Cepimex

Package leaflet: Information for the patient

CEPIMEX 1000 mg/ 3 ml powder and solvent for injectable solution

cefepime dihydrochloride monohydrate
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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What CEPIMEX is and what it is used for

CEPIMEX contains cefepime hydrochloride monohydrate, an active substance belonging to a group of antibiotics called "cephalosporins". These antibiotics are very similar to penicillin. CEPIMEX is effective against certain types of bacteria that are sensitive to the active substance cefepime.
CEPIMEX 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). If necessary, CEPIMEX may be safely used in combination with other antibiotics.
CEPIMEX is used:

• in ADULTS and in CHILDREN over 12 years of age (weighing more than 40 kg), for the treatment of:
  ➢ moderate and severe respiratory tract infections, for example of the lungs (pneumonia);
  ➢ complicated (i.e. associated with severe conditions) and uncomplicated infections of the lower urinary tract (bladder and urethra) and upper urinary tract (kidneys and ureters);
  ➢ skin and subcutaneous tissue infections;
  ➢ abdominal infections (such as peritonitis, cholecystitis infections);
  ➢ bloodstream infections (bacteraemia) due to, or suspected to be due to, one of the above-mentioned infections, including episodes of fever in patients with weakened immune defences;
  ➢ fever in patients with moderate or severe reduction in the number of certain white blood cells (immunocompromised and neutropenic patients).

• in CHILDREN aged between 1 month and 12 years, for the treatment of:
  ➢ central nervous system infections (bacterial meningitis).

CEPIMEX may also be used in ADULTS to prevent infections following abdominal surgery.

2. What you need to know before using CEPIMEX

Do not use CEPIMEX if:

• you are allergic to cefepime or to any of the other ingredients of this medicine (listed in section 6);
• you are allergic to other antibiotics belonging to the same class as CEPIMEX (cephalosporins);
• you are allergic to antibiotics belonging to the beta-lactam class (e.g. penicillins, monobactams, and carbapenems), as this may mean that you are also allergic to cefepime.

Warnings and precautions
Talk to your doctor or pharmacist before taking CEPIMEX if:

• you have kidney problems or conditions that may cause harmful effects on the kidneys, such as concomitant use of diuretic medicines or other antibiotics belonging to the aminoglycoside class (see "Other medicines and CEPIMEX"), as you may have a higher risk of experiencing adverse effects. In such cases, a dose reduction may be necessary;
• you suffer from asthma;
• you are prone to allergic reactions (allergic diathesis);
• you have previously experienced an allergic reaction to other beta-lactam antibiotics or other medicines. In such cases, your doctor will administer CEPIMEX with caution.

This active substance is not suitable for treating certain types of infections unless appropriate tests have shown the bacteria to be susceptible to this antibiotic.
Exercise particular caution

• CEPIMEX may alter the results of a blood test used to detect antibodies on red blood cells (Coombs test). If you are due to undergo this test, inform your doctor that you are taking this medicine.
• CEPIMEX 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 testing methods may be needed to monitor your diabetes.

Risk of superinfections with the use of CEPIMEX
Like other antibiotics, CEPIMEX may lead to uncontrolled growth of bacteria not sensitive to this antibiotic. In such cases, your condition may worsen, for example by developing a new infection in addition to the existing one. Contact your doctor, who will take appropriate measures.
Other medicines and CEPIMEX
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
This is particularly important if you are taking:

• diuretic medicines or other antibiotics belonging to the aminoglycoside class, as they may cause harmful effects on the kidneys (see "Warnings and precautions");
• antibiotics belonging to the class of bacteriostatic agents.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor before using this medicine, as it must be used under strict medical supervision.
Driving and using machines
CEPIMEX may cause disturbances in consciousness, dizziness, confusion, and hallucinations. Exercise particular caution before driving or operating machinery.

3. How to use CEPIMEX

If your doctor has prescribed CEPIMEX, use this medicine exactly as directed.
If in doubt, consult your doctor or pharmacist.
The dose of CEPIMEX is determined by the doctor based on age and/or body weight, type of bacteria, severity of infection, and kidney function. If you have 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 CEPIMEX intravenously.

Adults and children over 12 years of age and weighing more than 40 kg
The usual dose ranges from 500 mg to 2,000 mg, given twice daily (every 12 hours). In these cases, CEPIMEX may be administered by injection into a muscle or into a vein.

In case of severe infections, your doctor will administer CEPIMEX intravenously at doses of 2,000 mg, 2–3 times daily (every 8–12 hours).

