METRONIDAZOL AUROVITAS 250 mg FILM-COATED TABLETS

2. What you need to know before you take Metronidazole Aurovitas

Do not take Metronidazole Aurovitas

• If you are allergic to metronidazole, other 5-nitroimidazole derivatives, or any of the other ingredients of this medicine (listed in section 6).
• In the first trimester of pregnancy.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting treatment with metronidazole if you have:

• severe liver damage,
• blood formation disorders or
• brain, spinal cord, or nerve disease.

Therefore, your doctor will very carefully determine whether you should be treated with metronidazole.

If convulsive attacks or any other nervous condition (e.g., numbness in the limbs) become apparent during treatment, your treatment will be reviewed quickly.

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

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

If you take this medicine, your urine may darken.

There have been reports of severe liver toxicity/liver failure, including cases with a fatal outcome, in patients with Cockayne syndrome with metronidazole-containing medications.

If you have Cockayne syndrome, your doctor should also closely monitor your liver function while you are being treated with metronidazole and thereafter.

Tell 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.

Normally, treatment with metronidazole should not be prolonged for more than 10 days; the treatment period will only be extended in exceptional circumstances and if absolutely necessary. Repeated treatment with metronidazole will be limited to cases where it is absolutely necessary. In such cases, you will be closely monitored.

Other Medicines and Metronidazole Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Amiodarone (used to treat cardiac arrhythmias)

When you are being treated with this medicine, your heart function should be monitored.

You should see your doctor if you notice any abnormality in heart function, dizziness, or fainting.

Barbiturates (sleeping pills)

The duration of action of metronidazole is reduced by phenobarbital; therefore, your dose of metronidazole may need to be increased.

Contraceptive pills

Your contraceptive pill may be less effective while you are being treated with metronidazole.

Busulfan

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

Carbamazepine (medication for the treatment of epilepsy)

This combination also requires caution since metronidazole may increase the duration of action of carbamazepine.

Cimetidine (medication for the treatment of stomach disorders)

Cimetidine may reduce the elimination of metronidazole in isolated cases and subsequently lead to an increase in metronidazole blood 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 to reduce the dose during treatment with metronidazole.

Cyclosporin (medication used to reduce unwanted immune reactions)

When cyclosporin is administered together with metronidazole, cyclosporin blood levels may increase; therefore, your doctor will need to adjust your cyclosporin dose accordingly.

Disulfiram (used in the treatment of alcohol dependence)

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

Medicines containing alcohol

See the section "Taking Metronidazole Aurovitas with food, drinks, and alcohol".

Fluorouracil (anticancer medication)

The daily dose of fluorouracil may need to be reduced when administered together with metronidazole since it may lead to an increase in fluorouracil blood levels.

Lithium (used to treat mental illnesses)

Treatment with lithium preparations requires particularly close monitoring during treatment with metronidazole and may need to have the lithium preparation dose adjusted. Lithium treatment should be reduced or discontinued before metronidazole administration.

Mycophenolate mofetil (used to prevent organ rejection after transplantation)

Its effect may be weakened by metronidazole, so careful monitoring of its effect is recommended.

Phenytoin (medication for the treatment of epilepsy)

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

Tacrolimus (medication used to reduce unwanted immune reactions)

The blood levels of this medicine and its renal function should be monitored when starting and stopping treatment with metronidazole.

Taking Metronidazole Aurovitas with Food, Drinks, and Alcohol

Alcohol

Do not drink alcoholic beverages or take medicines containing alcohol while being treated with metronidazole and up to 48 hours after, as this may cause intolerance reactions such as dizziness and vomiting.

Pregnancy, Breast-feeding, and Fertility

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

Fertility

Animal studies only indicate a possible negative influence of metronidazole on the male reproductive system if high doses are administered that are far above the maximum recommended dose for humans.

Contraception in Men and Women

If you are taking a contraceptive pill, see the section "Other Medicines and Metronidazole Aurovitas".

Pregnancy

If you are pregnant, your doctor will not treat you with metronidazole unless it is considered absolutely necessary.

Breast-feeding

Do not breast-feed during treatment with metronidazole and do not resume breast-feeding for 2-3 days after because metronidazole passes into breast milk.

Driving and Using Machines

While being treated with this medicine, you may feel drowsy, dizzy, confused, see or hear things that are not there (hallucinations), have seizures, or have temporary vision problems (such as blurred or double vision). If this happens, do not drive or use any machinery or tools.

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet; this is essentially "sodium-free".

3. How to Take Metronidazole Aurovitas

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

Due to the lack of evidence on the risk of mutagenicity in humans, the doctor will assess whether it is necessary to use metronidazole for a longer period than usual.

Normally, the recommended dose is as follows:

Prevention of anaerobic bacterial infections (in gynecological or colorectal surgery)

Metronidazole will be administered preventively 24 hours before surgery until at least 4 hours after wound closure, or longer, depending on the risk of contamination.

