Urdoxa® 500 (Tablets) Instructions for Use
Marketing Authorization Holder
Aliym, JSC (Russia)
Contact Information
BINNOPHARM GROUP LLC (Russia)
ATC Code
A05AA02 (Ursodeoxycholic acid)
Active Substance
Ursodeoxycholic acid (Rec.INN registered by WHO)
Dosage Form
 |
Urdoxa® 500 | Film-coated tablets, 500 mg: 10, 30, 50, or 100 pcs. |
Dosage Form, Packaging, and Composition
Film-coated tablets white or almost white, oblong in shape with rounded ends, biconvex, with a score; the core on the cross-section is white or almost white; the tablet can be divided into equal doses.
| 1 tab. | |
| Ursodeoxycholic acid | 500 mg |
Excipients: microcrystalline cellulose, colloidal silicon dioxide (aerosil), povidone K-30, polysorbate 80 (tween 80), crospovidone, talc, magnesium stearate, hypromellose (hydroxypropyl methylcellulose), macrogol 6000 (polyethylene glycol 6000), talc.
10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
20 pcs. – blister packs (5) – cardboard packs.
Clinical-Pharmacological Group
Hepatoprotective agent with choleretic and cholelitholytic action
Pharmacotherapeutic Group
Drugs for the treatment of liver and biliary tract diseases; drugs for the treatment of biliary tract diseases; bile acid preparations; ursodeoxycholic acid
Pharmacological Action
A small amount of ursodeoxycholic acid is contained in bile.
After oral administration, Ursodeoxycholic acid reduces the cholesterol saturation of bile by inhibiting cholesterol absorption in the intestine and reducing its secretion into bile. Presumably, as a result of cholesterol dispersion and the formation of liquid crystals, gradual dissolution of cholesterol stones in the gallbladder occurs.
According to modern concepts, the action of ursodeoxycholic acid in liver diseases and cholestatic diseases is associated with the relative exchange of lipophilic, detergent-like, toxic bile acids for hydrophilic cytoprotective non-toxic ursodeoxycholic acid, which leads to an improvement in the secretory function of hepatocytes and immunoregulatory processes.
Children
Cystic fibrosis
According to clinical reports, there is long-term experience (up to 10 years and more) of treating pediatric patients suffering from hepatobiliary disease associated with cystic fibrosis with ursodeoxycholic acid. There is evidence that therapy with ursodeoxycholic acid can reduce bile duct proliferation, slow the progression of damage detected by histological examination, and even promote the regression of hepatobiliary system changes if therapy is started at early stages. To optimize the effectiveness of treatment, ursodeoxycholic acid therapy should be started as early as possible after diagnosis.
Pharmacokinetics
Absorption
After oral administration, Ursodeoxycholic acid is rapidly absorbed in the jejunum and proximal ileum by passive diffusion, and in the distal ileum by active transport. Approximately 60-80% is absorbed.
Distribution
Depending on the daily dose, the type of disease, or the condition of the liver, a larger amount of ursodeoxycholic acid accumulates in the bile. At the same time, a relative decrease in the content of other more lipophilic bile acids is observed.
Metabolism
After absorption, Ursodeoxycholic acid is almost completely conjugated in the liver with glycine and taurine and excreted in the bile. Up to 60% is metabolized during the “first pass” through the liver.
Under the action of intestinal bacteria, Ursodeoxycholic acid is partially decomposed to form 7-keto-lithocholic and lithocholic acids. Lithocholic acid is hepatotoxic; in some animal species, it causes damage to the liver parenchyma. In the human body, it is absorbed only in small amounts, sulfated in the liver, and thus detoxified before excretion into the bile and elimination in the feces.
Elimination
The T1/2 of ursodeoxycholic acid is 3.5-5.8 days.
Indications
The drug Urdoxa® 500 is indicated for use in adults and children aged 3 years and older.
Dissolution of cholesterol gallstones not exceeding 15 mm in diameter with normal gallbladder contractility.
