Each film-coated tablet contains: Ursodeoxycholic acid 250 mg.
Pharmacotherapeutic group: Bile acid preparations. ATC Code: A05AA02 and A05B.
Pharmacology: Pharmacodynamics: Small amounts of ursodeoxycholic acid are found 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 effect of ursodeoxycholic acid in hepatic and cholestatic diseases is thought to be due to a relative exchange of lipophilic, detergent-like, toxic bile acids for the hydrophilic, cytoprotective, non-toxic ursodeoxycholic acid, to an improvement in the secretory capacity of the hepatocytes, and 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%.
Depending on the daily dose and underlying disorder or condition of the liver, the more hydrophilic ursodeoxycholic acid accumulates in the bile. At the same time, a relative decrease in other more hydrophilic bile acids is observed.
Under the influence of intestinal bacteria, there is a partial degradation to 7-keto-lithocolic acid ad lithocolic acid.
Lithocolic acid is hepatotoxic and causes liver parenchyma damage in a number of animal species. In human, only very small amounts are absorbed which are sulphated in the liver and thus detoxified, before excreted in the bile and ultimately in the faeces.
The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.
Toxicology: Preclinical Safety Data: Acute toxicity: Acute toxicity studies in animals have not revealed any toxic damage.
Chronic toxicity: Subchronic toxicity studies in monkeys showed hepatotoxic effects in the groups given high doses, including functional changes (eg, liver enzyme changes) and morphological changes such as bile duct proliferation, port inflammatory foci and hepatocellular necrosis.
These toxic effects are most likely attributable to lithocolic acid, a metabolite of ursodeoxycholic acid, which in monkeys, unlike humans is not detoxified. Clinical experience confirms that the described hepatotoxic effects are of no apparent relevance in humans.
Mutagenic and tumorigenic potential: Long-term studies in mice and rats revealed no evidence of ursodeoxycholic acid having tumorigenic potential.
In vitro and in vivo genetic toxicology tests with ursodeoxycholic acid were negative.
Toxicity to reproduction: In studies in rats, tail malformation occurred after a dose of 2,000 mg ursodeoxycholic acid/kg body weight. In rabbits, no teratogenic effects were found, although there were embryotoxic effects (from a dose of 100 mg/kg body weight). Ursodeoxycholic acid had no effect on fertility in rats and did not affect perinatal/postnatal development of the offspring.
Used for the dissolution of cholesterol-rich gallstones in patients with functioning gallbladders. It is also used in primary biliary cirrhosis.
The use of Axialith is not age-restricted.
The following daily dose is recommended for various indications: To dissolve gallstones: 250 mg Axialith: Approx 10 mg Ursodeoxycholic acid per kg body weight, equivalent to: Up to 60 kg 2 film-coated tablets (equivalent to 500 mg ursodeoxycholic acid); 61-80 kg 3 film-coated tablets (equivalent to 750 mg ursodeoxycholic acid); 81-100 kg 4 film-coated tablets (equivalent to 1,000 mg ursodeoxycholic acid); above 100 kg 5 film-coated tablets (equivalent to 1,250 mg ursodeoxycholic acid).
The film-coated tablets should be taken unchewed together with some liquid in the evening before going to bed.
The tablets must be taken at regular intervals.
The duration until the gallstones have dissolved is generally 6-24 months. If the gallstones have not reduced in size after 12 months, therapy should not be continued.
The success of treatment should be reviewed by sonography or x-ray every 6 months. It should be checked in the follow ups whether the stones have calcified in the meantime. If this is the case, treatment should be discontinued.
For symptomatic treatment of primary biliary cirrhosis (PBC): The daily dose depends on the body weight ad is between 3 and 7 film-coated tablets (250 mg Axialith) (14±2 mg ursodeoxycholic acid per kg body weight.
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Intake of Axialith for primary biliary cirrhosis (PBC) may be continued indefinitely.
In patients with primary biliary cirrhosis (PBC), clinical symptoms can worsen in rare cases at the beginning of treatment, eg the itching may increase. If this is the case, therapy should be continued with 1 film-coated tablet of 250 mg Axialith daily; therapy should be continued gradually (increase in the daily dose by 1 film-coated tablet of 250 mg Axialith per week) until the recommended dosage has been reached.
Diarrhoea may occur in cases of overdoses. In general, other symptoms of overdose are unlikely because absorption of ursodeoxycholic acid decreases with increasing dose and therefore more is excreted with the faeces.
