Zinforo

Package leaflet: Information for the user

Zinforo 600 mg powder for concentrate for solution for infusion

Ceftaroline fosamil
Please read this leaflet carefully before using 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 nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Zinforo is and what it is used for

What Zinforo is
Zinforo is an antibiotic medicine that contains the active substance ceftaroline fosamil. It belongs
to a group of medicines called 'cephalosporin antibiotics'.
What Zinforo is used for
Zinforo is used to treat children (from birth) and adults with:

• skin and soft tissue infections
• a lung infection called 'pneumonia'.

How Zinforo works
Zinforo works by killing certain bacteria that can cause serious infections.

2. What you need to know before using Zinforo

Do not use Zinforo:

• if you are allergic to ceftaroline fosamil or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to other cephalosporin antibiotics
• if you have previously experienced severe allergic reactions after taking other antibiotics such as penicillins or carbapenems. Do not use Zinforo if any of the above conditions apply to you. If you are unsure, consult your doctor or nurse before using Zinforo.

Warnings and precautions
Talk to your doctor or nurse before using Zinforo:

• if you have kidney problems (your doctor may consider prescribing a lower dose)
• if you have ever had sudden attacks (epileptic seizures or convulsions)
• if you have previously experienced mild allergic reactions after taking other antibiotics such as penicillins or carbapenems
• if you have ever had severe episodes of diarrhea while taking other antibiotics in the past

You may develop another infection caused by different bacteria during or after treatment with Zinforo.
You may develop signs and symptoms of serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Immediately inform a doctor if you notice any of the symptoms related to these severe skin reactions described in section 4.
Laboratory tests
You may have an abnormal result in a laboratory test (called the Coombs test), which detects the presence of certain antibodies that may act against red blood cells. If your red blood cell count decreases, your doctor may check whether these antibodies have caused it.
If any of the above conditions apply to you (or if you have any doubts), consult your doctor or nurse before using Zinforo.
Other medicines and Zinforo
Inform your doctor or nurse if you are currently taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Ask your doctor for advice before using Zinforo if you are pregnant. Do not use this medicine during pregnancy unless specifically instructed by your doctor.
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before taking this medicine.
Driving and using machines
Zinforo may cause undesirable effects such as dizziness. These effects may impair your ability to drive or operate machinery.

3. How to use Zinforo

Zinforo will be administered to you by a doctor or nurse.
Dosage
The usual recommended dose for adults is 600 mg every 12 hours. Your doctor may increase the dose to 600 mg every 8 hours for certain infections. The usual recommended dose for children depends on the child's age and weight, and is given every 8 or 12 hours. It is administered by intravenous infusion over a period of 5 to 60 minutes if receiving the usual dose, or over 120 minutes if receiving a higher dose.
A treatment course usually lasts from 5 to 14 days for skin infections and from 5 to 7 days for pneumonia.
Patients with kidney problems
If you have kidney problems, your doctor may reduce the dose, as Zinforo is eliminated from the body through the kidneys.
If you use more Zinforo than you should
If you think you have been given too much Zinforo, inform your doctor or nurse immediately.
If you miss a dose of Zinforo
If you think you have missed a dose, inform your doctor or nurse immediately.
If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. The following side effects may occur with this medicine:
Immediately inform your doctor if you experience any of these symptoms, as you may require urgent medical treatment:

• Severe skin reactions (frequency not known, cannot be estimated from the available data) or reddish patches on the trunk, flat, target-shaped or circular, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Sudden swelling of the lips, face, throat or tongue; a severe form of skin rash; and difficulty swallowing or breathing. These may be signs of a severe allergic reaction (anaphylaxis) and can be life-threatening.
• Diarrhoea that worsens or does not resolve, or stools containing blood or mucus during or after treatment with Zinforo. In this case, do not take medicines that stop or slow intestinal motility.

