Cefepime Aptapharma

Leaflet accompanying the packaging: information for the user

Cefepime AptaPharma, 1 g, powder for solution for injection/infusion

Cefepime AptaPharma, 2 g, powder for solution for injection/infusion

Cefepime

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents

• 1. What is Cefepime AptaPharma and what is it used for
• 2. Important information before using Cefepime AptaPharma
• 3. How to use Cefepime AptaPharma
• 4. Possible side effects
• 5. How to store Cefepime AptaPharma
• 6. Contents of the packaging and other information

1. What is Cefepime AptaPharma and what is it used for

Cefepime AptaPharma is an antibiotic belonging to the group of cephalosporins, which are beta-lactam antibiotics.
This medicine is used to treat certain bacterial infections caused by microorganisms sensitive to cefepime.

2. Important information before using Cefepime AptaPharma

When not to use Cefepime AptaPharma

• If the patient is allergic to cefepime, other cephalosporin antibiotics, or other beta-lactam antibiotics (e.g., penicillins, monobactams, and carbapenems) or arginine (listed in section 6).

Warnings and precautions

Before starting treatment with Cefepime AptaPharma, consult a doctor, pharmacist, or nurse.
Special precautions

• Encephalopathy (brain disease)Using this medicine may be associated with a risk of encephalopathy (confusion, changes in consciousness, seizures, or abnormal movements). If the patient experiences any of these symptoms, they should immediately inform their doctor, pharmacist, or nurse. The likelihood of these symptoms is higher in cases of overdose or improper dose adjustment in patients with renal impairment (see sections 3 and 4).
• Allergic reactions

If an allergic reaction occurs during treatment, any symptoms of allergy (e.g., rash, itching) should be reported to the doctor immediately.
If the patient has experienced allergic reactions to antibiotics (cephalosporins or beta-lactam antibiotics) during previous treatment, they should inform their doctor.
In patients allergic to penicillin, there is a risk of an allergic reaction (5% to 10% of cases).
The patient should tell their doctor if they have had asthma or are prone to allergies.

• Diarrhea associated with Clostridioides difficile infectionOnset of diarrhea during antibiotic therapy or up to several weeks after completion of treatment should not be treated without consulting a doctor.
• Renal impairmentIf the patient has kidney problems, they should inform their doctor, as treatment may need to be adjusted.
• SuperinfectionsTreatment with cefepime may result in secondary infections caused by other microorganisms. The patient should tell their doctor if they develop another infection besides the one being treated.

Warnings
The patient should inform their doctor:

• if they have renal impairment,
• if they have had an allergic reaction, especially to antibiotics,
• if they have ever been diagnosed with asthma,
• if they experience diarrhea during treatment,
• if they develop an infection other than the one being treated. This medicine may affect the results of some laboratory tests (urine glucose, Coombs test).

Cefepime AptaPharma and other medicines

The patient should tell their doctor about all medicines they are currently taking, have recently taken, or plan to take, including those available without a prescription. This is important because some medicines should not be taken with Cefepime AptaPharma. In particular, the patient should tell their doctor if they are taking:

• any other antibiotics, especially aminoglycosides (such as gentamicin) or diuretics (such as furosemide); in such cases, renal function should be monitored;
• medicines that prevent blood clotting (such as warfarin); their effect may be enhanced;
• certain types of antibiotics that prevent bacterial growth, as they may affect the action of Cefepime AptaPharma.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
Pregnancy
There is no data on the use of cefepime in pregnant women. The use of this medicine during pregnancy is only allowed when absolutely necessary.
Breastfeeding
Small amounts of this medicine may pass into breast milk. The medicine can be used during breastfeeding, but precautions should be taken. If the baby experiences symptoms such as diarrhea, rash, or thrush (a yeast infection), breastfeeding should be stopped, as these symptoms in the baby may be caused by this medicine.
Fertility
There is no data on the effect of the medicine on fertility.

Driving and using machines

This medicine may have a significant impact on the ability to drive and use machines due to some possible side effects (changes in consciousness, dizziness, confusion, or hallucinations). Before driving or using machines, the patient should make sure how this medicine affects them.

