Metronidazol 0,5% Polpharma

Package Leaflet: Information for the User

Metronidazole 0.5% Polpharma

5 mg/ml, solution for injection and infusion

Metronidazolum

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

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or nurse. See section 4.

Table of Contents of the Package Leaflet

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

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

Metronidazole is a derivative of 5-nitroimidazole with antiprotozoal and antibacterial activity.
Metronidazole 0.5% Polpharma is used in adults and children:

• therapeutically in infections caused by anaerobic bacteria of the genus Bacteroides, Fusobacterium, Clostridium, Eubacterium, Veilonella, Peptococcus, Peptostreptococcus: septicemia, bacteremia, peritonitis, brain abscess, pneumonia, osteomyelitis, puerperal fever, pelvic abscess, pelvic cellulitis, surgical wound infections;
• for perioperative prophylaxis of infections caused by anaerobic bacteria, especially species of the genus Bacteroidesand Streptococcus. The drug reduces the frequency of postoperative infections caused by anaerobic bacteria. Official guidelines for the proper use of antibacterial agents should be taken into account.

2. Important information before using Metronidazole 0.5% Polpharma

When not to use Metronidazole 0.5% Polpharma:

• if the patient is hypersensitive to metronidazole or any of the other ingredients of this medicine (listed in section 6);
• if the patient is hypersensitive to other 5-nitroimidazole derivatives;
• if the patient is in the first trimester of pregnancy.

Warnings and precautions

Before starting treatment with Metronidazole 0.5% Polpharma, discuss it with your doctor, pharmacist, or nurse. Particular caution is advised when using Metronidazole 0.5% Polpharma:

• if the patient has active central nervous system disease (brain, spinal cord, or nerves);
• if the patient has experienced neurological disorders (numbness, tingling, or seizures) during treatment;
• if the patient has severe liver failure and hepatic encephalopathy (see section 3);
• if the patient has had significant blood count abnormalities before and after metronidazole treatment. If metronidazole needs to be reused, the patient should be under medical supervision.
• During treatment, the doctor should monitor the blood count. If the drug is used for more than 10 days, such monitoring is absolutely necessary.
• if the patient is taking corticosteroids and if the patient is prone to edema, as the drug contains a significant amount of sodium. After using metronidazole, candidiasis in the oral cavity, vagina, and gastrointestinal tract may occur, which requires appropriate treatment.

Metronidazole does not have direct bactericidal activity against aerobic and facultative anaerobic bacteria.
Despite the elimination of bacteria causing trichomoniasis, the infection may still persist.
Metronidazole may affect the results of some laboratory tests (ASAT, ALAT, LDH, triglycerides, glucose).
During metronidazole treatment, blistering skin reactions, sometimes fatal, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) (see section 4), may occur. If flu-like symptoms, progressive rash (often with blisters or mucosal lesions), occur, treatment should be discontinued and a doctor consulted.
During the use of metronidazole in patients with Cockayne syndrome, cases of severe hepatotoxicity (acute liver failure), including fatal cases, have been reported.
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 and discontinue metronidazole:

• abdominal pain, loss of appetite, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, sticky or loose stools, or skin itching.

The drug may cause darker urine color.

Metronidazole 0.5% Polpharma and other medicines

Tell your doctor about all the medicines you are taking now or have taken recently, as well as any medicines you plan to take, especially:

• anticoagulant medicines (e.g., acenocoumarol, warfarin); the drug does not interact with heparin;
• lithium salts (medicines used in psychiatric diseases);
• terfenadine and astemizole (antiallergic medicines);
• disulfiram (a medicine used in the treatment of alcoholism); metronidazole treatment can be started only after 2 weeks after the end of disulfiram therapy;
• 5-fluorouracil or busulfan (medicines used in cancer treatment);
• cyclosporine (a medicine used in patients after transplants);
• medicines that increase liver enzyme activity (e.g., phenytoin, phenobarbital);
• medicines that decrease liver enzyme activity (e.g., cimetidine);
• medicines metabolized by the liver enzyme P-450 CYP 3A4 (e.g., some antibiotics). See also section 4.

