Cepim

Package leaflet: Information for the patient

Cepim 500 mg/1.5 ml powder and solvent for injectable solution, 1000 mg/3 ml powder and solvent for injectable solution

cefepime
Please read this leaflet carefully before you or someone else uses this medicine, as 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 could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Cepim is and what it is used for

Cepim contains cefepime and belongs to the group of antibiotics known as beta-lactams, medicines capable of killing bacteria or preventing their growth.
Cepim may be used alone as a first-choice medicine, after obtaining the results of a test assessing whether a bacterium is sensitive to this antibiotic (sensitivity test), or, if necessary, it may be safely used in combination with other antibiotics.
Cepim is indicated

• in adults:
• for the treatment of moderate to severe infections caused by bacteria susceptible to this antibiotic, including:
• respiratory tract infections
• complicated (i.e. associated with serious conditions) and uncomplicated infections of the lower urinary tract (bladder and urethra) and upper urinary tract (kidneys and ureters)
• skin and soft tissue infections
• intra-abdominal infections, including peritonitis (inflammation of the membrane lining the abdominal walls and covering the internal organs) and biliary tract infections (the system transporting bile produced by the liver)
• bacteraemia (presence of bacteria in the blood) due to, or suspected to be due to, one of the above-mentioned infections, including episodes of fever in patients with low immune defences
• empirical treatment of febrile episodes in neutropenic patients, used as a single agent. Neutropenic patients have a reduced number of neutrophils, a type of white blood cell, in the blood (febrile neutropenia). In neutropenic patients at high risk of developing severe infections, monotherapy with Cepim may not be appropriate.
• infections caused by one or more groups of bacteria susceptible to this antibiotic
• in children over 1 month of age:
• for the treatment of bacterial meningitis (inflammatory disease of the membranes covering the brain and spinal cord and of the cerebrospinal fluid), caused by bacteria susceptible to this antibiotic

2. What you should know before using/being administered Cepim

Do not use Cepim

• If you are allergic to cefepime or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to cephalosporins or to other beta-lactam antibiotics (the same class of antibiotics as Cepim), such as penicillins, monobactams, and carbapenems.

Warnings and precautions
Talk to your doctor or pharmacist before using/being administered Cepim.
Inform your doctor:

• if you have kidney problems or other conditions affecting kidney function. In this case, especially if you are elderly, your doctor will need to adjust the recommended dose, reduce the maintenance dose, and monitor your kidney function. Repeated doses should be determined based on kidney function, severity of infection, and bacterial sensitivity to the antibiotic (see section 3 “How to use/how Cepim is administered”);
• if you suffer from asthma;
• if you are prone to allergic reactions (allergic diathesis);
• if you have previously experienced an allergic reaction to other beta-lactam antibiotics or other medicines, as your doctor will administer Cepim with caution.

This active substance is not suitable for the treatment of certain types of infections unless appropriate testing shows the bacteria to be susceptible to this antibiotic.
Possible consequences of using Cepim
Like other antibiotics, Cepim may cause uncontrolled growth of bacteria not sensitive to this antibiotic. If you develop a new infection in addition to the existing one, your doctor will take appropriate measures.
Exercise particular caution

• Cepim may alter the results of a blood test used to detect antibodies on red blood cells (Coombs test). If you need to undergo this test, inform your doctor that you are taking this medicine.
• Cepim may also alter the results of urine sugar tests (glycosuria). If you are diabetic and regularly undergo such tests, inform your doctor: during treatment with this medicine, alternative tests may be advisable to monitor diabetes.

Children and adolescents
In children and adolescents, the doctor must carefully evaluate the dose based on age, weight, severity and type of infection, and the patient’s kidney function.
Other medicines and Cepim
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Consult your doctor if you are taking:

• antibiotics such as bacteriostatic antibiotics or aminoglycoside antibiotics;
• potent diuretics (medicines that increase urine production), as they may potentially cause kidney problems. In this case, your doctor will advise careful monitoring of kidney function.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using/being administered this medicine.
The safety of Cepim during pregnancy has not been established; therefore, it is recommended to use the medicine only if clearly needed and under strict medical supervision.
If you are breastfeeding, your doctor will administer Cepim with caution, as small amounts of the drug may pass into breast milk.
Driving and using machines
Cepim may affect your ability to drive or operate machinery, as undesirable effects such as altered consciousness, dizziness, confusion, or hallucinations may occur (see section 4 “Possible side effects”).