Adults and adolescents over 12 years:

• Initially 4 tablets of 250 mg (1,000 mg), followed by 1 tablet three times a day until the preoperative fast.

Children under 12 years:

• 20-30 mg/kg as a single dose, administered 1-2 hours before the procedure.

Newborns, born before 40 weeks of gestation:

• 10 mg/kg as a single dose before surgery.

Bacterial infection

Metronidazole can be used therapeutically, only in combination with other antibacterial agents. The average treatment period should not exceed 7 days.

Adults and adolescents over 12 years:

• 1 or 2 tablets of 250 mg three times a day.

Children over 8 weeks to 12 years:

• The usual daily dose is 20-30 mg/kg as a single dose or in divided doses of 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection.

Children under 8 weeks:

• 15 mg/kg/day as a single dose or in divided doses of 7.5 mg/kg administered every 12 hours.

In infants born before 40 weeks of gestation, metronidazole accumulation may occur during the first week of life, so after a few days of treatment, metronidazole plasma concentrations should be monitored.

Trichomoniasis

Adults and children over 10 years:

• 8 tablets of 250 mg (2,000 mg) as a single dose or 1 tablet three times a day for seven days or 2 tablets twice a day for 5-7 days.

Note: Treatment is carried out simultaneously in sexual partners.

Children under 10 years:

• 40 mg/kg orally as a single dose or 15-30 mg/kg per day divided into 2-3 doses for 7 days. A single dose should not exceed 2,000 mg.

Bacterial vaginitis

Adults:

• 2 tablets of 250 mg (500 mg) in the morning and evening for seven days or 8 tablets (2,000 mg) as a single dose (once).

Young people:

• 8 tablets (2,000 mg) as a single dose (once).

Amoebiasis

Adults:

• 3 tablets of 250 mg (750 mg) three times a day for 5-10 days.

Young people and children over 10 years:

• 2 or 3 tablets of 250 mg (500 mg to 750 mg) three times a day for 5-10 days.

Children from 7 to 10 years:

• 250 mg three times a day for 5-10 days.

Alternative dosing regimen for this condition (dose expressed in mg per kg): 35-50 mg/kg/day in three divided doses for 5 to 10 days, not exceeding 2,400 mg daily.

Giardiasis

Adults:

• 1 tablet of 250 mg three times a day for 5-7 days or 8 tablets (2,000 mg) once a day for 3 days.

Young people and children over 10 years:

• 8 tablets (2,000 mg) once a day for 3 days or 2 tablets (500 mg) twice a day for 7 to 10 days.

Children from 7 to 10 years:

• 4 tablets of 250 mg (1,000 mg) once a day for 3 days.

Children from 3 to 7 years:

• 3 tablets of 250 mg (750 mg) once a day for 3 days.

Children from 1 to 3 years:

• 2 tablets of 250 mg (500 mg) once a day for 3 days.

Alternative dosing regimen for this condition (dose expressed in mg per kg): 15-40 mg/kg/day divided into 2-3 doses.

Treatment of Helicobacter pylori bacterial infection (called eradication)

Metronidazole is used for at least 7 days in combination with other prescribed medications for the treatment of Helicobacter pylori infections.

Adults:

• 2 tablets of 250 mg (500 mg) 2-3 times a day for 7-14 days.

Children and young people:

• 20 mg/kg/day, not more than 2 tablets (500 mg) twice a day for 7-14 days.

Before starting treatment, consult the official guidelines.

Acute ulcerative gingivitis

Adults:

• 1 tablet of 250 mg 2-3 times a day for three days.

Children:

• 35-50 mg/kg/day in three divided doses for three days.

Acute periodontal infections

Adults:

• 1 tablet of 250 mg 2-3 times a day for 3-7 days.

Babies and children weighing less than 10 kg:

• Administer proportionally smaller doses.

Method of administration

Oral.

For some of the doses described above, there are also other medicines that contain metronidazole with a different concentration (film-coated tablet, 500 mg) and in a different pharmaceutical form (infusion solution, 5 mg/ml).

Use in patients with liver impairment

In patients with liver damage or severe hepatic encephalopathy, drug accumulation may occur in the body; therefore, the doctor will reduce the prescribed daily dose by one-third, administered once a day.

Use in patients with renal impairment

No dose reduction is necessary in these patients.

Use in elderly patients

In elderly patients, this medicine should be used with caution, especially in high doses.

If you take more Metronidazole Aurovitas than you should

Consult your doctor immediately if you take more than the recommended dose.

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

If you forget to take Metronidazole Aurovitas

If you forget to take a dose, take it as soon as you remember. If it is almost time for the next dose, do not take the missed dose and take the next dose at the scheduled time.

Do not take a double dose to make up for the missed dose.

If you have any further questions on 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.

