Metronidazole B. Braun

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Metronidazolo B. Braun 5 mg/ml solution for infusion

Metronidazolo
Please read 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 questions, consult your doctor.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Metronidazolo B. Braun 5 mg/ml belongs to a group of medicines known as antibiotics and is used to treat serious infections caused by bacteria that can be killed by the active substance metronidazolo.
Your doctor may prescribe Metronidazolo B. Braun 5 mg/ml for the treatment of any of the following conditions:
➢ infections of the central nervous system, such as brain abscesses (localized infection with pus) and meningitis (inflammation of the membranes covering the brain);
➢ infections of the lungs and lung lining, such as pneumonia associated with tissue destruction, aspiration pneumonia (pneumonia following inhalation of gastric contents), and lung abscesses;
➢ gastrointestinal tract infections, such as inflammation of the inner lining of the abdominal cavity and pelvic wall, liver abscesses, surgery of the colon or rectum, and abdominal or pelvic infections with pus;
➢ infections of the female reproductive organs, such as endometritis (inflammation inside the uterus), following hysterectomy, caesarean section, spontaneous abortion complicated by sepsis, or puerperal fever;
➢ infections of the ear, nose, throat, and of the teeth, jaw, and mouth, such as gingivitis;
➢ inflammation of the inner lining of the heart (endocarditis);
➢ bone and joint infections, such as osteomyelitis (inflammation of the bone marrow);
➢ gas gangrene;
➢ sepsis caused by thrombosis and inflamed veins.
If necessary, your treatment may be combined with other antibiotics.
Metronidazolo B. Braun 5 mg/ml may also be prescribed as preventive treatment before surgical procedures associated with a high risk of infection from so-called anaerobic bacteria, particularly in gynaecology or gastrointestinal surgery.

2. What you should know before using Metronidazolo B. Braun 5 mg/ml

Do not use Metronidazolo B. Braun 5 mg/ml
➢ if you are allergic to metronidazole, to other similar substances, or to any of the other ingredients of
this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before being administered Metronidazolo B. Braun 5 mg/ml.
Pay particular attention to Metronidazolo B. Braun 5 mg/ml if you have:
➢ severe liver damage;
➢ a blood formation disorder; or
➢ a disease affecting the brain, spinal cord, or nerves.
Therefore, your doctor must carefully evaluate whether you can be treated with Metronidazolo B. Braun 5 mg/ml.
If seizures or other neurological symptoms (e.g. numbness of limbs) occur during treatment, your therapy must be immediately reassessed.
Normally, treatment with Metronidazolo B. Braun 5 mg/ml should not last longer than 10 days; the treatment period will be extended only under exceptional circumstances and if absolutely necessary. Repeated metronidazole therapy will be limited to cases where it is strictly required. In such cases, you will be monitored particularly closely.
Especially during prolonged metronidazole treatment or if you are immunocompromised, an imbalance of intestinal flora may occur.
Treatment must be immediately stopped or reassessed if you develop severe diarrhea, which could be due to a serious intestinal disease called "pseudomembranous colitis" (see also section 4).
Cases of liver toxicity (severe hepatotoxicity/acute liver failure), including fatal outcomes, have been reported with metronidazole-containing medicines in patients with Cockayne syndrome.
If you have Cockayne syndrome, your doctor will frequently monitor your liver function both during and after treatment with metronidazole.
Immediately inform your doctor and stop taking metronidazole if you experience:

• stomach pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, pale or greasy stools of gray-greenish color, 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 in association with Metronidazolo B. Braun 5 mg/ml treatment. Stop taking Metronidazolo B. Braun 5 mg/ml and consult your doctor immediately if you notice any symptoms related to these severe skin reactions, described in section 4. Since prolonged use of metronidazole may impair blood cell formation (see section “Possible side effects”), blood cell counts will be performed during treatment.

Other medicines and Metronidazolo B. Braun 5 mg/ml
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

Medicines that may cause heart rhythm disturbances
Inform your doctor if you are taking medicines that may cause a heart rhythm disorder (so-called QT interval prolongation visible on an electrocardiogram), such as certain antiarrhythmics (medicines used to treat heart rhythm disorders, e.g. amiodarone) and certain antibiotics (e.g. ciprofloxacin).
When taking these medicines, your heart function should be monitored. Consult your doctor if you notice any irregularities in heart function, dizziness, or fainting.

Barbiturates (active ingredient in sleeping pills)
The duration of action of metronidazole is reduced by phenobarbital; therefore, your metronidazole dose may need to be increased.

Busulfan
Metronidazole must not be administered to patients taking busulfan, as it increases the risk of toxic effects.

Carbamazepine (a medicine used to treat epilepsy)
This combination also requires caution, as metronidazole may increase the duration of action of carbamazepine.

Cimetidine (a medicine used to treat stomach disorders)
Cimetidine may reduce the elimination of metronidazole in isolated cases, thereby increasing metronidazole serum concentrations.

Cumarin derivatives (medicines that inhibit blood clotting)
Metronidazole may enhance the anticoagulant effect of cumarins. If you are taking a medicine that prevents blood clotting (e.g. warfarin), it may be necessary to reduce the dose of this medicine during metronidazole treatment.

Cyclosporine (a medicine used to suppress unwanted immune responses)
When cyclosporine is administered together with metronidazole, cyclosporine blood levels may increase; your doctor will therefore need to adjust your cyclosporine dose appropriately.

Disulfiram (used in alcohol detoxification therapy)
If you are taking disulfiram, metronidazole must not be prescribed, or you must discontinue disulfiram. The combined use of these two medicines may cause confusion and may even lead to a severe mental disorder (psychosis).

Fluorouracil (an anticancer medicine)
The daily dose of fluorouracil may need to be reduced when administered concomitantly with metronidazole, as metronidazole may increase fluorouracil blood levels.

Lithium (used in the treatment of mental disorders)
Treatment with lithium-containing preparations requires particularly careful monitoring during metronidazole therapy, and the dose of the lithium preparation may need to be adjusted.

Mycophenolate mofetil (used to prevent organ transplant rejection)
Its effect may be weakened by metronidazole; therefore, close monitoring of this medicine’s effect is recommended.

Phenytoin (a medicine used to treat epilepsy)
If you are taking phenytoin, your doctor will administer metronidazole only with particular caution, as metronidazole may increase the duration of action of phenytoin. On the other hand, phenytoin may reduce the effect of metronidazole.

Tacrolimus (used to suppress unwanted immune responses)
Blood levels of this agent and renal function should be monitored at the beginning and end of metronidazole treatment.

Metronidazolo B. Braun 5 mg/ml and alcohol
Alcohol
Do not drink alcoholic beverages during metronidazole treatment, as this may cause intolerance reactions such as dizziness and vomiting.

Pregnancy, breastfeeding, and fertility
Pregnancy
If you are pregnant, your doctor will not prescribe metronidazole unless it is considered absolutely necessary.

Breastfeeding
You must not breastfeed during treatment with metronidazole and must not resume breastfeeding for the following 2–3 days, as metronidazole passes into breast milk.

Fertility
Animal studies have shown only a potential negative effect of metronidazole on the male reproductive system when high doses, well above the maximum recommended human dose, are administered.

Driving and using machines
Do not drive or operate machinery during treatment with metronidazole, as metronidazole may impair your level of alertness. This is even more likely at the beginning of therapy or if alcohol is consumed.

Metronidazolo B. Braun 5 mg/ml contains sodium
This medicine contains 322 mg of sodium (main component of table salt) per 100 ml. This corresponds to 16% of the maximum daily dietary intake recommended for an adult.

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

Dosing
The dose depends on the nature and severity of your illness, your age and body weight, and your individual response to treatment.
The recommended usual doses are:
Adults and adolescents
Treatment of infections:
On the first day of treatment, you will normally receive 300 ml of the medicinal product (equivalent to 1500 mg of metronidazole).
From the second day of treatment onwards, you will receive 200 ml of the medicinal product (equivalent to 1000 mg of metronidazole) each day.
Alternatively, you may receive 100 ml of the medicinal product (equivalent to 500 mg of metronidazole) every 8 hours.
At the beginning of treatment, your doctor may administer a higher initial dose of metronidazole.
In most cases, treatment will last 7 days. Only in exceptional cases may treatment be prolonged beyond this period.
The dose will be the same for patients with renal disease.
For patients with hepatic disease, lower doses may be required.
If you have undergone dialysis, your doctor will adjust the dosage according to the treatment days.
Prevention of infections after surgery
If used to prevent infections in surgical procedures, you may be given 500 mg of the medicinal product before surgery. This dose will be repeated at 8 and 16 hours after surgery.
Use in children
In children, the dosage is based on body weight.
Treatment of infections:

The treatment usually lasts 7 days.
Prevention of infections that may occur after procedures:

Method of administration and duration of treatment
Metronidazolo B. Braun 5 mg/ml is administered by intravenous infusion.
Infusion of one vial usually takes 60 minutes, but must not be administered within less than 20 minutes.
This medicinal product may be diluted in an appropriate infusion solution.
The total course of treatment with metronidazole is usually 7 days and should not exceed 10 days, unless absolutely necessary (see also "Particular caution with Metronidazolo B. Braun 5 mg/ml").
If you are taking other antibiotics at the same time, your doctor will administer these drugs separately.
If you use more Metronidazolo B. Braun 5 mg/ml than you should
Adverse effects described in the following section may appear as signs or symptoms of overdose.
There is no known specific antidote or specific treatment in case of massive overdose, but metronidazole can be removed from the body by dialysis (treatment with artificial kidney).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Side effects mainly occur following the use of high doses or long-term use.
To describe the frequency of side effects, the following terminology is used:
“Very common”: occurs in more than 1 in 10 treated patients
“Common”: occurs in 1 to 10 in 100 treated patients
“Uncommon”: occurs in 1 to 10 in 1,000 treated patients
“Rare”: occurs in 1 to 10 in 10,000 treated patients
“Very rare”: occurs in less than 1 in 10,000 treated patients
“Not known”: frequency cannot be estimated from the available data

Stop taking Metronidazole B. Braun 5 mg/ml and contact your doctor immediately if you notice any of the following symptoms:

Rare:
➢ Severe persistent diarrhoea (possibly a sign of a serious intestinal infection called pseudomembranous colitis, see below).
➢ Severe acute hypersensitivity reactions up to anaphylactic shock.

