SUMMARY CMI

URSOFALK^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using URSOFALK?

URSOFALK contains the active ingredient ursodeoxycholic acid. URSOFALK is used to treat chronic cholestatic liver diseases.

For more information, see Section 1. Why am I using URSOFALK? in the full CMI.

2. What should I know before I use URSOFALK?

Do not use if you have ever had an allergic reaction to ursodeoxycholic acid or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use URSOFALK? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with URSOFALK and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use URSOFALK?

• Take URSOFALK, or give to your child, as directed by your doctor or pharmacist. This may differ from the information contained in this leaflet.

More instructions can be found in Section 4. How do I use URSOFALK? in the full CMI.

5. What should I know while using URSOFALK?

For more information, see Section 5. What should I know while using URSOFALK? in the full CMI.

6. Are there any side effects?

Ursodeoxycholic acid is generally well tolerated with few side effects. The common side effect is diarrhoea. Allergic reactions have been reported in some patients. Other adverse reactions reported include increased cholestasis, nausea, vomiting and sleep disturbance. The serious side effects include severe right-sided upper abdominal pain and severe worsening (decompensation) of liver cirrhosis.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

URSOFALK^®

Active ingredient: ursodeoxycholic acid

Consumer Medicine Information (CMI)

This leaflet provides important information about using URSOFALK. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using URSOFALK.

Where to find information in this leaflet:

1. Why am I using URSOFALK?
2. What should I know before I use URSOFALK?
3. What if I am taking other medicines?
4. How do I use URSOFALK?
5. What should I know while using URSOFALK?
6. Are there any side effects?
7. Product details

1. Why am I using URSOFALK?

URSOFALK contains the active ingredient ursodeoxycholic acid. URSOFALK is a bile acid, which may have a protective effect on the liver by reducing the absorption of other potentially toxic bile salts.

URSOFALK is used to treat liver diseases such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and cystic fibrosis (CF)-related cholestasis.

However, your doctor may prescribe this medicine for another use.

If you or your child wants more information, ask your doctor.

Ask your doctor if you or your child have any questions about why this medicine has been prescribed for you or your child.

URSOFALK is not addictive.

2. What should I know before I use URSOFALK?

Warnings

Do not use URSOFALK if:

• you or your child are allergic to ursodeoxycholic acid, or any of the ingredients listed at the end of this leaflet.
  Always check the ingredients to make sure you can use this medicine.
• you or your child has a bile duct or gall bladder that is swollen, painful or blocked.
• the packaging is torn or shows signs of tampering.
• the capsules, tablets or suspension look to be deteriorating in any way.
• the expiry date (EXP) printed on the pack has passed, as it may not work as well.
• do not use URSOFALK suspension after 4 months of opening the bottle.

Check with your doctor if you or your child:

• take any medicines for any other condition;
• have allergies to any other medicines, foods, preservatives or dyes;
• have kidneys that do not work properly;
• have a gall bladder that cannot be seen on X-ray;
• have calcified gallstones;
• have a gall bladder which is not able to contract properly;
• suffer from frequent cramp-like pains in the upper abdomen (biliary colic);
• is on a controlled sodium diet (for patients taking URSOFALK suspension).

If you are not sure whether you or your child should start taking this medicine, talk to your doctor.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

URSOFALK may increase the effect of some medicines, including:

• medicines used to lower high levels of cholesterol in the blood, such as rosuvastatin, atorvastatin, fluvastatin, simvastatin, pitavastatin or pravastatin.

URSOFALK may decrease the effects / absorption of some medicines, including:

• nitrendipine (used to treat high blood pressure) and other medicines which are metabolised in the same way.
• medicines used to suppress the immune system, such as ciclosporin;
• antibiotics used to prevent certain infections, such as ciprofloxacin or dapsone.

Medicines that may reduce the effect of URSOFALK include:

• medicines used to lower high levels of cholesterol in the blood, such as colestyramine or colestipol;
• an absorbent, such as charcoal;
• medicines such as antacids containing aluminium hydroxide and/or smectite, which are used for indigestion.
  Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect URSOFALK.

4. How do I use URSOFALK?

How much to take

• The usual dosage for you or your child depends on the weight and medical conditions of you or your child and will be advised by your doctor.
• Follow the instructions provided and use URSOFALK until your doctor tells you to stop.
• If you or your child is unsure of how much of the medicine should be taken, ask your doctor or pharmacist.
• If you or your child has any questions about the prescribed dose, ask your doctor or pharmacist.

When to take URSOFALK

• Take URSOFALK at about the same time each day.
  Taking it at the same time each day will have the best effect. It will also help you or your child to rememberwhen to take it.
• If you or your child needs to take a cholesterol lowering medicine or an antacid, take it at least 2 hours before or 2 hours after the dose of URSOFALK.

