ADISOCOL 300 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Adisocol 300 mg Tablets EFG

Ursodeoxycholic Acid

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Adisocol and what is it used for
2. What you need to know before you take Adisocol
3. How to take Adisocol
4. Possible side effects
5. Storage of Adisocol
6. Contents of the pack and other information

1. What is Adisocol and what is it used for

Ursodeoxycholic acid influences the composition of bile, which dissolves cholesterol gallstones. The effect of ursodeoxycholic acid in primary biliary cholangitis and cystic fibrosis can be explained by several mechanisms, such as a protective effect on liver cells and an effect on the immune system.

1. Ursodeoxycholic acid is used in patients:

• with small gallstones,
• who do not want to undergo surgery or are not eligible for gallstone surgery
• in whom too much cholesterol has been found in the bile.

1. Ursodeoxycholic acid is used in patients with primary biliary cholangitis. Primary biliary cholangitis is a disease in which the liver tissue is damaged by defective bile drainage.

1. Ursodeoxycholic acid is used in children between 6 and 18 years old with liver and bile problems caused by cystic fibrosis. Cystic fibrosis, also known as mucoviscidosis, is a hereditary disease in which the mucous membranes are particularly rigid throughout the body. This can cause, among other conditions, obstructions and inflammation of the liver and bile ducts.

2. What you need to know before you take Adisocol

Do not take Adisocol:

• If you have acute inflammation of the gallbladder or bile ducts.
• If you have a blockage or obstruction of the bile duct.
• If you frequently experience painful cramps in the upper abdomen (biliary colic).
• If you have calcified gallstones that do not transmit X-rays.
• If you have a gallbladder that can no longer contract properly.
• If you are allergic to bile acids or any of the other components of this medicine (listed in section 6).
• If you have an active gastric or duodenal ulcer.

Children

In children with interrupted bile drainage due to the production of connective tissue in the bile duct (biliary atresia) in whom the flow of bile has not been restored by healing or through an artificial bile duct (portoenterostomy).

Warnings and precautions

This medicine should be taken under medical supervision.

Your doctor should examine your liver every 4 weeks during the first three months of treatment. After this, it should be done every 3 months. Apart from allowing the identification of patients who are being treated for primary biliary cholangitis among those who respond and those who do not, this monitoring should also allow for early detection of potential liver damage, particularly in patients with advanced primary biliary cholangitis.

When used to dissolve gallstones:

To be able to evaluate the therapeutic progression of gallstone dissolution and to identify in time the possible calcification of the gallstones, the gallbladder, depending on the size of the stones, should be visualized 6 to 10 months after the start of treatment (oral cholecystography) with a complete image and occlusions and in standing and lying positions (ultrasound control).

If the gallbladder cannot be visualized with X-rays, or in cases where the gallstones are calcified, in damaged contractility of the gallbladder or frequent episodes of biliary colic, treatment with ursodeoxycholic acid should be discontinued.

When used for the treatment of advanced primary biliary cholangitis

In very rare cases, decompensation of liver cirrhosis is observed, which decreases partially after discontinuation of treatment.

Women taking Adisocol to dissolve gallstones should stop taking the contraceptive pill and other methods to prevent pregnancy, because the hormones in the contraceptive pill can trigger the production of gallstones.

In the final stage of primary biliary cholangitis, it may rarely occur that liver function is highly reduced. Liver function will partially recover after discontinuation of treatment.

If you experience problems with diarrhea, your doctor will reduce the dose. If diarrhea persists, your doctor may decide to discontinue treatment.

Consult your doctor or pharmacist before starting to take this medicine.

Other medicines and Adisocol

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This also applies to medicines that are not subject to medical prescription.

The effects of the following medicines may be influenced (interactions):

It is possible that a reduced effectof the following medicines may occur:

• Medicines that bind to stomach acid containing aluminum hydroxide and substances that bind to bile acids (cholestyramine, colestipol) that can bind to ursodeoxycholic acid and thus prevent its absorption.

Therefore, these medicines cannot be taken simultaneously with ursodeoxycholic acid, but if always two hours before or after.

• Ursodeoxycholic acid may reduce the absorption of ciprofloxacin, dapsone (antibiotics), and nitrendipine (antihypertensive agent) from the intestine. When one of these medicines is used simultaneously with Adisocol, your doctor should monitor you closely.

It is possible that a strengthened effectof the following medicines may occur when using ursodeoxycholic acid:

• Ursodeoxycholic acid may increase the absorption of cyclosporin from the intestine: if necessary, the dose in the blood should be adjusted based on the cyclosporin concentration.

Estrogens, oral contraceptives ("the pill"), and cholesterol-lowering agents (such as clofibrate) may trigger the formation of gallstones and may counteract the effect of gallstone treatment with ursodeoxycholic acid.

