Dificlir 40 mg/ml granules for oral suspension

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

DIFICLIR 40 mg/ml granules for oral suspension

fidaxomicin

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

• Keep this leaflet, as 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, and you must not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the 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 less than 18 years of age, to treat infections of the colon lining (large intestine) caused by bacteria called Clostridioides difficile. This serious condition can cause severe and painful diarrhea. DIFICLIR works by killing the bacteria causing the infection and helps reduce the associated diarrhea.

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 think you may be having a severe allergic reaction such as difficulty breathing (dyspnea), swelling of the face or throat (angioedema), severe rash, severe itching (pruritus), or severe hives (urticaria), stop treatment with DIFICLIR and seek immediate medical attention from your doctor, pharmacist, or hospital emergency department (see section 4).

If you are allergic to macrolides (a type of antibiotic), consult your doctor before using this medicine. Your doctor will determine whether this medicine is suitable for you.

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

Limited data are available on the use of fidaxomicin in severe cases of the disease (e.g., pseudomembranous colitis). Your doctor will assess whether your condition falls into the severe category and will advise you if this medicine is appropriate for you.

Other medicines and DIFICLIR

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to 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. Some examples of such medicines are:

• cyclosporine (a medicine used to suppress the body's immune response, for example, after 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 gastric ulcer)
• verapamil (a medicine used to treat high blood pressure or to prevent chest pain attacks, or used after a heart attack to prevent another)
• dronedarone and amiodarone (medicines used to control heart rhythm)
• dabigatran etexilate (a medicine used to prevent blood clots after hip or knee replacement surgery).

You should not use DIFICLIR in combination with any of these medicines unless your doctor tells you otherwise. If you are taking any of these medicines, please consult your doctor before taking this medicine.

Pregnancy and breastfeeding

Do not take DIFICLIR during pregnancy unless your doctor instructs you to do so.

This is because it is unknown whether fidaxomicin could harm your baby.

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

It is unknown whether fidaxomicin passes into breast milk, although it is not expected to do so. If you are breastfeeding, consult your doctor or pharmacist before using this medicine.

Driving and using machines

DIFICLIR is not expected to affect your ability to drive or operate tools or 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 the risk of 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; hence, it is essentially "sodium-free".

3. How to take DIFICLIR

Follow exactly the instructions for using this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your weight.

The standard dosage for patients weighing at least 12.5 kg is 200 mg (5 ml of oral suspension) administered twice daily (every 12 hours) for 10 days (see Schedule 1 below). For adults and older children (e.g., adolescents), another formulation of this medicine (tablets) may be more suitable; consult your doctor or pharmacist.

Your doctor may have prescribed an alternative dosing regimen. The recommendation for an alternative dosing regimen is administration twice daily on days 1–5. Do not take the dose on day 6, and then once daily on alternate days from days 7 to 25 (see also Schedule 2 below).

Schedule 1 – Standard dosing

Schedule 2 – Alternate dosing

5 ml - Dificlir 40 mg/ml granulated for oral suspension

• Not a suspension

The recommended dose for children according to their body weight is the following:

You may take DIFICLIR before, during, or after meals.

How to administer the DIFICLIR dose using an oral syringe

Your pharmacist or healthcare professional will prepare the DIFICLIR oral suspension before giving it to you. If you have not been provided with the product as a suspension, contact your pharmacist or healthcare professional.

Instructions for use:

Use the oral syringe and adapter provided by your pharmacist or healthcare professional to ensure accurate measurement. If you have not been provided with an oral syringe and adapter, contact your pharmacist or healthcare professional.

Your pharmacist will inform you how to measure the medication using the oral syringe. Read the following instructions before using DIFICLIR suspension.

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 that the liquid appears uniform and free of lumps (i.e., homogeneous).

4. Remove the cap and attach the adapter to the bottle according to the instructions provided by your pharmacist or healthcare professional.

5. Insert the tip of the oral syringe into the adapter until it is securely in place.

6. Invert the bottle three times and keep it upside down so that the syringe is at the bottom.

7. Pull back the plunger of the oral syringe to draw the prescribed volume of medication from the inverted bottle.

8. Keep the syringe attached, then turn the bottle upright, taking care not to move the plunger. Gently remove the syringe from the adapter and confirm that you have measured the correct dose.

9. Slowly administer the oral suspension directly into the patient's mouth until all the liquid has been dispensed.

10. If you have a press-fit adapter, leave it attached to the neck of the bottle or follow the instructions provided by your pharmacist or healthcare professional.

