Metronidazole Noridem

PACKAGE LEAFLET

Package leaflet: information for the patient

Metronidazole Noridem 5 mg/mL infusion solution

metronidazole
Please read this leaflet carefully before you are given this medicine as 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

The name of your medicine is Metronidazole Noridem 5 mg/mL infusion solution
In the remainder of this leaflet, the medicine will be referred to as Metronidazole Noridem.
Contents of this leaflet

1. What Metronidazole Noridem is and what it is used for
2. What you need to know before Metronidazole Noridem is administered to you
3. How Metronidazole Noridem is administered
4. Possible side effects
5. How to store Metronidazole Noridem
6. Contents of the pack and other information

1. What Metronidazolo Noridem is and what it is used for

Metronidazolo Noridem belongs to a group of medicines called 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 Noridem to treat any of the following conditions:

• Infections of the blood, brain, lungs, bones, genital tract, pelvic area, liver, intestines, and stomach.
  If necessary, your treatment may be combined with other antibiotics.
  Metronidazolo Noridem may also be prescribed as a preventive treatment before surgeries associated with a higher risk of infection by so-called anaerobic bacteria, particularly in gynaecology or gastrointestinal surgery.

2. What you should know before being administered Metronidazole Noridem

Do not take Metronidazole Noridem

• 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, pharmacist, or nurse before being administered
Metronidazole Noridem if you have:

• severe liver damage
• a blood cell disorder, or
• a disease affecting the brain, spinal cord, or nerves

Therefore, your doctor must carefully evaluate whether you should be treated with
Metronidazole Noridem.
If seizures or other neurological disturbances (e.g., numbness of the limbs) occur during treatment, your treatment must be immediately reassessed.
Treatment must be immediately discontinued or reassessed if you develop severe diarrhoea, which may be due to a serious intestinal disease called "pseudomembranous colitis" (see also section 4). Since prolonged use of metronidazole may impair blood cell formation (see section "Possible side effects"), your blood cell count will be monitored during treatment.
If you have received this medicine, your urine may become dark.
Cases of severe liver toxicity/acute liver failure, including fatal outcomes, have been reported in patients with Cockayne syndrome treated with medicinal products containing metronidazole.
If you suffer from Cockayne syndrome, your doctor must also frequently monitor your liver function while you are taking metronidazole and afterwards.
Immediately inform your doctor and stop taking metronidazole if you develop:

• Stomach pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, tar-colored stools, or itching.

Treatment with Metronidazole Noridem should generally not be continued for more than 10 days; the treatment period will be extended only under exceptional circumstances and if absolutely necessary. Repeated courses of metronidazole therapy will be limited to cases where this is absolutely essential. In such cases, you will be monitored particularly closely.

Other medicines and Metronidazole Noridem
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Amiodarone (used to treat irregular heartbeat)
When receiving this medicine, your cardiac function must be monitored. You should contact your doctor if you notice any abnormalities in heart function, dizziness, or fainting.

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

Oral contraceptives
Your oral contraceptive may be less reliable while you are being administered metronidazole.

Busulfan
Metronidazole must not be administered to patients taking busulfan, as it increases the likelihood 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)
In isolated cases, cimetidine may reduce the elimination of metronidazole, thereby leading to increased metronidazole serum concentrations.

Coumarin derivatives (medicines that inhibit blood coagulation)
Metronidazole may enhance the anticoagulant effect of coumarins. Therefore, 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 treatment with metronidazole.

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 appropriately adjust the cyclosporine dose.

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

Medicines containing alcohol
Refer to the section "Metronidazole Noridem with food, drinks, and alcohol".

Fluorouracil (an anticancer medicine)
It may be necessary to reduce the daily dose of fluorouracil when administered concomitantly with metronidazole, as metronidazole may lead to increased fluorouracil blood levels.

Lithium (used in the treatment of mental illnesses)
Treatment with lithium-containing preparations requires particularly careful monitoring during treatment with metronidazole, and it may be necessary to adjust the dose of the lithium preparation. Lithium treatment should be gradually reduced or discontinued before administering metronidazole.

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

Phenytoin (a medicine for the treatment of epilepsy)
If you are taking phenytoin, your doctor will administer metronidazole with particular caution, as metronidazole may increase the duration of action of phenytoin. Conversely, phenytoin may reduce the effect of metronidazole.

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

Metronidazole Noridem with food, drinks, and alcohol
Alcohol
While being administered metronidazole and for up to 48 hours afterwards, you must not drink alcoholic beverages or take medicines containing alcohol, as this may cause intolerance reactions such as dizziness and vomiting.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Fertility
Animal studies indicate only a potential negative impact of metronidazole on the male reproductive system when high doses, exceeding the maximum recommended human dose, were administered.

