Cefepime solufarma

Package leaflet: information for the patient

Cefepime Solufarma, 500 mg, powder for solution for injection/infusion
Cefepime Solufarma, 1000 mg, powder for solution for injection/infusion
Cefepimum
Please read carefully this leaflet before using this medicine because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

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

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

Cefepime Solufarma is indicated for the treatment of adults, adolescents, and children over 2 months of age.

Adults and adolescents
For the treatment of infections caused by cefepime-susceptible microorganisms:

• Severe pneumonia;
• Complicated urinary tract infections;
• Intra-abdominal infections, including peritonitis: combination therapy with additional antibiotics is recommended, taking into account individual patient risk factors and expected or identified microorganisms, if necessary;
• Biliary tract infections (gallbladder and bile duct);
• Treatment of patients with bacteremia associated or suspected to be associated with any of the above-mentioned infections;
• Treatment of patients with moderate (neutrophils ≤1000/mm³) or severe (neutrophils ≤500/mm³) neutropenia with fever, when bacterial infection is suspected. In patients with neutropenia at high risk of severe infections (e.g., patients after recent bone marrow transplantation, patients with early hypotension when hematological disorders are suspected, or with severe or prolonged neutropenia), monotherapy with antibacterial agents may be inadequate.

There are insufficient data on the use of cefepime as monotherapy in these patients. Combination therapy with aminoglycosides or glycopeptides is recommended, taking into account the individual risk profile of the patient.

Children
Treatment of infections caused by microorganisms susceptible to cefepime:

• Severe pneumonia;
• Complicated urinary tract infections;
• Bacterial meningitis;
• Treatment of patients with moderate (neutrophils ≤1000/mm³) or severe (neutrophils ≤500/mm³) neutropenia with fever, probably caused by bacterial infection. In patients with neutropenia at high risk of severe infections (e.g., patients after recent bone marrow transplantation, patients with early hypotension when hematological disorders are suspected, or with severe or prolonged neutropenia), monotherapy with antibacterial agents may be inadequate. However, there are insufficient data on the use of cefepime as monotherapy in these patients. Combination therapy with an aminoglycoside or glycopeptide antibiotic is recommended, taking into account the individual patient risk profile.

Official guidelines on appropriate use of antibacterial agents should be taken into account.

2. Important information before using Cefepime Solufarma

When not to use Cefepime Solufarma

• if the patient is allergic to cefepime, or to any of the other components of this medicine (listed in section 6), or to beta-lactam antibiotics (such as penicillins, monobactams, and carbapenems).

Warnings and precautions
Before starting treatment with Cefepime Solufarma, discuss this with your doctor or pharmacist.

• As with any beta-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported during cefepime therapy.
• Cefepime Solufarma should be used with caution in patients with asthma or a history of allergies. After administration of the first dose, the patient should be closely monitored. If an allergic reaction occurs, treatment with Cefepime Solufarma must be discontinued immediately.
• Severe hypersensitivity reactions may require administration of epinephrine and other supportive therapies.
• During treatment with nearly all antibiotics, including Cefepime Solufarma, cases of Clostridium difficile-associated diarrhoea (CDAD), ranging from mild to life-threatening pseudomembranous colitis, have been observed. CDAD should be considered in all patients who develop diarrhoea following antibiotic therapy. A careful medical history is necessary, as cases of CDAD have been reported up to 2 months after antibiotic treatment.
• If there has been a previous allergic reaction to medications. Severe and sometimes fatal hypersensitivity reactions to beta-lactam antibacterial agents have been reported. If any allergic reaction occurs, treatment with Cefepime Solufarma should be discontinued and appropriate therapy initiated.
• Antibiotic use may lead to overgrowth of resistant pathogenic microorganisms; if superinfection occurs during treatment, appropriate measures should be taken.
• Since elderly patients are more likely to have impaired renal function, caution should be exercised in dose selection and renal function should be monitored.
• Diagnostic test abnormalities: A positive Coombs test result has been reported in patients treated with cefepime, without evidence of haemolysis. Cefepime may also cause a false-positive result in urine glucose tests using the copper reduction method (an enzymatic method should be used instead).

Cefepime Solufarma and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Consult your doctor if the patient is taking:

• Aminoglycoside antibiotics or potent diuretics, as they may potentially cause kidney problems. In such cases, the doctor will recommend close monitoring of kidney function.
• Anticoagulants derived from coumarin, as their effect may be enhanced by cephalosporins.
• Bacteriostatic antibiotics, as they may interfere with the therapeutic action of beta-lactam antibiotics.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child,
she should consult her doctor or pharmacist before using this medicine.
The safety of Cefepime Solufarma during pregnancy has not been established; therefore, the medicine is recommended only when clearly needed and under strict medical supervision.
If the patient is breastfeeding, the doctor should exercise caution when administering Cefepime Solufarma, as small amounts of the drug may pass into human milk.
Reproduction studies in animals have not shown any effect on fertility. However, there are no data available on the effect of cefepime on human fertility.

