Metronidazole S.A.L.F.

Package leaflet: Information for the user

METRONIDAZOLE S.A.L.F. 500 mg/100 ml infusion solution

Metronidazole
Generic medicine
Please read all of this leaflet carefully before you start using 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 nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What METRONIDAZOLE S.A.L.F. is and what it is used for
2. What you need to know before using METRONIDAZOLE S.A.L.F.
3. How to use METRONIDAZOLE S.A.L.F.
4. Possible side effects
5. How to store METRONIDAZOLE S.A.L.F.
6. Contents of the pack and other information

1. What METRONIDAZOLO S.A.L.F. is and what it is used for

METRONIDAZOLO S.A.L.F. contains the active substance metronidazole, which belongs to a group of
medicines called antibiotics, used for infections caused by microorganisms.
This medicine is indicated for the treatment of severe infections (septicaemia, bacteraemia) in adults and
children caused by the following bacteria: Bacteroides fragilis, Fusobacteria, Eubacteria, Clostridia, and anaerobic Gram-positive cocci.
METRONIDAZOLO S.A.L.F. is particularly indicated for:

• the treatment of infections such as those causing accumulation of infected material (brain and pelvic abscesses), severe lung infections (necrotizing pneumonia), bone and joint infections (osteomyelitis), uterine infections (puerperal fever), peritoneal infections (peritonitis), and infections causing wound complications following surgical procedures;
• prevention of infections caused by bacteria (Bacteroides and anaerobic Gram-positive cocci) that may occur following surgical procedures (in pre- and post-operative phases).

2. What you need to know before using METRONIDAZOLE S.A.L.F.

Do not use METRONIDAZOLE S.A.L.F.

• if you are allergic to metronidazole or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from any blood or bone marrow disorder (haematological dyscrasias);
• if you have neurological problems (active central nervous system diseases);
• if you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Consult your doctor or nurse before being administered METRONIDAZOLE S.A.L.F.
METRONIDAZOLE S.A.L.F. will always be administered under strict medical supervision.
Cases of liver toxicity (severe hepatotoxicity/acute liver failure), including fatal cases, have been reported with drugs containing metronidazole in patients affected by Cockayne syndrome.
If you have Cockayne syndrome, your doctor will frequently monitor your liver function both during and after treatment with metronidazole.
Immediately inform your doctor and stop taking metronidazole if you experience:

• stomach pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine, pale or greasy stools, or itching;
• seizures, numbness, or altered sensation in a limb (paresthesia);
• severe blistering skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, or acute generalized exanthematous pustulosis).
  During treatment, urine may turn reddish-brown due to the presence of soluble drug pigments.
  Prolonged therapy with metronidazole may be associated with bone marrow suppression, leading to impaired blood cell production (haematopoiesis). Therefore, blood cell counts should be closely monitored during prolonged treatment.

METRONIDAZOLE S.A.L.F. will be administered with great caution and at reduced doses if:

• you have severe kidney problems (impaired renal function);
• you have severe liver problems (severe hepatic disease);
• you suffer from severe active or chronic diseases of the peripheral and central nervous system.
  Metronidazole should only be used if the expected benefits clearly outweigh the potential risks.
  If METRONIDAZOLE S.A.L.F. is to be administered for longer than 10 days:
• your doctor will assess the risk of developing peripheral nervous system problems (peripheral neuropathy);
• regular clinical evaluations of your condition will be performed.

Children and newborns
This medicine can be administered cautiously in children.