3. How to use/how Cepim is administered

The dose will be determined by your doctor based on the type of bacteria, the severity of your infection, your kidney function, and your general condition.
Cepim will be administered to you by a doctor or healthcare professional into a muscle or a vein in your body. If you suffer from a severe infection that could be life-threatening, especially if septic shock (blood infection that may seriously endanger the patient's life) is present, your doctor will administer Cepim intravenously.

Use in children and adolescents
The doctor will determine the recommended dose based on the child's age, weight, severity and type of infection, and kidney function.

Duration of treatment
The doctor will determine the duration of treatment based on age, weight, severity and type of infection, and kidney function of you/your child.

If you use/are administered more Cepim than you should
If an excessive dose of Cepim is accidentally administered, overdose symptoms may include:

• encephalopathy (a disease characterized by widespread brain tissue damage)
• myoclonus (sudden, involuntary muscle jerking)
• seizures (violent, involuntary contractions of certain muscles).

If you think you have been given too much Cepim, contact your doctor or go to the nearest hospital emergency department.

If you forget to use Cepim
Do not use a double dose to make up for the missed dose.

If you stop treatment with Cepim
If you have any doubts about using 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.
The use of Cepim generally causes mild and transient side effects, which rarely require discontinuation of treatment.
If you experience any of the following serious side effects during Cepim administration, which may be life-threatening, contact your doctor immediately. The doctor will DISCONTINUE the treatment and initiate appropriate and specific therapy:

• severe allergic reactions, including anaphylactic shock;
• Clostridium difficile-associated diarrhea, a bacterium normally present in the gastrointestinal system which, following prolonged antibiotic use, may cause abdominal cramps or other diseases. This adverse effect may vary in severity, from mild diarrhea to life-threatening colitis (inflammation of the colon). This side effect may occur even within two months after the end of Cepim therapy;
• reversible encephalopathy (a condition characterized by diffuse brain tissue injury) which may cause disturbances in consciousness such as confusion, hallucinations, stupor (a dazed state severely impairing the ability to speak or act), and coma;
• seizures (violent, involuntary contractions of certain muscles), including non-convulsive status epilepticus (a brain disorder without motor manifestations caused by excessive activity of certain brain nerve cells);
• myoclonus (sudden, involuntary muscle jerks);
• renal failure (reduced ability of the kidneys to perform their function).

The assessment of adverse effects is based on the following frequency data.

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

• positive direct Coombs test (a test evaluating the presence of antibodies capable of attacking and destroying red blood cells)

Common (may affect up to 1 in 10 people):

• reduced hemoglobin levels in the blood (anemia)
• elevated blood concentration of eosinophils, a type of white blood cells (eosinophilia)
• inflammation of the vein at the infusion site (phlebitis)
• diarrhea
• appearance of red patches on the skin (rash)
• reaction, pain, and inflammation at the infusion/injection site
• increased blood levels of alkaline phosphatase (an enzyme mainly present in the liver, biliary tract, and bones), which may indicate skeletal or liver disease
• increased alanine aminotransferase (ALT, an enzyme predominantly present in the liver), which may indicate liver problems
• increased aspartate aminotransferase (AST, an enzyme predominantly present in muscles, liver, and heart), which may primarily indicate liver and heart problems
• increased blood bilirubin levels (a substance produced from aged or damaged red blood cells), indicating a liver problem
• prolonged blood clotting time (prolonged prothrombin time or prolonged activated partial thromboplastin time)

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

• fungal mouth infection caused by Candida species (oral candidiasis)
• vaginal infection
• reduced number of platelets in the blood (thrombocytopenia)
• reduced number of white blood cells in the blood (leukopenia)
• reduced number of neutrophils, a type of white blood cells, in the blood (neutropenia)
• headache
• antibiotic-associated inflammation of the colon (pseudomembranous colitis)
• inflammation of the colon (colitis)
• nausea
• vomiting
• skin irritation (erythema)
• appearance of red or white wheals of various sizes (urticaria)
• itching
• fever (elevated body temperature)
• inflammation at the infusion site
• increased blood urea levels, indicating reduced kidney function
• increased blood creatinine levels, indicating kidney damage