How to take URSOFALK

• URSOFALK capsules or tablets should be swallowed whole with a full glass of water because the content is bitter.
• For URSOFALK suspension, shake the bottle well before use and accurately measure the dose with a medicine measure.
• Shaking the bottle and using a medicine measure will make sure that you or your child gets the correct dose. You can buy a medicine measure from your pharmacist.
• Take URSOFALK capsules, tablets or suspension regularly.

How long to take URSOFALK

• Continue taking the medicine for as long as your doctor tells you or your child to.
• URSOFALK helps to control your or your child's condition, but does not cure it. It is important to keep taking the medicine even if you or your child feel well.
• If you are unsure whether you or your child should stop taking URSOFALK, talk to your doctor or pharmacist.
• You or your child may need to take URSOFALK for many months for it to work.

If you or your child forget to use URSOFALK

URSOFALK should be used regularly at the same time each day. If you or your child miss a dose at the usual time, take the required dose as soon as you or your child remembers, and then go back to taking it as you or your child would normally.

If it is almost time for your next dose, skip the dose you or your child missed and take the next dose as you or your child would normally.

Do not take a double dose to make up for the dose you or your child missed.

If you or your child is not sure what to do, ask your doctor or pharmacist.

If you or your child has trouble remembering to take, or give, the medicine, ask your pharmacist for some hints.

If you or your child uses too much URSOFALK

If you think that you or your child have used too much URSOFALK, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Symptoms of an overdose may include diarrhoea. If you or your child suffers from diarrhoea, make sure you or your child drinks enough liquids to replace the fluid and electrolyte balance.

5. What should I know while using URSOFALK?

Things you should do

If you or your child is about to be started on any new medicine, remind your doctor and pharmacist that you or your child is taking URSOFALK.

If you or your child is going to have surgery, tell the surgeon or anaesthetist that you or your child is taking this medicine.

If you or your child is about to have any blood tests, tell your doctor that you or your child is taking this medicine.

Keep all of your doctor's appointments so that you or your child's progress can be checked.

During the first three months of taking URSOFALK, your doctor should monitor you or your child's liver function every 4 weeks. After the first three months of taking this medicine, your doctor should monitor you or your child's liver function every 3 months.

Call your doctor straight away if you:

• become pregnant while taking this medicine.

Remind any doctor, dentist or pharmacist you visit that you or your child are using URSOFALK.

Things you should not do

• Do not take URSOFALK to treat any other complaints unless your doctor tells you or your child to.
• Do not give this medicine to anyone else, even if they have the same condition as you or your child.
• Do not stop taking URSOFALK or change the dosage without checking with your doctor or your child's doctor.

Driving or using machines

URSOFALK does not cause any negative effect on driving ability and operating machinery.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

• Store below 25°C.
• Keep URSOFALK capsules, tablets or suspension in the blister pack/bottle until it is time to take them. If you or your child take/takes URSOFALK out of the pack/bottle they will not keep well.

Follow the instructions on the carton on how to take care of your medicine properly.

Store URSOFALK capsules, tablets or suspension in a cool dry place away from moisture, heat or sunlight, for example, do not store it:

• in the bathroom or near a sink; or
• in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What URSOFALK Capsule contains

What URSOFALK Tablet contains

What URSOFALK Suspension contains

Do not take this medicine if you are allergic to any of these ingredients.

What URSOFALK looks like

URSOFALK Capsules are white, opaque, hard gelatin capsules. A box contains blister packs of 60 or 100 capsules.

URSOFALK Tablets are white, oblong tablets equipped with a breaking notch. A box contains blister of 50 or 100 tablets. Starter packs of 25 tablets are also available.

Not all pack sizes are currently marketed in Australia.

URSOFALK Suspension is a white liquid containing small air bubbles, and has a lemon flavour (87017). It comes in bottles of 250 mL.

Australian Registration Numbers:

URSOFALK Capsules AUST R 66042

URSOFALK Suspension AUST R 75484

URSOFALK Tablets AUST R 262732

Who distributes URSOFALK

Dr Falk Pharma Australia Pty Ltd
9 Help Street
Chatswood, NSW 2067
Australia

URSOFALK^® is a registered trademark of Dr Falk Pharma GmbH, Germany.

This leaflet was prepared in October 2024.

Published by MIMS February 2025

1 Name of Medicine

Ursodeoxycholic acid.

2 Qualitative and Quantitative Composition

Ursofalk Capsule contains ursodeoxycholic acid 250 mg.
Ursofalk Suspension contains ursodeoxycholic acid 50 mg/mL.
Ursofalk Tablet contains ursodeoxycholic acid 500 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

Excipient with known effect.