As part of complex therapy
- Primary biliary cirrhosis without signs of decompensation;
- Treatment of biliary reflux gastritis;
- Primary sclerosing cholangitis;
- Non-alcoholic steatohepatitis;
- Cystic fibrosis (as part of complex therapy) in adults and children over 6 years of age
ICD codes
| ICD-10 code | Indication |
| E84 | Cystic fibrosis |
| E84.8 | Cystic fibrosis with other manifestations |
| E84.9 | Cystic fibrosis, unspecified |
| K74.3 | Primary biliary cirrhosis |
| K76.0 | Fatty (change of) liver, not elsewhere classified |
| K80 | Cholelithiasis [cholelithiasis] (including biliary colic) |
| K83 | Other diseases of biliary tract |
| K83.0 | Cholangitis |
| ICD-11 code | Indication |
| CA25.2 | Subclinical cystic fibrosis |
| CA25.Z | Cystic fibrosis, unspecified |
| DB92.0 | Non-alcoholic fatty liver disease without steatohepatitis |
| DB92.Y | Other specified non-alcoholic fatty liver disease |
| DB92.Z | Non-alcoholic fatty liver disease, unspecified |
| DB96.1Z | Primary biliary cholangitis, unspecified |
| DC10.Z | Acquired structural (organic) changes of gallbladder or bile ducts, unspecified |
| DC11.Z | Cholelithiasis, unspecified |
| DC13 | Cholangitis |
| DC14.Z | Diseases of the biliary tract, unspecified |
| DC1Z | Diseases of gallbladder and biliary tract, unspecified |
| CA25.0 | Classic cystic fibrosis |
| 8C03.Y | Other specified secondary polyneuropathy |
| CA25.1 | Atypical cystic fibrosis |
| FB83.14 | Osteoporosis due to malabsorption |
Dosage Regimen
| The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen. |
For oral administration.
The tablets should be swallowed whole, without chewing, with liquid.
For patients who cannot swallow Urdoxa® 500 tablets or with a body weight of less than 47 kg, it is recommended to use ursodeoxycholic acid in capsules or suspension.
Dissolution of cholesterol gallstones
The recommended dose is 10 mg of ursodeoxycholic acid per 1 kg of body weight per day, which corresponds to
| Body weight (kg) | Daily dose (mg/kg) | Body weight (kg) | Daily dose (mg/kg body weight) |
Urdoxa® 500, film-coated tablets, 500 mg | ||
| morning | noon | evening | ||||
| 20-29 | 17-25 | 0.5 | – | 0.5 | ||
| 30-39 | 19-25 | 0.5 | ? | 0.5 | ||
| 40-49 | 20-25 | 0.5 | ? | 1 | ||
| 50-59 | 21-25 | 0.5 | 1 | 1 | ||
| 60-69 | 22-25 | 1 | 1 | 1 | ||
| 70-79 | 22-25 | 1 | 1 | 1.5 | ||
| 80-89 | 22-25 | 1 | 1.5 | 1.5 | ||
| 90-99 | 23-25 | 1.5 | 1.5 | 1.5 | ||
| 100-109 | 23-25 | 1.5 | 1.5 | 2 | ||
| > 110 | – | 1.5 | 2 | 2 | ||
Children
The dosage regimen for children aged 3 to 18 years does not differ from the dosage regimen for adults.
Children under 3 years of age are recommended to take ursodeoxycholic acid in the form of a suspension.
Adverse Reactions
Adverse reactions are grouped by MedDRA system-organ class with the frequency of their occurrence according to the WHO classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).
Gastrointestinal disorders in clinical studies, unformed stools or diarrhea were commonly observed during treatment with ursodeoxycholic acid.
Hepatobiliary disorders in very rare cases, calcification of gallstones may occur during treatment with ursodeoxycholic acid. In the treatment of advanced stages of primary biliary cirrhosis, in very rare cases, decompensation of liver cirrhosis was observed, which regresses after discontinuation of the drug.
Skin and subcutaneous tissue disorders in very rare cases, allergic reactions, including urticaria, may occur.
It is important to report suspected adverse reactions after registration of the drug in order to ensure continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.
Contraindications
- Hypersensitivity to ursodeoxycholic acid, other bile acids, or to any of the excipients included in the drug;
- Radiopaque (calcified) gallstones;
- Impaired gallbladder contractility;
- Acute inflammation of the gallbladder and biliary tract;
- Occlusion of the biliary tract (blockage of the common bile duct or cystic duct);
- Frequent episodes of biliary colic;
- Children under 3 years of age (for this dosage form);
- Decompensated liver cirrhosis;
- Severe hepatic and/or renal failure.
Pediatric population
- Failed portoenterostomy or without restoration of normal bile flow in children with biliary atresia.
Use in Pregnancy and Lactation
Pregnancy
Data on the use of ursodeoxycholic acid in pregnant women are limited or absent. Animal studies have shown reproductive toxicity in early pregnancy. During pregnancy, the drug Urdoxa® 500 should not be used, except when clearly necessary.
Lactation
According to several documented cases, the level of ursodeoxycholic acid in breast milk in women is very low, and therefore the occurrence of adverse reactions in breastfed children is not expected.
Fertility
According to animal studies, Ursodeoxycholic acid does not affect fertility. There are no data on the effect of ursodeoxycholic acid treatment on human fertility.