The frequency, type, and severity of adverse reactions in children are the same as in adults.

If you experience any of the following serious adverse effects, stop taking this medicine and contact your doctor immediately:

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

• Severe persistent diarrhea (possibly a symptom of a serious intestinal infection called pseudomembranous colitis, see below).
• Severe acute hypersensitivity reactions up to anaphylactic shock.

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

• Decrease during treatment of white blood cell and platelet counts (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia).
• Hepatitis (inflammation of the liver), jaundice, pancreatitis.
• Cerebral disorders, lack of coordination.
• Non-bacterial cerebral fever (aseptic meningitis).
• Severe inflammatory rash on mucous membranes and skin with fever, redness, and blisters, in extremely rare cases up to skin detachment in large areas (Stevens-Johnson syndrome).

Frequency not known (cannot be estimated from available data)

• Mild to moderate hypersensitivity reactions, swelling of the face, mouth, throat, and/or tongue (angioedema).
• Deviation of gaze, damage or inflammation of the eye nerves.
• Decreased white blood cell count (leukopenia), severe anemia (aplastic anemia).
• Seizures, nervous disorders such as numbness, pain, hairy sensation, or tingling in the arms or legs.
• Toxic epidermal necrolysis.
• Acute liver failure in patients with Cockayne syndrome (see section 2 "Warnings and precautions").

Other Adverse Effects

Frequent (may affect up to 1 in 10 people)

• Fungal infections (e.g., genital infections).
• Urethral burning/discomfort, dysuria, cystitis, polyuria, incontinence.

Infrequent (may affect up to 1 in 100 people)

• Darkened urine (due to metronidazole metabolite).
• Nasal congestion (stuffy nose).

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

• Changes in the electrocardiogram (ECG).

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

• Psychotic disorders, including confusion, hallucination.
• Headache, dizziness, drowsiness, fever, alteration of vision and movement, staggering, speech defects, seizures.
• Visual disturbances, e.g., double vision, myopia.
• Disorders of liver function (such as elevated serum levels of certain enzymes and bilirubin).
• Allergic reactions on the skin such as itching, urticaria.
• Joint and muscle pain.

Frequency not known (cannot be estimated from available data)

• Nausea, feeling of discomfort, diarrhea, inflammation of the tongue or mouth, belching and bitter taste, metallic taste, pressure above the stomach, hairy tongue.
• Difficulty swallowing.
• Anorexia.
• Sad mood (depressed).
• Hearing impairment/hearing loss.
• Ringing in the ears (tinnitus).
• Drowsiness or insomnia, muscle spasms.
• Redness and itching of the skin (erythema multiforme).
• Irritation of the venous wall (up to the point of inflammation of the veins and thrombosis) after intravenous administration, weakness, fever.

• A well-defined area of the skin with redness and sometimes blisters, which is caused by hypersensitivity to the drug (fixed drug eruption).

Emergency Treatment of Pseudomembranous Colitis

In case of severe persistent diarrhea, you should immediately inform your doctor because this may be due to pseudomembranous colitis, a serious disease that must be treated immediately. Your doctor will interrupt treatment with metronidazole and provide you with appropriate treatment.

If you consider that any of the adverse effects you are suffering from is serious or if you notice any adverse effect not mentioned in this leaflet, inform your doctor.

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 leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Metronidazole Aurovitas

Keep this medicine out of the sight and reach of children.

This medicine does not require special storage conditions.

Do not use this medicine after the expiration date that appears on the carton after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the containers and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition ofMetronidazole Aurovitas

• The active ingredient is metronidazole. Each film-coated tablet contains 250 mg of metronidazole.
• The other components are:

Core of the tablet:microcrystalline cellulose, pregelatinized corn starch, hydroxypropylcellulose, anhydrous colloidal silica, sodium carboxymethylcellulose (type A) (from potato) and stearic acid.

Coating of the tablet:hypromellose 2910 (5cps) and polyethylene glycol.

Appearance of the Product and Package Contents

Film-coated tablets, white to off-white in color, round in shape, marked with "M" and "250" on one side and smooth on the other.

Metronidazole Aurovitas 250 mg film-coated tablets are available in blisters of 20, 21, and 40 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Arrow Generiques – Lyon

26 avenue Tony Garnier,

Lyon, 69007

France

O

Generis Farmacêutica, S.A.

Rua João de Deus, 19

2700-487 Amadora

Portugal

This medicine is authorized in the Member States of the European Economic Area under the following names:

Spain: Metronidazole Aurovitas 250 mg film-coated tablets EFG

France: MÉTRONIDAZOLE ARROW 250 mg, film-coated tablet

Italy: Metronidazolo Aurobindo

Netherlands: Metronidazol Auro 250 mg, film-coated tablets

Poland: Metronidazol Aurovitas

Portugal: Metronidazol Generis

Date of the last revision of this leaflet: August 2023

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