Curoxim

Package leaflet: Information for the user

Curoxim 250 mg powder and solvent for injectable solution, 500 mg powder and solvent for injectable solution, 750 mg powder and solvent for injectable solution, 1 g powder and solvent for injectable solution, 2 g powder for infusion solution

cefuroxime
Please read all of 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 experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.
Contents of this leaflet:

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

1. What Curoxim is and what it is used for

Curoxim is an antibiotic used in adults and children. It works by killing the bacteria that cause infections and belongs to a group of medicines called cephalosporins.
Curoxim is used to treat infections of:

• lungs or chest
• urinary tract
• skin and soft tissues
• abdomen

Curoxim is also used:

• to prevent infections during surgical procedures. Your doctor may identify the type of bacteria causing the infection and monitor whether the bacteria are sensitive to Curoxim during treatment.

2. What you must know before being administered Curoxim

Do not be given Curoxim if:

• you are allergic to any antibiotic of the cephalosporin class or to any of the other ingredients of Curoxim (listed in section 6).
• you have had a severe allergic reaction (hypersensitivity) to any other type of beta-lactam antibiotics (penicillins, monobactams, and carbapenems).
• you have developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after treatment with cefuroxime or with any other antibiotic of the cephalosporin class. Talk to your doctor before starting treatment with Curoxim if you think this applies to you, because in this case Curoxim must not be administered to you.

Take special care with Curoxim
Severe skin reactions have been reported in association with cefuroxime treatment,
including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with
eosinophilia and systemic symptoms (DRESS). Seek immediate medical advice if you notice any
of the symptoms related to these severe skin reactions described in section 4.
Be alert for certain symptoms such as allergic reactions, skin rashes, gastrointestinal
disorders such as diarrhoea, or fungal infections while being treated with Curoxim. This will
reduce the risk of potential problems. See (Conditions requiring caution) in section 4.
If you have previously had any allergic reaction to other antibiotics such as penicillin, you may
also be allergic to Curoxim.
If you need blood or urine tests
Curoxim may interfere with the results of urine or blood tests for sugar and with the blood test known as the Coombs test. If you are undergoing these tests:
Inform the person collecting the sample that you are being treated with Curoxim.
Other medicines and Curoxim
Inform your doctor if you are taking any other medicines, if you have recently started taking any, or if you start taking new ones. This includes also medicines without a prescription.
Some medicines may affect the activity of Curoxim or make it more likely that you experience side effects. These include:

• aminoglycoside-type antibiotics
• diuretic medicines such as furosemide
• probenecid
• oral anticoagulants
  Inform your doctor if this applies to you. You may need additional monitoring to check kidney function while being treated with Curoxim.

Oral contraceptives
Curoxim may reduce the effectiveness of oral contraceptives. If you are taking oral contraceptives while being treated with Curoxim, you should also use a barrier method of contraception (such as condoms). Please consult your doctor for advice.
Pregnancy, breastfeeding and fertility
Inform your doctor before being administered Curoxim:

• if you are pregnant, think you might be pregnant, or are planning a pregnancy
• if you are breastfeeding

Your doctor will assess the benefit of treatment with Curoxim against the risk to your baby.
Driving and using machines
Do not drive or operate machinery if you do not feel well.
Curoxim contains sodium
You need to take into account the following information if you are on a sodium-controlled diet.
250 mg
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. essentially "sodium-free".
500 mg
This medicine contains 28 mg of sodium (the main component of table salt) in each vial. This corresponds to 1.4% of the maximum daily sodium intake recommended in an adult's diet.
750 mg
This medicine contains 42 mg of sodium (the main component of table salt) in each vial. This corresponds to 2.1% of the maximum daily sodium intake recommended in an adult's diet.
1 g
This medicine contains 56 mg of sodium (the main component of table salt) in each vial. This corresponds to 2.8% of the maximum daily sodium intake recommended in an adult's diet.
2 g
This medicine contains 111 mg of sodium (the main component of table salt) in each vial. This corresponds to 5.55% of the maximum daily sodium intake recommended in an adult's diet.

