Dificlir

Package leaflet: Information for the user

DIFICLIR 200 mg film-coated tablets

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What DIFICLIR is and what it is used for

DIFICLIR is an antibiotic that contains the active substance fidaxomicin.
DIFICLIR film-coated tablets are used in adult patients, adolescents, and children with a body weight of at least 12.5 kg to treat infections of the inner lining of the colon (large intestine) caused by a bacterium called Clostриdioides difficile. This serious condition can cause severe, painful diarrhoea.
DIFICLIR works by eliminating the bacteria causing the infection and helps reduce the associated diarrhoea.

2. What you need to know before taking DIFICLIR

Do not take DIFICLIR

• if you are allergic to fidaxomicin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking DIFICLIR:
If you feel you may be having a severe allergic reaction such as breathing difficulties (dyspnoea), swelling
of the face or throat (angioedema), a severe skin rash, severe itching or severe hives, stop taking DIFICLIR
and seek immediate medical advice from your doctor, pharmacist or the nearest hospital emergency
department (see section 4).
If you are allergic to macrolides (a class of antibiotics), consult your doctor before taking this
medicine. Your doctor will advise whether this medicine is suitable for you.
If you have kidney or liver problems, consult your doctor before using this medicine. Your doctor
will advise whether this medicine is appropriate for you.
Available data on the use of fidaxomicin in severe cases of disease (e.g. pseudomembranous colitis)
are limited. Your doctor will determine whether your condition is severe and advise whether this
medicine is suitable for you.
Children and adolescents
Do not give this medicine to children with a body weight below 12.5 kg, as a reduced dose is required
for these children. For appropriate dosing in such patients, DIFICLIR granules for oral suspension may
be used.
Other medicines and DIFICLIR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicine.
Blood levels of DIFICLIR may be affected by other medicines you are taking, and blood levels of other
medicines may be affected by taking DIFICLIR. Examples of such medicines include:

• cyclosporine (a medicine used to suppress immune responses, for example after organ or bone marrow transplantation, for psoriasis or eczema, or for rheumatoid arthritis or nephrotic syndrome);
• ketoconazole (a medicine used to treat fungal infections);
• erythromycin (a medicine used to treat ear, nose, throat, chest and skin infections);
• clarithromycin (a medicine used to treat chest infections, throat and sinus infections, skin and soft tissue infections, and Helicobacter pylori-associated infections in duodenal or gastric ulcers);
• verapamil (a medicine used to treat high blood pressure, to prevent chest pain attacks, or after a heart attack to prevent further attacks);
• dronedarone and amiodarone (medicines used to control heart rhythm);
• dabigatran etexilate (a medicine used to prevent blood clots after hip or knee replacement surgery). Do not use DIFICLIR in combination with any of these medicines unless your doctor advises otherwise. If you are taking any of these medicines, contact your doctor for advice before taking this medicine.

Pregnancy and breastfeeding
Do not take DIFICLIR during pregnancy unless your doctor advises you to do so.
This is because it is unknown whether fidaxomicin could harm the unborn baby.
If you are pregnant or suspect you may be pregnant, consult your doctor or pharmacist before taking
this medicine.
It is not known whether fidaxomicin passes into breast milk, although this is not expected.
If you are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
DIFICLIR is not expected to affect your ability to drive vehicles or operate tools or machinery.
DIFICLIR contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially “sodium-free”.

3. How to take DIFICLIR

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose for patients weighing at least 12.5 kg is one tablet (200 mg) twice daily
(one tablet every 12 hours) for 10 days (see schedule 1).
Your doctor may have prescribed an alternative dosing regimen. The recommendation for an alternative
dose is administration twice daily every day for days 1-5. Do not take a tablet on day 6, then take one tablet once daily on alternate days for days 7-25 (see schedule 1).
Schedule 1 – Standard dosage
DAY 1 2 3 4 5 6 7 8 9 10
Schedule 2 – Alternative dosage
DAY 1 2 3 4 5
DAY 6 7 8 9 10 11 12 13 14 15

• DAY 16 17 18 19 20 21 22 23 24 25
• 200 mg - Dificlir 200 mg film-coated tablets
• No tablet