Tell your doctor or pharmacist if you are taking or have taken other medicines. This also applies to medicines that are not subject to medical prescription.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Do not take this medicine while you are pregnant unless your doctor considers it absolutely necessary.

Women of childbearing age

Even if you are not pregnant, you should discuss this possibility with your doctor, because women of childbearing age can only be treated if they are using a reliable contraceptive method. Non-hormonal contraceptives or low-dose estrogen contraception are recommended. However, if you use this medicine for the treatment of gallstones, you can only use non-hormonal contraception because hormonal contraception triggers the formation of gallstones.

Breastfeeding

Tell your doctor if you are breastfeeding or about to start breastfeeding. According to a few documented cases of breastfeeding women, the levels of ursodeoxycholic acid in milk are very low and adverse reactions in breastfed infants are unlikely.

Driving and using machines

The influence of ursodeoxycholic acid on driving and using machines is zero or insignificant.

3. How to take Adisocol

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your weight.

Take the tablets after a meal with a glass of milk or a snack. Take the prescribed number of tablets distributed throughout the day.

1. Dissolution of gallstones:

Four to six 150 mg tablets, two to three 300 mg tablets, or two 450 mg tablets per day (600-900 mg of ursodeoxycholic acid per day).

Two tablets should always be taken after dinner.

When taking a dose two or three times a day: for example, one tablet after lunch and two tablets after dinner.

When taking a dose of two tablets per day: take both tablets preferably two hours after dinner and one hour before bedtime.

1. Primary biliary cholangitis (liver tissue damage due to defective bile flow):

• Phase I-III:

Four to eight 150 mg tablets, two to four 300 mg tablets, or two 450 mg tablets per day (600-1200 mg of ursodeoxycholic acid per day).

Take the prescribed dose in two or three divided doses after meals.

• Phase IV:

Based on the examination of liver function, your doctor will determine whether you are prescribed a normal dose, as in phase I-III, or half of this dose.

Children between 6 and 18 years old with cystic fibrosis

1. Liver and bile duct diseases caused by cystic fibrosis (mucoviscidosis):

Four to ten 150 mg tablets, two to five 300 mg tablets, or two to three 450 mg tablets per day (600-1500 mg of ursodeoxycholic acid per day).

Take the tablets with a glass of milk or a snack. Take the prescribed dose in two or three divided doses after meals.

The scored tablets can be divided if you have problems swallowing due to the size of the tablet, so that you take it sequentially, half a tablet at a time.

If you notice that this medicine is too strong or, on the contrary, too weak, consult your doctor or pharmacist.

If you take more Adisocol than you should

You should inform your doctor if you have taken more ursodeoxycholic acid than you should. It is unlikely that you will notice any problems, but you may experience diarrhea.

If you forget to take Adisocol

Take the prescribed amount at the next intake.

Do not take a double dose to make up for forgotten doses.

How long should you take Adisocol?

The duration of treatment depends on the size of the gallstone, but it is usually not less than 3 to 4 months. Treatment should not be discontinued prematurely, even if symptoms have disappeared. Only an X-ray or ultrasound scan can show that the gallstones have completely dissolved. After it has been seen with the help of an ultrasound that the gallstones have completely disappeared, treatment should still be continued for three or four months.

Treatment with Adisocol for primary biliary cholangitis and liver and bile disorders as a result of cystic fibrosis will be continued to maintain the protective effect of Adisocol.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common side effects(occur in less than 1 in 10 patients but in more than 1 in 100 patients)

• pasty stools or diarrhea

Rare side effects(may affect up to 1 in 10,000 patients)

• in the treatment of primary biliary cholangitis: acute pain in the upper right abdomen, severe deterioration (decompensation) of liver cirrhosis that decreases partially after discontinuation of treatment;
• calcification of gallstones;
• urticaria (hives).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects that are not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Adisocol

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging after (EXP). The expiry date is the last day of the month indicated.

Do not store above 25°C.

Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to a pharmacy. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Adisocol

• The active substance is ursodeoxycholic acid
• The other excipients are microcrystalline cellulose (Microcel 101) (E460), polyvinylpyrrolidone (Plasdona K-90) (E1201), magnesium stearate (E572), sodium carboxymethylcellulose Type A (Primojel).

Appearance of the product and contents of the pack

Adisocol 300 mg are white to almost white, round tablets, approximately 11.5 mm in size, with a score and "G" "443" engraved on one side and smooth on the other.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Glenmark Arzneimittel GmbH

Industriestr. 31

82194 Gröbenzell

Germany

Manufacturer:

Glenmark Pharmaceuticals s.r.o.

Fibichova 143

566 17 Vysoke Myto

Czech Republic

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Glenmark Farmacéutica, S.L.U.

C/ Retama 7, 7ª planta

28045 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet:April 2018

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).