Very common (may affect more than 1 in 10 people)

• Changes in a blood test called the ‘Coombs test’, commonly observed in patients treated with this type of antibiotic. This test detects the presence of certain antibodies that may act against red blood cells.

Common (may affect up to 1 in 10 people)

• Fever
• Headache
• Dizziness
• Itching, skin rash
• Diarrhoea, stomach pain
• Feeling unwell (nausea) or being unwell (vomiting)
• Increased levels of liver enzymes (detected by blood tests)
• Pain and irritation of the veins
• Redness, pain or swelling at the injection site.

Uncommon (may affect up to 1 in 100 people)

• Anaemia
• Skin rash with itching (urticaria)
• Increased levels of creatinine in the blood. Creatinine indicates how well the kidneys are functioning.
• Bleeding or bruising more than usual. This may occur due to a decrease in the number of platelets in the blood.
• Changes in blood tests measuring blood clotting ability.
• Decrease in the total number of white blood cells or in the number of a certain type of white blood cells in the blood (leucopenia and neutropenia).
• Changes in mental state such as confusion, reduced level of consciousness, abnormal movements or seizures (encephalopathy), observed in people who received too high a dose of the medicine, particularly in people with kidney problems.

Rare (may affect up to 1 in 1,000 people)

• Marked decrease in a certain type of white blood cells in the blood (agranulocytosis). Symptoms may include fever, flu-like symptoms, sore throat or any other infection that could be serious.
• Increase in the number of a certain type of white blood cells in the blood (eosinophilia).

Not known (frequency cannot be estimated from the available data)

• A form of lung disease in which eosinophils (a type of white blood cells) appear in increased numbers in the lungs (eosinophilic pneumonia).

With other medicines of the same type, sudden chest pain has been observed, which could be a sign of a potentially serious allergic reaction called Kounis syndrome. If this occurs, seek immediate medical advice from a doctor or nurse.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Zinforo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
Store below 30°C.
Keep in the original packaging to protect the medicine from light.
Medicines must not be disposed of via wastewater or household waste. Hospitals will ensure the safe disposal of all materials. This will help protect the environment.

6. Package contents and other information

What Zinforo contains

• Each vial contains 600 mg of ceftaroline fosamil.
• The other component is arginine.

Description of the appearance of Zinforo and contents of the pack
Zinforo is a powder for concentrate for solution for infusion, pale white-yellowish to light yellow in colour, contained in a vial. It is available in packs containing 10 vials.

Marketing Authorisation Holder
Pfizer Ireland Pharmaceuticals Unlimited Company
Operations Support Group
Ringaskiddy, County Cork
Ireland

Manufacturer
ACS Dobfar S.p.A.
Nucleo Industriale S. Atto
64100 Teramo
Italy
ACS Dobfar S.p.A.
Via A. Fleming 2
37135 Verona
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Latvija
Luxembourg/Luxemburg Pfizer Luxembourg SARL filiāle Latvijā
Pfizer NV/SA Tel: +371 670 35 775
Tél/Tel: +32 (0)2 554 62 11

България Lietuva
Пфайзер Люксембург САРЛ, Клон България Pfizer Luxembourg SARL filialas Lietuvoje
Тел.: +359 2 970 4333 Tel. +3705 2514000

Česká republika Magyarország
Pfizer, spol. s r.o. PFIZER Kft.
Tel: +420-283-004-111 Tel. + 36 1 488 37 00

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf.: +45 44 20 11 00 Tel: +35621 344610

Deutschland Nederland
PFIZER PHARMA GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

Eesti Norge
Pfizer Luxembourg SARL Eesti filiaal Pfizer AS
Tel: +372 666 7500 Tlf: +47 67 52 61 00

Ελλάδα Österreich
Pfizer ΕΛΛΑΣ Α.Ε. Pfizer Corporation Austria Ges.m.b.H.
Τηλ.: +30 210 67 85 800 Tel: +43 (0)1 521 15-0