3 Pharmaceutical Form

Ursofalk Capsules contain 250 mg ursodeoxycholic acid and are presented as white, opaque, hard gelatin capsules.
Ursofalk Suspension contains 50 mg/mL ursodeoxycholic acid and is presented as a white homogenous suspension containing small air bubbles and with lemon flavour.
Ursofalk Tablets contain 500 mg ursodeoxycholic acid and are presented as white, oblong tablets equipped with a double-sided breaking notch.

4 Clinical Particulars

4.1 Therapeutic Indications

Ursofalk is indicated in the treatment of chronic cholestatic liver diseases.

4.2 Dose and Method of Administration

Dosage for adults and the elderly.

Dosage for children.

Administration.

4.3 Contraindications

Ursofalk must not be used if there is hypersensitivity to the active ingredient or any of the excipients.

4.4 Special Warnings and Precautions for Use

During the first three months of therapy, it is advisable to monitor the liver parameters of AST (SGOT), ALT (SGPT), and GGT every 4 weeks, subsequently every 3 months.
Apart from allowing for identification of responders and non-responders in patients being treated for primary biliary cholangitis, this monitoring would also enable early detection of potential hepatic deterioration, particularly in patients with advanced stage primary biliary cholangitis.
Ursofalk is not recommended in patients with dominant stenoses of the bile ducts unless the obstructed bile ducts are dilated (see Section 4.2 Dose and Method of Administration).
If diarrhoea occurs, the dose must be reduced and in cases of persistent diarrhoea, the therapy should be discontinued.
One measuring cupful (5 mL) Ursofalk suspension contains 0.50 mmol (11.39 mg) sodium. This should be taken into consideration by patients on a controlled sodium diet.

Treatment of patients with primary sclerosing cholangitis.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Some drugs, such as cholestyramine, charcoal, colestipol and certain antacids (containing aluminium hydroxide and/or smectite [aluminium oxide]) bind to ursodeoxycholic acid in the intestine and thereby inhibit 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 Ursofalk.
Ursodeoxycholic acid may affect the absorption of ciclosporin in transplantation and nontransplant patients. Therefore, monitoring ciclosporin plasma concentrations are recommended and ciclosporin dose adjusted if necessary.
Ursodeoxycholic acid has been reported to decrease the absorption of ciprofloxacin in a few cases.
In a clinical study in 12 healthy volunteers with the OATP1B1*1b/*1b genotype, predicting high OATP1B1 activity, it was demonstrated that concomitant use of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in a significant increase in the plasma levels of rosuvastatin. Ursodeoxycholic acid increased the AUC of rosuvastatin by approximately 60%, from 145.5 nanogram/mL per hour to 231.9 nanogram/mL per hour (p=0.004).
Administration of ursodeoxycholic acid for 14 days also significantly increased total bilirubin by 139 ± 39% (p=0.003), conjugated bilirubin by 127 ± 29% (p=0.005) and unconjugated bilirubin by 151 ± 52% (p=0.004). The proposed biological mechanism for this interaction is that bilirubin and rosuvastatin are both metabolites of organic anion transporting polypeptide 1B1 (OATP1B1). OATP1B1 expression is regulated by transcription factor hepatic nuclear factor (HNF) 1α. Ursodeoxycholic acid acts as an inhibitor of HNF 1α and consequently may decreased expression of OAT1B1. A dose reduction in rosuvastatin should be considered in any individuals exposed to both rosuvastatin and ursodeoxycholic acid. The clinical relevance of this interaction with regard to other statins is unknown. However, it is biologically possible that this interaction may also occur between ursodeoxycholic acid and other statins which are known substrates of OAT1B1, such as atorvastatin, fluvastatin, simvastatin acid, pitavastatin and pravastatin.
Ursodeoxycholic acid reduces the peak plasma concentrations (C_max) and the area under the curve (AUC) of the calcium channel blocker, nitrendipine. On the basis of this, together with a single case report of an interaction with the substance dapsone (reduction of the therapeutic effect) and in vitro findings, it may be assumed that ursodeoxycholic acid induces the medicinal product-metabolising enzyme cytochrome P450 3A4. Caution should, therefore, be exercised in cases of co-administration of medicinal products metabolised by this enzyme, and a dose adjustment may be necessary. Induction has, however, not been observed in a well-designed interaction study with budesonide which is a known cytochrome P450 3A substrate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of this registration.

