Date of approval.
Date of revision.
Ursodeoxycholic Acid Capsules Instructions
Please read the instructions carefully and use under the guidance of a physician.
Drug Name]
Generic Name: Ursodeoxycholic Acid Capsules
Trade name: Ursodeoxycholic Acid English name: Ursodeoxycholic Acid Capsules Chinese pinyin: Xiongquyangdansuan Jiaonang
Ingredients
Chemical name: 3α,7β-dihydroxy-5β-cholestan-24-oic acid.
Chemical structure formula.
Molecular formula: C24H40O4
Molecular weight: 392.58
【Properties】.
This product is white opaque hard capsule, the content is white powder or granule.
【Indications】.
1. gallbladder cholesterol stones – must be stones that can be penetrated by X-rays, while the gallbladder contraction function must be normal.
2. cholestatic liver disease (e.g., primary biliary cirrhosis).
3. bile reflux gastritis.
Specification】250mg
Dosage]
Gallbladder cholesterol stones and cholestatic liver disease
Take with a small amount of water at regular intervals. Daily dose by body weight is 10mg/kg, i.e.
Body weight daily dose dosing time gallstones cholestatic liver disease evening morning medium evening 60kg 2 capsules 2 1 – 1 80kg 3 capsules 3 1 1 1 100kg 4 capsules 4 1 1 2 Lithotripsy treatment: generally takes 6~24 months, stop taking if stones do not become smaller after 12 months of administration. The result of treatment is judged by ultrasound or X-ray examination every 6 months.
2. Bile reflux gastritis
Swallowed with water at night before bedtime, it must be taken regularly, one capsule (250mg) once a day. Usually take it for 10~14 days and follow the doctor’s advice to decide whether to continue taking the medicine.
[Adverse Reactions].
The assessment of adverse reactions is based on the following frequency data.
Very common:³ 10% common:³ 1%~ < 10% occasional:³ 0.1%~ < 1% rare:³ 0.01%~ < 0.1% very rare:< 0.01% or available data cannot be assessed
Gastrointestinal disorders.
Reports of loose stools or diarrhea with treatment with ursodeoxycholic acid were common in clinical trials.
Severe right upper abdominal pain is very rare when treating primary biliary cirrhosis.
Hepatobiliary dysfunction.
The occurrence of calcification of gallstones is very rare when treatment with ursodeoxycholic acid is administered.
When treating advanced primary biliary cirrhosis, the occurrence of cirrhotic decompensation is very rare and partially recovers after stopping treatment.
Allergic reactions.
The occurrence of urticaria is very rare.
Contraindications
Ursodeoxycholic acid capsules are contraindicated in the following cases.
-Acute cholecystitis and cholangitis.
-Obstruction of the biliary tract (common bile duct and cystic duct).
-Frequent episodes of biliary colic.
-calcified gallstones that cannot be penetrated by radiation
-impaired gallbladder function.
-when the gallbladder cannot be seen under X-ray
-Hypersensitivity to bile acids or any of the ingredients of this product.
Precautions]
Ursodeoxycholic acid capsules must be used under medical supervision.
The treating physician must check some liver function indicators such as AST (SGOT), ALT (SGPT) and γ-GT of the patient every 4 weeks for the first 3 months of treatment and every 3 months thereafter. In addition to identifying responders or non-responders in patients with primary biliary cirrhosis, this test also allows for early detection of potential liver function deterioration, especially in patients with advanced primary biliary cirrhosis.
When used to dissolve cholesterol stones, gallbladder Χ-rays (oral cholecystography) should be done 6 to 10 months after the start of treatment, depending on the size of the stones, in order to evaluate the effectiveness of treatment and to detect gallstone calcification early. Take Χ radiographs in the standing and lying position (ultrasound monitoring).
Pregnant women and nursing mothers
Animal studies have not shown an effect of ursodeoxycholic acid on fertility (see [Pharmacology and Toxicology]). No human data are available on the effect of ursodeoxycholic acid on fertility after treatment.
Embryotoxicity has been found with ursodeoxycholic acid in early gestation through animal studies. Experimental data from the first trimester of human pregnancy are lacking. Ursodeoxycholic acid capsules should be used in women of childbearing age only after safe contraceptive measures have been taken. Before starting treatment, it is important to exclude that the patient is pregnant. For safety reasons, ursodeoxycholic acid capsules should not be taken during the first trimester of pregnancy.
The use of non-hormonal or oral low-dose estrogens for contraception is recommended. However, patients taking ursodeoxycholic acid capsules to dissolve gallstones should use effective non-hormonal contraception, as oral hormonal contraception may increase gallstones.
Ursodeoxycholic acid levels in breast milk are extremely low based on the very few documented data from lactating women.
Use in Children】Take according to weight and medical condition, or as directed by a physician.
Geriatric Use】Use with caution in elderly patients.
Drug Interactions
Ursodeoxycholic acid capsules should not be taken together with causticum (abbreviated cholinesterase), causticum (hypocholinesterase), and antacids containing aluminum hydroxide and/or montmorillonite (aluminum oxide) because these drugs can bind to ursodeoxycholic acid in the intestine, thereby impeding absorption and affecting efficacy. If these drugs must be taken, ursodeoxycholic acid capsules should be taken two hours before or two hours after the administration of the drug.
Ursodeoxycholic acid capsules can affect the absorption of cyclosporine in the intestine. Patients taking cyclosporine should have their cyclosporine serum concentrations monitored and the dose of cyclosporine taken should be adjusted if necessary.
