Metronidazole 0.5% fresenius

Package leaflet: Information for the user

METRONIDAZOL 0,5% FRESENIUS, 5 mg/mL, infusion solution
Metronidazolum
Please read carefully the entire leaflet before use, as it contains
important information for the patient.
­ Keep this leaflet, as you may need to read it again.
­ If you have any questions, please consult your doctor, pharmacist, or nurse.
­ This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm
another person, even if their symptoms are the same.
­ If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor,
pharmacist, or nurse. See section 4.
Table of contents

1. What Metronidazol 0,5% Fresenius is and what it is used for
2. What you need to know before using Metronidazol 0,5% Fresenius
3. How to use Metronidazol 0,5% Fresenius
4. Possible side effects
5. How to store Metronidazol 0,5% Fresenius
6. Contents of the pack and other information

1. What Metronidazol 0,5% Fresenius is and what it is used for

Metronidazol 0,5% Fresenius is indicated for use in adult patients and children for the prophylaxis and
treatment of the following infections caused by anaerobic bacteria sensitive to metronidazole,
requiring intravenous administration of the drug.
Metronidazol 0,5% Fresenius is used in the treatment of, among others:
­ intra-abdominal infections following surgery of the large intestine (colon), peritonitis, pelvic infections (abscess, soft tissue infection);
­ gynaecological infections (e.g. after hysterectomy and other gynaecological surgical procedures);
­ septicaemia, especially of gastrointestinal or female genital origin;
­ necrotizing pneumonia;
­ brain abscess;
­ osteomyelitis;
­ endocarditis.
Metronidazol 0,5% Fresenius is used in:
­ perioperative prophylaxis, especially when previous or suspected infections such as peritonitis, subdiaphragmatic abscesses, or pelvic infections (abscesses) have occurred, and
­ prior to surgical procedures where infection with anaerobic bacteria may occur (e.g. from the gastrointestinal tract, female genital organs, oral cavity, and pharynx).
Metronidazol 0,5% Fresenius is also used in the treatment of gynaecological infections caused by protozoa of the genera: Trichomonas, Entamoeba histolytica, Giardia lamblia, Balantidium coli.

2. Important information before using Metronidazol 0,5% Fresenius

When not to use Metronidazol 0,5% Fresenius
– if the patient is allergic to metronidazole, nitroimidazole derivatives, or any of the other
components of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Metronidazol 0,5% Fresenius, discuss this with your doctor.
The medicine should be used with caution if:
– the patient has severe liver impairment;
– the patient has blood abnormalities, mainly leukopenia (a significant decrease in white blood cell count) – in such a case, the doctor will order blood tests during treatment;
– the patient has hepatic encephalopathy (neuropsychiatric disorders resulting from liver damage, especially liver cirrhosis), as this may lead to increased drug concentration in the blood, worsening encephalopathy symptoms;
– the patient is elderly (over 65 years of age) – in this case, the doctor will reduce the dose;
– the patient is prone to developing edema;
– the patient has renal impairment;
– the patient is receiving corticosteroids;
– the patient has active or severe chronic disease of the peripheral and central nervous system.

If neurological disorders occur, the doctor will consider whether treatment with metronidazole should continue.
If the patient is being treated with metronidazole and undergoing hemodialysis, Metronidazol 0,5% Fresenius should be administered again immediately after dialysis.
During prolonged use of the medicine (for at least 10 days), adverse effects may occur (see section 4 "Possible side effects"), therefore the doctor will regularly order blood tests.
In laboratory tests (depending on the method used), metronidazole may interfere with the results of aspartate aminotransferase (so-called liver function tests).
Severe hepatotoxicity (acute liver failure), including fatal cases, has been reported in patients with Cockayne syndrome receiving metronidazole-containing medicines. In patients with Cockayne syndrome, the doctor should monitor liver function during and after treatment with metronidazole.

If any of the following symptoms occur, the patient should immediately inform the doctor:
– abdominal pain, loss of appetite, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, pale or loose stools, or skin itching.

Seek immediate medical attention:
– in case of severe hypersensitivity reaction, as urgent treatment will be required;
– if diarrhea occurs during or after treatment, especially if it is severe and persistent.
Diarrhea may be a sign of pseudomembranous colitis (in most cases caused by Clostridium difficile), which may be life-threatening. In such cases, do not take medications that inhibit intestinal peristalsis or have constipating effects.