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

• infection caused by the fungus Candida albicans (candidiasis)
• severe, rapidly developing allergic reaction that may be fatal (anaphylactic reaction)
• swelling of the face, eyes, lips, tongue, and throat, possibly causing breathing and swallowing difficulties (angioedema)
• altered sensation in limbs or other body parts (paresthesia)
• altered taste (dysgeusia)
• dizziness
• increased diameter of blood vessels (vasodilation)
• shortness of breath (dyspnea)
• abdominal pain
• constipation
• genital itching
• chills

Frequency not known (the frequency cannot be estimated from the available data):

• reduced hemoglobin levels in the blood due to insufficient red blood cell production in the bone marrow (aplastic anemia)
• reduced hemoglobin levels in the blood due to formation of antibodies destroying red blood cells (hemolytic anemia)
• almost complete destruction and detachment of the skin and mucous membranes (toxic epidermal necrolysis)
• destruction and detachment of the skin and mucous membranes due to an allergic reaction (Stevens-Johnson syndrome)
• appearance of target-like lesions with bright red color (erythema multiforme or polymorphous)
• bleeding from blood vessels (hemorrhage)
• kidney disease caused by chemicals, physical factors, or drugs (toxic nephropathy)
• falsely positive result in urine glucose measurement (laboratory test for glycosuria)
• severe decrease in the number of granulocytes (a type of white blood cells) in the blood (agranulocytosis)

Following the instructions in this leaflet reduces the risk of side effects.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cepim

Do not store above 30°C. Keep protected from light.
Do not store the reconstituted solution above 25°C for longer than 24 hours; alternatively,
store the reconstituted solution between 2 and 8°C for up to 7 days.
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 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 Cepim contains
Cepim 500 mg/1.5 ml powder and solvent for injectable solution
Vial:

• The active substance is cefepime dihydrochloride monohydrate, equivalent to 500 mg of cefepime.
• The other component is: L-arginine.

Solvent vial:
Each solvent vial contains water for injectable preparations.

Cepim 1000 mg/3 ml powder and solvent for injectable solution
Vial:

• The active substance is cefepime dihydrochloride monohydrate, equivalent to 1000 mg of cefepime.
• The other component is: L-arginine.

Solvent vial:
Each solvent vial contains water for injectable preparations.

Description of the appearance of Cepim and contents of the pack
Powder and solvent for injectable solution for intramuscular or intravenous use.
Cepim 500 mg/1.5 ml powder and solvent for injectable solution is available in a carton containing:
1 vial with a yellow plastic cap engraved with “Read Insert” (=”Read the Package Leaflet”) and 1 solvent vial containing 1.5 ml of water for injectable preparations.
Cepim 1000 mg/3 ml powder and solvent for injectable solution is available in a carton containing:
1 vial with a white plastic cap engraved with “Read Insert” (=”Read the Package Leaflet”) and 1 solvent vial containing 3 ml of water for injectable preparations.

Marketing Authorization Holder
POLIFARMA S.p.A., Viale dell’Arte, 69 – 00144 Rome, Italy

Manufacturer
Corden Pharma Latina S.p.A.
Via Murillo Km 2.800
Sermoneta - Latina

---

The following information is intended exclusively for physicians or healthcare professionals:
HOW TO USE CEPIM
Cepim can be administered intravenously or intramuscularly.
The dosage and route of administration depend on the susceptibility of the causative organism, the severity of the infection, renal function, and the patient's general condition.

Adults and children over 12 years of age (>40 kg)
A dosing guideline for cefepime in adults and children over 12 years of age (>40 kg) with normal renal function is provided in Table 1.
The intravenous route is preferred for patients with severe infections, particularly those that are life-threatening, especially when septic shock is present.

Table 1
Adults and children over 12 years of age (>40 kg) with normal renal function *

• The duration of therapy usually ranges between 7 and 10 days.
  More severe infections may require a longer treatment period.
  Empirical treatment of febrile neutropenia (in immunocompromised patients) should last 7 days or until resolution of neutropenia.
  Surgical prophylaxis (adults): the recommended doses for prevention of bacterial infections during and after surgical procedures are as follows:

• A single 2 g intravenous dose of Cepim (30-minute infusion, see "Instructions for use") to be started 60 minutes before surgery. A single 500 mg intravenous dose of metronidazole, if considered appropriate, may be administered immediately after completion of the Cepim infusion. The metronidazole dose must be prepared and administered according to the product's technical information. Due to incompatibility, Cepim and metronidazole must not be mixed in the same container; it is recommended to flush the infusion line with a compatible fluid before administering metronidazole.