Swallow the tablets whole with a glass of water. You may take DIFICLIR before, during, or after meals.
DIFICLIR granules for oral suspension should be used in patients with a body weight below 12.5 kg. This formulation (oral suspension) of the medicine may also be more suitable for children weighing more than 12.5 kg; please consult your doctor or pharmacist.
If you take more DIFICLIR than you should
If you have taken more tablets than you should, contact your doctor. Take the medicine packaging with you so the doctor can see what you have taken.
If you forget to take DIFICLIR
Take the tablet as soon as you remember, unless it is almost time for your next dose. In this case, skip the missed dose. Do not take a double dose to make up for a forgotten tablet.
If you stop taking DIFICLIR
Do not stop taking DIFICLIR unless your doctor has advised you to do so.
Continue taking the medicine until the treatment course is complete, even if you feel better.
Stopping the medicine too early may cause the infection to return.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Severe allergic reactions may occur, including difficulty breathing (dyspnea), swelling of the face or throat (angioedema), severe skin rash, or intense itching (see section 2). If you experience any of these reactions, stop taking DIFICLIR and seek immediate medical advice from your doctor, pharmacist, or the nearest hospital emergency department.

The most common side effects (may affect up to 1 in 10 people) are:

• vomiting
• nausea
• constipation

Other possible side effects are:

Uncommon side effects (may affect up to 1 in 100 people)

• loss of appetite
• dizziness, headache
• dry mouth, altered taste sensation (dysgeusia)
• feeling of bloating, gas (flatulence)
• rash, itching

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• swelling of the face and throat (angioedema), breathing problems (dyspnea)

Additional side effects in children and adolescents

• urticaria

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in Annex V*.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store DIFICLIR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after 'Exp'. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What DIFICLIR contains

• The active substance is fidaxomicin. Each film-coated tablet contains 200 mg of fidaxomicin.
• The other components are:
  Tablet core: microcrystalline cellulose, pregelatinized starch, hydroxypropylcellulose, butylated hydroxytoluene, sodium starch glycolate, magnesium stearate.
  Coating: polyvinyl alcohol, titanium dioxide (E171), talc, polyethylene glycol, lecithin (soy)

Description of the appearance of DIFICLIR and contents of the pack
DIFICLIR 200 mg film-coated tablets are capsule-shaped, white to off-white tablets, with "FDX" printed on one side and "200" on the other side.
DIFICLIR is available in:
Alu/alu unit dose divisible blister; 100 x 1 film-coated tablet.
Alu/alu unit dose divisible blister; 20 x 1 film-coated tablet.
DIFICLIR is also available in the formulation of granules for oral suspension.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Tillotts Pharma GmbH
Warmbacher Strasse 80
79618 Rheinfelden
Germany

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

Package leaflet: Information for the user

DIFICLIR 40 mg/ml granules for oral suspension

fidaxomicin
Please read this entire leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What DIFICLIR is and what it is used for

DIFICLIR is an antibiotic that contains the active substance fidaxomicin.
DIFICLIR oral suspension is used in adults, adolescents, and children from birth up to but less than 18 years of age to treat infections of the inner lining of the colon (large intestine) caused by a bacterium called Clostridioides difficile. This serious disease can cause severe, painful diarrhoea.
DIFICLIR works by killing the bacteria causing the infection and helps reduce the associated diarrhoea.

2. What you need to know before taking DIFICLIR

Do not take DIFICLIR

• if you are allergic to fidaxomicin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking DIFICLIR:
If you feel you may be having a severe allergic reaction such as breathing difficulties (dyspnoea), swelling of the face or throat (angioedema), severe skin rash, or severe itching or severe hives, stop taking DIFICLIR and contact your doctor, pharmacist or the nearest hospital emergency department urgently (see section 4).
If you are allergic to macrolides (a class of antibiotics), consult your doctor before taking this medicine. Your doctor will advise whether this medicine is suitable for you.
If you have kidney or liver problems, consult your doctor before using this medicine. Your doctor will advise whether this medicine is suitable for you.
Available data on the use of fidaxomicin in severe cases of the disease (e.g. pseudomembranous colitis) are limited. Your doctor will determine whether your condition is severe and whether this medicine is appropriate for you.

Other medicines and DIFICLIR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Blood levels of DIFICLIR may be affected by other medicines you are taking, and blood levels of other medicines may be affected by taking DIFICLIR. Examples of such medicines include:

• cyclosporine (a medicine used to suppress the body's immune responses, used e.g. after organ or bone marrow transplantation, for psoriasis or eczema, or for rheumatoid arthritis or nephrotic syndrome);
• ketoconazole (a medicine used to treat fungal infections);
• erythromycin (a medicine used to treat infections of the ear, nose, throat, chest and skin);
• clarithromycin (a medicine used to treat chest infections, throat and sinus infections, skin and soft tissue infections, and Helicobacter pylori infections associated with duodenal or gastric ulcers);
• verapamil (a medicine used to treat high blood pressure, to prevent chest pain attacks, or used after a heart attack to prevent another one);
• dronedarone and amiodarone (medicines used to control heart rhythm);
• dabigatran etexilate (a medicine used to prevent blood clots after hip or knee replacement surgery).
  Do not use DIFICLIR in combination with any of these medicines unless your doctor advises otherwise. If you are taking any of these medicines, contact your doctor for advice before taking this medicine.