Driving and using machines
No studies on the effect of the medicine on the ability to drive or operate machinery have been conducted. However, possible adverse effects such as disturbances in consciousness, dizziness, confusion, or hallucinations may affect the ability to perform these activities.

3. How to use/how to administer Cefepime Solufarma
Cefepime Solufarma will be administered intramuscularly or intravenously by a doctor or healthcare professional.
The dose and route of administration usually vary depending on the severity of infection, renal function, and the patient's general condition.
In cases of severe infection that may be life-threatening, especially if septic shock occurs, Cefepime Solufarma will be administered intravenously.
For direct intravenous injection, the final solution should be injected directly into the vein over 3 to 5 minutes or administered via an infusion set while the patient is receiving intravenous fluids.
For intravenous infusion, the final solution should be administered over approximately 30 minutes.

The table below provides dosing guidelines for cefepime in adults and children weighing more than 40 kg with normal renal function.

Severity of infection Dose and route of administration Interval between doses
Severe infections: 2 g (i.v.) every 12 hours
Very severe (life-threatening) infections: 2 g (i.v.) every 8 hours
* Duration of treatment is usually 7 to 10 days.
More severe infections may require longer treatment. In empirical treatment of febrile neutropenia, treatment should last 7 days or until resolution of neutropenia.

In patients with body weight ≤ 40 kg, the pediatric dosing regimen is recommended.

Children with normal renal function
The usual recommended dose in children is:

• Pneumonia, urinary tract infections: Children older than 2 months of age and body weight ≤ 40 kg: 50 mg/kg every 12 hours for 10 days; in more severe infections, an 8-hour interval between doses should be maintained.
• Bacterial meningitis and empirical treatment of febrile neutropenia: Children older than 2 months of age and body weight ≤ 40 kg: 50 mg/kg every 8 hours for 7 to 10 days.

Experience with the use of Cefepime Solufarma in patients under 2 months of age is limited.
Despite experience with a dose of 50 mg/kg, pharmacokinetic data from children over 2 months of age suggest that a dose of 30 mg/kg every 12 or 8 hours may be appropriate for children aged 1 to 2 months. Careful monitoring of Cefepime Solufarma administration is required in these patients.
In children and adolescents with body weight > 40 kg, the adult dose may be used. In patients over 12 years of age with body weight ≤ 40 kg, the dosing regimen for younger patients with body weight ≤ 40 kg should be applied. The pediatric dose should not exceed the adult dose (2 g every 8 hours).
Experience with intramuscular administration in children is limited.

In elderly patients and adults with impaired renal function, patients undergoing dialysis, and children with impaired renal function: the doctor will determine the appropriate dose.

Administration of a higher than recommended dose of Cefepime Solufarma
If an overdose of Cefepime Solufarma is accidentally administered or taken, symptoms may include:

• encephalopathy (a disease characterized by diffuse brain tissue damage)
• myoclonus (sudden, involuntary muscle jerks)
• seizures (violent, involuntary muscle contractions).

In cases of severe overdose, especially in patients with impaired renal function, cefepime can be removed from the body by haemodialysis. Peritoneal dialysis is not effective.
Accidental overdoses have occurred when high doses were administered to patients with impaired renal function.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Cefepime Solufarma may cause one or more of the following adverse reactions:

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

• positive Coombs test (without haemolysis);

Common (may occur in 1 in 10 people):

• anaemia, eosinophilia (increased number of certain blood cells, eosinophils);
• phlebitis at the infusion site;
• diarrhoea;
• rash;
• irritation at the infusion site;
• pain and inflammation at the injection site;
• increased levels of certain blood parameters (alanine aminotransferase, aspartate aminotransferase, bilirubin, alkaline phosphatase). Prolonged prothrombin time or partial thromboplastin time (prolonged blood clotting time).

Uncommon (may occur in 1 in 100 people):

• fungal infections of the mouth with white coating (oral candidiasis);
• vaginal inflammation;
• decreased number of certain blood cells (thrombocytopenia, leukopenia, neutropenia);
• headache;
• colitis (inflammation of the large intestine) with abdominal pain;
• nausea;
• vomiting;
• skin redness (erythema);
• urticaria;
• skin itching;
• increased blood urea levels;
• increased blood creatinine levels;
• fever;
• inflammation at the injection site.

Rare (may occur in 1 in 1000 people):

• fungal infections (candidiasis);
• allergic reactions;
• seizures;
• sensory disturbances, e.g. tingling and numbness (paraesthesiae);
• taste disturbances (dysgeusia);
• dizziness;
• vasodilation;
• shortness of breath;
• abdominal pain;
• constipation;
• genital itching;
• chills.