• If the duration of surgery exceeds 12 hours, a second dose of Cepim followed by metronidazole, if appropriate, should be administered 12 hours after the initial prophylactic dose.

Children aged 1 month to 12 years with normal renal function
Bacterial meningitis
Recommended dosage: patients over 2 months of age and weighing ≤ 40 kg: 50 mg/kg every 8 hours for 7–10 days.
Experience with the use of Cepim in patients under 2 months of age is limited. While this experience has been based on a dose of 50 mg/kg, pharmacokinetic data obtained in individuals over 2 months of age suggest that a dosage of 30 mg/kg every 12 or 8 hours may be considered adequate for pediatric patients between 1 and 2 months of age. The doses of 30 mg/kg between 1 and 2 months and 50 mg/kg between 2 months and 12 years are comparable to the 2 g dose in adults. Administration of Cepim in these patients should be closely monitored.
For pediatric patients weighing more than 40 kg, adult dosing regimens may be applied (see Table 1). For patients over 12 years of age and weighing ≤ 40 kg, the dosing regimen for younger patients weighing ≤ 40 kg should be used.
The pediatric dose should not exceed the adult dose (2 g every 8 hours). Experience with intramuscular administration in pediatric patients is limited.
Elderly
Dosage adjustment is not required, unless there is concomitant renal impairment (see "Precautions for use").
Impaired Hepatic Function
Dosage adjustment is not required, unless there is concomitant renal impairment.
Impaired Renal Function
In patients with renal dysfunction, the cefepime dosage should be adjusted to compensate for reduced renal elimination.
The recommended initial dose of cefepime in patients with mild to moderate renal dysfunction should be the same as in patients with normal renal function (Table 1).
The recommended maintenance dose of cefepime in adult patients with renal impairment is shown in the following table (Table 2).
TABLE 2
Maintenance dose in adults with renal impairment*

Patients undergoing haemodialysis
In patients undergoing haemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be eliminated during a 3-hour period. For these patients, the pharmacokinetic model indicates that dosage adjustment is required. Patients receiving cefepime who are also undergoing haemodialysis should receive the following dosage: a loading dose of 1 g on the first day of therapy, followed by 500 mg of cefepime daily for all infections, except febrile neutropenia, which requires 1 g daily. On dialysis days, cefepime should be administered immediately after dialysis. Cefepime should be administered at the same time each day whenever possible.

Patients undergoing continuous peritoneal dialysis
In continuous peritoneal dialysis, Cepim may be administered at the doses normally recommended for patients with normal renal function (i.e., 500 mg, 1 g, or 2 g depending on the severity of infection), but with a 48-hour interval between doses.

Paediatric patients with impaired renal function
Since urinary excretion is the primary route of elimination for cefepime, dosage adjustment is recommended in paediatric patients with impaired renal function. As recommended in Table 2, the same increases in dosing intervals and/or reduction in doses should be applied.

Duration of treatment
The duration of therapy depends on the course of the infection and should therefore be determined by the physician.

Instructions for use

Intravenous administration
To prepare a Cepim solution for intravenous administration, use the following diluents:

• Water for injections Ph. Eur.
• Sodium chloride 0.9% solution (physiological saline), with or without 5% glucose
• Ringer's solution, with or without 5% glucose
• 5% or 10% glucose solution
• 6 M sodium lactate solution

Cepim may be injected slowly intravenously over a period of 3–5 minutes. The drug may also be administered directly into infusion lines or via continuous intravenous infusion. When administered by infusion, the drug should be infused over approximately 30 minutes.

Intramuscular administration
Cepim 0.5 g should be reconstituted with 1.5 ml of sterile water for injections (supplied in the package).
Cepim 1 g should be reconstituted with 3 ml of sterile water for injections (supplied in the package).

Reconstitution volumes
The reconstitution volumes for Cepim for intravenous and intramuscular administration are summarised in the following table:

TABLE 3
Instructions for reconstitution
Vial Solvent volume Approximate volume after Approximate concentration
(ml) reconstitution (ml) after reconstitution (mg/ml)

The solution should be reconstituted at the time of use.
It is preferable to administer the drug immediately after reconstitution.
Cepim may be administered simultaneously with other antibiotics or other medications, provided they are not mixed in the same syringe or infusion fluid.
Like other cephalosporins, Cepim solutions may vary in color depending on the storage period. This characteristic does not affect the drug's efficacy or tolerability.
OVERDOSAGE
Symptoms of overdose include encephalopathy, myoclonus, and seizures.
In case of severe overdose, especially in patients with impaired renal function, serum levels of Cepim can be reduced by hemodialysis. Peritoneal dialysis is not helpful.
Accidental overdose may occur following high drug doses in patients with renal dysfunction (see "How to use Cepim", "Warnings and precautions", and "Undesired effects").