3. How Curoxim is administered

Curoxim is generally administered by a doctor or a nurse. It can be given as an intravenous infusion or as an injection directly into a vein or into a muscle.
Recommended dose
The appropriate dose of Curoxim will be decided by your doctor and depends on: the severity and type of infection; whether you are being treated with other antibiotics; your body weight and age; and the condition of your kidneys.
Newborns (from 0 to 3 weeks)
For each kg of the child's body weight, 30 to 100 mg of Curoxim per day will be administered, divided into two or three doses.
Infants (over 3 weeks) and children
For each kg of the infant's or child's body weight, 30 to 100 mg of Curoxim per day will be administered, divided into three or four doses.
Adults and adolescents
750 mg to 1.5 g of Curoxim two, three or four times daily. Maximum dose: 6 g per day.
Patients with kidney problems
If you have kidney problems, your doctor may adjust the dose.
Talk to your doctor if this applies to you.

4. Possible side effects

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

Conditions requiring attention
A small number of people being treated with Curoxim may experience an allergic reaction or a potentially serious skin reaction. Symptoms of these reactions include:

• Severe allergic reaction. Signs include raised, itchy rash, swelling, sometimes of the face or mouth, causing difficulty breathing.
• Skin rash with blisters resembling small targets (a dark spot in the center surrounded by a pale area with a black ring around the edge).
• Widespread rash with blisters and peeling of the skin. (These may be signs of Stevens-Johnson syndrome or toxic epidermal necrolysis).
• Widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Chest pain occurring in the context of allergic reactions, which may be a symptom of allergy-induced heart attack (Kounis syndrome).

Other symptoms you should be aware of while being treated with Curoxim:

• Fungal infections. Rarely, medicines such as Curoxim may lead to overgrowth of fungi ( Candida ) in the body, potentially causing fungal infections (such as thrush). This side effect is more likely if Curoxim is taken for a prolonged period.
• Severe diarrhoea ( pseudomembranous colitis ). Medicines such as Curoxim may cause inflammation of the colon (large intestine), resulting in severe diarrhoea, usually with blood and mucus, stomach pain, and fever. Contact your doctor or nurse immediately if you experience any of these symptoms.

Common side effects
These may affect up to 1 in 10 patients:

• Pain at the injection site, swelling and redness along the vein. Inform your doctor if any of these conditions concern you.

Common side effects that may be detected by blood tests:

• Increases in substances ( enzymes ) produced by the liver
• Changes in the number of white blood cells ( neutropenia or eosinophilia )
• Low levels of red blood cells ( anemia )

Uncommon side effects
These may affect up to 1 in 100 patients:

• Skin rash, itching, irregular rash ( urticaria )
• Diarrhoea, nausea, stomach pain
  Inform your doctor if you experience any of these conditions.

Uncommon side effects that may be detected by blood tests:

• Low levels of white blood cells ( leucopenia )
• Increased bilirubin (a substance produced by the liver)
• Positive Coombs test

Other side effects
Other side effects have occurred in a very small number of people, but their exact frequency is unknown:

• Fungal infections
• High temperature ( fever )
• Allergic reactions
• Inflammation of the colon (large intestine) causing diarrhoea, usually with blood and mucus, stomach pain
• Inflammation in the kidneys and blood vessels
• Too rapid destruction of red blood cells ( haemolytic anaemia )
• Skin rash with blisters resembling small targets (a dark spot in the center surrounded by a pale area with a black ring around the edge) ( erythema multiforme ). Inform your doctor if you experience any of these conditions.

Side effects that may be detected by blood tests:

• Decrease in the number of platelets (cells that help blood clotting – thrombocytopenia )
• Increased blood levels of urea and creatinine.

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 reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Curoxim

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp". The expiry date refers to the last day of that month.
Store below 25°C. Keep the vial in the outer packaging to protect it from light.
Once reconstituted for injection, the medicine can be stored for up to 5 hours if kept below 25°C, or for up to 72 hours if stored between 2–8°C.
Once reconstituted for infusion, the medicine can be stored for up to 3 hours if kept below 25°C, or for up to 72 hours if stored between 2–8°C.
From a microbiological point of view, the medicine should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless reconstitution has taken place under controlled and validated aseptic conditions.
Do not dispose of medicines via wastewater or household waste. Unused medicines will be disposed of by your doctor or nurse. This will help protect the environment.

