METRONIDAZOL B.BRAUN 5 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Metronidazole B. Braun 5 mg/ml Solution for Infusion

metronidazole

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.

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

Contents of the Package Leaflet:

1. What Metronidazole B. Braun 5 mg/ml is and what it is used for
2. What you need to know before you start using Metronidazole B. Braun 5 mg/ml
3. How to use Metronidazole B. Braun 5 mg/ml
4. Possible side effects
5. Storage of Metronidazole B. Braun 5 mg/ml
6. Contents of the pack and further information

1. What Metronidazole B. Braun 5 mg/ml is and what it is used for

Metronidazole B. Braun 5 mg/ml belongs to a group of medicines known as antibiotics and is used to treat severe infections caused by bacteria that can be eliminated by the active ingredient metronidazole.

Metronidazole B. Braun 5 mg/ml can be administered in adults and children for the treatment of any of the following diseases:

• Infections of the central nervous system such as brain abscesses (infections with pus in the brain), inflammation of the meninges (lining of the brain).
• Infections of the lungs and lung lining, such as pneumonia accompanied by tissue destruction, pneumonia after stomach contents enter the lungs, lung abscesses.
• Infections of the gastrointestinal tract, such as inflammation of the inner lining of the abdomen and pelvic walls, liver abscesses, surgery of the large intestine or rectum, infections with pus in the abdomen and pelvis.
• Infections of the female genital organs, such as inflammation inside the uterus, after uterus removal, cesarean section, spontaneous abortion accompanied by blood poisoning (sepsis), puerperal fever.
• Infections of the ear, nose, and throat, and of the teeth, jaw, and mouth, such as Vincent's angina.
• Inflammation of the inner lining of the heart.
• Bone and joint infections, such as inflammation of the bone marrow.
• Gas gangrene.
• Blood poisoning due to blood clots and inflamed veins.

Your treatment may be complemented with other antibiotics if necessary.

Metronidazole B. Braun 5 mg/ml may be administered as a preventive measure before operations associated with a higher risk of infection with so-called anaerobic bacteria, mainly in gynecology or stomach and intestine surgery.

2. What you need to know before you start using Metronidazole B. Braun 5 mg/ml

Do not use Metronidazole B. Braun 5 mg/ml

• If you are allergic to metronidazole or to other similar substances or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor before receiving Metronidazole B. Braun 5 mg/ml.

Be particularly careful with Metronidazole B. Braun 5 mg/ml if you have:

• Severe liver dysfunction.
• Blood formation disorders.
• Brain, spinal cord, or nerve disease.

Your doctor will carefully determine if you should be treated with Metronidazole B. Braun 5 mg/ml.

If during treatment you experience seizures or any other nervous disorder (such as numbness in the limbs), the continuation of treatment will be reviewed.

Treatment with Metronidazole B. Braun 5 mg/ml should not exceed 10 days; the treatment period will only be extended in exceptional circumstances and if absolutely necessary. Repeated treatment with metronidazole will be limited to cases where it is absolutely necessary. In such cases, you will be closely monitored.

Especially with prolonged treatment with metronidazole or if you have immunosuppression, an imbalance of the intestinal flora may occur. Treatment should be interrupted or reviewed immediately if you have severe diarrhea that may be due to a disease called "pseudomembranous colitis" (see also section 4).

There have been reports of severe liver toxicity/acute liver failure, some of which were fatal, in patients with Cockayne syndrome taking metronidazole-containing medications.

If you have Cockayne syndrome, your doctor should frequently monitor your liver function while you are receiving treatment with metronidazole and thereafter.

Tell your doctor immediately and stop taking metronidazole if you experience:

• Stomach pain, loss of appetite, nausea, vomiting, fever, general malaise, fatigue, jaundice, dark urine, clay-colored stools, or itching.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported with Metronidazole B. Braun 5 mg/ml. Discontinue use of Metronidazole B. Braun 5 mg/ml and seek immediate medical attention if you notice any symptoms related to these severe skin reactions described in section 4.

Since prolonged use of metronidazole may harm blood formation (see section "Possible side effects"), your blood count will be monitored during treatment.