No specific counter measures are necessary and the consequences of diarrhea should be treated symptomatically with restoration of fluid and electrolyte balance.
Axialith must not be used in cases of: Hypersensitivity to bile acids or to any of the excipients; acute inflammations of the gallbladder and biliary tract; occlusion of the biliary tract (choledochal or cystic duct obstruction); frequent episodes of biliary colic; radio-opaque calcified gallstones; impaired contractility of the gallbladder.
Axialith should be taken under medical supervision.
During the first 3 months of treatment, liver function parameters AST (SGOT), ALT (SGPT) and gamma-GT should be monitored by the physician every 4 weeks, thereafter every 3 months. This monitoring would enable early detection of potential hepatic dysfunction, particularly in patients with advanced stage of primary biliary cirrhosis.
In addition, it will be detected in good time whether a patient with primary biliary cirrhosis responds to treatment.
When used for dissolution of cholesterol gallstones: In order to assess therapeutic progress and for timely detection of any calcification of the gallstones, depending on stone size, the gallbladder should be visualized (oral cholecystography) with overview and occlusion views in standing and supine positions (ultrasound control) 6-10 months after the beginning of treatment.
If the gallbladder cannot be visualized on x-ray images, or in cases of calcified gallstones, impaired contractibility of the gallbladder and or frequent episodes of biliary colic, Axialith should not be used.
When used for the treatment of patients with primary biliary cirrhosis in advanced stage: In very rare cases, decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
If diarrhoea occurs, the dose must be reduced and in cases of persistent diarrhoea, the therapy should be discontinued.
Interaction with other medicinal products and other forms of interaction: Axialith should not be administered concomitantly with colestyramine, colestipol or antacids containing aluminum hydroxide and/or smectite (aluminum oxide), because these preparations bind ursodeoxycholic acid in the intestines and thereby inhibits 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 ursodeoxycholic acid.
Axialith can increase the absorption of ciclosporin from the intestine. In patients receiving ciclosporin treatment, blood concentrations of these substances should therefore be checked by the physician and the ciclosporin dose adjusted if necessary.
In isolated cases, Axialith can reduce the absorption of ciclosporin.
Ursodeoxycholic acid has been shown to reduce the plasma peak concentration (Cmax) and the area under the curve (AUC) of the calcium antagonist nitrendipine. A reduction in the therapeutic effect of dapsone was also reported.
These observations together with in vitro findings could indicate a potential for ursodeoxycholic acid to induce cythochrome P450 3A enzymes. Controlled clinical trials have shown, however, that ursodeoxycholic acid does not have a relevant induction effect on cythochrome P450 3A enzymes.
Oestrogenic hormones and blood cholesterol-lowering substances such as clofibrate may increase biliary lithiasis, which is a counter effect to ursodeoxycholic acid used for dissolution of gallstones.
Effects on the Ability to Drive and Use Machines: No effects on the ability to drive and use machines have been observed.
There are no adequate data on the use of ursodeoxycholic acid, particularly in the first trimester of pregnancy. Animal studies have provided evidence of teratogenic effect during the early phase of gestation. Axialith must not be used during pregnancy unless clearly necessary. Women of child-bearing potential should be treated only if they use reliable contraception; non-hormonal or low-estrogen oral contraceptive measures are recommended. However, in patients taking Axialith for dissolution of gallstones, effective non-hormonal contraception should be used, since hormonal oral contraceptives may increase biliary lithiasis. The possibility of a pregnancy must be excluded before beginning treatment.
It is not known whether ursodeoxycholic acid passes into breast milk. Therefore, Axialith should not be taken during lactation. If treatment with Axialith is necessary, the infant should be weaned.
The evaluation of undesirable effects is based on the following frequency data: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
In clinical trials, reports of pasty stools or diarrhea during ursodeoxycholic acid therapy were common.
Very rarely, severe right upper abdominal pain has occurred during the treatment of primary biliary cirrhosis.
During treatment with ursodeoxycholic acid, calcification of gallstones can occur in very rare cases.
During therapy of advanced stages of primary biliary cirrhosis, in very rare cases, decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
Skin and subcutaneous tissue disorders:
Very rarely, urticaria can occur.
Special precautions for storage: This medicinal product do not require any special storage conditions.
Incompatibilities: None known.
Store at temperatures not exceeding 25°C.
A05AA02 - ursodeoxycholic acid ; Belongs to the class of bile acids. Used in bile therapy.