CEFEPIMA QILU 2 g POWDER FOR INJECTION AND INFUSION SOLUTION

2. What you need to know before you use Cefepima Qilu

Do not use CefepimaQilu:

• if you are allergic to cefepime or any of the other components of this medication (listed in section 6).
• if you are allergic to the class of antibiotics of cephalosporins or other similar antibiotics (beta-lactam antibiotics, such as penicillins, monobactams, or carbapenems).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Cefepima Qilu.

Particular caution is required, especially:

• If you have renal insufficiency, as this will affect the excretion of cefepime.
• If you have any allergy (e.g., allergy to pollen, hives) and have had previous allergies to beta-lactam antibiotics (penicillins, monobactams, or carbapenems) or other medications. If you experience an allergic reaction during treatment with cefepime, contact your doctor immediately, as it could have serious consequences. In this case, your doctor will interrupt your treatment immediately.
• If you have ever had asthma or tend to have allergic reactions.
• If you are going to have blood or urine tests. It is essential that you inform your doctor that you are receiving Cefepima Qilu, as this medication may affect the results of some tests.
• If you experience persistent diarrhea while receiving Cefepima Qilu or after it. You should inform your doctor, who will study whether the antibiotic treatment has caused inflammation of the intestinal walls and, if necessary, take appropriate measures to treat it.

Treatment with Cefepima Qilu could cause secondary infections with other germs (e.g., fungal infection of the mucous membranes, with redness and white deposits on the mucous membranes). Your doctor will treat these secondary infections as appropriate.

Children

In the case of infants and children, special administration guidelines must be applied (see section 3).

Elderly patients

In elderly patients, the dosage regimen should be chosen with caution and taking into account kidney function, as the likelihood of reduced kidney function is higher (see section 3).

Use of CefepimaQilu with other medications

Inform your doctor if you are taking, have recently taken, or may need to take any other medication.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Cefepima Qilu should not be administered during pregnancy unless it is strictly necessary.

Breastfeeding

Cefepime is excreted in breast milk; therefore, Cefepima Qilu should only be administered during breastfeeding after carefully weighing the benefits and risks.

Driving and using machines

Do not drive or use tools or machines, as treatment with Cefepima Qilu may cause effects such as altered consciousness, dizziness, confusion, or hallucinations.

3. How to use Cefepima Qilu

The doctor should use Cefepima Qilu according to the information provided below or the information contained in the Summary of Product Characteristics or Package Leaflet. If you have any doubts, consult your doctor or pharmacist.

Dosage in patients with normal renal function:

Adults and children over 40kg body weight (around 12years):

The duration of treatment is usually 7 to 10 days. Cefepima Qilu should generally be used for at least 7 days and no more than 14 days per treatment. When treating febrile episodes in patients with deficient defenses against infections (neutropenia), the usual duration of treatment is 7 days or until neutropenia improves.

Children from 1month of age to 40kg body weight (around 12years):

In the case of children from 1 to 2 months of age, a dose of 30 mg/kg body weight every 12 or 8 hours is sufficient. These children should be closely monitored during administration.

In the case of children over 40 kg body weight, the adult dosage recommendation should be applied (see the previous table). In the case of children 12 years of age with a body weight of less than 40 kg, the dosage recommendations for younger patients with a body weight of ≤ 40 kg should be applied. The dose in children should not exceed the maximum adult dose (2 g every 8 hours).

Dosage in patients with renal insufficiency:

Adults and children with a body weight of 40kg and over (around 12 years):

If you have renal insufficiency, a dose adjustment is required to counteract the slower excretion through the kidneys. The first dose in patients with mild to moderate renal insufficiency is the same as in patients with normal renal function, i.e., 2 g of cefepime.

The following tables show the subsequent dosage recommendations (maintenance dose):

Patients on dialysis:

If you require hemodialysis, you will receive a lower dose:

• 1 g of cefepime on the first day of treatment and, thereafter, 500 mg of cefepime/day on subsequent days for all injections, except in the case of febrile episodes in patients with deficient defenses against infections (neutropenia), in which case the dose is 1 g/day.

When possible, cefepime should be administered at the same time every day, and on dialysis days, it should be administered after completing dialysis.

