Ursoxyn

Package leaflet: Information for the user

URSOXYN, 250 mg, hard capsules
Acidum ursodeoxycholicum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person only. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Ursoxyn is and what it is used for
2. Important information before taking Ursoxyn
3. How to take Ursoxyn
4. Possible side effects
5. How to store Ursoxyn
6. Contents of the pack and other information

1. What Ursoxyn is and what it is used for

This medicine contains ursodeoxycholic acid – a naturally occurring bile acid, present in small amounts in human bile.
Indications

• Dissolution of cholesterol gallstones in patients:
• who have one or more radiolucent gallstones not exceeding 2 cm in diameter, with preserved normal gallbladder function;
• in whom surgery is not possible;
• in whom increased cholesterol concentration in bile (bile supersaturation) has been confirmed by laboratory bile analysis.
• Before and after extracorporeal shock wave lithotripsy (ESWL) of gallstones.
• Treatment of a condition in which destruction of bile ducts leads to bile accumulation in the liver, potentially resulting in liver scarring. The liver should not be so severely damaged as to impair its normal function. This condition is known as primary biliary cholangitis/cirrhosis (PBC).
• Treatment of liver disease associated with cystic fibrosis (mucoviscidosis) in children and adolescents aged 6 to 18 years.

2. Important information before taking Ursoxyn
When not to use Ursoxyn

• if you are allergic to ursodeoxycholic acid, bile acids, or any of the other ingredients of this medicine (listed in section 6);
• if you have acute inflammation of the gallbladder or bile ducts;
• if you have obstruction of the bile duct (common bile duct or cystic duct);
• if you have frequent upper abdominal pain resembling spasms (biliary colic);
• if your doctor has diagnosed calcified gallstones;
• in case of impaired gallbladder motility;
• if the child's bile ducts are closed (biliary atresia) and bile flow is insufficient, even after surgical intervention.

If you are unsure about any of the above symptoms, consult your doctor.
If you have previously experienced any of these symptoms, or are uncertain whether they occurred, inform your doctor.
Warnings and precautions
Before starting Ursoxyn, discuss it with your doctor or pharmacist. This medicine should be used under medical supervision.
During therapy, liver function parameters should be monitored regularly every 4 weeks for the first 3 months. Subsequent checks should be performed every 3 months.
If this medicine is used to dissolve gallstones, your doctor should perform an ultrasound examination of the gallbladder after 6–10 months of treatment.
Female patients using this medicine for gallstone dissolution should use effective non-hormonal contraceptive methods, as hormonal contraceptives ("birth control pills") may promote gallstone formation.
When Ursoxyn is used in the treatment of primary biliary cholangitis (PBC), in rare cases symptoms (e.g. itching) may initially worsen. In such a case, contact your doctor to consider reducing the initial dose.
If diarrhoea occurs, consult your doctor immediately, as it may be necessary to reduce the dose or discontinue Ursoxyn treatment.
Children
There are no age restrictions for the use of Ursoxyn 250 mg hard capsules, except for its use in children aged 6 to 18 years with cystic fibrosis (mucoviscidosis).
Ursoxyn and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
The effects of the following medicines may be altered (interactions):
Concomitant use of the following medicines with Ursoxyn may reduce its effectiveness:

• colestyramine, colestipol (lipid-lowering agents), aluminium hydroxide, smectite (aluminium oxide) (bile acid-binding agents). If you are taking a medicine containing any of these active substances, take it either two hours before or two hours after Ursoxyn.
  Concomitant use of Ursoxyn may reduce the effectiveness of the following medicines:
• ciprofloxacin, dapsone (antibiotics), nitrendipine (used to treat high blood pressure), and other drugs eliminated from the body in a similar manner; if necessary, your doctor may adjust the dose of these medicines.

Concomitant use of Ursoxyn may alter the effect of the following medicines:

• cyclosporine (a medicine that suppresses the immune system). If you are taking cyclosporine, your doctor should monitor its blood concentration and adjust the dose if necessary;
• rosuvastatin (a medicine used to treat high blood lipid levels).