Pregnancy and breastfeeding
Do not take DIFICLIR during pregnancy unless your doctor advises you to do so.
This is because it is not known whether fidaxomicin could harm the unborn baby.
If you are pregnant or suspect you may be pregnant, consult your doctor or pharmacist before taking this medicine.
It is not known whether fidaxomicin passes into breast milk, although this is not expected.
If you are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
DIFICLIR is not expected to affect your ability to drive or operate machinery.

DIFICLIR contains sodium benzoate (E211)
This medicine contains 2.5 mg of sodium benzoate (E211) in each ml of oral suspension. Sodium benzoate (E211) may increase jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age).

DIFICLIR contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 5 ml of suspension, i.e. it is essentially "sodium-free".

3. How to take DIFICLIR

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate dose based on body weight.

• The standard dose for patients weighing at least 12.5 kg is 200 mg (5 ml of oral suspension) administered twice daily (once every 12 hours) for 10 days (see schedule 1). Your doctor may have prescribed an alternative dosing regimen. The recommendation for an alternative dosing regimen is administration twice daily every day for days 1–5. Do not take the tablet on day 6; subsequently, take once daily on alternate days for days 7–25 (see also schedule 2).

Schedule 1 – Standard dosage
DAY 1 2 3 4 5 6 7 8 9 10
Schedule 2 – Alternative dosage
DAY 1 2 3 4 5
DAY 6 7 8 9 10 11 12 13 14 15
DAY 16 17 18 19 20 21 22 23 24 25
5 ml - Dificlir 40 mg/ml granules for oral suspension
No administration

Another formulation of this medicine (tablets) may be more suitable for adults and older children (e.g. adolescents); please consult your doctor or pharmacist.
The recommended dose for children according to body weight is as follows:

You may take DIFICLIR before, during, or after meals.
How to take the DIFICLIR dose using an oral syringe
The pharmacist or healthcare provider will prepare the DIFICLIR oral suspension before giving it to you.
If the product has not been provided to you as a suspension, contact the pharmacist or healthcare staff.
Instructions for use:
Use the oral syringe and adapter supplied by the pharmacist or healthcare provider to ensure you measure the correct amount. If you have not been provided with an oral syringe and an oral adapter, contact the pharmacist or healthcare provider.
The pharmacist will advise you on how to measure the medicine using the oral syringe. Before using DIFICLIR suspension, see the instructions below.

1. Remove the bottle from the refrigerator 15 minutes before administration.
2. After 15 minutes, gently shake the bottle 10 times and let it stand for 1 minute.
3. Check whether the liquid is smooth and not lumpy (i.e., homogeneous).
4. Remove the cap and attach the adapter to the bottle according to the instructions provided by the pharmacist or healthcare provider.
5. Insert the tip of the oral syringe into the adapter until it is securely in place.
6. Shake the bottle up and down 3 times, then invert it so that the syringe is at the bottom.
7. Pull back the plunger of the oral syringe to draw the prescribed amount from the inverted bottle.
8. Keep the syringe in place and return the bottle to an upright position, ensuring the plunger does not move. Carefully remove the syringe from the adapter and confirm that the correct dose has been measured.
9. Slowly administer the oral suspension directly into the patient's mouth until all the medicinal fluid has been delivered.
10. If you have been supplied with a press-fit adapter, leave the adapter on the neck of the bottle or follow the instructions provided by the pharmacist or healthcare provider.
11. After administration, store the remaining suspension in the refrigerator.
12. To allow reuse of the oral syringe, rinse the syringe with warm drinking water (at least 3 times) or until clean water comes out of the syringe. Dry the outer and inner surfaces as thoroughly as possible. Leave it to dry until next use.

If you started using this product in hospital, the pharmacist or healthcare provider will supply you with the suspension, oral syringe, and adapter at discharge.
If you take more DIFICLIR than you should
If you have taken more oral suspension than you should, consult your doctor. Take the medicine packaging with you so the doctor can see what you have taken.
If you forget to take DIFICLIR
Take the oral suspension as soon as you remember, unless it is almost time for your next dose. In that case, do not take the missed dose. Do not take a double dose to make up for the forgotten dose.
If you stop taking DIFICLIR
Do not stop taking DIFICLIR unless advised by your doctor. Continue taking the medicine for the full duration of the treatment, even if you feel better. If you stop taking the medicine too early, the infection may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Severe allergic reactions may occur, including difficulty in breathing (dyspnoea), swelling of the face or throat (angioedema), severe skin rash (rash), or intense itching (see section 2). If you experience any of these reactions, stop taking DIFICLIR and seek immediate medical advice from your doctor, pharmacist or at the nearest hospital emergency department.

