Metronidazole Baxter S.P.A.

Package leaflet: Information for the patient

METRONIDAZOLE BAXTER S.P.A. 500 mg/100 ml infusion solution

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, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What METRONIDAZOLE BAXTER S.P.A. is and what it is used for
2. What you need to know before using METRONIDAZOLE BAXTER S.P.A.
3. How to use METRONIDAZOLE BAXTER S.P.A.
4. Possible side effects
5. How to store METRONIDAZOLE BAXTER S.P.A.
6. Contents of the pack and other information

1. What METRONIDAZOLE BAXTER S.P.A. is and what it is used for

The active substance contained in this medicinal product is metronidazole. Metronidazole is an antibacterial agent (also known as an antibiotic), i.e. a medicine that kills bacteria or inhibits their multiplication and growth.
This medicine is used for the treatment and prevention of severe infections caused by certain bacterial species.
It is used in adults and children for:

• treating infections caused by anaerobic bacteria against which metronidazole exerts a bactericidal action (kills the bacteria). Metronidazole may be administered to treat one of the following infections in which metronidazole-sensitive bacteria have been identified:
  • systemic infections at blood level (septicaemia),
  • presence of bacteria in the blood (bacteraemia),
  • infections of the central nervous system, such as brain abscesses (cerebral abscesses),
  • lung infections, such as pneumonia associated with tissue destruction (necrotizing pneumonia),
  • bone infections, such as inflammation of the bone marrow (osteomyelitis),
  • infections of the female genital organs, such as inflammation of the inner lining of the uterus following childbirth, caesarean section or spontaneous abortion (puerperal fever),
  • gastrointestinal tract infections, such as inflammation of the inner lining of the abdominal cavity (peritonitis) and of the pelvic wall (pelvic abscesses),
  • wounds occurring in the post-operative period.
• preventing post-operative infections (which may arise following surgical procedures) associated with a high risk of anaerobic bacterial infections.

2. What you should know before taking METRONIDAZOLE BAXTER S.P.A.

Do not use METRONIDAZOLE BAXTER S.P.A.:

• if you are allergic to metronidazole or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking METRONIDAZOLE BAXTER S.P.A.
Cases of liver toxicity (severe hepatotoxicity/acute liver failure), including cases leading to death, have been reported with medicines containing metronidazole in patients affected by Cockayne syndrome.
If you suffer from 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, loss of appetite, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, pale and greasy stools, or itching.

Your doctor will exercise particular caution with this medicine if you:

• have severe liver disease.
• currently suffer from a nervous system disorder. In this case, inform your doctor, especially if you experience poor coordination (ataxia), partial hearing loss (hearing impairment), dizziness, or confusion during treatment.
• have blood cell disorders.
• are undergoing renal dialysis.

Your doctor may ask you to undergo certain monitoring tests if this medicine is administered for more than 10 days.
Other medicines and METRONIDAZOLE BAXTER S.P.A.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

• warfarin and other drugs that inhibit blood clotting (oral anticoagulants); if you are treated concomitantly with metronidazole, your doctor may adjust the dosage of these drugs.
• busulfan (used to treat leukemia, a cancer of blood cells): concomitant treatment with metronidazole may lead to severe busulfan-related toxic effects.
• disulfiram (used to treat alcohol dependence).
• medicines used to treat epilepsy, such as phenobarbital, phenytoin, and carbamazepine.
• cimetidine (used to treat stomach ulcers).
• medicines used to correct irregular heartbeats, such as amiodarone and quinidine.
• medicines used after organ transplants, such as cyclosporine and tacrolimus.

METRONIDAZOLE BAXTER S.P.A. and alcohol
Do not drink alcohol during treatment with this medicine and for 72 hours afterwards, as unpleasant side effects may occur, such as feeling unwell and vomiting, abdominal pain, hot flushes, palpitations, and headache.
Pregnancy and breastfeeding
This medicine should be avoided during pregnancy or breastfeeding, unless your doctor considers it essential. If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
During treatment with this medicine, you may experience certain side effects (including, for example, drowsiness, dizziness, headache, lack of coordination, transient episodes of loss of consciousness, and uncontrolled body movements) that may impair your ability to drive or operate machinery. Therefore, you must not drive or operate machinery during treatment with this medicine.
METRONIDAZOLE BAXTER S.P.A. contains sodium
Talk to your doctor or pharmacist if you need 2 or more vials per day for a prolonged period, especially if you have been advised to follow a low-sodium diet.

