AXIALITH

Description

The Cathay Drug Co., Inc.

URSODEOXYCHOLIC ACID

 

FORMULATION

Each film – coated tablet contains:

Ursodeoxycholic acid……………………… 250 mg

 

PHARMACODYNAMICS

Pharmacotherapeutic group: bile acid preparation

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 and lithocolic acid. Lithocolic acid is hepatoxic 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 being excreted in the bile and ultimately in the feces. The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.

 

INDICATIONS

Ursodeoxycholic acid is used for the dissolution of cholesterol-rich gallstones in patients with functioning gallbladders. It is also used in primary biliary cirrhosis.

 

DOSAGE AND ADMINISTRATION

The use of AXIALITH is not age-restricted.

The following daily dose is recommended for various indications:

 

To dissolve cholesterol 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 1000 mg ursodeoxycholic acid)
• Above 100 kg: 5 film – coated tablets (equivalent to 1250 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 and is between 3 and 7 film – coated tablets (250 mg Axialith)

(14 + 2 mg ursodeoxycholic acid per kg body weight)

The following scheme is recommended during the first 3 months of treatment

250 mg Axialith

Body Weight	Film – coated tablet/day	Morning	Midday	Evening
47-62 kg	3	1	1	1
63-78 kg	4	1	1	2
79-93 kg	5	1	2	2
94-109 kg	6	2	2	2
Above 110 kg	7	2	2	3

With improvement of the liver values, the daily dose may be administered once daily in the evening.

250 mg Axialith

Body Weight	Daily dose mg/kg BW	Film – coated tablets/day (evening)
47 – 62 kg	12-16	3
63 -78 kg	13-16	4
79 – 93 kg	13-16	5
94 – 109 kg	14-16	6
Above 110 kg		7

250 mg Axialith

Body Weight	Daily dose mg/kg BW	Film – coated tablets/day (evening)
50 – 62 kg	13-16	2
63 -78 kg	13-16	2 ½
79 – 93 kg	13-15	3
94 – 109 kg	13-15	3 ½
Above 110 kg		4

The film – coated tablets should be taken unchewed with some fluid. Care should be taken to ensure that they are taken regularly.

CONTRAINDICATION

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

UNDESIRABLE EFFECTS

The evaluation of undesirable effects is based on the following frequency data

• Very common (> 1/10)
• Common ((> 1/1400 to <1/10)
• Uncommon (> 1/1000 to <1/100)
• Rare (> 1/10000 to <1/1000)
• Very rare (<1/10000)

Gastrointestinal disorders: 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.

Hepatobiliary disorders: 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, urticarial can occur.

 

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

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 frequent episodes of biliary colic, Axialith should not be used.

When used for the treatment of patients with primary biliary cirrhosis in the advanced stage

In very rare cases, decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.

If diarrhea occurs, the dose must be reduced and in cases of persistent diarrhea, the therapy should be discontinued.

 

Pregnancy and Lactation

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.

 

INTERACTIONS WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION

Axialith should not be administered concomitantly with colestyramine, colestipol or antacids containing aluminium hydrochloride and/or smectide (aluminium 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 usodeoxycholic acid to induce cytochrome P450 3A enzymes. Controlled clinical trials have shown, however, that ursodexycholic acid does not have a relevant induction effect on cytochrome 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 machine have been observed.

 

AVAILABILITY

PVC/PVDC/Alu Blister Pack x 10’s (Box of 100’s).

 

OVERDOSAGE

Diarrhea 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 feces.

No specific counter measures are necessary and the consequences of diarrhea should be treated symptomatically with restoration of fluid and electrolyte balance.

 

STORAGE

STORE AT TEMPERATURES NOT EXCEEDING 25°C.

 

 

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

 

Distributed by

THE CATHAY DRUG CO., INC.

2/F Vernida 1 Condominium, 120 Amorsolo St.

Legaspi Village, Makati City

 

Manufactured by

LEK S.A.

Podlipie Str. 16, 95-010 Strykow, Poland

Date of revision: September 2018