Other medicines and METRONIDAZOLE S.A.L.F.
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines. In particular, inform your doctor if you are taking:

• Disulfiram (a drug used to treat chronic alcohol dependence) within the previous two weeks: METRONIDAZOLE S.A.L.F. may cause psychotic reactions (e.g. confusion, behavioural changes, hallucinations).
• Warfarin, acenocoumarol, dicoumarol, phenprocoumon (oral anticoagulants): METRONIDAZOLE S.A.L.F. may increase bleeding time; therefore, your doctor may request frequent prothrombin time (INR) tests and possibly adjust your anticoagulant dose.
• Lithium: METRONIDAZOLE S.A.L.F. may increase serum lithium levels (lithiemia); therefore, lithium therapy should be discontinued during treatment with METRONIDAZOLE S.A.L.F. If concomitant use of lithium and METRONIDAZOLE S.A.L.F. is necessary, regular monitoring of blood levels of lithium, creatinine, and electrolytes (sodium, potassium, chloride) is essential.
• Phenytoin, phenobarbital (antiepileptic drugs): by increasing liver activity, they may accelerate the elimination of METRONIDAZOLE S.A.L.F., thereby reducing its blood concentration.
• Cyclosporine (an immunosuppressant): METRONIDAZOLE S.A.L.F. may reduce the liver’s ability to eliminate cyclosporine, leading to its accumulation in the blood and risk of toxicity.
• Cimetidine (a drug used for ulcers, reflux esophagitis, or gastritis): may slow down the elimination of METRONIDAZOLE S.A.L.F. from the blood, increasing its concentration.
• Tacrolimus (a drug used to prevent transplant rejection): concomitant use with METRONIDAZOLE S.A.L.F. may increase the risk of cardiac disturbances (QT prolongation and arrhythmias). METRONIDAZOLE S.A.L.F. may also reduce the liver’s elimination of tacrolimus, leading to its accumulation in the blood and risk of toxicity.
• Drugs causing cardiac disturbances (QT prolongation): concomitant use with METRONIDAZOLE S.A.L.F. may increase the risk of such disturbances.
• Cholestyramine (a drug used to lower blood cholesterol): may reduce the effectiveness of METRONIDAZOLE S.A.L.F.
• Carbamazepine (a drug used in epilepsy and trigeminal neuralgia): METRONIDAZOLE S.A.L.F. may slow down the elimination of carbamazepine, leading to its accumulation in the blood and risk of central nervous system toxicity.
• Amprenavir (a drug used to treat HIV): METRONIDAZOLE S.A.L.F. should not be administered together with oral amprenavir solution due to the potential risk of toxicity from an excipient in amprenavir (propylene glycol).
• Mycophenolate mofetil (a drug used to prevent acute organ transplant rejection): if METRONIDAZOLE S.A.L.F. is administered concomitantly with norfloxacin (an antibiotic) and mycophenolate mofetil, exposure to the latter may be reduced. No interactions have been observed when METRONIDAZOLE S.A.L.F. or norfloxacin are administered together with mycophenolate mofetil but separately from each other.
• Herbal preparations containing silymarin (e.g. milk thistle): may reduce the blood concentration of METRONIDAZOLE S.A.L.F., thereby reducing its efficacy.
• Ergotamine and dihydroergotamine (drugs used to treat migraine): METRONIDAZOLE S.A.L.F. may increase blood levels of these drugs, increasing the risk of toxicity.
• Busulfan (a drug used in preparatory treatment for haematopoietic stem cell transplantation): METRONIDAZOLE S.A.L.F. may increase busulfan blood levels, increasing the risk of toxicity.
• 5-fluorouracil (an anticancer drug): METRONIDAZOLE S.A.L.F. may increase blood levels of this drug, increasing the risk of toxicity.

METRONIDAZOLE S.A.L.F. and alcohol
Do not drink alcohol while being treated with METRONIDAZOLE S.A.L.F., as you may experience symptoms such as nausea, vomiting, and abdominal cramps.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or nurse before receiving this medicine.
Do not use METRONIDAZOLE S.A.L.F. if you are definitely or possibly pregnant or if you are breastfeeding.

Driving and using machines
This medicine does not affect the ability to drive or operate machinery.

METRONIDAZOLE S.A.L.F. contains sodium
This medicine contains 310 mg (13.5 mmol) of sodium (the main component of table salt) per 100 ml of solution. This corresponds to 15.6% of the maximum daily dietary intake recommended for an adult. This should be taken into account in patients with impaired renal function or those on a low-sodium diet.