Patient Information Leaflet

Cepim 2000 mg/10 ml powder and solvent for injectable solution

cefepime
Please read this leaflet carefully before this medicine is administered to you, as 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.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Cepim is and what it is used for
2. What you need to know before being administered Cepim
3. How Cepim is administered to you
4. Possible side effects
5. How to store Cepim
6. Package contents and other information

2. What Cepim is and what it is used for

Cepim contains cefepime and belongs to the class of antibiotics known as beta-lactams, medicines capable of killing bacteria or inhibiting their growth.
Cepim may be used alone as a first-choice treatment, after obtaining results from the test assessing whether a bacterium is sensitive to this antibiotic (sensitivity test), or, if necessary, may be safely used in combination with other antibiotics.
Cepim is indicated

• in adults:
• for the treatment of moderate to severe bacterial infections caused by organisms susceptible to this antibiotic, including:
• respiratory tract infections
• complicated (i.e. associated with serious underlying diseases) and uncomplicated urinary tract infections of the lower urinary tract (bladder and urethra) and upper urinary tract (kidneys and ureters)
• skin and soft tissue infections
• intra-abdominal infections, including peritonitis (inflammation of the membrane lining the abdominal walls and covering the internal organs) and biliary tract infections (the system transporting bile produced by the liver)
• bacteraemia (presence of bacteria in the blood) due to, or suspected to be due to, one of the above-mentioned infections, including episodes of fever in patients with low immune defences
• empirical treatment of febrile episodes in neutropenic patients, used as monotherapy. Neutropenic patients have a reduced number of neutrophils, a type of white blood cell (febrile neutropenia). In neutropenic patients at high risk of developing severe infections, monotherapy with Cepim alone may not be appropriate.
• infections caused by one or more groups of bacteria susceptible to this antibiotic
• for surgical prophylaxis in abdominal surgery, i.e. prior to abdominal surgical procedures
• in children older than 1 month:
• for the treatment of bacterial meningitis (inflammatory disease of the membranes surrounding the brain and cerebrospinal fluid), caused by bacteria susceptible to this antibiotic

2. What you need to know before being given Cepim

You must not be given Cepim if

• You are allergic to cefepime or to any of the other ingredients of this medicine (listed in section 6).
• You are allergic to cephalosporins or to other beta-lactam antibiotics (the same class of antibiotics to which Cepim belongs), such as penicillins, monobactams, and carbapenems.

Warnings and precautions
Talk to your doctor or pharmacist before you are given Cepim.
Inform your doctor:

• If you have kidney problems or other conditions affecting kidney function. In such cases, especially if you are elderly, your doctor may need to adjust the recommended dose, reduce the maintenance dose, and monitor your kidney function. Repeated dosing should be based on kidney function, severity of infection, and bacterial sensitivity to the antibiotic (see section 3 "How Cepim is administered").
• If you have asthma.
• If you are prone to allergic reactions (allergic diathesis).
• If you have previously experienced an allergic reaction to other beta-lactam antibiotics or other drugs, as your doctor will administer Cepim with caution.

This active substance is not suitable for the treatment of certain types of infections unless appropriate testing shows that the bacteria are susceptible to this antibiotic.
Possible consequences of using Cepim
Like other antibiotics, Cepim may cause uncontrolled growth of bacteria not sensitive to this antibiotic. If you develop a new infection in addition to the one already present, your doctor will take appropriate measures. Be especially careful

• Cepim may alter the results of a blood test used to detect antibodies on red blood cells (Coombs test). If you need to undergo this test, inform your doctor that you are taking this medicine.
• Cepim may also alter the results of urine sugar tests (glycosuria). If you have diabetes and regularly undergo such tests, inform your doctor: during treatment with this medicine, it may be advisable to use other types of tests to monitor your diabetes.

Children and adolescents
In children and adolescents, the doctor must carefully evaluate the dose to be administered based on age, weight, severity and type of infection, and kidney function.