Use of the drug by women of childbearing potential is possible only if they use reliable methods of contraception. It is recommended to use non-hormonal contraceptives or oral contraceptives with low estrogen content, since hormonal oral contraceptives may increase gallstone formation. Before starting treatment, possible pregnancy should be excluded.
Use in Hepatic Impairment
Contraindicated in severe hepatic failure, in decompensated liver cirrhosis.
Use in Renal Impairment
Contraindicated in severe renal failure.
Pediatric Use
Contraindicated in children under 3 years of age for this dosage form.
Contraindicated in children and adolescents under 18 years of age with failed portoenterostomy or without restoration of normal bile flow in children with biliary atresia.
Special Precautions
Administration of the drug Urdoxa® 500 should be carried out under medical supervision. During the first 3 months of treatment, liver function parameters (AST, ALT, and GGT) should be monitored every 4 weeks, and then every 3 months. Such monitoring will allow for the early detection of potential deterioration of liver condition, especially in patients with late-stage primary biliary cirrhosis. In addition, this can quickly determine whether a patient with primary biliary cirrhosis is responding to the treatment.
When used in patients for dissolution of cholesterol gallstones
To assess treatment progress and for the timely detection of signs of stone calcification depending on the size of the stones, the gallbladder should be visualized (oral cholecystography) with examination of opacities in the “standing” and “supine” positions (ultrasound) 6-10 months after the start of treatment.
If the gallbladder cannot be visualized on X-rays or in cases of stone calcification, weak gallbladder contractility, or frequent colic attacks, the drug Urdoxa® 500 should not be used.
When treating patients with late stages of primary biliary cirrhosis
Very rarely, cases of decompensation of liver cirrhosis have been noted after discontinuation of therapy.
In patients with primary biliary cirrhosis, in rare cases at the beginning of treatment, an increase in clinical symptoms may occur, for example, itching may intensify. In this case, the dose of the drug must be reduced to 250 mg (0.5 tablet), and then gradually increased again, as described in the “Dosage Regimen” section.
When used in patients with primary sclerosing cholangitis
Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with this pathology may cause serious adverse reactions.
In patients with diarrhea, the dose of the drug should be reduced. If diarrhea persists, treatment should be discontinued.
Effect on ability to drive vehicles and operate machinery
Ursodeoxycholic acid does not affect the ability to drive vehicles and operate machinery, or this effect is minimal.
Overdose
Symptoms in case of overdose, diarrhea is possible. In general, other symptoms of overdose are unlikely, since with an increase in the dose of ursodeoxycholic acid, its absorption decreases and excretion in feces increases.
Treatment specific treatment is not required, the consequences of diarrhea are treated symptomatically with restoration of water-electrolyte balance.
Drug Interactions
Cholestyramine, colestipol, and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its uptake and effectiveness. If the use of drugs containing at least one of these substances is still necessary, they should be taken at least 2 hours before taking the drug Urdoxa® 500.
Ursodeoxycholic acid may affect the absorption of cyclosporine from the intestine. Therefore, in patients simultaneously taking cyclosporine, the concentration of cyclosporine in the blood should be determined and, if necessary, the dose of cyclosporine should be adjusted.
Ursodeoxycholic acid may reduce the absorption of ciprofloxacin.
In a clinical study involving healthy volunteers, the simultaneous use of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) led to a slight increase in the plasma level of rosuvastatin. The clinical significance of this interaction, including in relation to other statins, is unknown.
It has been proven that Ursodeoxycholic acid reduces the Cmax and AUC of the calcium antagonist nitrendipine. In case of simultaneous use of nitrendipine and ursodeoxycholic acid, careful monitoring is recommended. An increase in the dose of nitrendipine may be required. In addition, a decrease in the therapeutic effect of dapsone has been reported.
This information, as well as data obtained in vitro, suggest that Ursodeoxycholic acid may induce cytochrome P450 (CYP) 3A isoenzymes. However, the results of controlled clinical studies indicate that Ursodeoxycholic acid does not have a pronounced inducing effect on the CYP3A isoenzyme.
Estrogens, hypolipidemic drugs such as clofibrate, increase cholesterol secretion in the liver and may reduce the litholytic effect of ursodeoxycholic acid.
Storage Conditions
The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).
Shelf Life
Shelf life – 3 years.
Dispensing Status
The drug is dispensed by prescription.
Important Safety Information
This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.
Medical Disclaimer![Urdoxa® 500 [Tablets] 1](https://www.medixlife.com/wp-content/uploads/Medixlife_favi_512.png "Urdoxa® 500 [Tablets] 2")