Fosfogliv URSO, 35 mg+250 mg capsules 50 pcs

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

ATX code: A05C

Pharmacological properties.

Pharmacodynamics

Combined drug, hepatoprotective agent, also has choleretic, cholitholytic, antioxidant, anti-inflammatory actions, affects fibrogenesis.

Ursodeoxycholic acid

Ursodeoxycholic acid has a choleretic effect. It reduces the synthesis of cholesterol in the liver, its absorption in the intestine and its concentration in the bile, increases the solubility of cholesterol in the biliary system, stimulates the formation and excretion of bile. It decreases bile lithogenicity and increases bile acids content; it causes intensification of gastric and pancreatic secretion, increases lipase activity and has hypoglycemic effect. Causes partial or complete dissolution of cholesterol stones in enteral administration, reduces bile saturation with cholesterol, which promotes mobilization of cholesterol from gallstones. It has immunomodulatory effect, influences immunological reactions in the liver: it decreases the expression of some antigens on the membrane of hepatocytes, affects the number of T-lymphocytes, formation of introleukin-2, decreases the number of eosinophils.

Glycyrrhizic acid

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

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

Glycyrrhizic acid reduces inflammation through its inhibitory effect on NF-kB- and TLR4-signaling pathways; inhibition of pro-inflammatory cytokine production (TNF α, IL-1, IL-6, IL-8); stimulation of anti-inflammatory cytokine production (IL-2, IL-10, IL-12). Glycyrrhizic acid inhibits 11β-oxysteroid dehydrogenase, which increases endogenous cortisol in the blood (pseudocorticosteroid effect).

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

Pharmacokinetics

Ursodeoxycholic acid

. After ingestion, ursodeoxycholic acid is rapidly absorbed in the jejunum and proximal ileum by passive diffusion and in the distal ileum by active transport. Absorption is approximately 60-80%.

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

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 other more lipophilic bile acids.

In the intestinal bacteria, ursodeoxycholic acid is partially broken down to form 7-keto-lithocholic and lithocholic acids. In humans, lithocholic acid is absorbed only in small amounts, sulfated in the liver, excreted in the bile and excreted in the feces.

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

Glycyrrhizic acid

. After oral administration in the intestine, under the influence of β-glucuronidase enzyme produced by bacteria of normal microflora, glycyrrhizic acid forms an active metabolite – β-glycyrrhetic acid, which is absorbed into the systemic bloodstream. The maximum concentration (C_max) of β-glycyrrhetic acid in plasma is reached after 11 hours, being 267.319 ng/ml. The area under the pharmacokinetic curve (AUC_0-∞) is 5123.9 ng*h/ml. In blood β-glycyrrhetate binds to albumin and is almost completely transported to the liver. Excretion of β-glycyrrhetic acid occurs mainly in bile, with residual amounts in the urine. The elimination half-life reaches 19.23 hours.

Indications

– non-alcoholic steatohepatitis;

– alcoholic liver disease;

– chronic hepatitis of various genesis;

– biliary reflux gastritis;

– biliary dyskinesia;

– dissolution of cholesterol gallstones;

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

– primary sclerosing cholangitis.

Active ingredient

Composition

Composition per capsule:

Active substances:

Ursodeoxycholic acid – 250.0 mg,

Glycyrrhizinate sodium converted to 100% substance (trisodium salt of glycyrrhizic acid) – 35.0 mg.

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

Capsule shell (body and cap): titanium dioxide (E 171) – 1.92 mg, gelatin – 94.08 mg.

How to take, the dosage

To be taken orally. Children over 12 years of age and adults with body weight over 47 kg should swallow the capsule whole. The drug should be taken regularly.

For convenience, the 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 doses. The duration of therapy is 6-12 months or more.

Alcoholic liver disease:

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

Symptomatic treatment of chronic hepatitis of various genesis:

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

Biliary reflux gastritis:

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

Dyskinesia of the biliary tract :

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

Dissolution of cholesterol gallstones:

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

Body weight

Number of capsules

Up to 60kg

2

61 – 80 kg

3

81 – 100 kg

4

> 100 kg

5

The drug should be taken in a daily dose once daily in the evening, before bedtime. It usually takes 6 to 24 months to dissolve stones. If after 12 months of treatment the size of the stones has not decreased, the treatment should be stopped.

The effectiveness of treatment should be evaluated every 6 months with ultrasound or radiography. In an interim evaluation, it should be assessed whether calculi have calcified during this period. If calculi have calcified, treatment should be discontinued.

Primary biliary cirrhosis:

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

In the first 3 months of treatment, the drug intake should be divided into several intakes during the day. After improvement of hepatic parameters the daily dose of the drug can be taken once, in the evening. The following regimen of administration is recommended:

Body weight

Daily dose

Morning

In the afternoon

In the eveningIn the evening

47-50 kg

2 capsules

1 capsule

–

Interaction

Ursodeoxycholic acid

Colestyramine, colestipol and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce 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 Fosfogliv® URSO.

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

Ursodeoxycholic acid may decrease absorption of ciprofloxacin.

In concomitant use ursodeoxycholic acid may cause a slight increase in plasma levels of rosuvastatin. The clinical significance of this interaction, including with other statins, is not known.

Ursodeoxycholic acid reduces the concentration and the area under the pharmacokinetic curve “concentration-time” of slow calcium channel blocker nitrendipine. In case of concomitant use of nitrendipine and ursodeoxycholic acid, close monitoring is recommended. Increased dose of nitrendipine may be required. In addition, a decrease in therapeutic effect of dapsone has been reported.

These data, as well as data obtained in vitro, suggest that ursodeoxycholic acid may induce CYP3A isoenzymes. However, the results of controlled clinical trials suggest that ursodeoxycholic acid has no pronounced inducing effect on CYP3A isoenzyme.

Estrogens, hypolipidemic drugs such as clofibrate increase bile cholesterol saturation and may decrease the litholytic effect of ursodeoxycholic acid.

Glycyrrhizic acid

In cases of interdrug interactions have not been described.

Special Instructions

The drug should be taken under medical supervision.

Synopsis

Contraindications

– hypersensitivity to the drug components or other bile acids;
– X-ray-positive (with high calcium content) gallstones;
– impairment of gallbladder contractility;
– frequent episodes of biliary colic;
– biliary tract occlusion (occlusion of common bile or gall ducts);
– acute inflammatory diseases of gallbladder and bile ducts;
– Severe hepatic cirrhosis at the decompensation stage;
– expressed hepatic and/or renal insufficiency;
– pregnancy;
– breastfeeding period;
– children under 12 years of age;
– adults and children with body mass – Adults and children with body weight less than 47 kg (for this dosage form)
– Unsuccessful portoenterostomy or cases of absence 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 evaluation of adverse events is based on the following classification:

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

Gastrointestinal tract disorders:

often – loose stools or diarrhea; very rarely – dyspepsia (belching, nausea, bloating), abdominal discomfort, sharp pain in the right upper abdomen.

Hepatic and biliary tract disorders:

very rarely – calcification of gallstones, decompensation of liver cirrhosis (when treating advanced stages of primary biliary cirrhosis), which disappears after drug withdrawal.

Cardiovascular system disorders:very rarely – transient increase in blood pressure, peripheral edema.

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

Overdose

Pregnancy use