In patients with renal insufficiency receiving continuous peritoneal dialysis, the following dosage recommendation is suggested:

• 1 g of cefepime every 48 hours in the case of severe infections (blood infection, pneumonia, complicated urinary tract infections, infections of the gallbladder and bile ducts).
• 2 g of cefepime every 48 hours in the case of very severe infections (abdominal cavity infections, including peritonitis, febrile episodes in patients with deficient defenses against infections (neutropenia)).

Children from 1month of age to 40kg body weight (around 12years):

A dose of 50 mg/kg body weight in the case of children from 2 months to 12 years of age or a dose of 30 mg/kg body weight in the case of children from 1 to 2 months of age, which is equivalent to a dose of 2 g in adults.

Therefore, the same prolongation of the dose interval or reduction of the dose as in adults is recommended, according to the following tables.

Children from 2months of age to 40kg body weight (around 12years):

Infants from 1-2months:

Method of administration:

These solutions can be administered by slow intravenous injection (3-5 minutes) with a syringe or by intravenous infusion.

If you desire more information, consult the section This information is intended only for healthcare professionalsat the end of this package leaflet.

If you use more CefepimaQilu than you should

Contact your doctor or other healthcare professionals immediately, as you may experience more severe side effects in certain situations.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 915 620 420, indicating the medication and the amount ingested.

If you forget to use CefepimaQilu

Inform your doctor immediately.

If you stop treatment with Cefepima Qilu

If you stop receiving Cefepima Qilu too early, the underlying disease you are suffering from may worsen.

If you have any further questions about the use of this medication, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

In the event that you suffer from the following serious adverse events, inform your doctor immediately:

• severe allergic reaction, associated with sudden and progressive difficulty breathing, swelling of the head and body area, skin rash, circulatory disorders, drop in blood pressure
• sudden appearance of severe rash, blisters, or skin peeling, accompanied by fever (Stevens-Johnson syndrome)
• persistent diarrhea of mild to severe degree, accompanied by abdominal pain and fever, which can occur during treatment with antibiotics or up to two months after
• altered consciousness, accompanied by confusion, hallucinations, physical stiffness, loss of consciousness, muscle spasms, and convulsions

Very Common(may affect more than 1 in 10 people)

• positive result in the Coombs test (a method for determining antibodies)

Common(may affect up to 1 in 10 people)

• prolonged blood coagulation time (prolongation of prothrombin time and partial thromboplastin time)
• anemia
• increase in the count of certain blood cells (eosinophilia)
• inflammation of the blood vessel walls at the perfusion site
• diarrhea
• rash
• irritation at the perfusion site
• pain and inflammation at the injection site
• increase in certain blood values (alanine aminotransferase, aspartate aminotransferase, bilirubin, alkaline phosphatase)

Uncommon(may affect up to 1 in 100 people)

• fungal infection in the mouth, accompanied by white deposits
• vaginal inflammation
• reduction in the number of certain blood cells (thrombocytopenia, leukopenia, neutropenia)
• headache
• inflammation of the colon, accompanied by abdominal pain (colitis)
• nausea
• vomiting
• skin redness (erythema)
• hives (urticaria)
• itching of the skin
• increase in blood urea nitrogen
• increase in serum creatinine
• fever
• inflammation at the perfusion site

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

• non-specific fungal infection
• allergic reaction, convulsions (crisis)
• rare sensations in the skin, such as tingling or numbness (paresthesia)
• taste disorders
• dizziness
• dilation of blood vessels
• breathing difficulties
• abdominal pain
• constipation
• fluid accumulation in tissues (edema)
• joint pain
• itching in the genital area
• chills
• ringing in the ears (tinnitus)

Frequency Not Known(cannot be estimated from available data)

• decrease in certain blood cells (aplastic anemia), increase in red blood cell breakdown (hemolytic anemia)
• agranulocytosis (low white blood cell count), resulting in an increased risk of bleeding, bruising, and infection
• swelling (angioedema)
• false positive glucose in urine
• confusion
• hallucinations
• coma
• torpor
• non-inflammatory brain disease (encephalopathy)
• altered awareness
• muscle twitching
• bleeding
• gastrointestinal disorders
• death of skin cells (toxic epidermal necrolysis)
• inflammatory skin redness (erythema multiforme)
• kidney failure
• toxic kidney disease (nephropathy)

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Cefepima Qilu

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the box and vial after "CAD". The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C. Store in the original packaging to protect it from light.

Reconstituted Solution

Physical and chemical stability has been demonstrated for 2 hours at a temperature of 25°C and for 6 hours at 2-8°C.