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

• aplastic anaemia (a type of blood disorder), haemolytic anaemia (a type of blood disorder), agranulocytosis (reduced number of granulocytes, a type of white blood cells);
• anaphylactic shock (severe allergic reaction), angioedema (swelling);
• disorientation;
• hallucinations;
• coma;
• apathy;
• encephalopathy (non-inflammatory brain disorder);
• disturbances of consciousness;
• myoclonus (muscle jerking);
• bleeding;
• gastrointestinal disorders;
• severe skin reactions associated with discolouration, red spots, purple areas or blisters (such as toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme);
• renal failure;
• toxic nephropathy (kidney degeneration);
• falsely positive urine glucose test result.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie
181C PL-02 222
Warsaw
Tel.: + 48 22 49 21 301
Faks: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Cefepime Solufarma

Store below 25°C. Keep in the outer packaging to protect from light.
The solution reconstituted with sterile water for injections or 0.9% sodium chloride solution
shows chemical and physical stability at 25°C for 12 hours or alternatively at 2°C to 8°C for 3 days.
The solution reconstituted with 5% dextrose solution shows chemical and physical stability at 25°C for 12 hours.
Stability studies have not been carried out using the following diluents; therefore, the injection solution should be used immediately after reconstitution, and infusion solutions for i.m./i.v. use should be immediately added to the i.m./i.v. infusion fluid.
Cefepime Solufarma, 500 mg powder for solution for injection/infusion

• Water for injections (free)
• Ringer's solution
• 10% dextrose solution
• 1/6-molar sodium lactate solution

Cefepime Solufarma, 1000 mg powder for solution for injection/infusion

• 0.5% lidocaine hydrochloride for injection
• 1% lidocaine hydrochloride for injection
• 10% dextrose solution
• Sterile bacteriostatic water for injection with parabens
• Sterile bacteriostatic water for injection with benzyl alcohol
• 1/6-molar sodium lactate solution for injection
• 5% glucose and 0.9% sodium chloride solution for injection
• Ringer's lactate and 5% glucose solution for injection

From a microbiological point of view, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately.
If the solution is not used immediately, the responsibility for storage duration and conditions lies with the user.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word EXP. The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Cefepime Solufarma contains
Cefepime Solufarma, 500 mg powder for solution for injection/infusion

• the active substance is cefepime dihydrochloride monohydrate equivalent to 500 mg of cefepime
• other ingredients: L-arginine

Cefepime Solufarma, 1000 mg powder for solution for injection/infusion

• the active substance is cefepime dihydrochloride monohydrate equivalent to 1000 mg of cefepime
• other ingredients: L-arginine

What Cefepime Solufarma looks like and contents of the pack
Cefepime Solufarma, 500 mg, powder for solution for injection/infusion is supplied in a moulded vial with a capacity of 20 mL made of colourless glass (type I), fitted with a grey protective stopper (type 1), 20 mm in size, made of bromobutyl rubber, with an aluminium "flip-off" cap and a yellow polypropylene disc, packed in a cardboard box.
Cefepime Solufarma, 1000 mg, powder for solution for injection/infusion is supplied in a moulded vial with a capacity of 20 mL made of colourless glass (type I), fitted with a grey protective stopper (type 1), 20 mm in size, made of bromobutyl rubber, with an aluminium "flip-off" cap and a white polypropylene disc, packed in a cardboard box.
Pack sizes: 1, 5, 10, 50 vials in a cardboard box.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Solufarma Produtos Farmacêuticos, Lda.
Av. Bombeiros Voluntários, n.° 146, 1°
2765-201 Estoril
Portugal
Manufacturer/Importer
Infosaúde – Instituto de Formação e Inovação em Saúde Unipessoal, Lda
Rua Ferrarias Del-Rei 6, Urbanização de Fábrica Pólvora
2730-269 Barcarena
Portugal

Information intended exclusively for medical professionals:

Cefepime Solufarma can be administered intravenously (i.v.) or intramuscularly (i.m.).
After reconstitution, the solution is colorless to yellowish-brown in color.

Intravenous administration (i.v.)
For direct intravenous administration, the medicinal product Cefepime Solufarma should be dissolved in 10 mL of water for injections, 0.9% sodium chloride solution, or 5% dextrose.
The resulting solution may be injected directly into the vein over 3–5 minutes or administered via an infusion set while a compatible diluent is being administered intravenously to the patient.
The drug may also be administered through infusion lines or by continuous intravenous infusion (i.v.) while the patient is receiving a compatible intravenous fluid. In the case of infusion, the drug should be administered over approximately 30 minutes.

Intramuscular administration (i.m.)
Cefepime Solufarma 500 mg should be diluted with 1.5 mL of water for injections or with 0.5% (or 1%) lidocaine hydrochloride solution.
Cefepime Solufarma 1000 mg should be diluted with 3 mL of water for injections or with 0.5% (or 1%) lidocaine hydrochloride solution.

Cefepime Solufarma is compatible with the following solutions: 0.9% sodium chloride solution (with or without 5% dextrose), 5% dextrose, 10% dextrose, Ringer's lactate solution (with or without 5% dextrose), M/6 lactated solution, to achieve concentrations ranging from 1 to 40 mg/mL.

Cefepime Solufarma may be administered simultaneously with other antibiotics or other drugs, provided that they are not mixed in the same syringe with the infusion fluid and are not administered at the same injection site.

Any unused antibiotic solution and all materials used for administration should be disposed of in accordance with local regulations.

Like other cephalosporins, the Cefepime Solufarma solution may turn slightly yellow after reconstitution; however, this does not indicate a reduction in the potency of cefepime.