Very rare:
➢ Decrease in white blood cell and platelet counts during treatment (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia). With prolonged use, regular monitoring of blood cell counts is required.
➢ Hepatitis (liver inflammation), jaundice, inflammation of the pancreas (sporadic reports).
➢ Brain disorders, lack of coordination.

Not known:
➢ Hypersensitivity reactions ranging from mild to moderate, swelling of the face, mouth, throat and/or tongue (angioedema).
➢ Eye movement spasm, damage or inflammation of the ocular nerves.
➢ Reduced white blood cell count (leucopenia), severe anaemia (aplastic anaemia).
➢ Epileptic seizures, nerve disorders such as numbness, pain, sensation of coated tongue (white-yellowish coating) or tingling in arms or legs.
➢ Bacterial infection-unrelated brain fever (aseptic meningitis).
➢ Acute liver failure in patients affected by 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.
➢ Flat, red, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals and eyes. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
➢ Widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
➢ Generalized, red, scaly rash with pustule formation under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).

Other side effects include

Common:
➢ Fungal and bacterial superinfections.

Uncommon:
➢ Dark urine (due to a metabolite of metronidazole).

Rare:
➢ ECG changes.

Very rare:
➢ Psychotic disorders including confusion, hallucinations.
➢ Headache, dizziness, somnolence, fever, visual and motor disturbances, vertigo, speech disorders, seizures.
➢ Visual disturbances, double vision, myopia.
➢ Liver function disorders (such as elevated serum levels of certain enzymes and bilirubin).
➢ Allergic skin reactions such as itching, urticaria.
➢ Joint and muscle pain.

Not known:
➢ Stomach discomfort, nausea, diarrhoea, inflammation of the tongue and mouth, belching and bitter taste, metallic taste, feeling of heaviness in the stomach, coated tongue (white-yellowish coating).
➢ Difficulty swallowing.
➢ Anorexia.
➢ Depressed mood.
➢ Somnolence or insomnia, muscle spasms.
➢ Skin redness and itching (erythema multiforme).
➢ Irritation of the vein wall (up to phlebitis and thrombosis) after intravenous administration, weakness, fever.

Emergency management of pseudomembranous enterocolitis
If you experience severe persistent diarrhoea, you must inform your doctor immediately, as this may be due to pseudomembranous colitis, a serious condition requiring immediate treatment. Your doctor will discontinue metronidazole and prescribe appropriate therapy.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor or pharmacist. Side effects can also be reported directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Metronidazole B. Braun 5 mg/ml

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and vial. The expiry date refers to the
last day of that month.
Keep the vials in the outer packaging to protect them from light.
This medicine is for single use only. Dispose of any unused contents.
From a microbiological standpoint, dilutions must be used immediately. If not used immediately, the
storage duration after opening and the conditions prior to use are the responsibility of the user and should
normally not exceed 24 hours at 2–8°C, unless the dilution has been carried out under controlled and
validated aseptic conditions.
Use only if the solution is clear and free from visible particles, and if the vial and closure are intact.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Metronidazole B. Braun 5 mg/ml contains
➢ The active substance is metronidazole.
1 ml of Metronidazole B. Braun 5 mg/ml solution for infusion contains 5 mg of metronidazole.
A 100 ml polyethylene vial contains 500 mg of metronidazole.
➢ The excipients are sodium chloride, disodium phosphate dodecahydrate, citric acid, water for
injections.
Description of the appearance of Metronidazole B. Braun 5 mg/ml and contents of the pack
Metronidazole B. Braun 5 mg/ml is a clear, colourless or slightly yellowish aqueous solution.
Metronidazole B. Braun 5 mg/ml is supplied in 100 ml polyethylene vials.
The solution is available in packs of 10 or 20 vials.
Not all pack sizes may be marketed.
Marketing Authorization Holder
B. Braun Melsungen AG
Carl-Braun-Straße 1
34212 Melsungen, Germany
Postal address:
34209 Melsungen, Germany
Tel. +49-5661-71-0
Fax +49-5661-71-4567
Manufacturer(s)
B. Braun Melsungen AG B. Braun Medical, S.A.
Carl-Braun-Straße 1 Carretera de Terrassa 121
34212 Melsungen, Germany 08191 Rubí, Barcelona, Spain
This medicinal product is authorized in the European Economic Area Member States under the
following names:

This patient information leaflet was last reviewed on