From a microbiological point of view, the drug should be used immediately, unless the opening and reconstitution method avoids the risk of microbiological contamination.

If not used immediately, the observation of time and storage conditions during use is the responsibility of the healthcare professional responsible for treatment.

Diluted Solution

Physical and chemical stability has been demonstrated for 2 hours at a temperature of 25°C and for 6 hours at 2-8°C when cefepima is mixed with solutions of amikacin, clindamycin, heparin, potassium chloride, theophylline, for peritoneal dialysis, and parenteral nutrition.

From a microbiological point of view, the drug should be used immediately, unless the opening and reconstitution method avoids the risk of microbiological contamination.

If not used immediately, the observation of time and storage conditions during use is the responsibility of the healthcare professional responsible for treatment.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines that are no longer needed at the SIGRE point in the pharmacy or in any other system for collecting medicinal waste. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Cefepima Qilu

The active ingredient is cefepima.

Each vial of Cefepima Qilu 2g contains 2g of cefepima (in the form of cefepima dihydrochloride monohydrate).

The other components are: arginine.

Appearance of Cefepima Qilu and Package Contents

Cefepima Qilu is a powder for solution for injection and infusion, white to light yellow in color. Cefepima Qilu is presented in packs of 1, 10, and 50 glass vials, closed with a butyl rubber stopper coated with a 20mm film and sealed with a combined aluminum and plastic cap.

Marketing Authorization Holder

QILU PHARMA SPAIN S.L.

Paseo de la Castellana 40,

8th floor, 28046-Madrid,

Spain

Local Representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya, 53-55

08007 – Barcelona, Spain

Manufacturer

KYMOS, S.L.

Ronda de Can Fatjó,

7B (Parque Tecnológico del Vallès),

Cerdanyola del Vallès, 08290

Barcelona, Spain

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road,

Portmarnock, Co. Dublin,

Ireland

Tillomed Malta Ltd.

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000,

Malta

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

Date of Last Revision of this Prospectus: October 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

If you want more information about resistance datato cefepima, consult the Technical Data Sheet or Summary of Characteristics of Cefepima Qilu.

Form of administration:

Preparation and administration of the solution ready for use for intravenous (IV) use:

The powder should be dissolved in:

• Water for injectable preparations or with one of the solutions listed below for intravenous use in section b):

• Sodium chloride solution 0.9% (9mg/ml).

Sodium chloride solution 0.9% (9mg/ml) with glucose 5% (50mg/ml).

Glucose solution 5% (50mg/ml) or glucose solution 10% (100mg/ml).

Composite lactate solution.

Composite lactate solution with glucose 5% (50mg/ml).

Sodium lactate solution 1/6M.

The volume of solvent to be added to the corresponding vial and the resulting cefepima concentration are shown in the following table:

These solutions should be used immediately as a slow intravenous injection (3-5 minutes) with a syringe or by intravenous infusion.

Alternatively, it can be added to one of the infusion solutions listed in section b), administered as a brief intravenous infusion over a period of approximately 30 minutes.

Cefepima should not be mixed with other medicines or solutions that are not listed above in sections a) and b).

Compatibility (miscibility):

Simultaneous intravenous administration of cefepima with other antibiotics that are not amikacin and clindamycin (with which compatibility has been demonstrated; see below) is possible, but they should not be administered mixed with cefepima or through the same intravenous line (see section 6.2).

The following table shows which medicines and solutions cefepima is compatible with (can be mixed) and under what conditions the infusion solution can be stored (temperature, period):

Mixtures of cefepima with solutions of amikacin, clindamycin, heparin, potassium chloride, theophylline, peritoneal dialysis, and parenteral nutrition are physically and chemically stable at room temperature (25°C) for 2 hours and in the refrigerator (2-8°C) for 6 hours.

However, regardless of the demonstrated physical and chemical stability, given the possible microbiological contamination of the preparation, the solution in question should be prepared shortly before administration, whenever possible. If not possible, the ready-to-use solution should be stored in the refrigerator (2-8°C) for up to 6 hours.

Information on the use of the ready-to-use solution.

Note:

Solutions ready for use that have been prepared following the instructions may acquire a light yellow to yellow-brown color. This is not a sign of loss of cefepima efficacy.

The contents of a vial are intended for single use. Any remaining solution ready for use should be discarded.

The ready-to-use solution should be visually inspected before administration for any suspended particles. If particles are observed, the solution should not be used.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.