4.8 Adverse Effects (Undesirable Effects)

Ursodeoxycholic acid is generally well tolerated with few side effects. Diarrhoea is the main reported side effect. The incidence of diarrhoea in controlled studies was up to 3%.
Some patients may experience increased pruritus in the early weeks of treatment. In such cases a dose reduction, and thereafter a slow (weekly) increase of dose to the recommended dose, may help.
Severe right upper abdominal pain has occurred during the treatment of PBC (≤ 1 in 10,000 patients). During advanced stages of PBC, in very rare cases (≤ 1 in 10,000 patients), decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
Calcification of gallstones can occur in ≤ 1 in 10,000 patients.
Allergic reactions have been reported in some patients. Urticaria can occur in ≤ 1 in 10,000 patients.
Other adverse reactions reported include increased cholestasis, nausea, vomiting and sleep disturbance.

Reporting suspected adverse effects.

4.9 Overdose

Diarrhoea may occur in cases of overdosage. If diarrhoea occurs, the dose must be reduced and in cases of persistent diarrhoea, the therapy should be discontinued. No specific countermeasures are necessary and the consequence of diarrhoea should be treated symptomatically with restoration of fluid and electrolyte balance.
In general, other symptoms of overdosage are unlikely because the absorption of ursodeoxycholic acid decreases with increasing dose and, therefore, more is excreted with the faeces.
Serious adverse effects are also unlikely to occur in overdosage. However, liver function should be monitored. If necessary, ion-exchange resins may be used to bind bile acids in the intestines.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Primary biliary cholangitis.

Primary sclerosing cholangitis.

Cystic fibrosis-related cholestasis.

5.2 Pharmacokinetic Properties

Ursodeoxycholic acid occurs naturally in the body. After oral administration of a single 500 mg dose of ursodeoxycholic acid to healthy volunteers, peak plasma concentrations were 2.7 to 6.3 microgram/mL. T_max occurs at 60 minutes and a second peak plasma concentration occurs at 180 minutes. After oral administration of 250 mg, 500 mg, 1,000 mg and 2,000 mg single doses, respective absorption rates were 60.3%, 47.7%, 30.7% and 20.7% based on recovery from bile within 24 hours in patients with external biliary drainage.
In plasma, protein binding is 96-98%.
First pass extraction of ursodeoxycholic acid from the portal vein by the liver ranges from 50-70%. Ursodeoxycholic acid is conjugated to glycine and taurine and then excreted into bile and passes to the small bowel. In the intestine, some conjugates are deconjugated and reabsorbed in the terminal ileum. Conjugates may also be dehydroxylated to lithocholic acid, part of which is absorbed, sulfated by the liver and excreted by the biliary tract. In healthy volunteers given ursodeoxycholic acid 500 mg with ¹⁴C tracer, 30-44% of the dose was excreted in faeces in the first three days as ursodeoxycholic acid (2-4%), lithocholic acid (37%) and 7-ketolithocholic acid (5%).
The biological half-life, obtained by radioactive labelling, of orally administered ursodeoxycholic acid is 3.5-5.8 days due to the effective enterohepatic circulation of ursodeoxycholic acid in the body.
In patients with severe liver disease, renal excretion becomes a major route for elimination of bile acids.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ursofalk Capsule contains the following excipients: maize starch, colloidal anhydrous silica, magnesium stearate, gelatine, titanium dioxide, sodium lauryl sulfate and purified water.
Ursofalk Suspension contains the following excipients: benzoic acid, purified water, xylitol, glycerol, Avicel RC-591, propylene glycol, sodium citrate dihydrate, sodium cyclamate, citric acid, sodium chloride and 87017 lemon flavour.
Ursofalk Tablet contains the following excipients: magnesium stearate, polysorbate 80, povidone, microcrystalline cellulose, colloidal anhydrous silica, crospovidone, purified talc, hypromellose and macrogol 6000.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australia Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
Do not use Ursofalk Suspension after 4 months of opening the bottle.

6.5 Nature and Contents of Container

Ursofalk Capsules are supplied in clear PVC blister strips of aluminium foil backing packed in cardboard cartons. Each carton contains 60 or 100 capsules. Not all pack sizes are currently marketed in Australia.
Ursofalk Suspension is available in amber glass bottles of 250 mL and is supplied with a calibrated measuring cup.
Ursofalk Tablets are supplied in clear PVC/PVDC/Al blister strips packed in cardboard cartons. Each carton contains 50 or 100 tablets. Starter packs of 25 tablets are also available. Not all pack sizes are currently marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Ursodeoxycholic acid is a white or almost white powder. It is practically insoluble in water, readily soluble in alcohol, sparingly soluble in acetone, in chloroform and in ether. It melts at 200-204°C. The IUPAC chemical name of ursodeoxycholic acid is 3α, 7β-dihydroxy-5- cholan-24-oic acid.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes