METRONIDAZOL NORMON 5 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you use Metronidazole Normon 5 mg/ml Solution for Infusion

Do not use Metronidazole Normon

• If you are allergic to metronidazole, other similar substances, or any of the other components of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor before starting to receive Metronidazole 5 mg/ml.

Be especially careful with metronidazole 5mg/ml if you have:

• severe liver damage,
• a blood formation disorder or
• a brain, spinal cord, or nervous system disease.

Therefore, your doctor will determine with great care if you should be treated with Metronidazol 5mg/ml.

If convulsive attacks or any other nervous problem (such as numbness in the limbs) become evident during treatment, your treatment will be reviewed immediately.

Treatment with metronidazole 5 mg/ml should not be prolonged for more than 10 days; the treatment period will only be extended in exceptional circumstances and if it is absolutely necessary. Repeated therapy with metronidazole will be limited to cases where it is absolutely necessary. In such cases, it will be monitored with special attention.

• Treatment should be discontinued or reviewed immediately if you experience severe diarrhea that may be due to a serious intestinal disease called "pseudomembranous colitis" (see also section 4).

There have been reports of severe liver toxicity/liver failure, some of which were fatal, in patients with Cockayne syndrome taking metronidazole-containing medications.

If you have Cockayne syndrome, your doctor should monitor your liver function frequently while you are receiving treatment with metronidazole and thereafter.

Inform your doctor immediately and stop taking metronidazole if you experience:

• stomach pain, loss of appetite, nausea, vomiting, fever, general malaise, fatigue, jaundice, dark urine, clay-colored stools, or itching.

There have been reports of severe blistering skin reactions with metronidazole, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or acute generalized exanthematous pustulosis (AGEP) (see "Possible side effects"). If symptoms or signs of AGEP, SJS, or TEN occur, treatment with Metronidazole Normon should be discontinued immediately.

Since prolonged use of metronidazole can affect blood cell formation (see the section "Possible side effects"), your blood count will be monitored during treatment.

Other medicines and Metronidazole Normon

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine, including those obtained without a prescription.

There is no therapeutic incompatibility with any of the anti-infectives commonly used. It can be administered simultaneously, although separately (i.e., not in the same container), with other anti-infectives.

Amiodarone (used to treat irregular heartbeats)

When receiving this medicine, your heart function will be monitored. You should consult your doctor if you notice any anomaly in heart function, dizziness, or fainting.

Barbiturics (active ingredient of medicines for treating epilepsy or convulsions)

Phenobarbital reduces the duration of action of metronidazole; therefore, it may be necessary to increase your metronidazole dose.

Contraceptive pills

Your contraceptive pill may be less reliable while you are receiving metronidazole.

Busulfan

Metronidazole should not be administered to patients receiving busulfan because, in that case, toxic effects are more likely to occur.

Carbamazepine (medicine for treating epilepsy)

This combination also requires caution because metronidazole can increase the duration of action of carbamazepine.

Cimetidine (medicine for treating stomach disorders)

Cimetidine may reduce the elimination of metronidazole in isolated cases and subsequently leads to an increase in metronidazole serum concentrations.

Coumarin derivatives (medicines that inhibit blood coagulation)

Metronidazole may increase the inhibition of blood coagulation caused by coumarins. Therefore, if you are taking a medicine that inhibits blood coagulation (e.g., warfarin), you may need less of it during treatment with metronidazole.

Cyclosporine (drug used to suppress undesirable immune responses)

When cyclosporine is administered with metronidazole, cyclosporine blood levels may increase; therefore, your doctor will adjust your cyclosporine dose as necessary. Additionally, your kidney function will be monitored.

Disulfiram (used for treating alcohol abstinence)

If you are taking disulfiram, you should not receive metronidazole, or you should discontinue disulfiram treatment. The combined use of these two drugs can lead to confusion up to the point of severe mental disorder (psychosis).

Fluorouracil (anti-cancer medicine)

It may be necessary to reduce the daily dose of fluorouracil when administered with metronidazole because metronidazole can cause an increase in fluorouracil blood levels.

Lithium (used for treating mental illness)

Treatment with lithium preparations requires especially careful monitoring during treatment with metronidazole, and the dose of the lithium preparation may need to be adjusted.

