MINISTRY OF PUBLIC HEALTH OF THE REPUBLIC OF BELARUS
THERAPEUTIC DRUG MANAGEMENT
(Information for Patients)
Commercial Name: Metronidazole.
International Nonproprietary Name: Metronidazole.
Production Form: 0.5% solution for infusion.
Appearance: Transparent colorless or with a faint greenish-yellow shade liquid.
Composition: 1 ml of the solution contains:
active substance: Metronidazole – 5.0 mg;
adjuvant components: sodium chloride and water for injection.
Pharmacotherapeutic Group: Synthetic antibacterial agents. Imidazole derivatives.
ATX Code: J01XD01
Antiprotozoal and antimicrobial preparation. It is active with regard to Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis (Lamblia intestinalis), as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicro and Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (Prevotella bivia, Prevotella buccae and Prevotella disiens) and some gram-positive microorganisms (sensitive strains of Eubacterium, Clostridium spp., Peptococcus spp. and Peptostreptococcus spp.). In combination with amoxicillin it displays activity in respect of Helicobacter pylori. Aerobic microorganisms and facultative anaerobes are Metronidazole-insensitive, but in presence of a mixed flora (aerobes and anaerobes), Metronidazole acts synergistically with the antibiotics, which are effective against common aerobes. It increases tumor sensitivity to radiotherapy and stimulates reparative processes.
Indications for Use
Protozoal infections: extraintestinal amebiasis, amebic liver abscess included, intestinal amebiasis (amebic dysentery), trichomoniasis, balantidiasis, lambliasis (giardiasis), dermal leishmaniasis, trichomonal vaginitis and trichomonal urethritis.
Infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicro and Bacteroides vulgatus): bone and joint infections, central nervous system infections, including meningitis, cerebral abscess, bacterial endocarditis, pneumonia, pulmonary empyema and abscess and sepsis.
Infections caused by species Clostridium spp., Peptococcus and Peptostreptococcus: abdominal cavity infections (peritonitis and hepatic abscess) and pelvis minor organ infections (endometritis, Fallopian tube and ovary abscess and vaginal vault infections).
Pseudomembranous colitis (antibiotics administration related). Gastritis or duodenal ulcer related to Helicobacter pylori.
Post-surgery complication prevention (particularly operative interventions in colon and pararectal area, appendectomy and gynecological surgeries).
Radiotherapy of tumor patients – as a radiation sensitizing medicinal agent in cases the tumor resistance is due to the tumor cell hypoxia.
Method of Administration and Dosage
Adults and children older than 12 years of age: initial dose of 0.5-1 g intravenously, drop-by-drop (infusion duration – 30-40 min) and then 500 mg every 8 h at the rate of 5 ml/min. In case of a good tolerance, jet introduction is administered after the first 2 or 3 infusions. The treatment course is 7 days. If needed, intravenous introduction is continued for a longer period of time. The maximum daily dose is 4 g. On indications, maintenance ingestion is administered in a 400 mg dose 3 times per day. Children younger than 12 years of age: a single 7.5 mg/kg dose is prescribed under the same scheme. At purulent-septic diseases usually 1 treatment course is administered.
As a prevention, prescribed to adults and children older than 12 years of age intravenously, drop-by-drop, 0.5-1 g doses before the surgery, on the surgery day and the next day – 1.5 g per 24 h (500 mg doses every 8 h). After 1 or 2 days maintenance ingestion therapy is administered.
Patients with a chronic renal insufficiency and creatinine level less than 30 ml/min and/or hepatic insufficiency: maximum daily dose – not more than 1 g administered twice per 24 h.
As a radiation sensibilizer, the medicinal agent is introduced intravenously, drop-by-drop, based on the principle of 160 mg/kg or 4-6 g/sq m of body surface 0.5-1 h before irradiation starts. Administered before each irradiation session for 1 or 2 weeks. During the remaining ray therapy period Metronidazole is not used. The maximum single dose should not exceed 10 g and the maximum treatment course dose should not exceed 60 g.
As a relief from the intoxication caused by irradiation, drop-by-drop introduction of a 5% dextrose or Hemodez solution or a 0.9% NaCl solution is applied.
From digestive system: diarrhea, dysorexia, nausea, vomiting, intestinal colic, constipation, metallic off-flavor in the mouth, dry mouth, glossitis, stomatitis and pancreatitis.
From nervous system: dizziness, motive incoordination, ataxia, mental confusion, irritability, depression, high excitability, asthenia, insomnia, headache, convulsions, hallucinations and peripheral neuropathy.
Allergic reactions: nettle rash, skin eruption, dermal hyperaemia, stuffiness in nose, fever and arthralgia.
From urinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis and urine tinting in reddish-brown color.
Local reactions: thrombophlebitis (pain, hyperaemia or oedema in injection spot).
Other: granulocytopenia, leukocytopenia and T-tooth flattening in an ECG.
Hypersensitivity, leukocytopenia (also in anamnesis), organic central nervous system affections (also epilepsy), hepatic insufficiency (if large doses are prescribed), pregnancy (trimester I) and lactation period.
With caution. Pregnancy (trimesters II-II) and renal/hepatic insufficiency.
Symptoms: nausea, vomiting, ataxia and in grave cases peripheral neuropathy and epileptic fits.
Treatment: symptomatic one, no specific antidote available.
Metronidazole for intravenous introduction is not recommended for mixing with other medicinal agents.
During the treatment period, ethanol taking is counter-indicative (development of disulfiram-like reactions is a possibility: abdominal pain of a spastic nature, nausea, vomiting, headache or sudden hot flashes).
In combination with amoxicillin, it is not recommendable for administration in patients under 18 years of age.
During a long therapy, the blood picture has to be monitored.
At leukocytopenia, a possible treatment continuation depends on the infection process development risk.
Appearing ataxia, dizziness and any other neurological status deterioration in patients requires a treatment discontinuation.
It can immobilize treponemata and lead to a false-positive Nelson test. It tinctures urine in a dark color.
When treating trichomonal vaginitis in females and trichomonal urethritis in males, sexual life has to be abstained from. Simultaneous treatment of the sexual partners is obligatory. After trichomoniasis therapy, check tests should be made during 3 next cycles before and after the menstruation. After the treatment of lambliasis, if symptoms persist, after 3 or 4 weeks 3 feces tests should be made with several-day intervals (in some successfully treated patients lactose intolerance caused by an invasion may persist for several weeks or months and resemble the lambliasis symptoms).
If the preparation has to be prescribed during the lactation period, breast feeding should be discontinued.
Interaction with Other Medicinal Agents
It intensifies the effect of indirect anticoagulants, which leads to an increase in the prothrombin time. Similar to disulfiram, it causes ethanol intolerance. A simultaneous administration with disulfiram may lead to the development of various neurological symptoms (the inter-administration interval is at least 2 weeks). Cimetidine suppresses the Metronidazole metabolism, which may lead to its higher concentration in the blood serum and increase the risk of by-effect development. A simultaneous prescription of the medicinal agents stimulating the hepatic microsomal oxidation enzymes (phenobarbital and phenytoin) may accelerate Metronidazole elimination, which results in its lower plasma concentrations. In case of a simultaneous administration with the Li+ preparations, the latter's plasma concentrations may go up and cause an intoxication symptom development. It is not recommendable for combination with nondepolarizing muscle relaxants (vecuronium bromide). The sulfanilamides boost up Metronidazole's antimicrobial effect.
To be kept away from light at a temperature of 15ºС to 25ºС. Do not freeze.
To be kept away from children.
Do not use upon expiry of the shelf life indicated on the packing.
100 ml in bottles.