Metronidazol 0,5% Fresenius and other medicines
Tell your doctor, nurse, or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, especially:
– oral anticoagulants, e.g. warfarin (medicines used to reduce blood clotting);
– lithium (a medicine used to treat depression);
– phenobarbital, hexobarbital, carbamazepine, or phenytoin (medicines used to treat epilepsy);
– cimetidine (a medicine used to treat peptic ulcer disease), as it increases metronidazole blood levels, increasing the risk of adverse effects;
– fluorouracil (a medicine used to treat certain cancers);
– cyclosporine or tacrolimus (immunosuppressive medicines);
– busulfan (a medicine used to treat leukemia);
– amiodarone (a medicine used to treat heart rhythm disorders);
– oral contraceptives (some antibiotics may reduce the effectiveness of oral contraceptives);
– mycophenolate mofetil (a medicine used to prevent transplant rejection);
– antibiotics such as tetracyclines, spiramycin, clindamycin, acylureidopenicillins, rifampicin, and nalidixic acid, as they may have enhanced effects when used with metronidazole;
– disulfiram (a medicine used to treat alcoholism).

Metronidazol 0,5% Fresenius and alcohol
Do not drink alcohol during metronidazole treatment and for at least 48 hours after stopping the medicine, as this may cause redness of the skin of the head and neck, nausea, vomiting, headache, and dizziness.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.

Pregnancy
There are insufficient data on the use of metronidazole in pregnant women.
The medicine is contraindicated during the first trimester of pregnancy. In the second and third trimesters, the medicine may be used only if, in the doctor's opinion, the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding
Since metronidazole passes into human milk, breastfeeding must be discontinued during treatment.
Breastfeeding should not be resumed until 2 to 3 days after completion of metronidazole treatment, due to the persistence of the drug in the body.

Fertility
There is no data available on the effect of metronidazole on fertility.

Driving and operating machinery
Metronidazole may impair the ability to drive or operate machinery. During treatment with metronidazole, drowsiness, dizziness, disorientation, hallucinations, seizures, or transient visual disturbances may occur.

Metronidazol 0,5% Fresenius contains sodium
The medicine contains 310 mg of sodium (the main component of table salt) per 100 mL of solution. This corresponds to 15.5% of the maximum recommended daily sodium intake in the adult diet.
This should be taken into account in patients with impaired kidney function and in patients who are monitoring sodium intake in their diet.

3. How to use Metronidazol 0,5% Fresenius

This medicine is administered exclusively by medical personnel. Do not use this medicine yourself. In case of doubts,
consult your doctor.
The dosage is determined individually by the doctor for each patient, depending on the clinical condition, age,
and laboratory test results.
Use of a higher than recommended dose of Metronidazol 0,5% Fresenius
If a higher than recommended dose is used, inform the doctor or nurse immediately.
Administration of a higher than recommended dose of the medicine may cause:
- nausea, vomiting;
- anxiety;
- ataxia (difficulty maintaining balance, unsteady gait);
- seizures;
- peripheral neuropathy (tingling and burning sensations in hands and feet, sometimes loss of sensation in limbs).
Missed administration of Metronidazol 0,5% Fresenius
If you have any further doubts regarding the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions are mainly associated with long-term use. The most commonly observed ones include:
nausea, taste disturbances and neuropathies (nerve damage). The frequency, type and severity of adverse
reactions are similar in children and adults.
If any of the following adverse reactions worsen, inform your doctor or nurse, who may discontinue
the administration of the medicine.
The following adverse reactions have been observed during treatment with Metronidazol 0,5% Fresenius.
Common (may occur in fewer than 1 in 10 patients):
­ phlebitis, including thrombophlebitis.
Uncommon (may occur in fewer than 1 in 100 patients):
­ decreased number of white blood cells (leukopenia, granulocytopenia), thrombocytopenia;
­ mild to moderate hypersensitivity reactions such as itching, urticaria, erythema multiforme (red-blue
spots on the skin or mucous membranes), angioedema (symptoms include sudden swelling of the
face, limbs or oral cavity, breathing difficulties) and drug fever;
­ psychotic disorders, including hallucinations, agitation, depression;
­ headache, dizziness, excessive drowsiness, insomnia; during intensive and (or) prolonged use of
metronidazole (over 10 days), peripheral neuropathy (e.g. numbness, pain, sensation of touching fur
and tingling in the limbs) and seizures have been observed; in most cases, neuropathy resolves after
discontinuation of treatment or after dose reduction of metronidazole;
­ visual disturbances, double vision, myopia;
­ nausea, vomiting, diarrhoea, glossitis, stomatitis, bitter regurgitation, metallic taste in the mouth,
gastrointestinal disturbances, coated tongue;
­ liver function disorders (e.g. increased aminotransferase activity and increased bilirubin levels);
­ muscle and joint pain;
­ dark urine;
­ weakness.
Rare (may occur in fewer than 1 in 1,000 patients):
­ genital infections caused by yeast;
­ pain during urination, cystitis, urinary incontinence.
Very rare (may occur in fewer than 1 in 10,000 patients):
­ agranulocytosis (lack of white blood cells in blood, life-threatening), aplastic anaemia (reduction in
all blood cells and platelets);
­ severe, acute hypersensitivity reactions: anaphylactic reaction up to anaphylactic shock (symptoms
include, among others: skin itching, erythema, facial and lip swelling, dyspnoea, nausea, vomiting,
tachycardia, cardiac arrhythmia, dizziness and headache, loss of consciousness);
­ aseptic meningitis, encephalopathy (e.g. confusion, fever, headache, paralysis, photophobia, visual
and movement disturbances, neck stiffness) and subacute cerebellar syndrome [e.g. ataxia (difficulty
maintaining balance, unsteady gait)], speech disorders, gait disturbances, nystagmus and seizures,
which usually resolve after dose reduction or discontinuation of the medicine;
­ severe, prolonged, life-threatening diarrhoea during and after treatment;
­ cholestatic hepatitis, transient jaundice after discontinuation of the medicine.
Frequency not known (frequency cannot be determined from available data):
­ severe skin reactions, such as Stevens-Johnson syndrome (extensive blistering rash, peeling skin,
particularly around the mouth, nose, eyes and genital organs), toxic epidermal necrolysis;
­ anorexia;
­ paroxysmal, compulsive eye deviation with rotation of the eyeballs, optic neuropathy;
­ transient pancreatitis after discontinuation of the medicine;
­ acute liver failure in patients with Cockayne syndrome. See section 2 "Important information before
using Metronidazol 0,5% Fresenius".
Reporting of adverse reactions
If any symptoms of adverse reactions occur, including any adverse reactions not listed in this leaflet,
inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of
Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices
and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Metronidazol 0,5% Fresenius

