Metronidazol 0,5% Fresenius

Leaflet attached to the packaging: information for the user

METRONIDAZOLE 0.5% FRESENIUS, 5 mg/mL, solution for infusion

Metronidazole

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

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Keep this leaflet, so you can read it again if you need to.
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In case of any doubts, consult a doctor, pharmacist, or nurse.
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This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
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If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Metronidazole 0.5% Fresenius and what is it used for
• 2. Important information before using Metronidazole 0.5% Fresenius
• 3. How to use Metronidazole 0.5% Fresenius
• 4. Possible side effects
• 5. How to store Metronidazole 0.5% Fresenius
• 6. Contents of the packaging and other information

1. What is Metronidazole 0.5% Fresenius and what is it used for

Metronidazole 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.
Metronidazole 0.5% Fresenius is used to treat, among others:
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infections in the abdominal cavity after colon surgery (colectomy), peritonitis, purulent diseases in the pelvic area (abscess, connective tissue inflammation);
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gynecological infections (e.g., after hysterectomy and other gynecological surgical procedures);
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septicaemia, especially of gastrointestinal and female genital tract origin;
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gangrenous pneumonia;
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brain abscess;
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osteomyelitis;
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endocarditis.
Metronidazole 0.5% Fresenius is used in:
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perioperative prophylaxis, especially when infections have occurred or are suspected, such as peritonitis, subphrenic abscess, or pelvic infections (abscesses), and
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before procedures that may lead to anaerobic bacterial infection (e.g., from the gastrointestinal tract, female genital tract, oral cavity, and pharynx).
Metronidazole 0.5% Fresenius is also used to treat gynecological infections caused by protozoa of the genus: Trichomonas, Entamoeba histolytica, Giardia lamblia, Balantidium coli.

2. Important information before using Metronidazole 0.5% Fresenius

When not to use Metronidazole 0.5% Fresenius

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Warnings and precautions

Before starting treatment with Metronidazole 0.5% Fresenius, the patient should discuss it with their doctor.
The medicine should be used with caution if:
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the patient has severe liver failure;
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the patient has an abnormal blood count, mainly leukopenia (a significant decrease in the number of white blood cells) - in such cases, the doctor will order a blood test during treatment;
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the patient has hepatic encephalopathy (neuropsychiatric disorders caused by liver damage, especially liver cirrhosis), as this may lead to increased blood levels of the medicine, exacerbating encephalopathy symptoms;
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the patient is elderly (over 65 years old) - in such cases, the doctor will reduce the dose of the medicine;
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the patient has a tendency to develop edema;
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the patient has renal failure;
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the patient is taking corticosteroids;
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the patient has active or severe, chronic peripheral and central nervous system disease.
In case of neurological disorders, the doctor will consider whether metronidazole treatment is possible.
If the patient is being treated with metronidazole and is undergoing hemodialysis, they should receive Metronidazole 0.5% Fresenius again immediately after the procedure.
During long-term use of the medicine (for at least 10 days), side effects may occur (see section 4 "Possible side effects"), so the doctor will regularly order blood tests.
In laboratory tests (depending on the method used), metronidazole may falsify the results of aspartate aminotransferase (liver tests).
During the use of metronidazole in patients with Cockayne syndrome, cases of severe hepatotoxicity (acute liver failure) have been reported, including fatal cases. In patients with Cockayne syndrome, the doctor should monitor liver function during and after metronidazole treatment.
If the patient experiences any of the following symptoms, they should immediately inform their doctor:
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abdominal pain, loss of appetite, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, sticky or loose stools, or skin itching.
The patient should immediately consult their doctor:
­­Clostridium difficile), which can be life-threatening. In such cases, the patient should not take medications that slow down intestinal motility or have a constipating effect.

