Metronidazole Aurobindo

Package leaflet: Information for the user

Metronidazole Aurobindo 250 mg film-coated tablets

Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their
symptoms are the same as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
Contents of this leaflet:

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

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

Metronidazolo Aurobindo belongs to the pharmaceutical category of antiprotozoal and antibacterial agents. It is used in adults and children for:
prevention of postoperative anaerobic bacterial infections;
therapeutic treatment of infections caused by anaerobes (peritonitis, brain abscess, osteomyelitis, puerperal fever, pelvic abscess, post-surgical wound infections);
inflammation due to urogenital trichomoniasis in both women and men;
bacterial vaginosis;
diseases caused by protozoa – amoebiasis and giardiasis;
acute ulcerative gingivitis; acute periodontal infections;
infection with Helicobacter pylori associated with peptic ulcer, in combination with other recommended medications.

2. What you should know before taking Metronidazole Aurobindo

Do not take Metronidazole Aurobindo:

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Metronidazole Aurobindo if you have:

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

Therefore, your doctor will carefully determine whether you should be treated with Metronidazole Aurobindo.
If seizures or other nerve disorders (e.g. numbness of limbs) occur during treatment, the treatment will be promptly reviewed.
Treatment must be stopped or reviewed immediately in case of severe diarrhoea, which could be due to a serious intestinal disease called "pseudomembranous colitis" (see also section 4).
Since prolonged use of metronidazole may impair blood formation (see section "Possible side effects"), blood counts will be monitored during treatment.
If you are being treated with this medicine, your urine may darken.
Cases of severe hepatic toxicity / acute liver failure, including fatal cases, have been reported with metronidazole-containing medicines in patients affected by Cockayne syndrome.
If you suffer from Cockayne syndrome, your doctor will frequently monitor your liver function both during and after treatment with metronidazole.
Inform your doctor immediately and stop taking metronidazole if you experience:

• stomach pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, grey-green stools, or itching.

Treatment with Metronidazole Aurobindo should usually 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 Aurobindo
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

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

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

Oral contraceptives
The oral contraceptive pill may be less reliable while you are receiving metronidazole.

Busulfan
Metronidazole must not be administered to patients receiving busulfan, as toxic effects are more likely to occur in such cases.

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)
Cimetidine may reduce the elimination of metronidazole in isolated cases, thereby potentially increasing serum concentrations of metronidazole.

Coumarin derivatives (medicines that inhibit blood clotting)
Metronidazole may enhance the blood clotting inhibition caused by coumarins. Therefore, if you are taking a medicine that inhibits blood clotting (e.g. warfarin), it may be necessary to reduce the dose during treatment with metronidazole.

Cyclosporine (a medicine used to suppress unwanted immune responses)
When cyclosporine is administered together with metronidazole, blood levels of cyclosporine may increase; therefore, your doctor may need to adjust the cyclosporine dose as required.

Disulfiram (used in alcohol abstinence therapy)
If you are taking disulfiram, you must not take metronidazole, or disulfiram must be discontinued. The combined use of these two medicines may lead to confusion up to severe mental disturbance (psychosis).

Medicines containing alcohol
See section "Metronidazole Aurobindo with food, drinks and alcohol".

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

Lithium (used to treat mental illness)
Treatment with lithium preparations requires particularly careful monitoring during treatment with metronidazole, and it may be necessary to readjust the dose of the lithium preparation. Treatment with lithium should be reduced or stopped before starting metronidazole.

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

Phenytoin (a medicine used to treat epilepsy)
If you are taking phenytoin, your doctor will treat you with metronidazole cautiously, as metronidazole may increase the duration of action of phenytoin. On the other hand, phenytoin may reduce the effect of metronidazole.

Tacrolimus (used to suppress unwanted immune responses)
Blood levels of this agent and kidney function must be monitored when starting and stopping treatment with metronidazole.

Metronidazole Aurobindo with food, drinks and alcohol
Alcohol
You must not consume alcoholic beverages or medicines containing alcohol during treatment with metronidazole and for at least 48 hours afterwards, as this may cause intolerance reactions such as dizziness and vomiting.

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

Fertility
Animal studies indicate a potential negative effect of metronidazole on the male reproductive system at high doses above the maximum recommended human dose.

Contraception in males and females
If you are taking an oral contraceptive pill, see section "Other medicines and Metronidazole Aurobindo".

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

Breastfeeding
You must not breastfeed during treatment with metronidazole and should not resume breastfeeding for 2–3 days afterwards, as metronidazole passes into breast milk.