Metronidazole 0.5% Polpharma is incompatible with:

• cefamandole nafate
• cefoxitin sodium
• 10% glucose solution
• sodium lactate
• potassium benzylpenicillin.

Metronidazole 0.5% Polpharma and alcohol

Metronidazole enhances the toxic effects of alcohol. During treatment with metronidazole and for at least 48 hours after the end of treatment, do not consume alcoholic beverages, due to the possibility of adverse reactions. Alcohol consumption during treatment may cause undesirable reactions, such as a feeling of heat, sweating, headaches, nausea, vomiting, and abdominal pain.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Pregnancy
The drug is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the drug may be used only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding
Metronidazole is excreted in human milk, so do not take the drug during breastfeeding. If treatment is necessary, a decision to stop breastfeeding should be made.
Fertility
Only in animal studies has metronidazole shown a potentially negative effect on the reproductive system in males at high doses significantly exceeding the maximum recommended dose for humans.

Driving and using machines

Metronidazole 0.5% Polpharma may cause drowsiness, dizziness, disorientation, hallucinations, seizures, or transient visual disturbances. It is recommended not to drive vehicles or operate machines if such symptoms occur.

Metronidazole 0.5% Polpharma contains sodium

The drug contains 3.1 mg of sodium (the main component of common salt) per milliliter.
This corresponds to 0.15% of the maximum recommended daily sodium intake in the diet for adults.
The drug contains 62.04 mg of sodium (the main component of common salt) per 20 ml ampoule.
This corresponds to 3.1% of the maximum recommended daily sodium intake in the diet for adults.
The drug contains 310.21 mg of sodium (the main component of common salt) per 100 ml container.
This corresponds to 15.51% of the maximum recommended daily sodium intake in the diet for adults.
This should be taken into account in patients with reduced kidney function and in patients controlling their sodium intake.
The drug may be diluted. When calculating the total sodium content in the prepared, diluted solution, the sodium content from the diluent should be taken into account.
To obtain accurate information about the sodium content in the solution used for dilution, consult the package leaflet of the diluent used.

3. How to use Metronidazole 0.5% Polpharma

This medicine should always be used as directed by your doctor. If you are unsure, consult your doctor.
Due to insufficient evidence of the risk of mutagenicity in humans, the use of metronidazole for a longer period than usually recommended should be carefully considered.
Typically, the recommended dose is:

Anaerobic bacterial infections

Metronidazole is administered intravenously at the beginning of treatment in patients whose symptoms prevent oral administration.
Adults and adolescents over 12 years: intravenously 100 ml of 0.5% metronidazole solution (500 mg of metronidazole), every 8 hours. The drug is administered no faster than 5 ml/min.
The maximum daily intravenous dose of metronidazole for adults is 4 g.
Metronidazole is usually used for 7 days, although in severe anaerobic bacterial infections, it may be used for 2-3 weeks.
Children over 8 weeks to 12 years: the usual daily dose is 20-30 mg/kg body weight, as a single dose or divided into doses of 7.5 mg/kg body weight, every 8 hours. The daily dose may be increased to 40 mg/kg body weight, depending on the severity of the infection. The treatment duration is usually 7 days.
Children under 8 weeks: 15 mg/kg body weight per day, as a single dose or divided into doses of 7.5 mg/kg body weight, administered every 12 hours.
In preterm infants born before the 40th week of gestation, metronidazole accumulation may occur during the first week of life, so monitoring of serum metronidazole levels is recommended after a few days of treatment.

Prevention of anaerobic bacterial infections

especially during colon, rectal, or gynecological surgery.
Administration of the drug starts 5-10 minutes before the surgical procedure.
Adults and adolescents over 12 years: intravenously 100 ml of 0.5% metronidazole solution (500 mg of metronidazole) in slow infusion.
Subsequent doses of 0.5% metronidazole solution are administered every 8 hours until oral therapy can be started as soon as possible.
Children under 12 years: 20-30 mg/kg body weight as a single dose administered 1-2 hours before the procedure.
Preterm infants born before the 40th week of gestation: 10 mg/kg body weight as a single dose before surgery.
Prophylactically, the drug is used for no more than 12 hours after surgery.