Metronidazole 0.5% Fresenius and other medicines

The patient should tell their doctor, nurse, or pharmacist about all medicines they are currently taking, have recently taken, or plan to take, especially:
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oral anticoagulants, such as warfarin (medicines used to reduce blood clotting);
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lithium (a medicine used to treat depression);
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phenobarbital, hexobarbital, carbamazepine, or phenytoin (medicines used to treat epilepsy);
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cimetidine (a medicine used to treat stomach ulcers), as it increases metronidazole blood levels, which may increase the risk of side effects;
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fluorouracil (a medicine used to treat certain cancers);
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cyclosporine or tacrolimus (a medicine that weakens the immune system);
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busulfan (a medicine used to treat leukemia);
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amiodarone (a medicine used to treat heart rhythm disorders);
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oral contraceptives (some antibiotics may reduce the effectiveness of oral contraceptives);
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mycophenolate mofetil (a medicine used to prevent transplant rejection);
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antibiotics, such as tetracyclines, spiramycin, clindamycin, acylureidopenicillins, rifampicin, and nalidixic acid, as they may interact with metronidazole;

• disulfiram (a medicine used to treat alcoholism).

Metronidazole 0.5% Fresenius and alcohol

The patient should not drink alcohol during metronidazole treatment and for at least 48 hours after its completion, as this may cause flushing of the skin, nausea, vomiting, headaches, and dizziness.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
Pregnancy
There is insufficient data on the use of metronidazole in pregnant women.
The medicine is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the medicine may only be used when the expected benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding
Since metronidazole passes into breast milk, breastfeeding should be discontinued during treatment.
After completion of metronidazole treatment, breastfeeding should not be resumed for 2 to 3 days, due to the persisting levels of the medicine.
Fertility
There is no data on the effect of metronidazole on fertility.

Driving and using machines

Metronidazole may impair the ability to drive and use machines. During metronidazole treatment, the patient may experience drowsiness, dizziness, disorientation, hallucinations, seizures, or transient visual disturbances.

Metronidazole 0.5% Fresenius contains sodium

The medicine contains 310 mg of sodium (the main component of common salt) per 100 mL of solution. This corresponds to 15.5% of the maximum recommended daily intake of sodium in the diet for adults.
This should be taken into account in patients with reduced renal function and in patients on a controlled sodium diet.

3. How to use Metronidazole 0.5% Fresenius

This medicine is administered only by medical personnel. The medicine should not be used by the patient themselves. In case of doubts, the patient should consult their doctor.
The dosage is determined by the doctor individually for each patient, depending on their clinical condition, age, and laboratory test results.

Using a higher dose of Metronidazole 0.5% Fresenius than recommended

In case of using a higher dose of the medicine than recommended, the patient should immediately inform their doctor or nurse.
Using a higher dose of the medicine than recommended may cause:
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nausea, vomiting;
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restlessness;
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ataxia (difficulty maintaining balance, unsteady gait);
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seizures;
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peripheral neuropathy (tingling and burning in hands and feet, sometimes loss of sensation in a limb).

Missing a dose of Metronidazole 0.5% Fresenius

In case of any further doubts about using this medicine, the patient should consult their doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects are mainly associated with long-term use. The most common side effects include: nausea, taste disturbances, and neuropathy (nerve damage). The frequency, type, and severity of side effects are similar in children and adults.

If any of the following side effects worsen, the patient should inform their doctor or nurse, who may stop the administration of the medicine.