Driving and using machines
While taking Metronidazole Aurobindo, you may experience drowsiness, dizziness, confusion, seeing or hearing things that are not there (hallucinations), seizures, or temporary vision problems (such as blurred or double vision). In such cases, do not drive or operate machinery or tools.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

3. How to take Metronidazole Aurobindo

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Due to insufficient evidence regarding the risk of mutagenicity in humans, your doctor will assess whether it is necessary to use metronidazole for a longer period than usually recommended.

Recommended dose:

Prevention of infections caused by anaerobic bacteria (in gynecological or colorectal surgery)
Metronidazole will be administered prophylactically, starting 24 hours before surgery, and continued for a minimum of 4 hours after wound closure, or longer depending on the risk of contamination.

Adults and adolescents over 12 years:

• First, four 250 mg tablets (1000 mg) as a single dose, followed by one tablet three times a day until preoperative fasting.

Children under 12 years:

• 20 to 30 mg/kg as a single dose given 1 to 2 hours before the procedure.

Neonates born before 40 weeks of gestation:

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

Bacterial infection
Metronidazole may be used therapeutically, either alone or in combination with other antibacterial agents. The average treatment duration should not exceed 7 days.

Adults and adolescents over 12 years:

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

Children aged between 8 weeks and 12 years:

• The usual daily dose is 20 to 30 mg/kg, given as a single dose or 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 per day as a single dose or divided into doses of 7.5 mg/kg administered every 12 hours. In neonates born before 40 weeks of gestation, accumulation of metronidazole may occur during the first week of life; therefore, serum concentrations of metronidazole should be monitored after a few days.

Trichomoniasis
Adults and children over 10 years:

• 8 tablets of 250 mg (2000 mg) as a single dose, or one tablet three times a day for seven days, or 2 tablets twice a day for 5–7 days.
  Note: Treatment must be administered simultaneously to sexual partners.

Children under 10 years:

• 40 mg/kg orally as a single dose, or 15 to 30 mg/kg per day divided into 2–3 doses for 7 days. A single dose must not exceed 2000 mg.

Bacterial vaginosis
Adults:

• Two 250 mg tablets (500 mg) in the morning and evening for seven days, or eight tablets (2000 mg) as a single dose (once).

Young people:

• Eight tablets (2000 mg) as a single dose (once).

Amebiasis
Adults:

• Three 250 mg tablets (750 mg) three times a day for 5–10 days.

Adolescents and children over 10 years:

• Two or three 250 mg tablets (500–750 mg) three times a day for 5–10 days.

Children aged 7 to 10 years:

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

An alternative dosing regimen for this condition (dose in mg per kg) is 35 to 50 mg/kg daily in three divided doses for 5–10 days, not exceeding 2400 mg per day.

Giardiasis
Adults:

• One 250 mg tablet three times a day for 5–7 days, or eight tablets (2000 mg) once daily for 3 days.

Adolescents and children over 10 years:

• Eight tablets (2000 mg) once daily for 3 days, or 2 tablets (500 mg) twice a day for 7–10 days.

Children aged 7 to 10 years:

• Four 250 mg tablets (1000 mg) once daily for 3 days.

Children aged 3 to 7 years:

• Three 250 mg tablets (750 mg) once daily for 3 days.

Children aged 1 to 3 years:

• Two 250 mg tablets (500 mg) once daily for 3 days.

An alternative dosing regimen for this condition (dose in mg per kg) is 15 to 40 mg/kg per 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 medications prescribed for the treatment of Helicobacter pylori infections.

Adults:

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

Children and adolescents:

• 20 mg/kg per day, not exceeding two tablets (500 mg) twice a day for 7–14 days. Before starting treatment, refer to official guidelines.

Acute ulcerative gingivitis
Adults:

• One 250 mg tablet 2–3 times a day for three days.

Children:

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

Acute periodontal infections
Adults:

• One 250 mg tablet 2–3 times a day for 3–7 days.

Neonates and children weighing less than 10 kg:

• Administer proportionally smaller doses.

Method of administration
For oral use.
For some of the above dosages, other metronidazole-containing medicines are also available with different strengths (film-coated tablet, 500 mg) and in different pharmaceutical forms (infusion solution, 5 mg/ml).

Use in patients with hepatic impairment
In patients with severe liver impairment or hepatic encephalopathy, drug accumulation may occur; therefore, the doctor will prescribe a reduced daily dose of one-third of the usual dose, administered once daily.

Use in patients with renal impairment
Dose reduction is not required in these patients.

Use in elderly patients
The medicine should be used with caution in elderly patients, especially at high doses.

If you take more Metronidazole Aurobindo than you should
If you take more than the recommended dose, contact your doctor immediately.

