Phosphogliv URSO capsules 35mg+250mg, 50pcs

Composition

Composition per capsule:

Active ingredients:

ursodeoxycholic acid-250.0 mg,

sodium glycyrrhizinate in terms of 100% substance (trisodium salt of glycyrrhizic acid) – 35.0 mg.

Excipients: microcrystalline cellulose M 101-30.5 mg, sodium croscarmellose-6.6 mg, hyprolose (hydroxypropylcellulose) – 3.3 mg, magnesium stearate-2.8 mg, colloidal silicon dioxide (aerosil) – 1.8 mg.

The composition of the capsule shell (body and lid): titanium dioxide (E 171) – 1.92 mg, gelatin-94.08 mg

Pharmacological action

Pharmacotherapy group: drugs for the treatment of the liver and biliary tract in combination.

ATX code: A 05 C

Pharmacological properties

Pharmacodynamics

The combined drug, a hepatoprotective agent, also has choleretic, cholelitolytic, antioxidant, anti-inflammatory effects, affects fibrogenesis.

Ursodeoxycholic acid

Ursodeoxycholic acid has a choleretic effect. Reduces the synthesis of cholesterol in the liver, its absorption in the intestines and concentration in bile, increases the solubility of cholesterol in the biliary system, stimulates the formation and excretion of bile. Reduces the lithogenicity of bile, increases the content of bile acids in it; causes increased gastric and pancreatic secretion, increases the activity of lipase, has a hypoglycemic effect. Causes partial or complete dissolution of cholesterol stones with enteral application, reduces the saturation of bile with cholesterol, which contributes to the mobilization of cholesterol from gallstones. It has an immunomodulatory effect, affects immunological reactions in the liver: reduces the expression of certain antigens on the hepatocyte membrane, affects the number of T-lymphocytes, the formation of intraleukin-2, reduces the number of eosinophils.

Glycyrrhizic Acid

It has a hepatoprotective effect due to antioxidant, anti-inflammatory effects, as well as an effect on fibrogenesis.

Glycyrrhizic acid binds free oxygen radicals and inhibits enzymes that initiate lipid peroxidation (LPO) in hepatocytes.

Glycyrrhizic acid reduces inflammation by inhibiting the NF-kB and TLR4 signaling pathways; inhibiting the production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-8); and stimulating the production of anti-inflammatory cytokines (IL-2, IL-10, IL-12). Glycyrrhizic acid inhibits 11b-oxysteroid dehydrogenase, which contributes to an increase in endogenous cortisol in the blood (pseudocorticosteroid effect).

The effect on fibrogenesis is associated with a decrease in the expression of the type 1 collagen gene and a decrease in the production of collagen by stellate liver cells (Ito cells), as well as the destruction of activated Ito cells through the natural killer system, which helps slow down the progression of fibrosis.

Pharmacokinetics

Ursodeoxycholic acid

After oral use, 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.

After absorption, ursodeoxycholic acid is almost completely conjugated in the liver with glycine and taurine and is excreted in the bile. At the first passage through the liver, up to 60% is metabolized.

Depending on the daily dose, type of disease, or liver condition, more or less ursodeoxycholic acid accumulates in the bile. At the same time, there is a relative decrease in the content of other more lipophilic bile acids.

Under the action of intestinal bacteria, ursodeoxycholic acid partially decomposes to form 7-keto-litocholic and litocholic acids. In the human body, litocholic acid is absorbed only in small amounts, sulfated in the liver, excreted in the bile and excreted in the feces.

The elimination half-life of ursodeoxycholic acid is 3.5-5.8 days.

Glycyrrhizic Acid

After oral use in the intestine, under the influence of the enzyme β-glucuronidase, produced by bacteria of normal microflora, glycyrrhizic acid forms an active metabolite-β-glycyrrhetic acid, which is absorbed into the systemic circulation. The maximum concentration (cmax) of β-glycyrrhetic acid in blood plasma is reached after 11 hours, amounting to 267.319 ng / ml. The area under the pharmacokinetic curve (AUC_{0 -∞}) is 5123.9 ng * h / ml. In the blood, beta-glycyrrhetic acid binds to albumin and is almost completely transported to the liver. The release of β-glycyrrhetoic acid occurs mainly with bile, in the residual amount – with urine. The elimination half-life reaches 19.23 hours.