6. Package contents and other information

What Curoxim contains
250 mg powder and solvent for injectable or infusion solution
The active substance is cefuroxime. Each vial contains 250 mg of cefuroxime (as cefuroxime sodium).
500 mg powder and solvent for injectable solution
The active substance is cefuroxime. Each vial contains 500 mg of cefuroxime (as cefuroxime sodium).
750 mg powder and solvent for injectable or infusion solution
The active substance is cefuroxime. Each vial contains 750 mg of cefuroxime (as cefuroxime sodium).
Curoxim 1 g powder and solvent for injectable solution
The active substance is cefuroxime. Each vial contains 1 g of cefuroxime (as cefuroxime sodium).
Curoxim 2 g powder for infusion solution
The active substance is cefuroxime. Each vial contains 2 g of cefuroxime (as cefuroxime sodium).
No other components are present.

Description of the appearance of Curoxim and contents of the pack
Colourless glass vial with a bromobutyl rubber stopper and an aluminium seal with a plastic tamper-evident cap, containing 250 mg, 500 mg, 750 mg, 1 g or 2 g of cefuroxime (as cefuroxime sodium) in powder form.
Cefuroxime powder vials may also be supplied with ampoules of water for injectable preparations as solvent.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Sandoz S.p.A.
L.go U. Boccioni, 1
21040 Origgio (VA)
Italy

Manufacturer:
ACS Dobfar S.p.A
Via A. Fleming, 2
37135 Verona
Italy

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
250 mg powder for injectable or infusion solution
Finland, Hungary, Ireland, Lithuania, Malta, Norway, Sweden, United Kingdom (Northern Ireland) – Zinacef
Italy – Curoxim
France – Zinnat

500 mg powder for injectable solution
Italy – Curoxim

750 mg powder for injectable or infusion solution
Belgium, Cyprus, Czech Republic, Finland, Greece, Hungary, Iceland, Ireland, Luxembourg, Malta, Norway, Poland, Slovenia, Sweden, United Kingdom (Northern Ireland) – Zinacef
Italy – Curoxim
France – Zinnat

1 g powder for injectable solution
Italy – Curoxim

1.5 g powder for injectable or infusion solution
Austria – Curocef
Belgium, Cyprus, Czech Republic, Finland, Greece, Hungary, Iceland, Ireland, Luxembourg, Norway, Poland, Slovenia, Sweden, United Kingdom (Northern Ireland) – Zinacef
France – Zinnat

2 g powder for infusion solution
Italy – Curoxim

The following information is intended for medical or healthcare professionals only:
Reconstitution instructions
Addition of volumes and concentrations that may be useful when fractional doses are required.

*Reconstituted solution to be added to 50 or 100 ml of compatible infusion fluid (see compatibility information below).
**The resulting volume of the cefuroxime solution in the reconstitution medium is increased due to the displacement factor of the active substance, resulting in the concentrations listed in mg/ml.

Compatibility
1.5 g of cefuroxime sodium reconstituted with 15 ml of water for injections can be added to an injectable solution of metronidazole (500 mg/100 ml).
1.5 g of cefuroxime sodium is compatible with azlocillin 1 g (in 15 ml) or 5 g (in 50 ml).
Cefuroxime sodium (5 mg/ml) can be used in an injectable solution of 5% w/v or 10% w/v xylitol.
Cefuroxime sodium is compatible with aqueous solutions containing up to 1% lidocaine hydrochloride.
Cefuroxime sodium is compatible with the following infusion fluids:

• Sodium chloride 0.9% w/v for injections BP
• Glucose 5% for injections BP
• Sodium chloride 0.18% w/v plus Glucose 4% for injections BP
• Glucose 5% and Sodium chloride 0.9% w/v for injections BP
• Glucose 5% and Sodium chloride 0.45% w/v for injections
• Glucose 5% and Sodium chloride 0.225% w/v for injections
• Glucose 10% for injections
• Lactated Ringer's solution for injections USP
• Sodium lactate M/6 for injections
• Compound sodium lactate for injections BP (Hartmann's solution)

The stability of cefuroxime sodium in sodium chloride 0.9% w/v solution for injections BP and in glucose 5% solution for injections is not affected by the presence of sodium phosphate hydrocortisone.

Cefuroxime sodium has also been found compatible when mixed in intravenous infusion with:
Heparin (10 and 50 units/ml) in 0.9% w/v sodium chloride injectable solution; Potassium chloride (10 and 40 mEq/L) in 0.9% w/v sodium chloride injectable solution.