3. How to use Cefepime AptaPharma

The doctor or nurse will decide what dose of the medicine to administer to an adult or child patient, depending on the type and severity of the infection and the patient's age. In infants and children, the dose is calculated based on body weight.
Recommended dose:

• Adults and children over 12 years old with a body weight > 40 kg: 1 g twice a day to 2 g twice or three times a day.
• Children from 2 months to 12 years old with a body weight ≤ 40 kg: 50 mg/kg body weight, three times a day. The dose should be adjusted in case of renal problems.

Cefepime AptaPharma, 1g: This medicine is administered intravenously (iv.) or intramuscularly (im.).
Cefepime AptaPharma, 2g: This medicine is administered intravenously (iv.).
Intravenous administration:
Before use, the medicine should be dissolved in water for injections or another compatible solvent.
Volume of added solvent and resulting solution before administration
After dissolving the powder, the resulting solution can be administered directly by slow injection (3 to 5 minutes) or through an infusion line. Alternatively, the solution can be added to a compatible infusion fluid and administered intravenously by drip infusion (over 30 minutes).
Intramuscular administration:
The medicine (1 g of cefepime) is dissolved in water for injections or in a 5 mg/mL (0.5%) or 10 mg/mL (1%) lidocaine hydrochloride solution.

Compatibility

This medicine is compatible with the following solvents and solutions: sodium chloride 9 mg/mL (0.9%) (with or without glucose 50 mg/mL (5%)), glucose 50 mg/mL (5%) or 100 mg/mL (10%), and Ringer's lactate solution.

The medicine can be administered simultaneously with other antibiotics, but using the same syringe, infusion line, or injection site is prohibited.
The solution may change color to yellowish-amber, but it can still be used, as this change does not affect its effectiveness.

Frequency of administration

The medicine is administered 2 to 3 times a day.

Duration of treatment

To be effective, the medicine should be used regularly in the prescribed doses for the entire period prescribed by the doctor.
Resolution of fever or other symptoms does not mean complete recovery. If the patient feels tired, it is not due to antibiotic treatment, but rather the infection itself.
Reducing the dose or stopping treatment will not affect this symptom and will delay recovery.

Using a higher dose of Cefepime AptaPharma than recommended

Like all antibiotics in this therapeutic group, administration of this medicine, especially in case of overdose, may cause a risk of encephalopathy, which can cause confusion, changes in consciousness, seizures, or abnormal movements. If these symptoms occur, the patient should immediately inform their doctor or pharmacist (see sections 2 and 4).

Missing a dose of Cefepime AptaPharma

If the patient thinks they have not received an injection or infusion, they should tell their doctor.

Stopping treatment with Cefepime AptaPharma

This medicine should be used for the entire treatment period, even if the patient feels better after the first few doses.
In case of any further doubts about using this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Adult patients and children usually tolerate Cefepime AptaPharma well.
Side effects that may occur due to treatment are listed according to frequency:

Very common(may occur more often than 1 in 10 people)

• positive Coombs test (used to test for antibodies against red blood cells)

Common(may occur no more often than 1 in 10 people)

• decrease in red blood cell count and/or hemoglobin concentration (anemia)
• increase in the number of certain white blood cells: leukocytes (eosinophilia)
• diarrhea
• widespread rash
• infusion site reaction
• increase in alkaline phosphatase activity (enzymes)
• increase in aminotransferase activity (liver enzymes)
• increase in bilirubin concentration in the blood (bilirubinemia)
• prolongation of blood clotting time (prolongation of prothrombin time and activated partial thromboplastin time)

Uncommon(may occur no more often than 1 in 100 people)

• oral thrush (fungal infection of the mouth)
• increase in the number of certain white blood cells: leukocytes (leukopenia)
• increase in the number of certain white blood cells: neutrophils (neutropenia)
• abnormally low platelet count (thrombocytopenia)
• phlebitis (vein inflammation) or thrombophlebitis (inflammation of a vein caused by a blood clot) after intravenous administration
• nausea, vomiting
• itching (pruritus), hives, skin redness (flushing)
• inflammation at the infusion site
• pain and inflammation at the injection site (intravenous or intramuscular administration)
• fever
• increase in renal function indicators (blood urea and/or creatinine concentration)

Rare(may occur no more often than 1 in 1000 people)

• fungal infections (candidiasis)
• allergic reactions (anaphylactic reactions)
• fluid retention under the skin or in mucous membranes (angioedema)
• headache
• tingling or numbness (paresthesia)
• breathing difficulties (dyspnea)
• constipation
• renal failure
• genital itching
• chills

Very rare(may occur less often than 1 in 10,000 people)

• vaginitis (vaginal infection)
• severe generalized allergic reaction (severe discomfort with a drop in blood pressure) (anaphylactic shock)
• seizures, taste disturbances (taste disorders), dizziness
• drop in blood pressure (hypotension)
• increase in blood vessel diameter (vasodilation)
• inflammation of the colon (colitis)
• inflammation of the colon with diarrhea and/or abdominal pain (pseudomembranous colitis)
• abdominal pain
• mouth ulcers
• decrease in blood phosphorus concentration (hypophosphatemia)

Frequency not known(cannot be estimated from available data)

• decrease in red blood cell count (aplastic anemia)
• breakdown of red blood cells (hemolytic anemia)
• significant decrease in the number of certain white blood cells: neutrophils (agranulocytosis)
• severe neurological disorders called encephalopathy with confusion, changes in consciousness and alertness, seizures, abnormal movements, coma, or hallucinations, especially in cases of high doses and/or renal impairment, especially in elderly patients (see sections 2 and 3)
• bleeding risk
• severe skin disease called toxic epidermal necrolysis (blistering and peeling of the skin)
• inflammatory skin redness with blisters and fever (Stevens-Johnson syndrome)
• skin redness (erythema multiforme)
• kidney damage (nephrotoxicity)
• false-positive urine glucose test results (false-positive glycosuria)

Reporting side effects

If any side effects occur, including any not listed in the leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Cefepime AptaPharma

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiration date stated on the carton and label after EXP.
The expiration date refers to the last day of the month.
There are no special storage instructions for the medicine. The vial should be kept in the outer packaging to protect it from light.
Information on storage and use of Cefepime AptaPharma after reconstitution and preparation for use is described in the practical information for healthcare professionals (at the end of this leaflet).
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Cefepime AptaPharma contains

• 1 g: The active substance is 1.19 g of cefepime dihydrochloride monohydrate, equivalent to 1.0 g of cefepime.
• 2 g: The active substance is 2.38 g of cefepime dihydrochloride monohydrate, equivalent to 2.0 g of cefepime.
• The other ingredient is arginine.

What Cefepime AptaPharma looks like and contents of the pack

Cefepime AptaPharma is a white or off-white crystalline powder for solution for injection/infusion.
Cefepime AptaPharma1 g
Vials of 20 mL capacity made of type I colorless glass, closed with a gray rubber stopper with a diameter of 20 mm and an aluminum flip-off seal in salmon color.
Cefepime AptaPharma2 g
Vials of 20 mL capacity made of type I colorless glass, closed with a gray rubber stopper with a diameter of 20 mm and an aluminum flip-off seal in brown color.
The medicine is available in packs containing 1, 10, or 25 vials in a cardboard box.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:
Apta Medica Internacional d.o.o.
Likozarjeva ulica 6
1000 Ljubljana
Slovenia
Phone: 00386 51 615 015
e-mail: [email protected]
Manufacturer:
ACS Dobfar S.p.A.
Via Alessandro Fleming 2
37135 Verona
Italy

This medicine is authorized in the Member States of the European Economic Area under the following names:

Austria
Cefepim AptaPharma 1 g Pulver zur Herstellung einer Injektions-/Infusionslösung
Cefepim AptaPharma 2 g Pulver zur Herstellung einer Injektions-/Infusionslösung
Bulgaria
Цефепим АптаФарма 1 g прах за инжекционен / инфузионен разтвор
Цефепим АптаФарма 2 g прах за инжекционен / инфузионен разтвор
Croatia
Cefepim AptaPharma 1 g prašak za otopinu za injekciju/infuziju
Cefepim AptaPharma 2 g prašak za otopinu za injekciju/infuziju
Cyprus
Cefepime AptaPharma 1g powder for solution for injection/infusion
Cefepime AptaPharma 2g powder for solution for injection/infusion
Czech Republic
Cefepime AptaPharma
Malta
Cefepime AptaPharma 1g powder for solution for injection/infusion
Cefepime AptaPharma 2g powder for solution for injection/infusion
Poland
Cefepime AptaPharma
Romania
Cefepima AptaPharma 1 g pulbere pentru soluție injectabilă/perfuzabilă
Cefepima AptaPharma 2 g pulbere pentru soluție injectabilă/perfuzabilă
Slovakia
Cefepime AptaPharma 1 g prášok na injekčný/infúzny roztok
Cefepime AptaPharma 2 g prášok na injekčný/infúzny roztok
Slovenia
Cefepim AptaPharma 1 g prašek za raztopino za injiciranje/infundiranje
Cefepim AptaPharma 2 g prašek za raztopino za injiciranje/infundiranje
Hungary
Cefepim AptaPharma 1 g por oldatos injekcióhoz vagy infúzióhoz
Cefepim AptaPharma 2 g por oldatos injekcióhoz vagy infúzióhoz
Date of last revision of the leaflet:
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Information intended for healthcare professionals only:

Dosage

Adult patientswith normal renal function:
Usual recommended doses in monotherapy or in combination with other medicines are as follows:

* The dose of 2 g three times a day was used only in monotherapy
Treatment usually lasts from 7 to 10 days, although in more severe infections, it may be longer.
Empirical treatment of febrile episodes in neutropenic patients usually lasts 7 days or until the resolution of neutropenia.
Patients with renal impairment:
Cefepime is excreted by the kidneys solely by glomerular filtration. Therefore, in patients with renal impairment (glomerular filtration rate <50 ml min), the dosage should be adjusted to compensate for reduced renal excretion. determine maintenance dose, glomerular filtration rate assessed.
Criteria for dose adjustment in patients with renal impairment are described in the table below:

* On days of dialysis, the medicine should be administered after dialysis.
If only the serum creatinine concentration is available, the creatinine clearance can be estimated using the Cockcroft and Gault formula. The serum creatinine concentration should reflect renal function in a steady state:
body weight (in kg) x (140 - age [in years])
men: CrCl = ---------------------------------------------------------
72 x serum creatinine concentration (in mg/dL)
women: CrCl = 0.85 x creatinine clearance calculated for men
In patients undergoing hemodialysis, the pharmacokinetic properties of cefepime indicate the need for dose reduction. These patients should receive a loading dose of 1 g on the first day of treatment, followed by 500 mg on subsequent days. About 68% of the total amount of cefepime present in the body is eliminated during 3 hours of dialysis. On dialysis days, cefepime should be administered after dialysis. If possible, cefepime should be administered at the same time every day.
Patients undergoing continuous ambulatory peritoneal dialysis can be given cefepime in doses recommended for patients with normal renal function, but every 48 hours.

Method of administration

Intravenous administration:
Cefepime should be dissolved in water for injections or another compatible solvent for preparing the injection solution (see compatibility section below).

Volume of reconstitution before administration

Solutions for intravenous administration after reconstitution can be administered directly by slow injection (3 to 5 minutes) using a syringe or infusion line or added to a compatible infusion fluid and administered intravenously by drip infusion (over 30 minutes).
Intramuscular administration:
1 g of cefepime should be dissolved in water for injections or in a 5 mg/mL (0.5%) or 10 mg/mL (1%) lidocaine hydrochloride solution.

Volume of added solvent and resulting solution before administration

Compatibility:

Cefepime is compatible with the following solvents and solutions: sodium chloride 9 mg/mL (0.9%) (with or without glucose 50 mg/mL (5%)), glucose 50 mg/mL (5%) or 100 mg/mL (10%), and Ringer's lactate solution.
Cefepime can be administered simultaneously with other antibiotics. However, using the same syringe, infusion line, or injection site is prohibited.

Visual inspection

After reconstitution, the solution is clear and does not contain visible particles.
Medicines for parenteral use should be inspected before administration to ensure they do not contain solid particles. The medicine should not be used if solid particles are detected.
Like other cephalosporins, the reconstituted solution may turn yellowish-amber, which does not indicate a loss of effectiveness.
The reconstituted product is intended for single use only.
Any unused product or waste material should be disposed of in accordance with local regulations.

Shelf life

For intravenous, intramuscular, or infusion use.
Chemical and physical stability after reconstitution has been demonstrated for 7 days when stored at 2°C - 8°C (in a refrigerator) and for 24 hours when stored at a temperature below 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the storage time and conditions before use are the responsibility of the user. The storage time should not exceed 24 hours at 2°C - 8°C, unless reconstitution took place in controlled and validated aseptic conditions.