fidaxomicin: package leaflet

DIFICLIR is an antibiotic which contains the active substance fidaxomicin.

DIFICLIR film-coated tablets are used in adults, adolescents and children with a body weight of at least 12.5 kg to treat infections of the lining of the colon (large intestine) with certain bacteria called Clostridioides difficile. This serious illness can result in painful, severe diarrhoea. DIFICLIR works by killing the bacteria that cause the infection and helps to reduce the associated diarrhoea.

Do not take DIFICLIR
−
If you are allergic to fidaxomicin or 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 that you might have a severe allergic reaction such as trouble breathing (dyspnea), swelling of the face or throat (angioedema), severe rash, severe itching (pruritus) or severe hives (urticaria), stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local hospital emergency department (see section 4).

If you are allergic to macrolides (a class of antibiotics), ask your doctor for advice before using this medicine. Your doctor will tell you whether this medicine is suitable for you.

If you have kidney or liver problems, ask your doctor for advice before using this medicine. Your doctor will tell you whether this medicine is suitable for you.

There are limited data available on the use of fidaxomicin in severe cases of the disease (e.g.
pseudomembranous colitis). Your doctor will know whether your disease falls in the severe categories and will tell you 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, because these children require a reduced dose. For appropriate dosing in these patients, DIFICLIR granules for oral suspension may be used.

Other medicines and DIFICLIR
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

DIFICLIR blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking DIFICLIR. Examples of such medicines are:
− cyclosporin (a medicine used to dampen down the body’s immune reactions, used e.g. after an organ or bone marrow transplant, 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 tissue infections and Helicobacter pylori infections associated with duodenal or stomach ulcer) − verapamil (a medicine used to treat high blood pressure or to prevent chest pain attacks, or used following a heart attack to prevent another one) − dronedarone and amiodarone (medicines used to control the heartbeat) − dabigatran etexilat (a medicine used to prevent the formation of blood clots after hip or knee replacement surgery) You should not use DIFICLIR in combination with one of these medicines, unless your doctor tells you otherwise. If you use one of these medicines, please ask your doctor for advice before taking this medicine.

Pregnancy and breast-feeding
You should not take DIFICLIR if you are pregnant, unless your doctor tells you otherwise.
This is because it is not known whether fidaxomicin can harm your baby.
If you are pregnant or think you may be pregnant, ask your doctor or pharmacist for advice before taking this medicine.

It is not known whether fidaxomicin passes into breast milk, but it is not expected to do so.
If you are breastfeeding ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
DIFICLIR is not expected to affect your ability to drive, use tools or machines.

DIFICLIR contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

Always take this medicine exactly as your doctor or pharmacist has told you. You should check with your doctor or pharmacist if you are not sure.

The standard dosing for patients weighing at least 12.5 kg is one tablet (200 mg) twice daily (one tablet every 12 hours) for 10 days (see scheme 1 below).

It is possible that your doctor has prescribed an alternate dosing. The recommendation for an alternate

dosing is twice daily administration for days 1-5. Do not take a tablet on day 6, then once daily every other day for the days 7-25 (see also scheme 2 below).

Scheme 1 - Standard dosing
DAY
Morning
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
Evening
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg
200 mg

Scheme 2 - Alternate dosing
200 mg - Dificlir 200 mg film-coated tablet
- No tablet

Swallow the tablets whole with a glass of water. You can take DIFICLIR before, during or after meals.

DIFICLIR granules for oral suspension should be used for patients with a body weight of less than 12.5 kg. This form of this medicine (oral suspension) may also be more suitable for patients above 12.5 kg; ask your doctor or pharmacist.

If you take more DIFICLIR than you should
If you have taken more tablets than you should have, talk to a doctor. Take the medicine pack with you so the doctor knows what you have taken.

If you forget to take DIFICLIR
Take the tablet as soon as you remember, unless it is time for the next dose. In that case, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking DIFICLIR
Do not stop taking DIFICLIR, unless your doctor has advised you to do so.
Keep taking this medicine until the course is finished, even if you feel better.
If you stop taking this medicine too soon, the infection may come back.

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

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

A severe allergic reaction may occur, including trouble breathing (dyspnea), swelling of the face or throat (angioedema), severe rash or severe itching (pruritus) (see section 2). If such reaction occurs, stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local hospital emergency department.