Children under 12 years of age or weighing less than 40 kg
The doctor will determine the correct dose by adjusting the adult doses according to the child's age and weight, severity and type of infection, and kidney function.

Patients with kidney problems
The doctor will determine the appropriate dose by adjusting the adult doses according to kidney function.

Method of administration
CEPIMEX may be administered:

• by intramuscular injection (into a muscle), given deeply. To prepare the injection, dissolve the powder in the vial with the solvent provided in the ampoule contained in the package;
• by slow injection (over 3–5 minutes) or by infusion (up to 30 minutes) intravenously (into a vein). In such cases, administration must be performed exclusively in a hospital setting and by medical personnel.

The solution for injection must be prepared immediately before use.
CEPIMEX may be administered concurrently with other antibiotics or other medicines, provided they are not mixed in the same syringe or infusion fluid.

Additional “Information intended exclusively for physicians or healthcare professionals” is available at the end of this leaflet.

If you take more CEPIMEX than you should, especially if you have kidney problems, you may experience:
reversible encephalopathy (a condition manifesting with altered consciousness, confusion, hallucinations, stupor, and coma), involuntary muscle spasms (myoclonus), seizures.
In case of overdose, contact your doctor immediately or go to the nearest hospital, as appropriate measures (e.g., hemodialysis) may be required.

If you forget to take CEPIMEX
Do not take a double dose to make up for the missed dose. Continue your treatment as scheduled.

If you stop treatment with CEPIMEX
Do not stop treatment with CEPIMEX even if you feel better; continue treatment as directed by your doctor. Stopping treatment prematurely may allow some bacteria to survive, and the infection may return.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, CEPIMEX can cause side effects, although not everybody will experience them.
Stop taking CEPIMEX and contact your doctor immediately if you notice:

• the following symptoms of severe allergic reactions: swelling (angioedema) of the face, eyes, lips, throat, with breathing difficulties and possible sudden drop in blood pressure (anaphylaxis);
• reversible encephalopathy, a condition presenting with altered consciousness, confusion, hallucinations, stupor (a dazed state impairing the ability to speak or act), and coma;
• sudden involuntary muscle contractions (myoclonus);
• 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);
• severe diarrhoea, blood in diarrhoeic stools, stomach cramps or fever, which may be signs of colitis or pseudomembranous colitis (colitis caused by a bacterium called Clostridium difficile). This side effect may also occur up to two months after stopping CEPIMEX treatment.

Inform your doctor if you experience any of the following symptoms:
Very common side effects (may affect more than 1 in 10 people)

• positive result in a blood test used to detect antibodies that attack and destroy red blood cells (direct Coombs test).

Common side effects (may affect up to 1 in 10 people)

• diarrhoea;
• injection site reactions, for example inflammation of a vein, if CEPIMEX was administered into a vein (intravenous);
• pain and inflammation in a muscle, if CEPIMEX was administered into a muscle (intramuscular);
• skin rashes;
• decrease in the number of red blood cells (anaemia), increase in eosinophils (eosinophilia);
• increased levels of transaminases in the blood, which may indicate liver problems;
• increased alkaline phosphatase levels in the blood (a protein found mainly in the liver, bile ducts and bones), which may indicate bone or liver disease;
• increased total bilirubin levels in the blood (a substance produced by aged or damaged red blood cells), indicating liver problems;
• prolonged blood clotting time (prothrombin time and partial thromboplastin time).

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

• headache, fever;
• nausea, vomiting, fungal mouth infections (oral candidiasis);
• decrease in the number of platelets (thrombocytopenia), decrease in white blood cells (leucopenia), decrease in neutrophils (neutropenia);
• increased levels of nitrogen and creatinine in the blood (values indicating kidney damage);
• skin redness, urticaria, itching;
• inflammation at the injection site, if CEPIMEX was administered intravenously;
• vaginal infections (vaginitis).

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

• abdominal pain, difficulty passing stools (constipation);
• altered sensation in certain body parts (paraesthesia), dizziness, taste disturbances;
• blood vessel dilation;
• difficulty breathing (dyspnoea);
• fungal infections (unspecified candidiasis), genital itching;
• chills.

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

• severe skin reactions, presenting with redness, blistering or pus formation, and skin detachment (e.g. erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis);
• decreased number of red blood cells due either to destruction of red blood cells (haemolytic anaemia) or bone marrow problems (aplastic anaemia), severe decrease in granulocytes (agranulocytosis);
• kidney problems caused by chemicals, physical factors or medicines (toxic nephropathy or kidney failure);
• bleeding;
• positive result in a test used to detect sugar in the urine (urinary glucose test).