Other medicines and Cepim
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Talk to your doctor if you are taking:

• Antibiotics such as bacteriostatic antibiotics or aminoglycoside antibiotics.
• Potent diuretics (medicines that increase urine production), as they may potentially cause kidney problems. In such cases, your doctor will advise careful monitoring of kidney function.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, or are planning to become pregnant, ask your doctor or pharmacist for advice before being given this medicine.
The safety of Cepim during pregnancy has not been established; therefore, the medicine is recommended only when clearly needed and under strict medical supervision.
If you are breastfeeding, your doctor will administer Cepim with caution, as small amounts of the drug may pass into breast milk.

Driving and using machines
Cepim may affect your ability to drive vehicles or operate machinery, as it may cause undesirable effects such as altered consciousness, dizziness, confusion, or hallucinations (see section 4 "Possible side effects").

3. How Cepim is administered to you

The dose will be determined by your doctor based on the type of bacteria, the severity of your infection, your kidney function, and your general condition.
Cepim will be administered into a vein in your body by a doctor or healthcare professional.

Use in children and adolescents
Your doctor will determine the recommended dose based on the child's age, weight, severity and type of infection, and kidney function.

Duration of treatment
Your doctor will determine the duration of treatment based on age, weight, severity and type of infection, and kidney function (yours or your child's).

If you are given more Cepim than you should
It is unlikely that you will be given an excessive dose of Cepim.
However, if an overdose of Cepim is accidentally administered, symptoms of overdose may include:

• encephalopathy (a disease characterized by widespread brain tissue damage)
• myoclonus (sudden, involuntary muscle jerking)
• seizures (violent, involuntary contractions of certain muscles).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The use of Cepim generally causes mild and transient side effects that rarely require discontinuation of treatment.
If, during administration of Cepim, you experience any of the following serious side effects, which may be life-threatening, contact your doctor immediately. The doctor will DISCONTINUE treatment and initiate appropriate and specific therapy:

• severe allergic reactions, including anaphylactic shock;
• Clostridium difficile-associated diarrhoea, a bacterium normally present in the gastrointestinal system which, during prolonged antibiotic use, may cause abdominal cramps or other diseases. This adverse effect may vary in severity, from mild diarrhoea to fatal colitis (inflammation of the colon). This side effect may occur even within two months after completion of Cepim therapy;
• reversible encephalopathy (a disease characterized by diffuse brain tissue injury) which may cause disturbances in consciousness such as confusion, hallucinations, stupor (a dazed state severely impairing speech and movement), and coma;
• seizures (violent, involuntary contractions of certain muscles), including non-convulsive status epilepticus (a brain disorder without motor manifestations, caused by excessive activity of certain cerebral nerve cells);
• myoclonus (sudden, involuntary muscle jerking);
• renal failure (reduced ability of the kidneys to perform their function).

The evaluation of adverse effects is based on the following frequency data.

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

• positive direct Coombs test (a test assessing the presence of antibodies capable of attacking and destroying red blood cells)

Common (may affect up to 1 in 10 people):

• reduced haemoglobin levels in the blood (anaemia)
• elevated blood levels of eosinophils, a type of white blood cell (eosinophilia)
• inflammation of a vein at the infusion site (phlebitis)
• diarrhoea
• appearance of red patches on the skin (rash)
• reaction, pain, and inflammation at the infusion/injection site
• increased blood levels of alkaline phosphatase (a protein mainly present in the liver, biliary tract, and bones), which may indicate skeletal or liver disease
• increased alanine aminotransferase (ALT, a protein predominantly found in the liver), which may indicate liver problems
• increased aspartate aminotransferase (AST, a protein predominantly found in muscles, liver, and heart), which may primarily indicate liver and heart problems
• increased blood levels of bilirubin (a substance produced by aged or damaged red blood cells), indicating a liver problem
• prolonged blood clotting time (prolonged prothrombin time or prolonged activated partial thromboplastin time)

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

• fungal mouth infection caused by Candida species (oral candidiasis)
• vaginal infection
• reduced number of platelets in the blood (thrombocytopenia)
• reduced number of white blood cells in the blood (leucopenia)
• reduced number of neutrophils in the blood, a type of white blood cell (neutropia)
• headache
• antibiotic-associated inflammation of the colon (pseudomembranous colitis)
• inflammation of the colon (colitis)
• nausea
• vomiting
• skin irritation (erythema)
• appearance of red or white raised wheals of varying sizes (urticaria)
• itching
• fever (elevated body temperature)
• inflammation at the infusion site
• increased blood levels of urea, indicating reduced kidney function
• increased blood levels of creatinine, indicating kidney damage