Indications

-non-alcoholic steatohepatitis;

– alcoholic liver disease;

– chronic hepatitis of various origins;

– biliary reflux gastritis;

– biliary dyskinesia;

– dissolution of cholesterol gallstones;

– primary biliary cirrhosis of the liver in the absence of signs of decompensation;

– primary sclerosing cholangitis.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (due to insufficient data on its use in these groups of patients).

Contraindications

-hypersensitivity to the components of the drug or other bile acids; – X-ray positive (with a high content of calcium) gallstones; – violation of the contractility of the gallbladder;- frequent episodes of biliary colic; – biliary tract occlusion (occlusion of the common bile duct or cystic duct);- acute inflammatory diseases of the gallbladder and bile ducts;- cirrhosis of the liver in the stage of decompensation;- severe hepatic insufficiency and / or renal insufficiency;- pregnancy;- breast – feeding period; – children under 12 years of age; – adults and children weighing up to 47 kg (for this dosage form) – unsuccessfully performed portoenterostomy or cases of lack of restoration of normal bile flow in children with biliary tract atresia.

With caution – in patients with portal hypertension;- in patients with arterial hypertension.

Side effects

The assessment of adverse events is based on the following classification: :

Very common (≥1/10), common (≥1/100 – <1/10), infrequent (≥1/1000 – <1/100), rare (≥1/10000 – <1/1000), very rare (

Disorders of the gastrointestinal tract:

often-unformed stools or diarrhea; very rarely-dyspepsia (belching, nausea, bloating), abdominal discomfort, acute pain in the upper right part of the abdomen.

Liver and biliary tract disorders:

very rarely – calcification of gallstones, decompensation of liver cirrhosis (in the treatment of advanced stages of primary biliary cirrhosis), which disappears after discontinuation of the drug.

From the cardiovascular system: very rarely – transient increase in blood pressure, peripheral edema.

Allergic reactions:  very rarely – urticaria, skin rash, difficulty in nasal breathing, conjunctivitis, cough.

Interaction

Ursodeoxycholic acid

Colestyramine, colestipol and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its absorption 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 Phosphogliv ® URSO.

Concomitant use of ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine. Therefore, in patients taking cyclosporine, it is necessary to determine the concentration of cyclosporine in the blood and, if necessary, adjust the dose of cyclosporine.

Ursodeoxycholic acid may reduce the absorption of ciprofloxacin.

Concomitant use of ursodeoxycholic acid may cause a slight increase in the level of rosuvastatin in blood plasma. The clinical significance of this interaction, including in relation to other statins, is not known.

Ursodeoxycholic acid reduces the concentration and area under the concentration-time pharmacokinetic curve of the slow calcium channel blocker nitrendipine. Careful monitoring is recommended for concomitant use of nitrendipine and ursodeoxycholic acid. You may need to increase the dose of nitrendipine. In addition, a decrease in the therapeutic effect of dapsone has been reported.

These data, as well as data obtained in vitro, suggest that ursodeoxycholic acid can induce CYP3A isoenzymes. However, the results of controlled clinical trials indicate that ursodeoxycholic acid does not have a pronounced inducing effect on the CYP3A isoenzyme.

Estrogens, lipid-lowering drugs such as clofibrate, increase the saturation of bile with cholesterol and may reduce the litholitic effect of ursodeoxycholic acid.

Glycyrrhizic Acid

No cases of drug-drug interactions have been described.

How to take it, course of use and dosage

Take orally. Children over 12 years of age and adults weighing more than 47 kg should swallow the capsule whole. The drug should be taken regularly.

For convenience, dosage regimens for different indications are presented in terms of ursodeoxycholic acid.

Non-alcoholic steatohepatitis:

The average daily dose is 10-15 mg / kg in 2-3 divided doses. The duration of therapy is from 6-12 months or more.

Alcoholic liver disease:

The average daily dose is 10-15 mg / kg in 2-3 divided doses. The duration of therapy is from 6-12 months or more.

Symptomatic treatment of chronic hepatitis of various origins:

The average daily dose is 10-15 mg / kg in 2-3 divided doses. The duration of therapy is 6-12 months or more.

Biliary reflux-gastritis:

Take 1 capsule of the drug daily in the evening before going to bed. The course of treatment is from 10-14 days to 6 months, if necessary-up to 2 years.