Other medicines and Metronidazole B. Braun 5 mg/ml:

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

• Medicines that can cause heart rhythm disorders

Tell your doctor if you are taking any medicine that can cause a heart rhythm disorder (called QT interval prolongation, which can be seen on an ECG), such as certain anti-arrhythmics (medicines that treat heart rhythm disorders, e.g., amiodarone) and certain antibiotics (e.g., ciprofloxacin).

Your heart function will be monitored when you receive these medicines. You should consult your doctor if you notice any heart function abnormalities, dizziness, or fainting.

• Barbiturates (active ingredient in sleeping pills):

Phenobarbital may reduce the duration of the effect of metronidazole; the dose of metronidazole should be increased.

• Busulfan:

Metronidazole should not be administered to patients treated with busulfan, as toxic effects are more likely to occur.

• Carbamazepine (medicine for treating epilepsy):

This combination also requires caution, as metronidazole may increase the duration of action of carbamazepine.

• Cyclosporin (medicine used to reduce unwanted immune reactions):

When cyclosporin is administered with metronidazole, cyclosporin blood levels may increase; therefore, your doctor will adjust the dose of cyclosporin as necessary.

• Cimetidine (medicine for treating stomach disorders):

Cimetidine may reduce the elimination of metronidazole in isolated cases and subsequently lead to an increase in metronidazole blood concentrations.

• Coumarin derivatives (medicines that inhibit blood coagulation):

Metronidazole may increase the inhibition of blood coagulation caused by coumarins. Therefore, if you are taking a medicine that inhibits blood coagulation (e.g., warfarin), you may need to reduce the dose during treatment with metronidazole.

• Disulfiram (used in the treatment of alcohol dependence):

If you are taking disulfiram, you should not be given metronidazole, or you should discontinue treatment with disulfiram. The combined use of these two medicines can lead to confusion and even severe mental disorders (psychosis).

• Fluorouracil (anticancer medicine):

The daily dose of fluorouracil may need to be reduced when administered with metronidazole, as it may lead to an increase in fluorouracil blood levels.

• Lithium (used to treat mental illnesses):

Treatment with lithium preparations requires particularly close monitoring during treatment with metronidazole and may need to be adjusted. Lithium treatment should be reduced or discontinued before administration of metronidazole.

• Myphenolate mofetil (used to prevent organ rejection after transplantation):

Its effect may be reduced by metronidazole; careful monitoring of its effect is recommended.

• Phenytoin (medicine for treating epilepsy);

If you are taking phenytoin, your doctor will treat you with metronidazole with caution, as it may increase the duration of action of phenytoin. On the other hand, phenytoin may reduce the effect of metronidazole.

• Tacrolimus (medicine used to reduce unwanted immune reactions):

The blood levels of this medicine and its renal function should be monitored when starting and stopping treatment with metronidazole.

Using Metronidazole B. Braun 5 mg/ml with alcohol

You should not consume any alcoholic beverages while being treated with metronidazole, as this may cause intolerance reactions such as dizziness and vomiting.

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.

Pregnancy

If you are pregnant, your doctor will only treat you with metronidazole if it is absolutely necessary.

Breastfeeding

Breastfeeding should be discontinued during treatment with metronidazole. Once treatment with metronidazole is completed, breastfeeding should not be resumed before 2-3 days, as metronidazole passes into breast milk.

Fertility

Animal studies only indicate a possible negative influence of metronidazole on the male reproductive system if high doses are administered that are far above the maximum recommended dose for humans.

Driving and using machines

You should not drive or use machines while being treated with metronidazole, as it may affect your alertness. This is especially true at the beginning of treatment or if you have consumed alcohol.

Metronidazole B. Braun 5 mg/ml contains sodium:

This medicine contains 322 mg of sodium (main component of table salt/cooking salt) per 100 ml. This is equivalent to 16% of the maximum recommended daily sodium intake for an adult.

3. How to use Metronidazole B. Braun 5 mg/ml

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

The dose depends on the nature and severity of the disease, age, body weight, and individual response to treatment.

The recommended dose in adults and adolescents (over 12 years) is:

Treatment of infections

500 mg (100 ml) every 8 hours.

Alternatively, a single dose of 1500 mg (300 ml) may be administered on the first day of treatment, followed by single doses of 1000 mg (200 ml) on subsequent days. At the beginning of your treatment, your doctor may give you a higher initial dose of metronidazole.