The following side effects have been observed during the use of Metronidazole 0.5% Fresenius.
Frequent(may occur in less than 1 in 10 patients):
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phlebitis, including thrombophlebitis.
Uncommon(may occur in less than 1 in 100 patients):
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decreased white blood cell count (leukopenia, granulocytopenia), thrombocytopenia;
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mild to moderate hypersensitivity reactions, such as itching, urticaria, erythema multiforme (red-purple spots on the skin or mucous membranes), angioedema (symptoms include sudden swelling of the face, limbs, or mouth, difficulty breathing) and fever;
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psychotic disorders, including hallucinations, agitation, depression;
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headache, dizziness, excessive drowsiness, insomnia; during intensive and/or long-term use of metronidazole (more than 10 days), peripheral neuropathy (e.g., numbness, pain, sensation of fur and tingling in limbs) and seizures have been observed, in most cases, neuropathy resolved after treatment completion or dose reduction;
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visual disturbances, double vision, myopia;
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nausea, vomiting, diarrhea, stomatitis, oral mucositis, bitter taste, metallic taste, gastrointestinal disorders, coated tongue;
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liver function disorders (e.g., increased aminotransferase activity and increased bilirubin levels);
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muscle and joint pain;
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dark urine color;
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weakness.
Rare(may occur in less than 1 in 1,000 patients):
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genital infections caused by fungi;
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dysuria, cystitis, urinary incontinence.
Very rare(may occur in less than 1 in 10,000 patients):
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agranulocytosis (lack of white blood cells in the blood, life-threatening), aplastic anemia (reduced number of all blood cells and platelets);
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severe, acute hypersensitivity reactions: anaphylactic reaction up to anaphylactic shock (symptoms include itching, rash, swelling of the face, lips, or tongue, difficulty breathing, nausea, vomiting, rapid heartbeat, arrhythmia, dizziness, and headache);
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aseptic meningitis, encephalopathy (e.g., confusion, fever, headache, paralysis, sensitivity to light, visual and movement disorders, stiffness of the neck) and subacute cerebellar syndrome [e.g., ataxia (difficulty maintaining balance, unsteady gait)], speech disorders, gait disorders, nystagmus, and seizures, which usually resolve after dose reduction or discontinuation of the medicine;
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severe, prolonged, life-threatening diarrhea during and after treatment;
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cholestatic hepatitis, transient jaundice after discontinuation of the medicine.
Frequency not known(frequency cannot be estimated from the available data):
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severe skin reactions, such as Stevens-Johnson syndrome (widespread rash with blisters, peeling skin, especially around the mouth, nose, eyes, and genitals), toxic epidermal necrolysis;
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loss of appetite;
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seizures with eye rotation, optic neuropathy;
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transient pancreatitis after discontinuation of the medicine;
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acute liver failure in patients with Cockayne syndrome. See section 2 "Important information before using Metronidazole 0.5% Fresenius".

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Metronidazole 0.5% Fresenius

The medicine should be stored out of sight and reach of children.
Do not freeze. Store the container in the outer packaging to protect it from light.
The packaging should not be stored and used again after opening. Unused medicine should not be used.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Do not use this medicine if you notice contamination or color changes, or if the packaging is damaged.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Metronidazole 0.5% Fresenius contains

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The active substance of the medicine is metronidazole.
1 mL of solution contains 5 mg of metronidazole.
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The other ingredients are: sodium chloride, disodium phosphate dodecahydrate ,citric acid monohydrate, water for injections.
The osmolality of the solution is 300 mOsmol/L, pH: 4.5 – 7.0.

What Metronidazole 0.5% Fresenius looks like and what the packaging contains

The medicine is a clear solution for infusion.
The packaging of the medicine is 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 authorization holder

Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw

Manufacturer

Fresenius Kabi Polska Sp. z o.o.
Infusion Fluids Factory
ul. Sienkiewicza 25
99-300 Kutno
To obtain more detailed information, the patient should contact the marketing authorization holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
tel. +48 22 345 67 89

Date of last revision of the leaflet:

Information intended for healthcare professionals only:

Dosage and administration

Dosage
The dose of metronidazole depends on the type and severity of the infection, the patient's age and weight, and clinical response.
Unless the doctor has prescribed otherwise, the following dosage is recommended.

Infections caused by anaerobic bacteria

Adult patients and adolescents over 12 years old
Patients with a body weight of approximately 70 kg: 1500 mg of metronidazole (corresponding to 300 mL of solution) once a day in an infusion lasting at least 60 minutes or 500 mg of metronidazole (corresponding to 100 mL of solution) three times a day in slow intravenous infusion at a rate of 5 mL/min (corresponding to 25 mg of metronidazole/min), which corresponds to 22.5 mg of metronidazole/kg body weight per day.
Children over 8 weeks to 12 years old
Usually, the dose is 20-30 mg/kg body weight per day, given in a single dose or divided into doses of 7.5 mg/kg every 8 hours. The dose may be increased to 40 mg/kg body weight per day, depending on the severity of the infection. Treatment usually lasts 7 days.
Children under 8 weeks old
15 mg/kg body weight given in a single dose once a day or divided into doses of 7.5 mg/kg every 12 hours.
In newborns under 40 weeks of gestational age, metronidazole may accumulate during the first week of life. Therefore, metronidazole blood levels should be monitored after a few days of treatment.