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

5. How to store CEPIMEX

Keep this medicine out of the sight and reach of children.
Store at a temperature not exceeding 30°C, protected from light.
The reconstituted solution (powder and solvent mixed together), if not used immediately, may be stored
at a temperature not exceeding 25°C for 24 hours or in the refrigerator (2°C – 8°C) for 7 days.
As with other cephalosporins, CEPIMEX solutions may vary in colour depending on the storage period.
This characteristic does not affect the drug's efficacy or tolerability.
Do not use this medicine after the expiry date stated on the packaging. 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 CEPIMEX contains
The active substance is: cefepime dihydrochloride monohydrate.
Each vial of CEPIMEX 1000 mg contains: 1000 mg of cefepime dihydrochloride monohydrate.
The excipients are:

• in the powder vial: L-arginine;
• in the solvent vial: water for injections.

Description of the appearance of CEPIMEX and contents of the pack
CEPIMEX 1000 mg is available in a pack containing 1 vial of 1000 mg powder and 1 vial of 3 ml solvent.
CEPIMEX is available in packs containing 1 powder vial and 1 solvent vial (suitable for intramuscular administration).

Marketing Authorization Holder
Bruno Farmaceutici S.p.A., Via delle Ande, 15 – 00144 ROMA (RM)
Manufacturer
Mitim S.r.l., Via Cacciamali 34-38, 25125 Brescia

Information intended exclusively for physicians or healthcare professionals. For further details,
please refer to the Summary of Product Characteristics.
ADMINISTRATION
CEPIMEX can be administered intravenously or intramuscularly. When administered intramuscularly alone, CEPIMEX generally does not cause pain.
The dose 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 guideline for cefepime dosing 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 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 from 7 to 10 days; more severe infections may require longer treatment. 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 CEPIMEX (30-minute infusion) 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 CEPIMEX infusion. The metronidazole dose must be prepared and administered according to the product's technical information. Due to incompatibility, CEPIMEX 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 CEPIMEX 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 dose: patients over 2 months of age and weighing ≤ 40 kg: 50 mg/kg every 8 hours for 7–10 days.
Experience with CEPIMEX use in patients under 2 months of age is limited. While this experience has been obtained with a dose of 50 mg/kg, pharmacokinetic data obtained in individuals over 2 months suggest that a dose 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 CEPIMEX 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.
The pediatric dose should not exceed the adult dose (2 g every 8 hours). Experience with intramuscular administration in pediatric patients is limited.
Elderly
Dose adjustment is not required, except in cases of concomitant renal impairment.
Hepatic impairment
Dose adjustment is not required, except in cases of concomitant renal impairment.
Renal impairment
In patients with renal dysfunction, the cefepime dose 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. The recommended maintenance dose of cefepime in adult patients with renal impairment is shown in the following table.
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 is eliminated within 3 hours.
For these patients, the pharmacokinetic model indicates that dose reduction is required. Patients receiving cefepime who are simultaneously 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. When possible, cefepime should be administered at the same time each day.

Patients undergoing continuous peritoneal dialysis
In continuous peritoneal dialysis, CEPIMEX 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 of cefepime, dosage adjustment is recommended in paediatric patients with impaired renal function.
As recommended in Table 2, the same prolongation of dosing intervals and/or reduction in doses should be applied.

METHOD OF ADMINISTRATION
Intravenous administration
To prepare the CEPIMEX 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

CEPIMEX 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 while the patient is receiving a compatible intravenous fluid. In the case of infusion administration, the drug should be given over approximately 30 minutes.

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

It is preferable to administer the medicinal product immediately after reconstitution.
CEPIMEX may be administered concomitantly with other antibiotics or other drugs, provided they are not mixed in the same syringe or infusion fluid.
As with other cephalosporins, solutions of CEPIMEX may vary in colour depending on the storage period. This characteristic does not affect the efficacy and tolerability of the medicinal product.
Intramuscular administration
CEPIMEX 1 g should be diluted with 3 ml of water for injections (supplied in the package).
Management in case of overdose
In case of severe overdose, especially in patients with impaired renal function, serum levels of CEPIMEX can be reduced by haemodialysis. Peritoneal dialysis is not helpful.
Accidental overdose may occur following administration of high doses of the medicinal product in patients with renal dysfunction.