Keep the medicine out of the sight and reach of children.
Do not freeze. Store the container in the outer packaging to protect from light.
The packaging must not be reused after opening. Any unused portion of the medicine
must not be used subsequently.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Do not use this medicine if contamination or discoloration is observed, or if the packaging is damaged.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Metronidazol 0,5% Fresenius contains
­ The active substance is metronidazole.
1 mL of solution contains 5 mg of metronidazole.
­ Other components are: sodium chloride, disodium phosphate dodecahydrate, citric acid monohydrate,
water for injections.
The osmolarity of the solution is 300 mOsmol/L, pH: 4.5 – 7.0.

What Metronidazol 0,5% Fresenius looks like and contents of the pack
The medicine is a clear infusion solution.
The medicine is packed in a polyethylene container KabiPac with a cap, with a capacity of 100 mL.
Pack sizes:
1 container of 100 mL
40 containers of 100 mL in a cardboard box

Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warszawa

Manufacturer
Fresenius Kabi Polska Sp. z o.o.
Infusion Solutions Manufacturing Plant
ul. Sienkiewicza 25
99-300 Kutno

For further information, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warszawa
tel. +48 22 345 67 89

Information intended exclusively for healthcare professionals:

Dosage and administration

Dosage
The dose of metronidazole depends on the type and severity of infection, patient's age and body weight, and clinical response.
Unless otherwise directed by the physician, the following dosage regimens are recommended.

Infections caused by anaerobic bacteria

Adults and adolescents above 12 years of age
Patients with a body weight of approximately 70 kg: 1500 mg metronidazole (corresponding to 300 mL of solution) once daily by infusion lasting no less than 60 minutes, or 500 mg metronidazole (corresponding to 100 mL of solution) three times daily by slow intravenous infusion at a rate of 5 mL/min (corresponding to 25 mg metronidazole/min), equivalent to 22.5 mg metronidazole/kg body weight per day.

Children above 8 weeks up to 12 years of age
The usual dose is 20–30 mg/kg body weight per day, administered as a single dose or divided into doses of 7.5 mg/kg body weight every 8 hours. The dosage may be increased to 40 mg/kg body weight per day depending on the severity of infection. Treatment usually lasts 7 days.

Children below 8 weeks of age
15 mg/kg body weight administered as a single dose once daily or divided into doses of 7.5 mg/kg body weight every 12 hours.
In neonates below 40 weeks of gestational age, accumulation of metronidazole may occur during the first week of life. Therefore, after several days of treatment, monitoring of serum metronidazole concentration is recommended.

Prophylaxis of perioperative infections

Adults and adolescents
500 mg metronidazole (corresponding to 100 mL of solution) by slow intravenous infusion at a rate of 5 mL/min, administered no later than 1 hour before surgical procedure. The 500 mg dose should be repeated 8 and 16 hours after the first dose.