11. After administration, store any remaining suspension in the refrigerator.

12. To reuse the oral syringe, rinse it thoroughly with lukewarm drinking water (at least 3 times) or until clear water comes out of the syringe. Dry the internal and external surfaces as thoroughly as possible. Allow it to air dry until the next use.

If you started using this product in a hospital, your pharmacist or healthcare professional will provide you with the suspension, oral syringe, and adapter at the time of discharge.

If you take more DIFICLIR than you should

If you have taken more oral suspension than prescribed, consult a doctor immediately. Bring the medicine packaging with you so the doctor knows 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, skip the missed dose. Do not take a double dose to make up for a missed dose.

If you stop taking DIFICLIR

Do not stop taking DIFICLIR unless your doctor has advised you to do so.

Continue taking this medicine for the full duration of treatment, even if you feel better.

If you stop taking this medicine too early, the infection may return.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

A serious allergic reaction may occur, including difficulty breathing (dyspnea), swelling of the face or throat (angioedema), severe rash or severe itching (pruritus) (see section 2). If such reactions occur, stop treatment with DIFICLIR immediately and seek urgent medical advice from your doctor, pharmacist, or hospital emergency service.

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

• vomiting
• nausea
• constipation

Other possible adverse effects are the following:

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

• decreased appetite
• dizziness, headache
• dry mouth, altered taste (dysgeusia)
• feeling of fullness, gas (flatulence)
• rash, itching (pruritus)

Adverse effects of unknown frequency (frequency cannot be estimated from available data)

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

Other adverse effects in children and adolescents

• hives

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 the month indicated.

DIFICLIR will be supplied as a suspension that can be stored for a maximum of 27 days. Store in the refrigerator (between 2 °C and 8 °C). Do not use the suspension after the expiry date indicated on the vial label.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of DIFICLIR

• 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 and mixed berry flavour.

Presentation of the product and contents of the pack

DIFICLIR is supplied in an amber glass bottle as an oral suspension granule with a colour ranging from white to off-white. Your pharmacist or healthcare professional will provide DIFICLIR to you as a suspension with a colour ranging from white to off-white. The pack does not contain the oral syringe or adapter required to administer this product. Both will be provided to you by your pharmacist or other healthcare professional.

DIFICLIR is also available as film-coated tablets.

Only certain pack sizes may be marketed.

Marketing Authorization 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

Date of the most recent review of this summary:

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

This information is intended for healthcare professionals only:

Reconstitution instructions:

1. Shake the glass bottle to ensure that the granules move freely and are not compacted.
2. Measure 105 mL of purified water and add it to the glass bottle. Note that the stability of fidaxomicin granules suspended in mineral water, tap water or other liquids has not been established.
3. Close the glass bottle and shake vigorously for at least 1 minute.
4. Check that there are no lumps or compacted granules remaining at the bottom of the bottle. If lumps or compacted granules are observed, shake the bottle vigorously again for at least 1 minute.
5. Allow the bottle to stand for 1 minute.
6. Check that the resulting suspension is homogeneous.
7. Record the expiry date of the reconstituted suspension on the bottle label (the reconstituted suspension is stable for 27 days).
8. Store the bottle at a temperature between 2 and 8 °C before and during use.
9. Select an appropriate oral syringe and bottle adapter available on the market to accurately measure the dose.

After reconstitution, the suspension (110 mL) will have a colour ranging from white to off-white.

The healthcare professional must select an oral syringe and bottle adapter available on the market that are suitable for dispensing liquid medicines and allow the patient or caregiver to accurately measure the dose. The adapter must be compatible with the selected oral syringe and fit securely onto the neck of the bottle (e.g., a 27 mm press-in bottle adapter or a universal bottle adapter).

If treatment with fidaxomicin is initiated in a hospital setting and the patient is discharged before completing treatment, the oral suspension should be supplied together with an appropriate oral syringe and adapter. Patients or their caregivers must not prepare the oral suspension at home.

The table below shows the recommended oral syringe capacity for accurate dosing.

Recommended oral syringe capacity for accurate administration

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

Administration through enteral feeding tube:

In case of administration through an enteral feeding tube, the healthcare professional should select a commercially available enteral feeding tube appropriate for use. Parenteral feeding tubes made of polyvinyl chloride (PVC) and polyurethane (PUR) have shown compatibility with the oral suspension. The following table shows the recommended enteral feeding tube size and recommended water flushing volume.

Enteral feeding tube size and recommended flushing volume

• Based on 120 cm tubes