The most common side effects (may affect up to 1 in 10 people) are:
− vomiting
− nausea
− constipation.

DAY

200 mg
200 mg
200 mg
200 mg
200 mg
Evening
200 mg
200 mg
200 mg
200 mg
200 mg
DAY

- 200 mg
- 200 mg
- 200 mg
- 200 mg
- 200 mg
DAY

• 200 mg
• 200 mg
• 200 mg
• 200 mg
• 200 mg

Other possible side effects are the following:
Uncommon side effects (may affect up to 1 in 100 people)
− decreased appetite
− dizziness, headache
− dry mouth, altered taste (dysgeusia)
− bloated feeling, wind (flatulence)
− rash, itching (pruritus)

Not known side effects (frequency cannot be estimated from the available data)
− swelling of the face and throat (angioedema), trouble breathing (dyspnea)

Additional side effects in children and adolescents
− hives

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 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.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

What DIFICLIR contains
−
The active substance is fidaxomicin. Each film-coated tablet contains 200 mg of fidaxomicin.
−
The other ingredients are:
Tablet core: microcrystalline cellulose, pregelatinised starch, hydroxypropyl cellulose, butylated hydroxytoluene, sodium starch glycolate and magnesium stearate Coating: polyvinyl alcohol, titanium dioxide (E171), talc, polyethylene glycol and lecithin (soy)

What DIFICLIR looks like and contents of the pack
DIFICLIR 200 mg film-coated tablets are capsule shaped tablets, white to off-white in colour, with “FDX” on one side and “200” on the other side.

DIFICLIR is available in:
100 x 1 film-coated tablet in alu/alu perforated unit dose blisters.
20 x 1 film-coated tablet in alu/alu perforated unit dose blisters.

DIFICLIR is also available in the form of granules for oral suspension.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Tillotts Pharma GmbH
Warmbacher Strasse 80

79618 Rheinfelden
Germany

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu

occurred.

granules suspended in mineral water, tap water, or other liquids has not been established.

any lumps. If caked granules or any lumps are observed, shake the glass bottle vigorously again for at least 1 minute.

7. Write the date of expiration of the reconstituted suspension on the bottle label (the shelf-life of the reconstituted suspension is 27 days).
8. Store the bottle at refrigerated temperature (2-8°C) before and during use.
9. Select an appropriate oral syringe and bottle adaptor suitable for dispensing liquid medicinal product to measure the correct dose.

After reconstitution, the suspension (110 ml) will appear as white to yellowish white.

An appropriate commercially available oral syringe and adaptor suitable for dispensing of liquid medicines should be selected by the healthcare professional in order to allow the patient or caregiver to measure the correct dose. The adaptor should be suitable for use in combination with the selected oral syringe and fits the bottle neck size, for example a press-in bottles adaptor (27 mm) or universal bottle adapter.

In case the treatment with fidaxomicin started in a hospital setting and the patient is discharged before the end of the treatment at the hospital, the patient should be provided with the oral suspension and a suitable oral syringe and adaptor. Patients or caregivers should not prepare the oral suspension at home.

Recommended oral syringe capacity for measuring the dose of the oral suspension is presented in the table below.

Suggested oral syringe capacity for accurate dispensing
Prescribed dosing volume
Recommended oral syringe capacity
1 ml
1 ml oral syringe
2 – 5 ml
5 ml oral syringe

If possible, the graduation corresponding to the appropriate dose should be marked or highlighted (according to the dosing table in section 3) on the oral syringe.

Administration via an enteral feeding tube:
In case of administration using an enteral feeding tube, an appropriate commercially available tube should be selected by the healthcare professional. Enteral feeding tubes made of polyvinylchloride (PVC) and polyurethane (PUR) have been shown compatible with the oral suspension. The recommended enteral feeding tube size and flush volume of water are provided in the table below.

Recommended enteral feeding tube size and flush volume
Recommended tube size (diameter)
Recommended flush volume*
4 Fr at least 1 mL
5 Fr at least 2 mL
6 – 7 Fr at least 3 mL
8 Fr at least 4 mL
* Based on tubes of 120 cm