Prophylaxis of postoperative infections

Adult patients and adolescents
500 mg of metronidazole (corresponding to 100 mL of solution) in slow intravenous infusion at a rate of 5 mL/min, no later than 1 hour before surgery. The dose of 500 mg should be repeated after 8 and 16 hours from the administration of the first dose.
Children under 12 years old
20-30 mg/kg body weight in a single dose given 1-2 hours before surgery.
Newborns under 40 weeks of gestational age: 10 mg/kg body weight in a single dose before surgery.

Infections caused by protozoa

Trichomoniasis caused by Trichomonas vaginalis
Adult patients and adolescents
2000 mg in a single dose or 200 mg three times a day for 7 days or 400 mg twice a day for 5-7 days.
Children under 10 years old
15-30 mg/kg body weight per day given in 2-3 doses for 7 days, a single dose should not exceed 2000 mg.
Giardiasis
Children over 10 years old: 2000 mg once a day for 3 days or 400 mg three times a day for 5 days, or 500 mg twice a day for 7-10 days.
Children 7 to 10 years old: 1000 mg once a day for 3 days.
Children 3 to 7 years old: 600-800 mg once a day for 3 days.
Children 1 to 3 years old: 500 mg once a day for 3 days, alternatively 15-40 mg/kg body weight per day given in 2-3 doses.
Amebiasis
Children over 10 years old: 400-800 mg three times a day for 5-10 days.
Children 7 to 10 years old: 200-400 mg three times a day for 5-10 days.
Children 3 to 7 years old: 100-200 mg four times a day for 5-10 days.
Children 1 to 3 years old: 100-200 mg three times a day for 5-10 days, alternatively 35-50 mg/kg body weight per day given in 3 doses for 5-10 days, the daily dose should not exceed 2400 mg per day.
Eradiation of Helicobacter pyloriin children and adolescents
As part of combination therapy, at a dose of 20 mg/kg body weight per day, not exceeding 500 mg, given twice a day for 7-14 days.
Before starting treatment, current guidelines for the treatment of Helicobacter pylorishould be considered.
Special patient groups
Patients with renal impairment
In patients with severe renal impairment, metronidazole is excreted in the bile in the feces.
Dose reduction is not required.
Patients with liver impairment
In patients with advanced liver failure, metronidazole elimination is prolonged, so they should be closely monitored, and metronidazole blood levels should be regularly checked. The daily dose of Metronidazole 0.5% Fresenius should be reduced to 1/3 and can be given once a day.
Elderly patients
In elderly patients, the medicine should be used with caution, especially in high doses, due to limited data on dose adjustment.

Preparation of the medicine for use

Use only a clear solution without visible impurities.
Unused medicine should not be used.
Do not use this medicine if you notice contamination or color changes, or if the packaging is damaged.
Follow the principles of asepsis.
Instructions for using the KabiPac container:

• 1. Before use, carefully check the appearance of the container and the solution – the solution should be clear, without impurities (do not use damaged and/or previously used containers).
• 2. Preparation of the infusion: a) Place the KabiPac container on a stable and even surface. b) Remove the plastic cover/plug from the larger port (infusion port) with the arrow pointing outward. c) Insert the infusion set needle into the infusion port, gently rotating the set with one hand, while holding the neck of the container with the other hand.

Note: The ports are sterile, do not require disinfection before first use.

Medical devices intended for drug administration should be used in accordance with their instructions for use.

Incompatibilities

The medicine should not be mixed with other medicines.
Metronidazole 0.5% Fresenius is incompatible with 10% glucose solution.

Storage conditions

Do not freeze. Store the container in the outer packaging to protect it from light.
The packaging should not be stored and used again after opening. From a microbiological point of view, the medicine should be used immediately. Otherwise, the user is responsible for the storage conditions and storage time of the remaining medicine in the packaging.

Disposal of unused medicine

Any unused medicine or waste material should be disposed of in accordance with local regulations.