España Polska
Pfizer, S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel.: +48 22 335 61 00

France Portugal
Pfizer Laboratórios Pfizer, Lda.
Tél: +33 (0)1 58 07 34 40 Tel: +351 21 423 5500

Hrvatska România
Pfizer Croatia d.o.o. Pfizer România S.R.L.
Tel: + 385 1 3908 777 Tel: +40 (0)21 207 28 00

Ireland Slovenija
Pfizer Healthcare Ireland Unlimited Company Pfizer Luxembourg SARL
Tel: +1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
+44 (0)1304 616161 farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0)1 52 11 400

Ísland Slovenská republika
Icepharma hf. Pfizer Luxembourg SARL, organizačná zložka
Sími: +354 540 8000 Tel: +421–2–3355 5500

Italia Suomi/Finland
Pfizer S.r.l. Pfizer Oy
Tel: +39 06 33 18 21 Puh./Tel: +358 (0)9 430 040

Κύπρος Sverige
Pfizer ΕΛΛΑΣ Α.Ε. (CYPRUS BRANCH) Pfizer AB
Τηλ: +357 22 817690 Tel: +46 (0)8 550 520 00

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

The following information is intended for healthcare professionals only:
Important: Refer to the Summary of Product Characteristics before prescribing this medicinal product.
An aseptic technique must be used when preparing the infusion solution. The contents of the Zinforo vial must be reconstituted with 20 mL of sterile water for injections.
Instructions for reconstituting the Zinforo vial are summarised below:

The reconstituted solution must be further diluted to obtain the Zinforo solution for infusion. For preparation of the infusion, an infusion bag of 250 mL, 100 mL or 50 mL may be used, based on the volume appropriate for the patient. Suitable infusion diluents are the following: sodium chloride 9 mg/mL (0.9%) solution for injection, dextrose 50 mg/mL (5%) solution for injection, sodium chloride 4.5 mg/mL and dextrose 25 mg/mL solution for injection (0.45% sodium chloride and 2.5% dextrose), or Ringer's lactate solution. The resulting solution should be administered according to the selected dose over 5-60 minutes for the standard dose or over 120 minutes for the high dose, with infusion volumes of 50 mL, 100 mL or 250 mL.
Infusion volumes for paediatric patients will vary depending on the child's body weight. The concentration of the infusion solution during reconstitution and administration must not exceed 12 mg/mL of ceftaroline fosamil.
The time required for reconstitution is less than 2 minutes. Gently mix to reconstitute the medicinal product and ensure that the contents are completely dissolved. Parenteral medicinal products should be inspected visually for particulate matter prior to administration.
The colour of Zinforo infusion solutions varies from clear, light yellow to dark yellow depending on concentration and storage conditions. It contains no particles. When stored as recommended, the potency of the medicinal product remains unchanged.
Chemical and physical in-use stability has been demonstrated for up to 12 hours at a temperature of 2-8°C and for 6 hours at a temperature of 25°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the medicinal product should be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.
The compatibility of Zinforo with other medicinal products has not been established. Zinforo must not be mixed or physically added to solutions containing other drugs.
Each vial is for single use only.
Unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.
Annex IV
Scientific conclusions and grounds for the variation of the terms of the marketing
authorisation/marketing authorisations
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for ceftaroline fosamil, the scientific conclusions of the PRAC are as follows:
In view of the available data on serious cutaneous adverse reactions (SCAR) from the literature and spontaneous reports, including in some cases a close temporal relationship, a positive de-challenge, and in view of a plausible mechanism of action, the PRAC considers that a causal relationship between ceftaroline fosamil and drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing ceftaroline fosamil should be modified accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the rationale of the recommendation.
Grounds for the variation of the terms of the marketing authorisation/marketing
authorisations
Based on the scientific conclusions for ceftaroline fosamil, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing ceftaroline fosamil remains unchanged, subject to the proposed modifications to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation/marketing authorisations.