Mycophenolate mofetil (used for preventing organ rejection after transplantation)

Its effect may be weakened by metronidazole, so careful monitoring of the effect of mycophenolate mofetil is recommended.

Phenytoin (drug for treating epilepsy)

If you are taking phenytoin, your doctor will treat you with metronidazole with caution because metronidazole can increase the duration of action of phenytoin. On the other hand, phenytoin may reduce the effect of metronidazole.

Tacrolimus

The blood levels of this agent and kidney function should be monitored after starting or stopping treatment with metronidazole.

Metronidazole 5 mg/ml with alcohol

You should not drink alcoholic beverages while receiving metronidazole, nor during the 48 hours following the end of treatment. Consuming alcohol during metronidazole 5 mg/ml treatment can cause you to feel unwell, with symptoms such as palpitations, flushing, sweating, dizziness, and vomiting.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

If you are pregnant, your doctor will only treat you with metronidazole if it is considered absolutely necessary.

Breastfeeding

Breastfeeding should be discontinued during treatment with metronidazole and should not be resumed until 2-3 days after treatment.

Fertility

Animal studies have indicated a negative influence on the male reproductive system; however, this was only observed at very high doses that far exceeded the recommended dose for humans.

Driving and using machines

You should not drive or use machines while being treated with metronidazole, as metronidazole can alter your state of alertness. This can occur especially at the start of treatment or in combination with alcohol consumption.

This medicine contains 359 mg of sodium (main component of table/cooking salt) in each 100 ml. This is equivalent to 18% of the maximum recommended daily sodium intake for an adult.

3. How to use Metronidazole Normon 5 mg/ml Solution for Infusion

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The dose depends on the nature and severity of your disease, your age, and weight, and your individual response to treatment.

The recommended dose is:

Adults and adolescents

• Treatment of infections

You will be administered 100 ml of this medicine (corresponding to 500 mg of metronidazole) every 8 hours. In most cases, treatment will last 7 days.

Alternatively, you may receive 300 ml of the medicine (corresponding to 1500 mg of metronidazole) on the first day of treatment.

In most cases, treatment will last 7 days. Exceptionally, treatment may be prolonged, although it should not exceed 10 days in general.

The dose will be the same for patients with kidney disease. For patients with liver disease, lower doses will be required. If you are being treated with a hemodialyzer, your doctor will adjust the dose on treatment days.

• Prevention of infections that may occur after surgical interventions

When used for the prevention of infection in surgical procedures, you will be administered 500 mg of the medicine before the procedure. The dose will be repeated 8 and 16 hours after the procedure.

Use in children

Dosage in children is based on body weight

Treatment of infections

In children over 8 weeks to 12 years of age: The usual daily dose is 20-30 mg/kg/day as a single dose or divided into 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. The duration of treatment is generally 7 days.

In children under 8 weeks of age: 15 mg/kg as a single daily dose or divided into 7.5 mg/kg every 12 hours.

In newborns with a gestational age of less than 40 weeks, metronidazole accumulation may occur during the first week of life; therefore, metronidazole plasma concentrations should be monitored, preferably after a few days of treatment.

• Prevention of infections that may occur after surgical interventions

In children under 12 years of age: 20-30 mg/kg as a single dose administered 1-2 hours before surgery.

In newborns with a gestational age of less than 40 weeks: 10 mg/kg body weight as a single dose before the operation.

Method of administration

Metronidazole Normon 5 mg/ml is administered by drip directly into a vein (intravenous infusion). The infusion of a vial usually lasts 60 minutes, but it should not be performed in less than 30 minutes.

If you are receiving other antibiotics simultaneously, your doctor will administer those medicines separately.

If you use more Metronidazole Normon than you should:

Your doctor or nurse will ensure that you receive the correct intravenous dose.

An accidental overdose could cause nausea, vomiting, cravings, metallic taste, headache, dizziness, insomnia, drowsiness, oliguria, and dark urine, hearing problems, and convulsions.

There is no specific antidote for metronidazole overdose. In cases where massive ingestion is suspected, treatment will be based on symptoms.