Contraception in males and females
If you are taking oral contraceptives, refer to the section "Other medicines and Metronidazole Noridem".

Pregnancy
If you are pregnant, your doctor will not prescribe metronidazole unless absolutely necessary.

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

Driving and using machines
While taking Metronidazole Noridem, you may feel drowsy, dizzy, confused, see or hear things that are not real (hallucinations), have seizures, or experience temporary vision problems (such as blurred or double vision). If this occurs, do not drive or operate tools or machinery.

Metronidazole Noridem contains sodium
This medicine contains 310.58 mg of sodium (a main component of table salt) per 100 mL. This is equivalent to 15.5% of the maximum recommended daily intake of sodium for an adult.

3. How Metronidazole Noridem is administered

Dosage
The dosage depends on the nature and severity of your illness, your age and body weight, and
your individual response to treatment.
The recommended usual dosages are:
Adults and adolescents
Treatment of amoebiasis
1,500 mg per day (500 mg three times a day, intravenous infusions).
Treatment of infections
Adults
You will be given 100 mL of the medicinal product (500 mg of metronidazole) every 8 hours.
In most cases, treatment will last 7 days. Only in exceptional cases may treatment be continued further, although treatment duration should normally not exceed 10 days.
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 treatment with artificial kidney (haemodialysis), your doctor will schedule administration after completion of dialysis. No adjustment of the usual dose is necessary.
Prevention of infections that may occur after surgery
If used for prevention of infections in surgical procedures, you may be given 500 mg of the medicinal product before surgery. The dose will be repeated 8 and 16 hours after surgery.
Elderly
Your doctor will give you this medicine with particular caution.
Use in children
In children, the dosage is based on body weight.
Treatment of amoebiasis
35–50 mg/kg/day intravenously, divided into 3 doses for 5–10 days. A maximum of 2,400 mg/day must not be exceeded.
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 Noridem is administered via a direct intravenous infusion into a vein (intravenous infusion).
The infusion of one vial usually takes 60 minutes, but must not be administered in less than 20 minutes.
The total duration of treatment with metronidazole is usually 7 days and must not exceed 10 days, unless absolutely necessary (see also "Warnings and precautions"). If you are taking other antibiotics at the same time, your doctor will administer these drugs separately.

If you are given more Metronidazolo Noridem than you should:
The adverse effects described in the next section may appear as signs or symptoms of overdose. Single oral doses of metronidazole up to 12 g have been reported in suicide attempts and cases of accidental overdose.
Symptoms were limited to vomiting, ataxia, and mild disorientation.
There is no known specific antidote or specific treatment for 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 gets them.
Side effects mainly occur at high doses or with prolonged use.
Immediately tell your doctor if you notice any of the following side effects:

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

• Severe persistent diarrhoea (possibly a symptom of a serious intestinal infection called pseudomembranous colitis; see section "Emergency treatment of pseudomembranous enterocolitis")
• Severe acute allergic reactions up to anaphylactic shock

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

• White blood cell and platelet counts may decrease during treatment (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia)
• Hepatitis (liver inflammation), jaundice, pancreatitis
• Brain disorders, lack of coordination
• Bacterial meningitis not caused by bacteria (aseptic meningitis)
• Severe inflammatory rash affecting mucous membranes and skin with fever, redness and skin rash with blisters; in extremely rare cases, extensive skin peeling may occur (Stevens-Johnson syndrome)

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

• Hypersensitivity reactions from mild to moderate, swelling of face, mouth, throat and/or tongue (angioedema)
• Eye movement spasm, damage or inflammation of ocular nerves
• Reduced white blood cell count (leucopenia), severe anaemia (aplastic anaemia)
• Seizures, nerve disorders such as numbness, pain, burning sensation or tingling in arms or legs
• Toxic epidermal necrolysis
• Acute liver failure in patients with Cockayne syndrome (see section 2 "Warnings and precautions")

Other side effects include
Common (may affect up to 1 in 10 people):

• Fungal infections (e.g. genital infections)

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

• Dark-coloured urine (due to a metabolite of metronidazole)

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

• Changes in ECG

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

• Psychotic disorders, including confusion and hallucinations
• Headache, dizziness, drowsiness, fever, visual and motor disturbances, vertigo, speech disorders, seizures
• Visual disturbances, e.g. double vision, myopia
• Liver function disorders (such as elevated serum levels of certain enzymes and bilirubin)
• Allergic skin reactions such as itching, urticaria
• Muscle and joint pain

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

• Stomach discomfort, nausea, diarrhoea, inflammation of tongue or mouth, belching and bitter taste, metallic taste, feeling of heaviness in the stomach, coated tongue (white-yellowish coating)
• Difficulty swallowing
• Anorexia
• Depressed mood (feeling sad)
• Drowsiness 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 caused by pseudomembranous colitis, a serious condition requiring immediate treatment.
Your doctor will stop metronidazole and prescribe appropriate therapy.
If any of the side effects worsen, or if you notice any side effect not listed in this leaflet, inform your doctor.

