Leaflet: Information for the User

Zepilen 1g powder for injectable solution and for EFG infusion

Cefazolina (as cefazolina sodium)

Read this leaflet carefully before starting to use this medicine,because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• 1. If you have any doubts, consult yourdoctor,pharmacistor nurse.

-This medicine has been prescribedonlyfor you, and you must not give it to others even if they havethe same symptomsas you, as it may harm them.

• If you experience any side effects,consult your doctor, pharmacist or nurse,evenif they are not listed in this leaflet. See section 4.

1.What is Zepilen and what it is used for

2.What you need to knowbeforestarting touse Zepilen

3.How to use Zepilen

4.Possible side effects

5Storage of Zepilen

6.Contents of the pack and additional information

Zepilen is a powder for the preparation of an injectable solution that contains the active ingredient cefazolin (as cefazolin sodium).

Cefazolin is an antibiotic medication and belongs to a group of medications called cephalosporins. Zepilen treats certain infections.

Zepilen is used to treat the following infections:

• Skin and soft tissue infections
• Bone and joint infections
• Infections caused by, or as a precaution against the development of an infection before, during, or after surgery.

Do not use Zepilen:

• if you are allergic to cefazolin, other cephalosporins, or any of the other components of this medication (including those in section6).
• if you have had an immediate and/or severe allergic reaction to penicillin or another type of beta-lactam antibiotic.
• Cefazolin should not be dissolved in lidocaine solution for administration to children under 1 year.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Zepilen:

• If you have a history of allergic reactions to penicillins or other medications, you may also be allergic to cefazolin. Treatment with this medication should be interrupted if an allergic reaction occurs, the allergic reaction should be treated, and renal function should be checked.
• In the case of an allergic reaction due to cefazolin, administration of the product will be interrupted. Your doctor will propose an alternative treatment.
• If you are administered the maximum dose and are severely ill or taking other medications that can be harmful to the kidneys (aminoglycosides or strong diuretics), your doctor will check your renal function and adjust the dose if necessary.
• If cefazolin is administered for a prolonged period, your doctor will check that non-susceptible bacteria do not grow uncontrollably.
• In some cases, bleeding disorders may occur during treatment with cefazolin. This risk is especially present if you have risk factors that cause vitamin K deficiency or risk factors that affect other mechanisms of blood coagulation. Additionally, blood coagulation may be affected in patients with disorders that cause or exacerbate bleeding, such as hemophilia, stomach and intestinal ulcers. In these cases, your blood coagulation will be monitored.
• You may experience persistent and severe diarrhea after treatment with cefazolin, caused by inflammation of the small and large intestine that causes damage to the mucous membranes (pseudomembranous colitis).

Consult your doctor if any of the above warnings apply to you or if they have applied to you in the past.

Children and adolescents

Cefazolin should not be used in neonates (newborns and children under 1 month), as the safety of use has not been established in this group.

Use of Zepilen with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Contraindicated combinations

• If you are taking antibiotics from certain groups (bacteriostatic agents) simultaneously, such as tetracyclines and macrolides, these may counteract the effect of cefazolin, making cefazolin less effective.

Not recommended combinations

• Simultaneous use of probenecid (for a metabolic disorder) may inhibit the excretion of cefazolin by the kidneys.

Use with caution

• If you are taking vitamin K1, cefazolin may cause an increase in vitamin K1 concentrations.
• Cephalosporins rarely may cause blood coagulation disorders. When administered together with anticoagulant medications (oral anticoagulants or heparin) in high doses, coagulation values should be monitored.
• If you take medications that have a nephrotoxic effect (toxic to the kidneys), such as certain antibiotics (aminoglycosides, polymyxin B) and certain diuretics (furosemide), renal function should be monitored during concomitant use.
• Cefazolin may have an adverse effect on the effectiveness of hormonal contraceptives. Therefore, it is recommended to use non-hormonal supplementary contraceptives.

Pregnancy, breastfeeding, and fertility

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

There are not enough data on the use of cefazolin during human pregnancy to evaluate the possible harm.

Zepilen should not be taken during pregnancy without a doctor's recommendation.

Cefazolin is excreted in breast milk in low concentrations, but it is not expected to affect breastfed infants. If you are pregnant or breastfeeding, your doctor will decide if cefazolin is suitable for you.

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive and operate machinery.

There are no data on the effects of cefazolin on the ability to drive or operate machinery. However, it is unlikely that effects will occur.

Zepilen contains sodium

This medication contains 50.6 mg of sodium (main component in cooking/salt) in each vial, which is equivalent to 2.53% of the maximum daily recommended sodium intake in an adult diet.

Follow exactly the administration instructions of this medication as indicated by your doctor.In case of doubt, consult your doctor or pharmacist again.