Bacterial vaginosis

Adolescents: 400 mg twice a day for 5-7 days or 2000 mg as a single dose.

Trichomoniasis

Adults and children over 10 years: 2000 mg as a single dose or 200 mg three times a day for 7 days or 400 mg twice a day for 5-7 days.
Note:treatment is carried out simultaneously in both sexual partners.
Children under 10 years: 40 mg/kg body weight orally as a single dose or 15-30 mg/kg body weight per day divided into 2-3 doses for 7 days, not exceeding 2000 mg/dose.

Giardiasis (lambliasis)

Adults and children over 10 years: 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 to 10 days.
Children from 7 to 10 years: 1000 mg once a day for 3 days.
Children from 3 to 7 years: 600 mg to 800 mg once a day for 3 days.
Children from 1 to 3 years: 500 mg once a day for 3 days.
Alternative dosing regimen for this indication (dose expressed in mg/kg body weight):
15-40 mg/kg body weight per day divided into 2-3 doses.

Amebiasis (peptic ulcer disease)

Adults and children over 10 years: 400 mg to 800 mg three times a day for 5-10 days.
Children from 7 to 10 years: 200 mg to 400 mg three times a day for 5-10 days.
Children from 3 to 7 years: 100 mg to 200 mg four times a day for 5-10 days.
Children from 1 to 3 years: 100 mg to 200 mg three times a day for 5-10 days.
Alternative dosing regimen for this indication (dose expressed in mg/kg body weight):
Children: 35-50 mg/kg body weight per day in 3 divided doses for 5 to 10 days, not exceeding 2400 mg/day.
Treatment of Helicobacter pylori infection (eradication)
Children: as part of combination therapy, 20 mg/kg per day not exceeding 500 mg twice a day for 7-14 days. Consult official guidelines before starting treatment.

Method of administration:

Metronidazole 0.5% Polpharma can be administered intravenously undiluted or (in patients receiving intravenous fluids) diluted in an appropriate amount of 0.9% sodium chloride solution, 5% glucose solution, 5% glucose solution in 0.9% sodium chloride solution, 20 and 40 mmol/l potassium chloride solution (the infusion solution should be prepared immediately before use).
The polyethylene container, after checking the seal and breaking the protective foil, is connected to a two-channel needle set.
The remaining solution after infusion must not be reused. The drug must not be used if visible changes in the solution occur.

Use in patients with liver failure

In patients with severe liver failure or hepatic encephalopathy, the drug may accumulate in the body, so the doctor will recommend reducing the daily dose to one-third, administered once a day.

Use in patients with renal failure

Dose reduction is not necessary in these patients.
In patients undergoing hemodialysis, metronidazole and its metabolites are removed during 8 hours of dialysis, so metronidazole should be administered again immediately after dialysis.
In patients undergoing intermittent or continuous ambulatory peritoneal dialysis, there is no need to change the dosage.

Use in elderly patients

Caution should be exercised when using the drug in elderly patients, especially when using high doses.

Use of a higher dose of Metronidazole 0.5% Polpharma than recommended

In case of using a higher dose of the drug than recommended, consult a doctor immediately.
Using a higher dose of the drug than recommended may cause neurotoxic symptoms, such as:
peripheral neuropathy (tingling and burning in hands and feet, sometimes loss of sensation in a limb), muscle tremors and seizures, as well as nausea, vomiting, and ataxia (difficulty maintaining balance, unsteady gait).

Missing a dose of Metronidazole 0.5% Polpharma

In case of missing a dose, take it as soon as possible. If it is already time for the next dose, do not take the missed dose. Do not take a double dose to make up for the missed dose.
If you have any further questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency, type, and severity of side effects in children are the same as in adults.

