23 | 1½ | 1½ |
| 36-38 | 21-23 | 1½ | 1¾ |
| 39-41 | 21-22 | 1¾ | 1¾ |
| 42-47 | 20-22 | 1¾ | 2 |
| 48-56 | 20-23 | 2¼ | 2¼ |
| 57-68 | 20-24 | 2¾ | 2¾ |
| 69-81 | 20-24 | 3¼ | 3¼ |
| 82-100 | 20-24 | 4 | 4 |
| >100 | | 4½ | 4½ |
* Conversion table
| Volume | Equivalent volume of oral suspension | Equivalent amount of ursodeoxycholic acid |
| 1 bottle | 5 ml | 250 mg |
| ¾ bottle | 3.75 ml | 187.5 mg |
| ½ bottle | 2.5 ml | 125 mg |
| ¼ bottle | 1.25 ml | 62.5 mg |
Children
For the dissolution of cholesterol gallstones and symptomatic treatment of PBC.
There are no age restrictions for the use of this medicine. Dosage according to the section "Method of administration and doses".
For the treatment of hepatobiliary disorders in cystic fibrosis.
Use in children from 1 month of age.
Overdose
Overdose may cause diarrhea. Overdose is unlikely, as the absorption of ursodeoxycholic acid decreases with increasing dose and most of it is excreted in the feces.
In case of diarrhea, the dose should be reduced; if diarrhea persists, therapy should be discontinued.
No specific countermeasures are necessary; the effects of diarrhea should be treated symptomatically, maintaining 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 assessment of the frequency of adverse events is based on the following data:
Very common: >1/10; Common: >1/100 and <1/10; Uncommon: >1/10 00 and <1/100; Rare: >1/10,000 and <1/1,000; Very rare: <1/10,000, including isolated cases.
Gastrointestinal side effects
There have been frequent reports of loose stools or diarrhea during ursodeoxycholic acid therapy.
Very rarely, severe pain in the right upper abdominal cavity has been observed during the treatment of primary biliary cirrhosis.
Liver and gallbladder disorders
Calcification of gallstones is very rarely possible during treatment with ursodeoxycholic acid.
During the treatment of advanced stages of primary biliary cirrhosis, decompensation of liver cirrhosis was very rarely observed, which partially regressed after discontinuation of treatment.
Hypersensitivity reactions
Very rarely, rashes (urticaria) are possible.
Expiration date
4 years.
The shelf life after opening the bottle is 4 months.
The medicine cannot be used 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
Oral suspension (250 mg/5 ml), 250 ml in a glass bottle together with a measuring cup in a cardboard box.
Vacation category
According to the recipe.
Producer
Location of the manufacturer and its business address
Leinenweberstrasse 5, 79108 Freiburg, Germany.