Reporting of side effects
If you get any side effects, 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
Website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Metronidazole Noridem

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and on the bottle after "Exp". The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions. The medicine must be used immediately after first opening. For single use only. Do not use this medicine if the container is leaking or if the solution is not clear. Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Metronidazole Noridem contains

• The active substance is metronidazole. Each infusion solution bottle contains 500 mg of metronidazole. Each mL of infusion solution contains 5 mg of metronidazole.
• The other components are disodium phosphate dodecahydrate, citric acid monohydrate, sodium chloride, water for injection solutions.

Description of the appearance of Metronidazole Noridem and pack contents
This medicine is a nearly colourless to light yellow injectable solution
contained in a 100 mL polypropylene bottle with a blow-fill-seal closure,
with a shaped plastic cap with rubber seal and tear-off opening, or with a plastic closure cap and port.
Metronidazole Noridem is available in packs containing 10, 20 or 24 bottles.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Noridem Enterprises Ltd.
Evagorou & Makariou,
Mitsi Building 3, Office 115,
Nicosia 1065, Cyprus

Manufacturer
DEMO S.A. PHARMACEUTICAL INDUSTRY
21st Km National Road Athens-Lamia
14568 Greece

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

The following information is intended exclusively for healthcare professionals:

Dosage and method of administration
Dosage
The dosage is adjusted according to the individual patient's response to therapy, their age, body weight, and the nature and severity of the disease.
The following dosage guidelines must be observed:
Adults and adolescents:
Amebiasis
1,500 mg daily (500 mg three times daily, intravenous infusions).
In hepatic amebiasis at the abscess stage, the abscess must be drained concurrently with metronidazole treatment. Duration of treatment: 5–10 days.
Treatment of anaerobic infections
500 mg (100 mL) every 8 hours. Alternatively, 1,000 mg – 1,500 mg may be administered daily as a single dose.
The duration of therapy depends on the therapeutic response. In most cases, a 7-day course of treatment is sufficient. If clinically indicated, treatment may be continued further, although the duration should normally not exceed 10 days.
Prophylaxis against postoperative infection caused by anaerobic bacteria
500 mg, administered approximately one hour before surgery. The dose should be repeated after 8 and 16 hours.
Elderly patients:
Caution is recommended in elderly patients, especially at higher doses, although limited information is available regarding dosage adjustments.
Paediatric population
Amebiasis
35–50 mg/kg/day intravenously, divided into three doses for 5 to 10 days. A maximum of 2,400 mg/day must not be exceeded.
In hepatic amebiasis at the abscess stage, the abscess must be drained concurrently with metronidazole treatment.
Treatment of anaerobic infections
Children from >8 weeks to 12 years of age:
The usual daily dose is 20–30 mg per kg body weight per day as a single dose or divided into 7.5 mg per kg body weight every 8 hours. The daily dose may be increased up to 40 mg per kg body weight depending on the severity of the infection.
Neonates and infants <8 weeks of age:
15 mg per kg body weight per day as a single dose or divided into 7.5 mg per kg body weight every 12 hours.
In neonates with a gestational age <40 weeks, accumulation of metronidazole may occur during the first week of life; therefore, serum concentrations of metronidazole should preferably be monitored after several days of therapy.
The usual duration of treatment is 7 days.
Prophylaxis against postoperative infections caused by anaerobic bacteria:
Children <12 years:
20–30 mg/kg body weight as a single dose administered 1–2 hours before surgery.
Neonates with gestational age <40 weeks:
10 mg/kg body weight as a single dose administered before surgery.
Patients with renal impairment
Limited data are available in this population. These data do not indicate the need for dose reduction.
In patients undergoing haemodialysis, the standard dose of metronidazole should be scheduled after haemodialysis on dialysis days to compensate for the removal of metronidazole during the procedure.
Routine dose adjustment is not necessary in patients with renal impairment undergoing intermittent peritoneal dialysis (IPD) or continuous ambulatory peritoneal dialysis (CAPD).
Patients with hepatic impairment
Since the serum half-life is prolonged and plasma clearance delayed in severe hepatic impairment, patients with severe liver disease require lower doses.
In patients with hepatic encephalopathy, the daily dose should be reduced to one-third of the usual dose and may be administered once daily.
Method of administration
Intravenous use
The contents of one vial must be infused slowly intravenously, i.e., 100 mL over not less than 20 minutes, usually over more than one hour.
Concomitantly prescribed antibiotics must be administered separately.