In case of noticing any of the following serious side effects, stop taking Metronidazole 0.5% Polpharma and contact your doctor immediately:

• rare side effects (occurring in less than 1 in 1,000 people):
• anaphylaxis manifesting as confusion, pallor, low blood pressure, sweating, oliguria, tachypnea, weakness, and syncope;
• very rare side effects (occurring in less than 1 in 10,000 people):
• agranulocytosis (lack of granulocytes in the blood; symptoms are fever, sore throat, superficial ulcers of the oral mucosa, flu-like symptoms, fatigue), neutropenia (low neutrophil count), thrombocytopenia (low platelet count; symptoms are bruising, petechiae, ecchymosis, nosebleeds), pancytopenia (low red and white blood cell and platelet count);
• psychotic disorders, including confusion and hallucinations;
• encephalopathy (brain disorders, such as disorientation, fever, headache, hallucinations, paralysis, sensitivity to light, vision and movement disorders, stiffness of the neck) and subacute cerebellar syndrome (e.g., coordination disorders, speech impairment, gait disturbances, nystagmus, and tremors), which may require discontinuation of treatment;
• hepatitis, liver cell damage, jaundice, and pancreatitis, which resolve after discontinuation of the drug;
• side effects with unknown frequency (frequency cannot be estimated from available data):
• angioedema (facial, tongue, and pharyngeal edema, which can cause respiratory disorders), urticaria, fever;
• in the course of intensive and/or prolonged metronidazole treatment, peripheral sensory neuropathy (numbness, tingling, or paresthesia, e.g., pricking, burning) or transient seizure-like episodes have been reported; in most cases, neuropathy resolved after discontinuation of the drug or dose reduction;

Other side effects may include:

• very rare side effects (less than 1 in 10,000 people):
• drowsiness, dizziness, seizures, headaches;
• visual disturbances, such as double vision and myopia, which are usually transient;
• increased liver enzyme activity (ASAT, ALAT, alkaline phosphatase);
• rash, pustular rash, itching, redness;
• muscle pain, joint pain;
• darkening of urine color due to the presence of water-soluble dyes formed during metronidazole metabolism.

Side effects with unknown frequency (frequency cannot be estimated from available data):

• leukopenia (low white blood cell count);
• loss of appetite;
• depression;
• hearing and/or balance disorders, tinnitus (ringing in the ears);
• taste disorders, oral mucosal inflammation, coated tongue, nausea, vomiting, gastrointestinal disorders, such as abdominal pain and diarrhea. In patients treated with metronidazole in combination with other antibiotics, cases of liver failure requiring transplantation have been reported.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, inform your doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Jerozolimskie Avenue 181C
02-222 Warsaw
Phone: +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 this medicine.

5. How to store Metronidazole 0.5% Polpharma

Keep the medicine out of the sight and reach of children.
Glass ampoules: Store in the original packaging. Do not store above 25°C.
Polyethylene containers: Store in the original packaging. Do not store above 25°C. Protect from the action of steam and chemically active gases or substances with a strong odor.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
The inscription on the packaging after the abbreviation EXP means the expiry date, and after the abbreviation Lot/LOT means the batch number.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Metronidazole 0.5% Polpharma contains

• The active substance of the medicine is metronidazole. Each milliliter of the solution contains 5 mg of metronidazole. Each 20 ml ampoule contains 100 mg of metronidazole. Each 100 ml container contains 500 mg of metronidazole.
• Other ingredients are: disodium phosphate dodecahydrate, citric acid monohydrate, sodium chloride, water for injections.

What Metronidazole 0.5% Polpharma looks like and contents of the package

Metronidazole 0.5% Polpharma is a clear solution with a slightly yellowish-greenish color.
Available packages:

• glass ampoules containing 20 ml of solution, 10 pieces, in a cardboard box.
• polyethylene container with Insocap adapter containing 100 ml of solution. 1 or 40 containers, in a cardboard box.

Marketing authorization holder and manufacturer

Polpharma S.A.
Pelplińska Street 19, 83-200 Starogard Gdański
phone: +48 22 364 61 01

Date of last revision of the package leaflet: