CEFEPIME APTAPHARMA 2 g Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Cefepime AptaPharma, 1 g, powder for solution for injection/infusion
3. Cefepime AptaPharma, 2 g, powder for solution for injection/infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents
4. What is Cefepime AptaPharma and what is it used for
5. Important information before using Cefepime AptaPharma
   1. When not to use Cefepime AptaPharma
   2. Warnings and precautions
   3. Cefepime AptaPharma and other medicines
   4. Pregnancy, breastfeeding, and fertility
   5. Driving and using machines
6. How to use Cefepime AptaPharma
   1. Compatibility
   2. Frequency of administration
   3. Duration of treatment
   4. Use of a higher than recommended dose of Cefepime AptaPharma
   5. Missing a dose of Cefepime AptaPharma
   6. Stopping the use of Cefepime AptaPharma
7. Possible side effects
   1. Reporting side effects
8. How to store Cefepime AptaPharma
9. Contents of the packaging and other information
   1. What Cefepime AptaPharma contains
   2. What Cefepime AptaPharma looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. This medicine is authorized in the Member States of the European Economic Area under the following names:
   5. Information intended for healthcare professionals only:
   6. Dosage
   7. Method of administration
   8. Volume of reconstitution before administration
   9. Volume of added solvent and resulting solution before administration
   10. Compatibility:
   11. Visual inspection
   12. Shelf life

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)The use of this medicine may be associated with a risk of encephalopathy (confusion, altered 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 case 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.
Patients allergic to penicillin have a risk of allergic reaction (5% to 10% of cases).
The doctor should be informed if the patient has a history of asthma or is prone to allergies.

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

Warnings
The doctor should be informed:

• if the patient has renal impairment,
• if the patient has had an allergic reaction, especially to antibiotics,
• if the patient has been diagnosed with asthma,
• if the patient experiences diarrhea during treatment,
• if the patient develops 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 doctor should be informed about all medicines the patient is currently taking, has recently taken, or plans to take, including those available without a prescription. This is important because some medicines should not be used with Cefepime AptaPharma. In particular, the doctor should be informed if the patient is taking:

• any other antibiotics, especially aminoglycosides (such as gentamicin) or diuretics (such as furosemide); in such cases, renal function needs to 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 child experiences symptoms such as diarrhea, rash, or thrush (fungal infection), breastfeeding should be stopped, as these symptoms in the child 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 (altered 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 will be given to the 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 impairment.

Cefepime AptaPharma, 1g: This medicine is administered intravenously (intravenous injection) or intramuscularly (intramuscular injection).
Cefepime AptaPharma, 2g: This medicine is administered intravenously (intravenous injection).
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 in a 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 in a 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 of the medicine 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 of treatment prescribed by the doctor.
Improvement 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 of the medicine or stopping treatment will not affect this symptom and will delay recovery.

Use of a higher than recommended dose of Cefepime AptaPharma

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, altered consciousness, seizures, or abnormal movements. If the above symptoms occur, the doctor or pharmacist should be informed immediately (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 inform their doctor.

Stopping the use of 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 the use of this medicine, the doctor, pharmacist, or nurse should be consulted.

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 as a result of 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
• increased alkaline phosphatase activity (enzymes)
• increased aminotransferase activity (liver enzymes)
• increased bilirubin concentration in the blood (bilirubinemia)
• prolonged blood clotting time (prolonged 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)
• low platelet count (thrombocytopenia)
• phlebitis (vein inflammation) or thrombophlebitis (vein inflammation with blood clot formation) after intravenous administration
• nausea, vomiting
• itching (pruritus), hives, skin redness (erythema),
• infusion site inflammation
• pain and inflammation at the injection site (intravenous or intramuscular administration)
• fever
• increased renal function parameters (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 low blood pressure) (anaphylactic shock)
• seizures, taste disturbances (dysgeusia), dizziness
• low blood pressure (hypotension)
• increased blood vessel diameter (vasodilation)
• colitis (inflammation of the colon)
• pseudomembranous colitis (colitis with diarrhea and/or abdominal pain)
• abdominal pain
• mouth ulcers
• decreased phosphorus concentration in the blood (hypophosphatemia)

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

• decrease in red blood cell count (aplastic anemia)
• red blood cell destruction (hemolytic anemia)
• significant decrease in the number of certain white blood cells: neutrophils (agranulocytosis)
• severe neurological disorders called encephalopathy with confusion, altered consciousness, seizures, abnormal movements, coma, or hallucinations, especially in case 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 doctor or pharmacist should be informed. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
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 expiry date stated on the carton and label after EXP.
The expiry date refers to the last day of the month.
There are no special storage instructions for the medicine. The vial should be stored 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 pharmacist should be asked 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, which corresponds to 1.0 g of cefepime.
• 2 g: The active substance is 2.38 g of cefepime dihydrochloride monohydrate, which corresponds 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 colorless glass type I, 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 colorless glass type I, 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 patients with neutropenia usually lasts 7 days or until the neutropenia resolves.
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 the 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 to reduce the dose. These patients should receive a loading dose of 1 g on the first day of treatment, and then 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.
Children and adolescents
Adolescents over 12years old with a body weight > 40 kg
The recommended dosage in monotherapy or in combination with other medicines is usually the same as for adults. The recommended duration of treatment is also the same as for adults.
Children from 2 months to 12 years old with a body weight ≤ 40 kg:
Dose of 50 mg/kg body weight, intravenous administration, three times a day. Available clinical data on infants and children do not allow for the recommendation of cefepime as monotherapy.
The duration of treatment is the same as for adults and usually lasts from 7 to 10 days, although in more severe infections, it may be longer. The duration of treatment for febrile episodes in patients with neutropenia is usually 7 days or until the neutropenia resolves.

Method of administration

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

Volume of reconstitution before administration

Solutions for intravenous administration after reconstitution can be administered directly in a slow intravenous injection (3 to 5 minutes) using a syringe or infusion line, or added to a compatible infusion fluid and administered intravenously in a drip infusion (over 30 minutes).
Intramuscular administration:
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.

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 visually for particulate matter and discoloration prior to administration. The medicine should not be used if particles are found.
Like other cephalosporins, the reconstituted solution may turn yellowish-amber, but this does not indicate a loss of potency.
The reconstituted product is intended for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.

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 times 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 has taken place in controlled and validated aseptic conditions.