Biliary dyskinesia :

The average daily dose is 10 mg / kg in 2 divided doses for 2 weeks to 2 months. If necessary, the course of treatment is recommended to be repeated.

Dissolving cholesterol gallstones:

The average daily dose of ursodeoxycholic acid is 10 mg / kg per day, which corresponds to:

The drug should be taken in a daily dose once a day in the evening, before going to bed. It usually takes 6-24 months for the stones to dissolve. If the size of the stones does not decrease after 12 months of treatment, then the treatment should be discontinued.

The effectiveness of treatment should be evaluated every 6 months by ultrasound or radiography. During the interim survey, it is necessary to assess whether calcification of stones has occurred during the elapsed period. In case of calcification of stones, treatment should be discontinued.

Primary biliary cirrhosis:

The daily dose depends on body weight and ranges from 2 to 6 capsules (approximately 10 to 15 mg of ursodeoxycholic acid per 1 kg of body weight).

In the first 3 months of treatment, the drug should be divided into several doses during the day. After improving liver parameters, the daily dose of the drug can be taken once, in the evening. The following application mode is recommended:

Capsules should be taken regularly, without chewing, with a small amount of water.

The use of Phosphogliv Urso for the treatment of primary biliary cirrhosis can be continued indefinitely.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may worsen at the beginning of treatment, for example, pruritus may become more frequent. In this case, treatment should be continued by taking one capsule daily, then gradually increasing the dosage (increasing the daily dose weekly by one capsule) until the recommended dosage regimen is reached again.

Primary sclerosing cholangitis:

The daily dose is 12-15 mg / kg; if necessary, the dose can be increased to 20 mg / kg in 2-3 doses. The duration of therapy is from 6 months to several years.

Overdose

In case of overdose of ursodeoxycholic acid, 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 with feces increases. The consequences of diarrhea are treated symptomatically (restoration of water and electrolyte balance). Cases of glycyrrhizic acid overdose have not yet been identified.

Description

Solid gelatin capsules No. 0. The case and lid are white in color. The contents of the capsules are white or cream-colored powder.

Special instructions

The drug should be taken under the supervision of a doctor.

During the first 3 months of treatment, it is necessary to monitor the activity of “hepatic” transaminases, alkaline phosphatase, gamma-glutamyltranspeptidase, and serum bilirubin concentrations every 4 weeks, and then every 3 months. Monitoring of these parameters allows detecting liver function disorders in the early stages. This also applies to patients in the late stages of primary biliary cirrhosis. In addition, it can quickly determine whether a patient with primary biliary cirrhosis is responding to treatment.

When used to dissolve cholesterol gallstones

To assess progress in treatment and to timely detect signs of calcification of stones, depending on their size, the gallbladder should be visualized (oral cholecystography) with examination of darkening 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 the case of calcification of stones, weak contractility of the gallbladder or frequent attacks of colic, the drug should not be used.

In the treatment of patients in the late stages of primary biliary cirrhosis

Cases of decompensation of cirrhosis of the liver were extremely rare. After discontinuation of treatment, there was a regression of decompensation symptoms.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may increase at the beginning of treatment, for example, pruritus may increase. In this case, the dose of the drug should be reduced to 250 mg (in terms of ursodeoxycholic acid), and then gradually increased again, as described in the section “Dosage and use”.

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 can cause serious side effects.

In patients with diarrhea, the dosage of the drug should be reduced. If persistent diarrhea occurs, treatment should be discontinued.

Women of childbearing age can only take the drug if they use reliable contraceptive methods. It is recommended to use non-hormonal contraceptives or oral contraceptives with a low estrogen content, since hormonal oral contraceptives can increase the formation of gallstones in the gallbladder. Possible pregnancy should be ruled out before starting treatment.

If blood pressure increases, treatment with the drug should be discontinued.

Influence on the ability to drive vehicles and mechanisms

The drug does not adversely affect the ability to drive vehicles or perform other work that requires increased concentration of attention and speed of psychomotor reactions. Or this effect is minimal.

Form of production

Capsules,250 mg + 35 mg.

10 capsules in a contour cell package made of polyvinyl chloride film and aluminum foil printed varnished.

5 contour cell packages together with the instructions for use are placed in a pack of cardboard or in a pack of cardboard using a metallized film.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Glycyrrhizic acid, Ursodeoxycholic acid

Conditions of release from pharmacies

By prescription

Dosage form

Capsules