3. How to use METRONIDAZOLE S.A.L.F.

Use this medicine exactly as directed by your doctor or nurse. If you have any doubts, consult your doctor or nurse.
This medicine must be administered only by slow intravenous infusion (5 ml/min).
This type of administration is particularly useful in emergency situations and is indicated in surgical patients when:

• anaerobic infection is present or suspected preoperatively, e.g. septicemia, peritonitis, subphrenic or pelvic abscess;
• signs of septic state caused by anaerobic organisms appear during surgery;
• there is a risk of contamination by anaerobes originating from the gastrointestinal tract, female genital tract, or oropharynx during surgery.

Avoid adding other medicines or additives, apart from metronidazole, to the infusion solution.

Use in adults and children over 12 years of age
The recommended dose is 100 ml for intravenous infusion (at a rate of 5 ml/min) every 8 hours. In most patients, 7 days of therapy are sufficient, but in some cases (e.g. areas inaccessible to drainage, new contamination, etc.) a longer treatment duration may be necessary.
The recommended dose for prevention of infections is 100 ml by intravenous infusion immediately before, during, or after surgery, followed by the same dose every 8 hours.

Use in children under 12 years of age and in newborns
The recommended dose is:

• children aged between 8 weeks and 12 years: 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 up to 40 mg/kg depending on the severity of the infection. Treatment duration is usually 7 days.
• children under 8 weeks of age: 15 mg/kg/day as a single dose or divided into 7.5 mg/kg every 12 hours.

In premature newborns: the doctor must administer the medicine with caution and monitor blood levels of the medicine.

The recommended dose for prevention of infections is:

• children under 12 years: 20–30 mg/kg as a single dose given 1–2 hours before surgery;
• premature newborns: 10 mg/kg body weight as a single dose before surgery.

Each bag or bottle must be used for a single administration only; any remaining solution must not be reused.

If you use more METRONIDAZOLE S.A.L.F. than you should

This medicine will be administered by trained healthcare professionals, so it is unlikely that you will receive an excessive dose. However, if an overdose is administered, contact your doctor, who will recommend appropriate treatment for any symptoms.
If you have been given too much of this medicine, contact your doctor or nurse immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If you experience neurological problems (neuropathy, epileptic seizures), treatment must be discontinued.

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

• Gastrointestinal disorders (of the digestive system),
• Anorexia (loss of appetite),
• Nausea,
• White tongue,
• Dry mouth,
• Metallic taste,
• Glossitis (inflammation of the tongue),
• Stomatitis (inflammation of the mucous membranes of the mouth),
• Headache,
• Skin rashes,
• Dizziness,
• Ataxia (lack of coordination of movements),
• Depression,
• Insomnia,
• Nasal congestion (stuffy nose),
• Urticaria,
• Pruritus,
• Angioedema (swelling of the skin of the face and mucous membranes which may cause difficulty in swallowing and breathing),
• Anaphylaxis (severe, rapidly occurring allergic reaction),
• Dysuria (difficulty in passing urine),
• Cystitis (inflammation of the urinary bladder),
• Fever,
• Polyuria (excretion of a larger than normal volume of urine),
• Pyuria (presence of pus in the urine),
• Decreased libido (reduced sexual desire),
• Psychotic disorders, including confusion, hallucinations,
• Encephalopathy (manifesting as confusion, fever, headache, hallucinations, paralysis, mild sensitivity, visual and movement disturbances, neck stiffness),
• Subacute cerebellar syndrome (manifesting as ataxia, dysarthria, gait disturbance, nystagmus and tremor),
• Eye disorders such as diplopia, myopia, optic neuropathy/neuritis,
• Cardiac disorders such as tachycardia, palpitations,
• Ear disorders such as impaired hearing, hearing loss (including sensorineural), tinnitus,
• Liver and pancreas disorders (elevated liver enzymes, cholestatic hepatitis, hepatocellular damage, jaundice and pancreatitis),
• Muscle pain,
• Joint pain,
• Stevens-Johnson syndrome and Toxic Epidermal Necrolysis (two severe, potentially fatal skin diseases), acute generalized exanthematous pustulosis (AGEP),
• Candida infections,
• Acute liver failure in patients with Cockayne syndrome (see section 2 “Warnings and precautions”).