The most common side effects (which may affect up to 1 in 10 people) are:

• vomiting
• nausea
• constipation

Other possible side effects are:

Uncommon side effects (may affect up to 1 in 100 people):

• loss of appetite
• dizziness, headache
• dry mouth, altered taste (dysgeusia)
• feeling of abdominal bloating, flatulence
• rash, itching

Side effects of unknown frequency (frequency cannot be estimated from the available data):

• swelling of the face and throat (angioedema), breathing problems (dyspnoea)

Additional side effects in children and adolescents

• urticaria

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system indicated in Annex V*.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store DIFICLIR

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 carton after "Exp". The expiry
date refers to the last day of that month.
DIFICLIR will be supplied to you as a suspension, which can be stored for up to 12 days. Store in
the refrigerator (2°C - 8°C). Do not use the suspension after the expiry date written
on the label of the bottle.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What DIFICLIR contains

• The active substance is fidaxomicin.
• The other components are: microcrystalline cellulose, sodium starch glycolate, xanthan gum, citric acid, sodium citrate, sodium benzoate (see section 2), sucralose, berry flavouring.

Description of the appearance of DIFICLIR and contents of the pack
DIFICLIR is presented as white to yellowish granules for oral suspension in an amber glass bottle.
DIFICLIR will be supplied to you as an oral suspension by the pharmacist or nurse and will appear as a white to yellowish white suspension.
The pack does not contain the oral syringe and adapter needed to use this product. These will be supplied by the pharmacist or nurse.
DIFICLIR is also available in the formulation of film-coated tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder
Tillotts Pharma GmbH
Warmbacher Strasse 80
79618 Rheinfelden
Germany

Manufacturer
Almac Pharma Services Limited
Seagoe Industrial Estate, Portadown, Craigavon,
BT63 5UA,
United Kingdom
Tillotts Pharma GmbH
Warmbacher Strasse 80
79618 Rheinfelden
Germany

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only

Instructions for reconstitution:

1. Shake the glass vial to ensure that the granules move freely and that no agglomeration has occurred.
2. Measure 105 mL of purified water and add it to the glass vial. Note that the stability of fidaxomicin granules suspended in mineral water, tap water, or other liquids has not been established.
3. Close the glass vial and shake vigorously for at least 1 minute.
4. Check that no granules are adhering to the bottom of the vial or clumps are present. If adherent granules or clumps are observed, shake the glass vial again vigorously for at least 1 minute.
5. Allow the vial to stand for 1 minute.
6. Verify that a homogeneous suspension is obtained.
7. Write the expiration date of the reconstituted suspension on the vial label (the shelf life of the reconstituted suspension is 27 days).
8. Store the bottle refrigerated (2–8 °C) before and during use.
9. Select an appropriate oral dosing syringe and a vial adapter suitable for dispensing liquid medications to measure the correct dose.

After reconstitution, the suspension (110 mL) will appear white to off-white.
An appropriate commercially available oral dosing syringe and vial adapter suitable for dispensing
liquid medications must be selected by healthcare personnel to allow the patient or caregiver to
measure the correct dose. The adapter must be suitable for use in combination with the selected
oral syringe and fit the vial neck size, for example, a press-on vial adapter (27 mm) or a universal
vial adapter.
If treatment with fidaxomicin is initiated in a hospital setting and the patient is discharged before
completing the hospital treatment course, the patient must be provided with the oral suspension and
an appropriate oral syringe and adapter. Patients or caregivers must not prepare the oral suspension at home.
The recommended oral syringe capacity for accurate dosing of the oral suspension is shown in the table below.
Recommended oral syringe capacity for accurate administration

If possible, the graduation corresponding to the appropriate dose should be marked or
highlighted on the oral syringe (according to the dosing table in section 3).
Administration via enteral feeding tube:
When administering via an enteral feeding tube, a healthcare professional must select a suitable
commercially available tube. Polyvinyl chloride (PVC) and polyurethane (PUR) enteral feeding tubes
have been found to be compatible with the oral suspension. The recommended enteral feeding tube
sizes and water flush volumes are provided in the table below.
Recommended enteral feeding tube size and flushing volume

• Based on a 120 cm probe