Rare (may affect up to 1 in 1000 people):

• infection caused by the fungus Candida albicans (candidiasis)
• severe, rapidly occurring allergic reaction which may be fatal (anaphylactic reaction)
• swelling of the face, eyes, lips, tongue, and throat, possibly causing breathing or swallowing difficulties (angioedema)
• altered sensation in limbs or other body parts (paraesthesia)
• altered taste (dysgeusia)
• dizziness
• increased diameter of blood vessels (vasodilation)
• shortness of breath (dyspnoea)
• abdominal pain
• constipation
• genital itching
• chills

Frequency not known (frequency cannot be estimated from the available data):

• reduced haemoglobin levels in the blood due to insufficient red blood cell production in the bone marrow (aplastic anaemia)
• reduced haemoglobin levels in the blood due to antibody formation destroying red blood cells (haemolytic anaemia)
• widespread destruction and detachment of the skin and mucous membranes (toxic epidermal necrolysis)
• destruction and detachment of the skin and mucous membranes due to an allergic reaction (Stevens-Johnson syndrome)
• appearance of target-like lesions with bright red colour (erythema multiforme or polymorphous erythema)
• bleeding from blood vessels (haemorrhage)
• kidney disease caused by chemical substances, physical factors, or drugs (toxic nephropathy)
• falsely positive result in urine glucose testing (glycosuria) when using reducing agents
• severe reduction in the number of granulocytes (a type of white blood cell) in the blood (agranulocytosis)

Following the instructions provided in this leaflet reduces the risk of side effects.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor. You may also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cepim

Do not store above 30°C. Keep protected from light.
Do not store the reconstituted solution above 25°C for longer than 24 hours; alternatively,
store the reconstituted solution at a temperature between 2 and 8°C for up to 7 days.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp".
The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Cepim contains
Cepim 2000 mg/10 ml powder and solvent for solution for injection
Vial:

• The active substance is cefepime dihydrochloride monohydrate, equivalent to 2000 mg of cefepime
• The other component is: L-arginine.

Solvent vial:
Each solvent vial contains water for injections
Description of the appearance of Cepim and contents of the pack
Powder and solvent for solution for injection for intravenous use.
Cepim 2000 mg/10 ml powder and solvent for solution for injection is available in a carton
containing:
1 vial with a purple plastic cap marked with “Read Insert” and 1 solvent vial containing 10 ml of water for injections.
Marketing Authorization Holder
POLIFARMA S.p.A., Viale dell’Arte, 69 – 00144 Roma
Manufacturer
Corden Pharma Latina S.p.A.
Via Murillo Km 2,800
Sermoneta - Latina

---

The following information is intended exclusively for physicians or healthcare professionals:
HOW TO USE CEPIM
Cepim can be administered intravenously or intramuscularly.
The dosage and route of administration depend on the susceptibility of the causative organism,
the severity of the infection, renal function, and the patient's general condition.
Adults and children over 12 years of age (>40 kg)
A dosing guideline for cefepime in adults and children over 12 years of age (>40 kg) with
normal renal function is provided in Table 1.
The intravenous route is preferred for patients with severe infections,
particularly life-threatening conditions, especially in the presence of septic shock.
Table 1
Adults and children over 12 years of age (>40 kg) with normal renal function *

* The duration of therapy usually ranges between 7 and 10 days.
More severe infections may require a longer treatment period.
Empirical treatment of febrile neutropenia (immunocompromised patients) should last 7 days or until resolution of neutropenia.
Surgical prophylaxis (adults): the recommended dosages for the prevention of bacterial infections during and after surgical procedures are as follows:

• A single 2 g intravenous dose of Cepim (30-minute infusion, see "Instructions for use") administered 60 minutes before surgery. A single 500 mg intravenous dose of metronidazole, if considered appropriate, may be administered immediately after completion of the Cepim infusion. The metronidazole dose must be prepared and administered according to the product’s technical information. Due to incompatibility, Cepim and metronidazole must not be mixed in the same container; it is recommended to flush the infusion line with a compatible fluid before administering metronidazole.

• If the duration of surgery exceeds 12 hours, a second dose of Cepim followed by metronidazole, if appropriate, should be administered 12 hours after the initial prophylactic dose.