3. How to take METRONIDAZOLE BAXTER S.P.A.

This medicine will be administered to you strictly according to your doctor's instructions. If you
have any doubts, consult your doctor or pharmacist.
Your doctor will determine the dose you need and when to administer it.
Each vial is for single use only and will be administered to you as a slow intravenous infusion at
a rate of approximately 5 ml/minute.
The amount administered to you will depend on:

• your age
• your body weight
• your clinical condition
• the reason for which it was prescribed

If you are given more METRONIDAZOLE BAXTER S.P.A. than you should
Since administration will be performed by a trained and qualified person, it is unlikely that you will
be given more METRONIDAZOLE BAXTER S.P.A. than required.
If this should happen, the infusion will be immediately stopped and, if necessary, your doctor will
administer appropriate therapy.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Serious side effects:
Rarely (may affect up to 1 in 1,000 people), the following serious side effects may occur:

• severe allergic reaction (which may cause sudden fainting, severe shortness of breath, abdominal pain, or swelling of the face and/or tongue and throat);
• severe neurological effects: seizures or convulsive attacks, brain disorders, nerve disorders, which may cause loss of vision, non-bacterial brain fever (aseptic meningitis);
• inflammation of the pancreas, which may cause stomach pain radiating to the back (pancreatitis);
• severe skin reactions (erythema, serious illness with blistering of the skin, mouth and genitals, and skin peeling);
• unexpected infections, mouth ulcers, bruising, bleeding gums, or severe fatigue. These effects may be caused by a blood disorder.

Not known (frequency cannot be estimated from the available data):

• acute liver failure in patients with Cockayne syndrome (see section 2 “Warnings and precautions”)
• speech disorder

If you experience any of these serious side effects, inform your doctor immediately. The doctor will stop the infusion.
Other side effects:
Common (may affect up to 1 in 10 people):

• unpleasant metallic taste sensation, inflammation of the mouth and/or tongue, dry mouth;
• muscle pain

Uncommon (may affect up to 1 in 100 people):

• decrease in the number of white blood cells detected by blood tests;
• headache;
• lack of energy or weakness.

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

• reduction in the number of certain blood cells detected by blood tests (agranulocytosis, pancytopenia, neutropenia, thrombocytopenia);
• drowsiness;
• dizziness, hallucinations;
• feeling unwell (nausea, malaise), vomiting, diarrhoea;
• double vision or myopia;
• yellowing of the skin and whites of the eyes (jaundice);
• darkening of the urine;
• fever;
• Jarisch-Herxheimer reaction (a systemic reaction occurring within the first 24 hours after starting antibiotic therapy, during treatment of certain types of infections);
• weakness, numbness and pain, usually in the hands and feet;
• loss of muscle control or poor coordination;
• pain in the upper abdomen;
• skin swelling;
• inflammation of mucous membranes;
• reaction at the injection site.

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

• infection occurring on top of an existing infection (candida superinfection);
• decreased sexual desire (libido);
• vertigo;
• inflammation of the urinary bladder (cystitis);
• increased urine volume (polyuria);
• presence of pus in the urine (pyuria).

Not known (frequency cannot be estimated from the available data):

• constipation, reduced or loss of appetite;
• confusion;
• depressed mood;
• poor quality of sleep;
• numbness, tingling;
• muscle stiffness, muscle contraction;
• joint pain;
• painful urination;
• itching, inflammation, swelling, skin rash, which occasionally may be severe in intensity; sweating;
• chest pain;
• chills;
• blood abnormalities, which may alter blood test results, abnormal liver function test results;
• hypersensitivity;
• rapid or irregular heartbeat;
• change in tongue colour;
• feeling unwell, malaise;
• partial hearing loss (hypacusis);
• recurrence of a skin rash at the same site after exposure to the drug (fixed eruption);
• decreased sensitivity, especially of the skin;
• difficulty breathing.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store METRONIDAZOLE BAXTER S.P.A.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after Exp. The expiry
date refers to the last day of that month.
This medicine does not require any special storage temperature.
Keep the vials in the outer packaging to protect the medicine from light.
Use only if the solution is clear and if the vial and closure are intact. Use immediately after
opening the vial.
Each vial is for single and uninterrupted administration only; any remaining solution must not be used.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What METRONIDAZOLE BAXTER S.P.A. Contains

• The active substance is metronidazole (100 ml of Metronidazole BAXTER S.P.A. 500 mg/100 ml infusion solution contains 500 mg of metronidazole).
• The other components are sodium chloride, sodium phosphate dibasic dodecahydrate (see section Metronidazole BAXTER S.P.A. contains sodium), citric acid monohydrate, water for injections q.s. to 100 ml.