In most cases, a 7-10 day treatment is sufficient. If clinically indicated, treatment may continue beyond this duration. The duration of therapy with metronidazole should not exceed 10 days. The maximum daily dose will not exceed 1500 mg/day.

The dose will be the same for patients with kidney disease.

For patients with liver disease, lower doses may be necessary.

If you are being treated with a kidney machine (dialysis), your doctor will adjust the dose on the days of your treatment.

Prevention of infections that may occur after surgery

When used for infection prevention in surgery, you will be administered 500 mg before surgery. The dose will be repeated after 8 and 16 hours of surgery.

Use in children:

Dosage in children is based on body weight.

Treatment of infections:

• Children over 8 weeks and up to 12 years:20-30 mg per kg of body weight per day as a single dose or 7.5 mg per kg of body weight every 8 hours. The daily dose may be increased to 40 mg per kg of body weight, depending on the severity of the infection.

• Children under 8 weeks:15 mg per kg of body weight as a single dose or 7.5 mg per kg of body weight every 12 hours.

• Newborns with a gestational age under 40 weeks:Since metronidazole may accumulate during the first week of life, metronidazole blood concentrations should be preferably monitored after a few days of treatment.

The duration of treatment is usually 7-10 days.

Prevention of infections that may occur after surgery:

• Children under 12 years:20-30 mg per kg of body weight as a single dose administered 1-2 hours before surgery.

• Newborns with a gestational age under 40 weeks:10 mg per kg of body weight as a single dose before surgery.

Method of administration

Metronidazole B. Braun 5 mg/ml is administered intravenously. The infusion of a vial usually lasts 60 minutes, but should not be done in less than 20 minutes.

This medicine may be diluted in a suitable vehicle solution for infusion.

If you are receiving other antibiotics simultaneously, your doctor will give you those medicines separately.

If you use more Metronidazole B. Braun 5 mg/ml than you should:

As signs and symptoms of overdose may appear, the undesirable effects described in section 4 "Possible side effects" may occur.

There is no specific antidote or symptomatic treatment for a massive overdose, but metronidazole can be eliminated from the body through dialysis (i.e., treatment with a kidney machine).

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone 915 620 420, indicating the product and the amount administered.

4. Possible Adverse Effects

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

Adverse reactions are mainly related to the dose and duration of treatment, so they usually disappear when the dose is decreased or therapy is interrupted.

Stop using Metronidazol B. Braun 5 mg/ml and seek immediate medical attention if you notice any of the following symptoms:

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

• Persistent severe diarrhea (possibly a symptom of a severe intestinal infection called pseudomembranous colitis).
• Severe acute hypersensitivity reactions up to anaphylactic shock.

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

• Decrease in white blood cell and platelet counts during treatment (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia).
• Hepatitis (inflammation of the liver), jaundice, pancreas inflammation.
• Cerebral disorders, lack of coordination.

Frequency not known (cannot be estimated from available data)

• Reduction in white blood cell count (leukopenia), severe anemia (aplastic anemia).
• Hypersensitivity reactions from mild to moderate, swelling of the face, mouth, throat, and/or tongue (angioedema).
• Deviation of gaze, damage or inflammation of the eye nerves.
• Seizures, nervous disorders such as numbness, pain, sensation of fur or tingling in the arms or legs.
• Non-bacterial cerebral fever (aseptic meningitis).
• Acute liver failure in patients with Cockayne syndrome (see section 2 "Warnings and precautions").
• Hearing impairment, hearing loss.
• Ringing in the ears (tinnitus).
• Skin rash, blisters, fever, or other signs and symptoms of hypersensitivity reactions.
• Reddish patches, not elevated, in a target or circular shape on the trunk, often with central blisters, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and pseudo-flu symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized skin rash, elevated body temperature, and enlargement of lymph nodes (DRESS or drug hypersensitivity syndrome).
• Red, scaly, and generalized skin rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the start of treatment (acute generalized exanthematous pustulosis).

Other Adverse Effects

Frequent (may affect up to 1 in 100 people)

• Fungal and bacterial superinfections

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

• Dark urine (caused by metronidazole metabolites).

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

• Changes in the electrocardiogram (ECG).