Children aged 1 month to 12 years with normal renal function
Bacterial meningitis
Recommended dosage: patients over 2 months of age and weighing ≤ 40 kg: 50 mg/kg every 8 hours for 7–10 days.
Experience with Cepim use in patients under 2 months of age is limited. While this experience has been based on a dose of 50 mg/kg, pharmacokinetic data obtained in individuals over 2 months of age suggest that a dosage of 30 mg/kg every 12 or 8 hours may be considered adequate for pediatric patients between 1 and 2 months of age. Doses of 30 mg/kg between 1 and 2 months and 50 mg/kg between 2 months and 12 years are comparable to the 2 g adult dose. Administration of Cepim in these patients should be carefully monitored.
For pediatric patients weighing more than 40 kg, adult dosing regimens may be applied (see Table 1). For patients over 12 years of age and weighing ≤ 40 kg, the dosing regimen for younger patients weighing ≤ 40 kg should be used.
Pediatric dosing must not exceed the adult dosage (2 g every 8 hours). Experience with intramuscular administration in pediatric patients is limited.
Elderly patients
Dosage adjustment is not required, except in cases of concomitant renal impairment (see "Precautions for use").
Hepatic impairment
Dosage adjustment is not required, except in cases of concomitant renal impairment.
Renal impairment
In patients with renal dysfunction, the cefepime dosage should be adjusted to compensate for reduced renal elimination.
The recommended initial dose of cefepime in patients with mild to moderate renal dysfunction should be the same as in patients with normal renal function (Table 1).
The recommended maintenance dose of cefepime in adult patients with renal impairment is shown in the following table (Table 2).
TABLE 2
Maintenance dose in adults with renal impairment*

Patients undergoing haemodialysis
In patients undergoing haemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be eliminated during a 3-hour period. According to the pharmacokinetic model, these patients require a reduced dosage. Patients receiving cefepime who are simultaneously undergoing haemodialysis should receive the following dosage regimen: a loading dose of 1 g on the first day of therapy, followed by 500 mg of cefepime daily for all infections, except febrile neutropenia which requires 1 g daily. On dialysis days, cefepime should be administered immediately after dialysis. Whenever possible, cefepime should be administered at the same time each day.

Patients undergoing continuous peritoneal dialysis
In continuous peritoneal dialysis, Cepim may be administered at the doses normally recommended for patients with normal renal function (i.e., 500 mg, 1 g or 2 g depending on the severity of infection), but with a 48-hour interval between doses.

Paediatric patients with impaired renal function
Since urinary excretion is the primary route of elimination for cefepime, dosage adjustment is recommended in paediatric patients with impaired renal function. As recommended in Table 2, the same increases in dosing intervals and/or reductions in dose should be applied.

Duration of treatment
The duration of therapy depends on the course of the infection and should therefore be determined by the physician.

Instructions for use
Intravenous administration
To prepare a Cepim solution for intravenous administration, the following diluents should be used:

• Water for injections Ph. Eur.
• Sodium chloride 0.9% solution (physiological saline), with or without 5% glucose
• Ringer's solution, with or without 5% glucose
• 5% or 10% glucose solution
• 6 M sodium lactate solution

Cepim may be injected slowly intravenously over a period of 3–5 minutes. The drug may also be administered directly into infusion lines or via continuous intravenous infusion. When administered by infusion, the drug should be given over approximately 30 minutes.

Intramuscular administration
Cepim 0.5 g should be reconstituted with 1.5 ml of sterile water for injections (supplied in the package).
Cepim 1 g should be reconstituted with 3 ml of sterile water for injections (supplied in the package).

Reconstitution volumes
The reconstitution volumes for Cepim for intravenous and intramuscular administration are summarised in the following table:
TABLE 3
Instructions for reconstitution

The solution should be reconstituted at the time of use.
It is preferable to administer the drug immediately after reconstitution.
Cepim may be administered simultaneously with other antibiotics or other medications, provided they are not mixed in the same syringe or infusion fluid.
Like other cephalosporins, Cepim solutions may vary in color depending on the storage period. This characteristic does not affect the drug's efficacy or tolerability.
OVERDOSAGE
Symptoms of overdose include encephalopathy, myoclonus, and seizures.
In case of severe overdose, especially in patients with impaired renal function, serum levels of Cepim can be reduced by hemodialysis. Peritoneal dialysis is not helpful.
Accidental overdose may occur following high-dose administration in patients with renal dysfunction (see "How to use Cepim", "Warnings and precautions", and "Undesired effects").