If you are taking Ursoxyn to dissolve gallstones, inform your doctor about any concomitant use of oestrogen-containing medicines (e.g. "birth control pills") and certain cholesterol-lowering agents such as clofibrate. These medicines may promote gallstone formation, which opposes the therapeutic effect of Ursoxyn.
Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine.
Pregnancy
There are no data or only limited data on the use of ursodeoxycholic acid in pregnant women. Ursoxyn should not be used during pregnancy unless the physician considers it absolutely necessary.
Animal studies indicate that ursodeoxycholic acid may affect fetal development.
Women of childbearing potential
Even if you are not pregnant, you should consult your doctor. Women of childbearing age should be treated with reliable contraception. Non-hormonal contraceptives or hormonal contraceptives containing low-dose oestrogen ("birth control pills") are recommended. If you are taking Ursoxyn to dissolve gallstones, non-hormonal contraceptives should be used, as hormonal contraceptives may promote gallstone formation.
Before starting treatment, pregnancy should be ruled out by your doctor.
Breastfeeding
There are only a few documented cases of ursodeoxycholic acid use during breastfeeding. The level of ursodeoxycholic acid in breast milk is very low. Therefore, adverse effects in breastfed infants are unlikely.
Effect on fertility/reproductive capacity
Animal studies have not shown any effect of this medicine on fertility/reproductive capacity. There is currently no experience demonstrating the effect of this medicine on fertility/reproductive capacity in humans.
Driving and using machines
No special precautions are required.

3. How to use Ursoxyn

This medicine should always be used exactly as directed by your doctor. If in doubt, consult your
doctor or pharmacist.
Use for dissolving cholesterol gallstones (alone or in combination with lithotripsy)
Dosage
The recommended dose is 2–4 capsules of Ursoxyn (8–10 mg/kg body weight of ursodeoxycholic acid),
taken with food according to the following schedule:

• for a daily dose of 2 capsules: both capsules during the evening meal;
• for a daily dose of 3 capsules: 1 capsule in the morning and 2 capsules in the evening;
• for a daily dose of 4 capsules: 2 capsules in the morning and 2 in the evening; OR

the total daily dose of 2–4 capsules may be taken in the evening, before bedtime.
Administration method
The capsule should be swallowed whole with water or another liquid. Capsules should be taken
regularly.
Duration of therapy
Gallstones usually dissolve within 6–24 months. The duration of treatment depends on the initial size of the gallstones. If the diameter of the gallstones has not decreased within 12 months, therapy should be discontinued.
Your doctor should assess the effectiveness of treatment every 6 months. During follow-up visits, the doctor should check whether calcification of the stones has occurred, leading to hardening of the stones. If this occurs, the doctor will discontinue therapy. Even if symptoms have disappeared, treatment should be continued: stopping treatment prematurely may prolong the total duration of therapy.
After dissolution of the gallstones, treatment should be continued for a further 3–4 months.
Treatment of primary biliary cirrhosis (chronic cholangitis)
Dosage
Stage I–III
The daily dose is based on body weight. During the first 3 months of therapy, Ursoxyn should be taken in the morning, afternoon, and evening. Once liver function parameters have improved, the daily dose may be taken once daily in the evening.

Stage IV
At the beginning of Ursoxyn therapy, take 2 to 3 capsules daily during meals:

• for a daily dose of 2 capsules: 1 capsule in the morning and 1 in the evening;
• for a daily dose of 3 capsules: 1 capsule in the morning and 2 in the evening.

If there is a good response to treatment at the administered doses (based on blood tests and/or physician's assessment), the doctor will prescribe a higher dose (corresponding to therapy in Stages I–III).

Method of administration
The capsules should be swallowed whole with a small amount of water or another liquid. The medicine should be taken regularly.

Duration of therapy
There are no time limitations regarding the use of Ursoxyn in primary biliary cirrhosis of the liver.

Note
In patients with primary biliary cirrhosis of the liver, symptoms of the disease (e.g., pruritus) may worsen at the beginning of treatment. This occurs only rarely. If this happens, therapy may be continued at a reduced daily dose of Ursoxyn. The doctor will then gradually increase the daily dose by weekly increments until the recommended dose is reached.

Use in children and adolescents (aged 6 to 18 years) for the treatment of liver disorders in cystic fibrosis
Dosage
The recommended daily dose is 20 mg/kg body weight, divided into 2–3 doses. If necessary, the doctor may recommend further increasing the dose up to 30 mg/kg body weight per day.