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

• Psychotic disorders, including confusion, hallucinations.

• Headache, dizziness, drowsiness, fever, alteration of vision and movement, staggering, speech defects, seizures.
• Visual disturbances, e.g., double vision, myopia.
• Liver function disorders (such as elevated serum levels of certain enzymes and bilirubin).
• Pain in joints and muscles.

Frequency not known (cannot be estimated from available data)

• Anorexia.
• Sad mood (depression).
• Drowsiness or insomnia, muscle spasms.
• Nausea, feeling of discomfort, diarrhea, inflammation of the tongue or mouth, belching, and bitter taste, metallic taste, pressure above the stomach, hairy tongue, difficulty swallowing.
• Redness and itching of the skin (erythema multiforme).
• Irritation of the venous wall (up to the point of vein inflammation and thrombosis) after intravenous administration, state of weakness, fever.

Emergency Treatment of Pseudomembranous Colitis

In case of persistent severe diarrhea, you should immediately inform your doctor because this may be due to pseudomembranous colitis, a serious disease that must be treated immediately. Your doctor will interrupt treatment with metronidazole and provide you with appropriate treatment. If you consider that any of the adverse effects you are suffering from is serious or if you notice any adverse effect not mentioned in this prospectus, please inform your doctor.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them 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 Metronidazol B. Braun 5 mg/ml

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

Do not use this medicine after the expiration date that appears on the packaging and carton. The expiration date is the last day of the month indicated.

Keep it in its outer packaging to protect it from light.

This medicine is intended for single use. Discard unused portions.

From a microbiological point of view, dilutions should be used immediately. If not used immediately, the storage times in use and the conditions prior to use are the responsibility of the user and will normally not exceed 24 hours at a temperature of 2 to 8°C, unless the dilution has been made in controlled and validated aseptic conditions.

It should only be used if the solution is clear and has no visible particles and if the container and its closure do not show visible signs of damage.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Metronidazol B. Braun 5 mg/ml

• The active principle is metronidazole.

1 ml of Metronidazol B. Braun 5 mg/ml solution for infusion contains 5 mg of metronidazole.

A 100 ml polyethylene bottle contains 500 mg of metronidazole. A 300 ml polyethylene bottle contains 1500 mg of metronidazole.

• The other components are sodium chloride, disodium phosphate dodecahydrate, citric acid monohydrate, and water for injection.

Appearance of the Product and Package Contents

Metronidazol B. Braun 5 mg/ml is a clear, colorless or slightly yellowish aqueous solution.

Metronidazol B. Braun 5 mg/ml is presented in polyethylene bottles (Ecoflac Plus) containing 100 and 300 ml, in a single unit package and clinical package of 20 units.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

• Braun Medical, S.A.

Ctra. Terrassa, 121 Rubí

08191 Barcelona (Spain)

Date of the Last Revision of this Prospectus:03/2025

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.es/

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This information is intended only for healthcare professionals:

Intravenous use.

The contents of a vial should be infused slowly intravenously, i.e., 100 ml at most, over no less than 20 minutes, but normally more than one hour.

Metronidazol B. Braun 5 mg/ml can also be diluted before administration by adding the medicine to an intravenous vehicle solution such as 0.9% sodium chloride or a 5% glucose infusion solution.

For single use. Discard the package and any unused contents after use.

It should only be used if the solution is clear and colorless or slightly yellowish and if the container and its closure do not show visible signs of damage.

In patients with severe liver damage or hematopoietic disorders (such as granulocytopenia), metronidazole should only be administered if the expected benefits clearly outweigh the possible risks.

Due to the risk of worsening, metronidazole should be used in patients with severe, active, or chronic diseases of the peripheral and central nervous system only if the expected benefits clearly outweigh the possible risks.

Seizures, myoclonus, and peripheral neuropathy have been reported in patients treated with metronidazole, the latter characterized mainly by numbness or paresthesia of a limb. The appearance of abnormal neurological signs requires prompt evaluation of the benefit/risk ratio of continuing treatment.

In case of severe hypersensitivity reactions (such as anaphylactic shock), treatment with Metronidazol B. Braun 5 mg/ml should be immediately interrupted and emergency treatment should be established by healthcare professionals.