Description of the Appearance of Metronidazole BAXTER S.P.A. and Contents of the Package
Metronidazole BAXTER S.P.A. is a clear, colourless or slightly yellowish solution, free from visible particles, intended for intravenous infusion.
The solution is contained in 100 ml glass vials, packed in cardboard boxes.
The following pack sizes are available:
1 vial of 100 ml
25 vials of 100 ml

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Baxter S.p.A. – Via Del Serafico 89 – 00142 Rome, Italy
Manufacturer
Bieffe Medital S.p.A. - Via Nuova Provinciale - Grosotto (SO)

The following information is intended exclusively for physicians or healthcare professionals:
This section contains practical information regarding administration. Please refer to the SmPC for complete information on dosage, method of administration, contraindications, warnings, etc.

Dosage and Method of Administration
The medicinal product must be used only for slow intravenous infusion.
This route of administration is particularly useful in emergency situations and is indicated in surgical patients when:

• anaerobic infection is present or suspected preoperatively, e.g. sepsis, peritonitis, subphrenic or pelvic abscess;
• signs of septic state caused by anaerobic organisms appear during surgery;
• there is a risk of contamination by anaerobes originating from the gastrointestinal tract, female genital tract, or oropharynx during surgery.
  In patients already receiving intravenous infusions, the medicinal product may be diluted with appropriate volumes of physiological saline, isotonic dextrose solution, 5% dextrose solution, or potassium chloride (20 mmol/l and 40 mmol/l). Avoid adding other drugs, apart from metronidazole, to the infusion solution.

Treatment

• Adults and children over 12 years: 100 ml for intravenous infusion (at a rate of 5 ml per minute) every 8 hours. In most patients, 7 days of therapy are sufficient, but in some cases (e.g. inaccessible areas for drainage, new contamination, etc.), longer treatment may be required.
• Children under 12 years: Infusion of 1.5 ml/kg body weight (7.5 mg metronidazole/kg body weight) every 8 hours.

Prophylaxis

• Adults and children over 12 years: 100 ml for intravenous infusion immediately before, during, or after surgery, followed by the same dose every 8 hours.
• Children under 12 years: As in adults, but with infusion at a dose of 1.5 ml/kg body weight (7.5 mg metronidazole/kg body weight) every 8 hours.

Special Warnings and Precautions for Use
Metronidazole has shown carcinogenic properties in animals under specific experimental conditions.
Regular clinical and biological monitoring is recommended if treatment exceeds 10 days. The physician intending to use the medicinal product for longer than the recommended duration (e.g. treatment of chronic conditions) should carefully weigh the potential benefit against the risk of developing peripheral neuropathy.

Renal Impairment
Patients undergoing peritoneal dialysis should be monitored for signs of toxicity due to potential accumulation of metronidazole metabolites.

Instructions for use and handling

Use immediately after opening the container (100 ml vial). The solution must be clear, colourless or slightly pale yellow and free from visible particles.
Each 100 ml vial must be used for a single, uninterrupted administration; any remaining residue must not be reused.
Avoid adding other medicinal products, apart from metronidazole, to the infusion solution.
Do not use plastic containers in series connections. Such use could result in gas embolism due to aspiration of residual air from the primary container before completion of fluid administration from the secondary container.
The use of a vented intravenous administration set with the vent in the open position may cause gas embolism. Vented intravenous administration sets with the vent in the open position must not be used with flexible plastic containers.

Additives:
Additives known to be incompatible or shown to be incompatible must not be used.
Before adding any substance or medicinal product, verify that it is soluble and stable in metronidazole and that the pH range of metronidazole is suitable. Additives may be incompatible. When introducing additives, consult the instructions for use of the medicinal product to be added and other relevant literature (see section 6.2).
Mix the solution thoroughly after addition of additives.
After adding substances, do not use the solution if there is a change in colour and/or formation of precipitates, insoluble complexes or crystals.
Do not store solutions containing additives.

Additional information regarding the occurrence of adverse reactions
Cases of peripheral neuropathies have been reported during intensive and prolonged treatments, generally with favourable evolution after discontinuation of treatment or reduction of dosage.

Overdose
Symptoms:
neurotoxic effects, including ataxia, mild disorientation, confusion, convulsive seizures and peripheral neuropathy.