In case of overdose or accidental administration/ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service (Telephone: 91 562 04 20), indicating the medicine and the amount ingested.

If you forget to use Metronidazole Normon

Do not use a double dose to make up for forgotten doses.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects occur mainly at high doses or with prolonged use.

The following terms are used to describe the frequency of adverse effects:

"Very common" affects more than 1 in 10 treated patients

"Common" affects between 1 and 10 in 100 treated patients

"Uncommon" affects between 1 and 10 in 1,000 treated patients

"Rare" affects between 1 and 10 in 10,000 treated patients

"Very rare" affects less than 1 in 10,000 treated patients

"Not known" The frequency cannot be estimated from the available data.

The following adverse effects may be serious and therefore require immediate treatment:

Rare:

• Severe persistent diarrhea (possibly a symptom of a serious intestinal infection called pseudomembranous colitis)

Emergency treatment of pseudomembranous enterocolitis

In case of severe persistent diarrhea, you should immediately inform your doctor because it may be due to pseudomembranous colitis, a serious disease that must be treated immediately.

Your doctor will interrupt treatment with metronidazole and apply the appropriate treatment.

• Acute and severe hypersensitivity reactions up to anaphylactic shock (swelling of the face, lips, and airways, as well as low blood pressure, difficulty breathing, fainting, and even death)

Very rare:

• Blood counts of platelets and white blood cells may decrease during treatment (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia). Regular monitoring of blood counts is required during prolonged use.
• Hepatitis (liver inflammation), jaundice, pancreas inflammation (isolated reports)
• Cerebral disorders, lack of coordination
• Severe inflammatory rash on mucous membranes and skin with fever, redness, and blisters, in extremely rare cases up to skin detachment in extensive areas (Stevens-Johnson syndrome, toxic epidermal necrolysis)

Not known:

• Hypersensitivity reactions between mild and moderate, a special type of rapid skin swelling of the face called angioedema
• Eye twitching, damage or inflammation of the eye nerves
• Reduced white blood cell count, severe anemia
• Seizures, nervous disorders such as numbness, pain, tingling or burning sensation in arms or legs.
• Inflammation of the meninges (or brain lining) that is not of bacterial origin (aseptic meningitis)

Other Adverse Effects

Common

• Fungal infections (e.g., genital infections)

Uncommon

• Darkened urine (due to a metronidazole metabolite)

Rare

• Changes in the ECG (heart electrical activity)

Very rare:

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

Not known:

• Dizziness, nausea, diarrhea, inflammation of the tongue or mouth, belching and bitter taste, metallic taste, pressure on the stomach, furry tongue
• Difficulty swallowing
• Decreased interest in food/appetite (anorexia)
• Sad mood (depressive)
• Drowsiness or insomnia, muscle spasms,
• Redness and itching of the skin (erythema multiforme)
• Irritation of the venous walls (up to the extreme of presenting inflamed and thrombosed veins) after intravenous administration, weakness, fever

The type and severity of adverse effects in children are the same as in adults.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Metronidazol Normon 5 mg/ml Solution for Infusion

Keep out of sight and reach of children.

Bags: Store below 30°C. Store in the original packaging to protect from light. Do not freeze or refrigerate.

Since metronidazole is sensitive to light, the overwrap of the bag will only be removed immediately before administration.

Do not use Metronidazol Normon after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Discard if alterations are observed in the packaging or in the liquid it contains.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Metronidazol Normon:

The active ingredient is metronidazole.

Each 100 ml of solution contains 500 mg of metronidazole.

The other components are: sodium hydrogen phosphate, citric acid monohydrate, sodium chloride, and water for injectable preparations.

Each 300 ml of solution contains 1.5 g of metronidazole.

The other components are: sodium hydrogen phosphate, citric acid monohydrate, sodium chloride, and water for injectable preparations.

Appearance of the Product and Package Contents:

Metronidazol Normon contains a clear, colorless or slightly yellowish solution.

It is presented in 100 and 300 ml plastic bags.

Marketing Authorization Holder and Manufacturer:

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Other Presentations

Metronidazol Normon 250 mg tablets

Date of the Last Revision of the Prospectus:June 2021.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http:/www.aemps.gob.es/.