Ursofalk

Ursodeoxycholic acid.

Active Substance: One Ursofalk capsule contains 250 mg of ursodeoxycholic acid.
Excipients/Inactive ingredients: Maize starch, Silica colloidal anhydrous, magnesium stearate, titanium dioxide [E171], sodium dodecyl sulphate, gelatin, water.

Pharmacology: Pharmacodynamics: Small amounts of ursodeoxycholic acid occur naturally in human bile.
After oral administration, it reduces cholesterol saturation of the bile by inhibiting cholesterol absorption in the intestine and decreasing cholesterol secretion into the bile. Presumably as a result of dispersion of the cholesterol and formation of liquid crystals, a gradual dissolution of cholesterol gallstones occurs.
According to current knowledge, the effects of ursodeoxycholic acid in hepatic and cholestatic diseases are thought to be due to a relative exchange of lipophilic, detergent-like, toxic bile acids for the hydrophilic, cytoprotective, non-toxic ursodeoxycholic acid, together with an improvement in the secretory capacity of the hepatocytes, as well as to immune-regulatory processes.
Pharmacokinetics: Orally administered ursodeoxycholic acid is rapidly absorbed in the jejunum and upper ileum through passive transport and in the terminal ileum through active transport. The rate of absorption is generally 60 - 80 %. After absorption, the bile acid undergoes almost complete hepatic conjugation with the amino acids glycine and taurine and is then excreted with the bile. First-pass clearance through the liver is up to 60 %.Under the influence of intestinal bacteria, there is partial degradation to 7-keto-lithocholic acid and lithocholic acid. Lithocholic acid is hepatotoxic and causes liver parenchyma damage in a number of animal species. In humans, only very small amounts are absorbed which are sulphated in the liver and thus detoxified, before being excreted in the bile and ultimately in the faeces.
The biological half-life of ursodeoxycholic acid is 3.5 - 5.8 days.

Dissolution of radiolucent cholesterol gallstones in the gallbladder less than 15 mm in diameter.
The gallstones must be radiolucent, and the gallbladder function must be intact; dissolution of gallstones with or without proceeding extracorporeal shock wave lithotripsy.
Cholestatic liver disease (e.g. compensated primary biliary cirrhosis, cholestasis of pregnancy).

For dissolution of cholesterol gallstones (approx. 10mg per kg bodyweight daily): (see Table 1).

Click on icon to see table/diagram/image

For the treatment of cholestatic liver disease: The daily dose depends on bodyweight, and is approx. 2 to 6 capsules (approx. 10 to 15 mg ursodeoxycholic acid per kg bodyweight). (See Table 2.)

Click on icon to see table/diagram/image

Route and duration of administration: Swallow the capsules whole with some liquid. Take the capsules regularly.
Dissolution of gallstones generally takes from 6 to 24 months to dissolve. If the gallstones have not become smaller after 12 months, do not continue treatment. The results of therapy should be monitored by ultrasonography or X-ray every 6 months.

Symptoms and treatment of overdosage: Following overdose, diarrhea may occur. In general, overdose is extremely unlikely, as the absorption rate of ursodeoxycholic acid decreases with increasing dosage, and the substance is thus increasing eliminated in faeces.
In cases of diarrhea it is advisable to reduce the dose. If diarrhea does not subside, therapy should be discontinued.
No specific counter-measures are necessary and the consequences of diarrhea should be treated symptomatically with restoration of fluid and electrolyte balance.

Ursofalk must not be used in the presence of: acute inflammation of the gallbladder and bile ducts; occlusion of the biliary tract (common bile duct).
Ursofalk should not be taken where the gallbladder cannot be visualized at X-ray, in patients with calcified or X-ray dense gallstones (non-cholesterol gallstones), disturbed contractility of the gallbladder, gallbladder filled more than half with gallstones, occlusion of ductus cysticus, frequent biliary colic.

Ursofalk capsules should be taken under medical supervision.
In the first 3 months of treatment, liver function parameters AST (SGOT), ALT (SGPT) and γ-GT) should be monitored by the physician every 4 weeks, thereafter every 3 months.
In order to assess therapeutic progress and for prompt detection of any calcification of the gallstones, depending on stone size, the gall bladder should be visualised (oral cholecystography) with overview and occlusion views in standing and supine positions (ultrasound control) 6 - 10 months after the beginning of treatment.
Use in pregnancy and lactation: Animal trials report evidence of possible teratogenic effects. There are no related data on use in man.
Women of child-bearing age should only receive ursodeoxycholic acid if they are using reliable contraceptive methods. It should be ensure that the patient is not pregnant before commencing therapy.
For reasons of safety, it is advisable not the use Ursofalk during the first three months of pregnancy and during lactation.

Animal trials report evidence of possible teratogenic effects. There are no related data on use in man.
Women of child-bearing age should only receive ursodeoxycholic acid if they are using reliable contraceptive methods. It should be ensure that the patient is not pregnant before commencing therapy.
For reasons of safety, it is advisable not the use Ursofalk during the first three months of pregnancy and during lactation.

The evaluation of undesirable effects is based on the following frequency data: (see Table 3.)

Click on icon to see table/diagram/image

Gastrointestinal side effects: In clinical trials, reports of pasty stools or diarrhoea during ursodeoxycholic acid therapy were common.
Very rarely, severe right-side upper abdominal pain has occurred during the treatment of primary biliary cirrhosis.
Hepatobiliary disorders: During treatment with ursodeoxycholic acid, calcification of gallstones can occur in very rare cases.
During therapy of the advanced stages of primary biliary cirrhosis, in very rare cases decompensation of the hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
Hypersensitivity reactions: Very rarely, urticaria can occur.

Ursofalk capsules should not be administered concomitantly with colestyramine, colestipol or antacids containing aluminium hydroxide and/or smectite (aluminium oxide), because these preparations bind ursodeoxycholic acid in the intestine and thereby reduce its absorption and efficacy. Should the use of a preparation containing one of these substances be necessary, it must be taken at least 2 hours before or after Ursofalk capsules.
Ursofalk capsules can increase the absorption of ciclosporin from the intestine. In patients receiving ciclosporin treatment, blood concentrations of this substance should therefore be checked by the physician and the ciclosporin dose adjusted if necessary.
In isolated cases, Ursofalk capsules can reduce the absorption of ciprofloxacin.
Ursodeoxycholic acid reduces peak plasma concentrations (C_max) and area under the curve (AUC) of the calcium antagonist nitrendipine. On the basis of this, together with a single case report of an interaction with the substance dapsone (reduction of the therapeutic effect) and in-vitro findings, it may be assumed that ursodeoxycholic acid induces the drug-metabolising enzyme cytochrome P450 3A4.Caution should therefore be exercised in cases of co-administration of drugs metabolised via this enzyme, and a dose adjustment may be necessary.

Store at 25°C or below.

Cholagogues, Cholelitholytics & Hepatic Protectors

A05AA02 - ursodeoxycholic acid ; Belongs to the class of bile acids. Used in bile therapy.

C