ZEPILEN 1G POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

2. What you need to know before you use Zepilen

Do not use Zepilen:

• if you are allergic to cefazolin, other cephalosporins, or any of the other ingredients of this medicine (including those in section 6).
• 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 a lidocaine solution for administration to children under 1 year of age.

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 medicines, you may also be allergic to cefazolin. Treatment with this medicine should be discontinued if an allergic reaction occurs, and the allergic reaction should be treated and kidney function checked.
• In the event of an allergic reaction due to cefazolin, the administration of the product will be discontinued. Your doctor will propose an alternative treatment.
• If you are given the maximum dose and are severely ill or are taking other medicines that can be harmful to the kidneys (aminoglycosides or strong diuretics), your doctor will check your kidney function and adjust the dose if necessary.
• If you are administered cefazolin for a prolonged period, your doctor will check that non-susceptible bacteria do not grow out of control.
• In some cases, blood coagulation disorders may occur during treatment with cefazolin. This risk is especially present if you have risk factors that cause a deficiency of vitamin K or risk factors that influence other blood coagulation mechanisms. 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 severe diarrhea after treatment with cefazolin, caused by inflammation of the small and large intestine that damages the mucous membranes (pseudomembranous colitis).

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

Children and adolescents

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

Using Zepilen with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Contraindicated combinations

• If you are taking certain antibiotics (bacteriostatic agents) such as tetracyclines and macrolides at the same time, they may counteract the effect of cefazolin, making cefazolin less effective.

Not recommended combinations

• Taking probenecid at the same time (for a metabolic disorder) may inhibit the excretion of cefazolin by the kidney.

Use with caution

• If you use vitamin K1, cefazolin may cause an increase in vitamin K1 concentrations.
• Cephalosporins can rarely cause blood coagulation disorders. When administered together with anticoagulant medicines (oral anticoagulants or heparin) in high doses, coagulation values should be monitored.
• If you take medicines that have a nephrotoxic effect (toxic to the kidneys), such as certain antibiotics (aminoglycosides, polymyxin B) and certain diuretics (furosemide), kidney 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, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

There is not enough data on the use of cefazolin during pregnancy in humans to assess potential harm.

Zepilen should not be taken during pregnancy without the recommendation of a doctor.

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

Driving and using machines

No studies have been conducted on the effects on the ability to drive and use machines.

There is no data on the effects of cefazolin on the ability to drive or use machines. However, it is unlikely that you will experience effects.

Zepilen contains sodium

This medicine contains 50.6 mg of sodium (a principal ingredient in cooking/salt) in each vial, which is equivalent to 2.53% of the maximum daily recommended sodium intake in an adult's diet.

3. How to use Zepilen

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

A qualified person, such as a doctor or nurse, will administer this medicine to you.

The recommended dose is:

Adults

• Infections caused by highly susceptible bacteria: 1 g to 2 g per day in two or three equal doses.
• Infections caused by less susceptible bacteria: 3 g to 4 g per day in three or four equal doses. If necessary, in cases of very severe infections, the total daily dose can be increased up to 6 g per day.
• As a precaution against the onset of infections:

• before an operation: 1 g administered 30 minutes to 1 hour before the start of surgery;
• during an operation: 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 an operation: 500 mg to 1 g administered every 6 to 8 hours for 24 hours.

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

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

Use in children and adolescents

Premature and newborn infants

Safety has not been determined in children under 1 month.

Infants

The doctor will determine the dose based on the child's body weight. The daily dose for children may 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.

Elderly people

No dose adjustment is necessary in elderly patients with normal kidney function.

Duration of treatment

The duration of treatment depends on the development of the disease. In accordance with the general principle of antibiotic treatment, treatment with cefazolin should continue for at least 2 to 3 days after the fever has disappeared 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 (convulsions), especially in patients with impaired kidney function. In that case, treatment with cefazolin should be discontinued, and appropriate treatment should be administered. Vital functions will be monitored.

If you forget to use Zepilen

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

If you stop using Zepilen

It is essential that you complete the full treatment, even if you feel better before. If you do not eliminate all the bacteria, the symptoms may return.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypersensitivity reactions:

Uncommon side effects (may affect up to 1 in 100 people)

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

Rare side effects (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 looks like a burn (toxic epidermal necrolysis).

Very rare side effects (may affect up to 1 in 10,000 people)

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

Infections and infestations

Uncommon side effects (may affect up to 1 in 100 people)

• Oral thrush (white or creamy deposits in the mouth and on the tongue).

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

• Genital bacterial infection with symptoms such as itching, redness, swelling, and discharge (genital candidiasis, moniliasis, vaginitis).

Blood and lymphatic system disorders

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

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

Hepatobiliary disorders

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

• Transient liver inflammation (hepatitis), transient jaundice (cholestatic jaundice).

Nervous system disorders

Uncommon side effects (may affect up to 1 in 100 people)

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

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

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

Gastrointestinal disorders

Common side effects (may affect up to 1 in 10 people)

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

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

You should avoid using self-medication that suppresses the contraction of the stomach and intestinal muscles (peristalsis).

Renal and urinary disorders

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

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

General disorders and administration site conditions

Common side effects (may affect up to 1 in 10 people)

• Pain at the injection site, sometimes with induration

Uncommon side effects (may affect up to 1 in 100 people)

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

Other side effects

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

In rare cases, the following have been reported for some cephalosporins:

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

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zepilen

Keep this medicine 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 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 and normally should not exceed 24 hours at 2°C - 8°C, unless the reconstitution has been performed under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date which is stated on the label, after EXP. The expiry date is the last day of the month indicated.

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. Container Contents and Additional Information

Zepilen Composition

• 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.

Product Appearance and Container Contents

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

Type I colorless glass vials with a nominal capacity of 10 ml, sealed with a bromobutyl stopper and an aluminum cap.

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Medochemie Ltd.

1-10 Constantinoupoleos Street

3011 Limassol

Cyprus

Manufacturer

Medochemie Limited (Factory C)

2 Michael Erakleous street, Agios Athanassios, Industrial Area,

4101 Agios Athanassios,

Limassol, Cyprus

For further information about this medicinal product, please contact the local representative of the Marketing Authorization 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 authorized in the EEA Member States under the following names:

Date of last revision of this leaflet: October 2021

Detailed information on this medicinal product 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:

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 must not be mixed with any other injection/infusion liquid other than that 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, and tetracyclines.

Reconstitution Instructions

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

Intramuscular Administration

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

Intravenous Injection

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

Intravenous Infusion

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

• sodium chloride 0.9%;
• sodium chloride 0.9% and dextrose 5%;
• Ringer's Lactate solution.

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 during use for 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 normally should not exceed 24 hours at 2°C - 8°C, unless the reconstitution has been carried out under controlled and validated aseptic conditions.