The absorption of ciprofloxacin can be reduced in individual cases with the administration of ursodeoxycholic acid capsules.
Rosuvastatin calcium plasma concentrations were slightly elevated in clinical studies conducted in healthy subjects taking ursodeoxycholic acid (500 mg/day) and rosuvastatin calcium (20 mg/day) in combination. The clinical relevance of this interaction with other statins is unknown.
Ursodeoxycholic acid in healthy subjects reduces the plasma peak concentration (Cmax) and area under the curve (AUC) of the calcium antagonist, nizandipine, and therefore close monitoring is recommended when nizandipine and ursodeoxycholic acid are combined. An increase in the dose of nifedipine may be required. Based on these observations and the report of one interaction with aminophene (reduced therapeutic effect) and the results of ex vivo studies, it is hypothesized that ursodeoxycholic acid may induce the drug metabolizing enzyme cytochrome P450 3A4. However, induction was not observed in well-designed interaction studies with budesonide (a known cytochrome P450 3A substrate). Therefore concomitant administration with drugs that undergo metabolism by this enzyme should be noted and the dose administered adjusted if necessary.
Estrogens and cholesterol-lowering drugs, such as Antomin, can increase hepatic cholesterol secretion and therefore may exacerbate gallstones, contrary to the effects of ursodeoxycholic acid used to dissolve gallstones.
Drug overdose]
Overdose can cause diarrhea. Generally speaking, overdose rarely occurs due to poor absorption of ursodeoxycholic acid at higher doses and excessive excretion in the feces.
Reduce the dose if diarrhea occurs; if diarrhea persists, discontinue treatment.
Diarrhea can be treated symptomatically, such as fluid and electrolyte supplementation, and no other special treatment is needed.
Pharmacology and Toxicology
Pharmacological effects
Ursodeoxycholic acid makes up a small percentage of human bile.
After oral administration of ursodeoxycholic acid, it reduces the cholesterol saturation in bile by inhibiting the reabsorption of cholesterol in the intestine and reducing the secretion of cholesterol into the bile. It is possible that cholesterol stones are gradually dissolved due to the dispersion of cholesterol and the formation of liquid crystals.
Based on the available knowledge, the treatment of liver and cholestatic diseases with ursodeoxycholic acid capsules is mainly based on the relative substitution of lipophilic, detergent-like toxic bile acids by hydrophilic, cytoprotective and non-cytotoxic ursodeoxycholic acid, as well as on the promotion of hepatocyte secretory action and immunomodulation.
Toxicological studies
Acute toxicity studies in animals showed no toxic effects; subchronic toxicity studies showed some hepatotoxicity (including some enzyme changes) and some morphological changes such as bile duct hypertrophy, portal vein inflammation and hepatocyte necrosis in monkeys at high doses, and these toxic reactions are most likely attributable to the ursodeoxycholic acid metabolite cholecalciferol, which is not metabolized and detoxified in monkeys (unlike humans), and clinical dosing Experience has confirmed that the hepatotoxic reactions described are not significantly relevant in humans; no carcinogenic potential has been found in long-term studies in mice and rats; and no mutagenic effects.
In rat experiments, only at doses of ursodeoxycholic acid up to 2000 mg/kg body weight (equivalent to a daily dose of 560 capsules of ursodeoxycholic acid for a 70 kg human) resulted in tail deformities; no teratogenic effects were seen in rabbits at doses up to 300 mg/kg body weight, and no effect on fertility in rats, while not impairing perinatal and postnatal development.
Pharmacokinetics]
After oral administration, the drug can be absorbed rapidly by passive transport in the jejunum and anterior ileum, and by active transport in the terminal ileum. Generally speaking, 60%~80% of the drug can be absorbed. After absorption, almost all bile acids are combined with glycine and taurine in the liver, and then secreted with bile. The first-pass clearance in the liver can reach 60%.
In the intestine a portion is degraded by bacteria to 7-ketocholic acid and cholecalciferolic acid. Gallstone acids are hepatotoxic and can cause damage to hepatic parenchymal cells in some species; in humans, only a small fraction is absorbed and detoxified by sulfation in hepatocytes, secreted with bile, and ultimately excreted in the feces.
The half-life of ursodeoxycholic acid is 3.5-5.8 days.
Storage】Seal and store below 30℃. Keep out of reach of children. Package】Aluminum-plastic package, 25 capsules/box.
Expiration date】60 months【Executive standard】【Approval number
Manufacturing Company
Company name: Dr. Falk Pharma GmbH
Address: Leinenweberstraβe 5 D-79108 Freiburg/Germany
Phone number: 0049-761 1514-0
Fax number: 0049-761 1514-321
Web address: http://www.drfalkpharma.de
Company name: Losan Pharma GmbH
Production address: Otto-Hahn-Straβe 13 D-79395 Neuenburg/Germany
Telephone number: 0049-7631 7906-0
Fax number: 0049-7631 7906-99
Web address: http://www.losan-pharma.de
Domestic Contact.
Company Name: Shenzhen Kangzhe Pharmaceutical Co.
Address: 6/F, 8/F, Building A, Tongfang Information Port, No. 11, Langshan Road, North District, Hi-tech Zone, Nanshan District, Shenzhen
Postcode：518057
Telephone number: 0755-82416868
Fax number: 0755-82416622
Web address: http://www.cms.net.cn