This medication will be administered by a qualified person, such as a doctor or nurse.

The recommended dose is:

Adults

• Before surgery: 1 g administered 30 minutes to 1 hour before the start of surgery;
• During surgery: for a prolonged operation (e.g., 2 hours or more), 500 mg to 1 g will be administered with a duration depending on the duration of the operation;
• After surgery: between 500 mg and 1 g administered every 6 to 8 hours for 24 hours.

A lower dose may be necessary in adults with impaired renal function.

The dose is determined based on blood levels or renal function values.

Use in children and adolescents

Preterm and Neonates

Safety has not been determined in children under one month.

Infants

The doctor will determine the dose based on the child's body weight. The daily dose for children can range from 25 to 50 mg per kilogram of body weight. Depending on the severity of the infection, this dose can be increased to 100 mg per kilogram of body weight.

Older adults

No dose adjustment is necessary in patients with normal renal function.

Treatment duration

The treatment duration depends on how the disease develops. In accordance with the general principle of antibiotic treatment, cefazolin treatment should continue for at least 2 to 3 days after the fever has subsided or until it is demonstrated that the cause has been controlled.

If you use more Zepilen than you should

If you have been administered too much Zepilen, contact your doctor immediately. High doses of cefazolin can cause seizures, especially in patients with impaired renal function. In this case, cefazolin treatment should be discontinued and appropriate treatment should be administered. Vital functions will be checked.

If you forget to use Zepilen

If you think you have not received a dose of cefazolin, inform your doctor immediately.

If you interrupt Zepilen treatment

It is essential to complete a full treatment, even if you feel better before. If not all bacteria are eliminated, symptoms may return.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Reactions of hypersensitivity:

Side effectsinfrequent(may affect up to 1 in 100people)

• Redness of the skin (erythema), generalized skin rash (erythema multiforme or exanthema), urticaria (papulovesicular skin rash with pruritus) on the skin surface (urticaria), fever, swelling under the skin (angioedema) and/or lung tissue swelling possibly with cough and breathing difficulties (interstitial pneumonia or pneumonitis).

Side effectsrare(may affect up to 1 in 1,000 people)

• Severe skin rash with redness, fever, blisters or ulcers (Stevens-Johnson syndrome) or severe rash with redness, peeling, and swelling of the skin that appears like a burn (toxic epidermal necrolysis).

Side effectsveryrare(may affect up to 1 in 10,000 people)

• Anal pruritus (pruritus anal), genital pruritus (pruritus genital), a severe allergic reaction (anaphylactic shock) with difficulty breathing, swelling of the throat, face, eyelids, or lips, increased heart rate, drop in blood pressure, decrease in consciousness.

Infections and infestations

Side effectsinfrequent(may affect up to 1 in 100people)

• Oral thrush (thick white or cream-colored deposits in the mouth and tongue).

Side effectsrare(may affect up to 1 in 1,000 people)

• Genital bacterial infection in males or females with symptoms such as pruritus, redness, swelling, and vaginal discharge (genital candidiasis, moniliasis, vaginitis).

Blood and lymphatic system disorders

Side effectsrare(may affect up to 1 in 1,000 people)

• Reversible abnormalities in the blood, including a reduction or increase in the number of red and white blood cells (leucopenia, granulocytopenia, neutropenia, thrombocytopenia, leucocytosis, granulocytosis, monocytosis, lymphocytopenia, basophilia, and eosinophilia) that may cause bleeding, easy bruising, and/or skin discoloration (confirmed by blood tests). These effects are reversible.

Hepatobiliary disorders

Side effectsrare(may affect up to 1 in 1,000 people)

• Transient liver inflammation (hepatitis), transient jaundice (icterus colestásica).

Nervous system disorders

Side effectsinfrequent(may affect up to 1 in 100people)

• Seizures/convulsions in patients with renal problems who have been treated with high, inadequate doses.

Side effectsrare(may affect up to 1 in 1,000 people)

• Dizziness, fatigue, and a general feeling of malaise. These symptoms often disappear during or after treatment.

Gastrointestinal disorders

Side effectscommon(may affect up to 1 in 10people)

• Mild gastrointestinal disturbances (loss of appetite, diarrhea, nausea, vomiting, severe and frequent diarrhea). These side effects usually disappear after a few days.

In the case of severe and frequent diarrhea during or after treatment with cefazolin, consult a doctor. Sometimes, diarrhea may indicate a more serious condition (pseudomembranous colitis) that needs immediate treatment.

It is recommended to avoid the patient using self-medication that suppresses the contraction of the stomach and intestinal muscles (peristalsis).