If you forget to take Metronidazole Aurobindo
If you miss a dose, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose and continue your treatment as usual. Do not take a double dose to make up for the missed dose.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Metronidazole Aurobindo can cause side effects, although not everyone experiences them.
The frequency, type and severity of adverse reactions in children are the same as in adults.
If any of the following serious side effects occur, stop taking
Metronidazole Aurobindo and contact your doctor immediately:

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

• Severe persistent diarrhoea (likely symptom of a serious intestinal infection called pseudomembranous colitis, see below)
• Severe hypersensitivity reactions up to anaphylactic shock

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

• Decreased white blood cell and platelet counts during treatment (granulocytopenia, agranulocytosis, pancytopenia, thrombocytopenia)
• Hepatitis (liver inflammation), jaundice, inflammation of the pancreas
• Brain disorders, lack of coordination
• Bacteria-free brain fever (aseptic meningitis)
• Severe inflammatory rash affecting mucous membranes and skin with fever, redness and blisters, in extremely rare cases leading to skin detachment over large areas (Stevens-Johnson Syndrome)

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

• Mild to moderate hypersensitivity reactions, swelling of face, mouth, throat and/or tongue (angioedema)
• Eye movement spasm, damage or inflammation of the optic nerves
• Reduced white blood cell count (leucopenia), severe anaemia (aplastic anaemia)
• Seizures, nerve disorders such as numbness, pain, tingling or prickling sensations in arms or legs
• Toxic epidermal necrolysis
• Acute liver failure in patients with Cockayne syndrome (see section 2 “Warnings and precautions”)

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

• Fungal infections (e.g. genital infections)
• Burning/discomfort in the urethra, dysuria, cystitis, polyuria, incontinence

Uncommon (may affect up to 1 in 100 people)

• Dark urine (due to a metabolite of metronidazole)
• Nasal congestion (stuffy nose)

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, hallucinations
• Headache, dizziness, somnolence, fever, visual and movement disturbances, vertigo, speech defects, 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
• Joint and muscle pain

Not known (frequency cannot be estimated from the available data)

• Malaise, nausea, diarrhoea, inflammation of the tongue or mouth, belching and bitter taste, metallic taste, epigastric pressure, hairy tongue
• Difficulty swallowing
• Anorexia
• Depressed mood
• Hearing impairment/hearing loss
• Ringing in the ears (tinnitus)
• Somnolence or insomnia, muscle contractions
• Redness and itching of the skin (erythema multiforme)
• Irritation of the vein wall (inflamed veins and thrombosis) after intravenous administration, weakness, fever
• Well-defined skin area with redness and sometimes blisters, caused by drug hypersensitivity (fixed drug eruption)

Management of pseudomembranous enterocolitis emergencies
In case of severe persistent diarrhoea, you must inform your doctor promptly, as this may be due to pseudomembranous colitis, a serious condition requiring immediate treatment. Your doctor will discontinue metronidazole and provide appropriate therapy.
If any of the side effects become severe or if you notice side effects not listed in this leaflet, inform your doctor.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Metronidazole Aurobindo

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the last day of that month.
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 Metronidazolo Aurobindo contains

• The active substance is metronidazole. Each film-coated tablet contains 250 mg of metronidazole.
• The other components are:
  Tablet core: microcrystalline cellulose, pregelatinized starch (corn starch), hydroxypropylcellulose, anhydrous colloidal silica, sodium starch glycolate, stearic acid.
  Tablet coating: hypromellose 2910 (5 cps), polyethylene glycol.

Description of the appearance of Metronidazolo Aurobindo and package contents
Film-coated tablet
White to almost white, round, coated tablets, imprinted with "M" and "250" on one side and smooth on the other side.
Metronidazolo Aurobindo film-coated tablets are available in blister packs containing 20, 21, and 40 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Aurobindo Pharma (Italia) S.r.l.
via San Giuseppe, 102
21047 – Saronno (VA)

Manufacturer
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far, Birzebbugia, BBG 3000 Malta
Generis Farmacêutica, S.A.
Rua João de Deus, 19, Venda Nova, 2700-487 Amadora, Portugal
Arrow Generiques
26 Avenue Tony Garnier
Lyon, Rhone – 69007
France

This medicinal product is authorized in the European Economic Area countries under the following names:
France: Métronidazole Arrow 250 mg, comprimé pelliculé
Italy: Metronidazolo Aurobindo
Netherlands: Metronidazol Auro 250 mg, filmomhulde tabletten
Poland: Metronidazol Aurovitas
Portugal: Metronidazol Generis
Spain: Metronidazol Aurovitas 250 mg comprimidos recubiertos con película EFG