Body weight (kg) Daily dose Ursoxyn, 250 mg, hard capsules
(mg/kg body
weight) Morning Afternoon Evening
20–29 17–25 1 -- 1
30–39 19–25 1 1 1
40–49 20–25 1 1 2
50–59 21–25 1 2 2
60–69 22–25 2 2 2
70–79 22–25 2 2 3
80–89 22–25 2 3 3
90–99 23–25 3 3 3
100–109 23–25 3 3 4

110 3 4 4

Method of administration
The capsules should be swallowed whole with a small amount of water or another liquid. The capsules should be taken regularly. If the capsule size causes difficulty in swallowing or if the patient's body weight is less than 47 kg, alternative medicines containing ursodeoxycholic acid are available.

If you feel that the effect of Ursoxyn is too strong or too weak, consult your doctor or pharmacist.

Use of a higher than recommended dose of Ursoxyn
Diarrhea may occur as a result of taking too high a dose of the medicine. If chronic diarrhea develops, consult a doctor immediately. During episodes of diarrhea, fluids should be replenished to maintain water-electrolyte balance.

Missed dose of Ursoxyn
Do not take a double dose to make up for a missed dose. Continue treatment with the prescribed dose.

Discontinuation of Ursoxyn therapy
Before stopping or prematurely ending therapy with Ursoxyn, consult your doctor.

If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Common adverse reactions (may occur in less than 1 in 10 patients):

• soft, loose stools or diarrhoea.

Very rare adverse reactions (may occur in less than 1 in 10,000 patients):

• during treatment of primary biliary cirrhosis: severe pain in the upper right quadrant of the abdomen, significant worsening of liver fibrosis, which partially resolves after discontinuation of therapy;
• calcification of gallstones (hardening of gallstones due to calcium accumulation);
• urticaria.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Ursoxyn

Do not store above 30°C.
Keep in the original packaging to protect from moisture.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blisters and carton after: "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Proper disposal helps protect the environment.

6. Contents of the package and other information

What Ursoxyn contains

• The active substance is ursodeoxycholic acid. One hard capsule contains 250 mg of ursodeoxycholic acid.
• The other ingredients are: maize starch, silicon dioxide, magnesium stearate; capsule shell: titanium dioxide (E 171), gelatin (E 441).

What Ursoxyn looks like and contents of the pack
White, hard, gelatin capsules of size 0, approximately 21.7 mm x 7.64 mm, containing white or
almost white powder.
Capsules are packed in PVC/Aluminium blisters in cardboard boxes.
10 capsules per blister.
Each cardboard box contains 5, 6 or 10 blisters (50, 60 or 100 capsules).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
AS GRINDEKS
Krustpils iela 53
LV-1057 Rīga
Latvia
Tel.: +371 67083205
Fax: +371 67083505
E-mail: [email protected]

For further information, please contact the representative of the Marketing Authorisation Holder:
Orion Corporation
Orionintie 1, FI-02200 Espoo, Finland

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria    Ursogrix 250 mg Hartkapseln
Belgium    URSOGRIX 250 mg harde capsules
Bulgaria    Ursogrix 250 mg hard capsules
          Урсогрикс 250 mg твърди капсули
Czech Republic URSOGRIX
Croatia     URSOGRIX 250 mg tvrde kapsule
Denmark    Ursogrix
Estonia     URSOGRIX
France     ACIDE URSODESOXYCHOLIQUE GRINDEKS 250 mg, gélule
Greece     Ursogrix 250 mg Σκληρά καψάκια
Latvia      URSOGRIX 250 mg cietās kapsulas
Lithuania   URSOGRIX 250 mg kietosios kapsulės
Spain      Ácido Ursodesoxicólico Grindeks 250 mg cápsulas duras
Netherlands  GRINTEROL 250 mg harde capsules
Ireland    Ursogrix 250 mg hard capsules
Poland     Ursoxyn
Germany    Ursogrix 250 mg Hartkapseln
Norway     URSOGRIX 250 mg harde kapsler
Portugal    GRINTEROL 250 mg cápsulas duras
Romania    Ursogrix 250 mg capsule
Slovakia    Ursogrix 250 mg tvrdé kapsuly
Sweden     Ursogrix 250 mg hårda kapslar
Hungary    Urzodezoxikólsav Grindeks 250 mg kemény kapszula
United Kingdom Ursodeoxycholic Acid 250 mg Capsules, hard