Children below 12 years of age
20–30 mg/kg body weight as a single dose administered 1–2 hours before surgical procedure.
Neonates below 40 weeks of gestational age: 10 mg/kg body weight as a single dose before surgical procedure.

Infections caused by protozoa

Trichomoniasis caused by Trichomonas vaginalis

Adults and adolescents
2000 mg as a single dose, or 200 mg three times daily for 7 days, or 400 mg twice daily for 5–7 days.

Children below 10 years of age
15–30 mg/kg body weight per day administered in 2–3 divided doses over 7 days; the single dose should not exceed 2000 mg.

Giardiasis

Children above 10 years of age: 2000 mg once daily for 3 days, or 400 mg three times daily for 5 days, or 500 mg twice daily for 7 to 10 days.
Children 7 to 10 years of age: 1000 mg once daily for 3 days.
Children 3 to 7 years of age: 600 to 800 mg once daily for 3 days.
Children 1 to 3 years of age: 500 mg once daily for 3 days,
alternatively 15 to 40 mg/kg body weight per day administered in 2–3 divided doses.

Amoebiasis

Children above 10 years of age: 400 to 800 mg three times daily for 5–10 days.
Children 7 to 10 years of age: 200 to 400 mg three times daily for 5–10 days.
Children 3 to 7 years of age: 100 to 200 mg four times daily for 5–10 days.
Children 1 to 3 years of age: 100 to 200 mg three times daily for 5–10 days,
alternatively 35 to 50 mg/kg body weight per day administered in 3 divided doses over 5 to 10 days; the total daily dose should not exceed 2400 mg per day.

Helicobacter pylori eradication in children and adolescents
As part of combination therapy, 20 mg/kg body weight per day (not exceeding 500 mg) administered twice daily for 7–14 days.
Before initiating treatment, current guidelines for Helicobacter pylori therapy should be considered.

Special patient groups

Patients with renal impairment
In patients with severe renal impairment, biliary excretion of metronidazole in faeces is increased. Dose reduction is not required.

Patients with hepatic impairment
In patients with advanced hepatic impairment, elimination of metronidazole is prolonged; therefore, these patients should be closely monitored and serum metronidazole concentrations should be regularly checked. The daily dose of Metronidazol 0,5% Fresenius should be reduced to one-third of the standard dose and may be administered once daily.

Elderly patients
Metronidazol 0,5% Fresenius should be used with caution in elderly patients, especially at high doses, due to limited data on dose adjustment.

Route of administration
For intravenous use only.
Metronidazol 0,5% Fresenius should be administered by slow intravenous infusion at a rate of approximately 5 mL/min (maximum 100 mL within 20 minutes).
Concomitant intravenous administration of metronidazole with selected antibiotics is possible, provided they are administered separately.

Duration of treatment
The duration of treatment with Metronidazol 0,5% Fresenius should not exceed 10 days. Treatment may be extended only in exceptional cases when absolutely necessary. Based on clinical and bacteriological assessment, the physician may decide to extend treatment, e.g., for infections in sites that cannot be drained or are prone to recurrent endogenous infections with anaerobic microorganisms from the intestine, throat, or genital organs. Re-treatment should be limited to exceptional cases whenever possible. Limitation of treatment duration is necessary because effects of metronidazole on human germ cells cannot be excluded, and increased incidence of certain types of tumours has been observed in animal studies.

Preparation of the medicinal product for administration
Use only clear solution free from visible particles.
Unused portion of the medicinal product must not be retained for later use.
Do not use this medicinal product if particulate matter or discoloration is observed, or if the container is damaged.
Follow aseptic principles.

Instructions for use of KabiPac container:

1. Before use, carefully inspect the appearance of the container and solution – the solution should be clear and free from particulate matter (do not use containers that are damaged and/or previously used).
2. Preparation of infusion:
   a) Place the KabiPac container on a stable and level surface.
   b) Remove the plastic cover/cap from the larger port (infusion port) with the arrow pointing outward from the package.
   c) Insert the spike of the infusion set vertically into the infusion port, gently rotating the set with one hand while holding the neck of the container with the other.

Note: Ports are sterile and do not require disinfection prior to first use.
Medical devices intended for administration of the medicinal product should be used in accordance with their instructions for use.

Pharmaceutical incompatibilities
Do not mix with other medicinal products.
Metronidazol 0,5% Fresenius is incompatible with 10% glucose solution.

Storage conditions
Do not freeze. Store the container in the outer packaging to protect from light.
The opened container must not be stored or reused. From a microbiological standpoint, the product should be used immediately. Otherwise, the responsibility for storage conditions and duration of the remaining medicinal product in the container lies with the user.

Disposal of unused medicinal product or waste
Any unused residues of the medicinal product or waste materials should be disposed of in accordance with local regulations.