Following prolonged or intensive therapy, isolated cases of transient leukopenia, agranulocytosis, neutropenia, thrombocytopenia, pancytopenia (low levels of white blood cells, granulocytes, and platelets in the blood), or peripheral neuropathy (damage to peripheral nerve endings) have been reported.

During treatment, urine may turn reddish-brown due to soluble drug pigments.

Side effects in children
The frequency, type, and severity of side effects in children are the same as in adults.

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 at 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 S.A.L.F.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word “EXP.”.
The expiry date refers to the last day of that month and applies to the product in its original sealed packaging and
properly stored.
Store in the original packaging to protect the medicine from light. Do not refrigerate or freeze.
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.
Each bottle or bag is for single use only; any remaining solution must not be reused.

6. Package contents and other information

What METRONIDAZOLE S.A.L.F. contains

• The active substance is metronidazole. Each 100 ml bag or bottle contains 500 mg of metronidazole.
• The other components are disodium phosphate dihydrate, citric acid monohydrate, sodium chloride, water for injections. Description of the appearance of METRONIDAZOLE S.A.L.F. and contents of the pack METRONIDAZOLE S.A.L.F. is available in packs of 20 bags of 100 ml or in packs of 30 polypropylene bottles of 100 ml. Marketing Authorization Holder and Manufacturer S.A.L.F. S.p.A. Laboratorio Farmacologico - Via Marconi, 2 - 24069 Cenate Sotto (BG) - Italy

The following information is intended exclusively for physicians or healthcare professionals

Dosage and administration
METRONIDAZOLE S.A.L.F. for injection is intended only for slow intravenous infusion (5 ml/min).
This route of administration is particularly useful in emergency situations and is indicated in surgical patients when:

• anaerobic infection is present or suspected preoperatively, e.g. septicemia, peritonitis, subphrenic or pelvic abscess;
• signs of septic state caused by anaerobic organisms appear during surgery;
• there is a risk of contamination by anaerobes originating from the gastrointestinal tract, female genital tract, or oropharynx during the procedure. Avoid adding other drugs, apart from metronidazole, to the infusion solution.

Treatment:
Adults and children over 12 years: 100 ml for intravenous infusion (at an initial rate of 5 ml per minute) every 8 hours. In most patients, 7 days of therapy are sufficient; however, in certain cases (e.g., inaccessible sites, recontamination, etc.), prolonged treatment may be required.

Children under 12 years and neonates: The recommended dose is:

• children aged between 8 weeks and 12 years: 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 up to 40 mg/kg depending on the severity of infection. Duration of treatment is usually 7 days.
• children under 8 weeks of age: 15 mg/kg/day as a single dose or divided into 7.5 mg/kg every 12 hours.
  In premature neonates: the physician must administer the drug with caution and monitor blood levels of the drug.

Prophylaxis:
Adults and children over 12 years: 100 ml for intravenous infusion immediately before, during, or after surgery, followed by the same dose every 8 hours.
Children under 12 years and neonates:

• children under 12 years: single dose of 20–30 mg/kg given 1–2 hours before surgical intervention;
• premature neonates: single dose of 10 mg/kg body weight before surgical intervention.

Each bag or bottle is for single use only; any unused portion must not be retained.

Overdose
As there are no specific antidotes for metronidazole overdose, treatment should be symptomatic.

Incompatibilities
Metronidazole S.A.L.F. 500 mg/100 ml infusion solution must not be mixed with cefamandole nafate, sodium cefoxitin, 10% glucose solutions, infusion solutions containing sodium lactate, or potassium penicillin G.

Instructions for use and handling

WARNING: Do not use the medicinal product after the expiry date stated on the packaging.
Do not use if the solution shows droplets or intense discoloration. The solution should be clear, colorless or pale yellow, and free from visible particles. The product must be visually inspected for particulate matter and discoloration before use. Do not reuse. Any unused solution must be discarded.