Renal and urinary disorders

Side effectsrare(may affect up to 1 in 1,000 people)

• Temporary increase in a certain value of renal function (urea nitrogen in blood), loss of proteins through urine (proteinuria), inflammation of the kidneys accompanied by blood in the urine, fever, and flank pain (interstitial nephritis), undefined renal diseases (nephropathies), kidney poisoning (nephrotoxicity), usually in patients treated concomitantly with other potentially nephrotoxic drugs.

General disorders and administration site conditions

Side effectscommon(may affect up to 1 in 10people)

• Pain at the site of intramuscular injection, sometimes with induration

Side effectsinfrequent(may affect up to 1 in 100people)

• Intravenous administration may cause venous inflammation with the formation of a blood clot, often as a hard thread under a red skin (thrombophlebitis).

Other side effects

• Other adverse reactions reported during treatment with cephalosporin are chest pain, difficulty breathing (pleural effusion, dyspnea), chest tightness, cough, nasal mucosa inflammation (rhinitis), increase or decrease in blood glucose concentration.

In rare cases, some cephalosporins have been reported:

• Decrease in hemoglobin and/or hematocrit level (blood volume), anemia, severe blood disorder (agranulocytosis) accompanied by high fever, sore throat, and mouth sores, anemia due to lack of red blood cell production (aplastic anemia), reduction of all types of blood cells (pancytopenia), anemia due to excessive blood degradation (hemolytic anemia).

The following cases have been reported during treatment with certain cephalosporins:

• Bad dreams, dizziness (vertigo), hyperactivity, nervousness (anxiety) or anxiety, insomnia, somnolence, weakness, hot flashes, altered color vision, confusion, seizure activity (epileptogenic activity).

Reporting of side effects

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

Keep this medication out of the sight and reach of children.

Store at a temperature below 25 °C.

The reconstituted solution should preferably be used immediately. Physical and chemical stability has been demonstrated during use for 24 hours at 2°C - 8°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C, unless reconstitution was performed under controlled and validated aseptic conditions.

Do not use this medication after the expiration date appearing on the label,afterCAD. The expiration dateis the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need.This will help protect the environment.

Composition of Zepilen

• The active ingredient is cefazolin as cefazolin sodium. Each vial contains 1 g of cefazolin in the form of cefazolin sodium.
• The medicine does not contain excipients.

Appearance of the product and contents of the package

White or almost white, very hygroscopic powder for injectable solution or infusion.

Colourless type I glass vials of 10 ml nominal capacity, sealed with a bromobutyl stopper and an aluminium cap.

It is presented in packs of 1, 10, 25, 50 or 100 vials.

Only some pack sizes may be marketed.

Marketing authorisation holder and manufacturer responsible

Marketing authorisation holder

Medochemie Ltd.

1-10 Constantinoupoleos Street

3011 Limassol

Cyprus

Manufacturer responsible

Medochemie Limited (Factory C)

2 Michael Erakleous street, Agios Athanassios, Industrial Area,

4101 Agios Athanassios,

Limassol, Cyprus

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

Medochemie Iberia S.A., Branch in Spain

Avenida de las Águilas, nº 2 B; 5th floor, office 6,

28044 Madrid

SPAIN

This medicinal product is authorised in the Member States of the EEA under the following names:

Last update of this leaflet: October 2021

The detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

This leaflet contains practical information on the preparation and/or handling of the medicinal product. Read this leaflet carefully before administering this medicinal product to the patient.

Incompatibilities:

Cefazolin should not be mixed with any other injection/perfusion liquid that is not indicated in the following section.

Cefazolin is incompatible with aminoglycosides, amobarbital-Na, ascorbic acid, bleomycin sulfate, calcium glucoheptonate, calcium gluconate, cimetidine, colistin methanesulfonate-Na, erythromycin glucoheptonate, lidocaine HCl, pentobarbital Na, polymyxin B sulfate, tetracyclines.

Instructions for reconstitution

The reconstitution/dilution of the product will be carried out in aseptic conditions. The solution will be visually inspected for particles and discoloration before administration. The solution should only be used if the solution is clear and free of particles.

Parenteral administration

The vial is reconstituted with 2.5 ml of injection water. Shake well to dissolve completely. The administration is by deep intramuscular injection.

Intravenous injection

The vial is first reconstituted with 2.5 ml of injection water and then diluted with injection water to a volume of 10 ml, until it dissolves completely (never less than 3 minutes) and is injected directly into a vein or into the intravenous infusion line over a period of 5 minutes.

Intravenous infusion

The vial is reconstituted with 2.5 ml of injection water until it dissolves completely and is diluted in 100 ml with one of the following diluents:

Special precautions for storage

This medicinal product does not require special storage conditions.

The reconstituted solution should preferably be used immediately. Physical and chemical stability has been demonstrated for use within 24 hours at 2°C - 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2°C - 8°C, unless the reconstitution was carried out in controlled and validated aseptic conditions.