Мetralin (metronidazole)

Мetralin (metronidazole)

Active substance (International unlicensed name):


АТХcode: J01XD0l

Pharmacotherapeutical group:

Antiprotozoal drug



Pharmacological properties

Antiprotozoal and antimicrobial preparation, derivative of 5-nitroimidazole. Action mechanism is included in biochemical restoration of 5-nitro group ofintracellular transport proteins of anaerobic microorganisms and protozoa. Restored 5­-nitro group correlates with DNA of cell, inhibiting synthesis of their nucleic acids that cause to bacteria death. It is active in relation to Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Girаdia intestinalis, Lamblia spp., and also obligate anaerobs Bacteroides spp. (including Bacteroides fragilis. Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus). Fusobacterium spp., Veillonela spp., Prevotella (P.bivia, P.buccae, P.disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). MPC fro these strains is 0,125-6,25 mkg/ml. In combination with amoxicillin it shows activity in relation to Helicobacter pylori (amoxicillin suppresses development of resistance to Metronidazole). Aerobic microorganisms and facultative anaerobes are not sensitive to Metronidazole, but with the presence of mixed flora (aerobes and anaerobes) Metronidazole acts  synergistically with antibiotics  which are effective against usual aerobes. It increases sensitivities of edemas to radiation, causes sensitizing to alcohol (action similar withdisulfiram), stimulates reparative processes.


Absorption is high (bio availability is not less than 80%). It possesses high penetrating capacity, achieving bactericidal concentrations in most of tissues and liquids of organism, including lungs, kidneys, liver, skin, spinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal fluid, seminal fluid, breast milk, penetrates through hemato-encephalitic and placental barrier. Volume of distribution: adults - approximately 0,55 l/kg, newborns – 0,54-0,81 l/kg. Maximal concentration of preparation in blood (Сmах) is from 6 to 40 mkg/ml, depending on dose. Time of reaching maximum concentration in blood Т(Смах) –1-3 hours.

            Binding with plasma proteins - 10-20%.       

Смахin the blood is achieved in 30-60 minutes, therapeutic concentrations kept within 6-8 hours. At intravenous introduction (i/v) 500 mg within 20 minutes, Сmахin blood serum in 1 hour -– ­35,2 mkg/ml, in 4 hours – 33,9 mkg/ml, in 8 hours – 25,7 mkg/ml; minimal concentration of blood preparations (Cmin) at following introduction is - 18 mkg/ml. At normal bile-formation concentration of metronidazole in bile after i/v introduction can significantly increase blood concentration. In organism about 30-60% of Metranidazole is inhibited by hydro oxyllation, oxidation and glucuronidation. The main metabolite (2-oximetronidazole) also render antiprotozoal and antibacterial action. Period of semi-excretion (Т½) at normal liver function - 8 hours (from 6 to 12 hours), at alcohol-induced liver injury - 18 hours (from 10 to 29 hours), at newborns: born at pregnancy term - 28-30 weeks – approximately 75 hours, correspondingly, 32-35 weeks - 35 hours, 36-40 weeks – 25 hours. It is excreted by kidneys 60-80% (20% in unchanged form), through intestine - 6-15%. Renal clearance – 10,2 ml/minute. At patient with compromised kidney function cumulation of metronidazole in blood serum can be observed (so, at patients with strong renal failure acceptance frequency should be reduced). Metronidazole and main metabolites are quickly removed from blood at hemodialysis (Т1/2 is reduced up to 2,6 hours). At peritoneal dialysis it introduced with small quantities.

Instructions for use

Protozoal infections: extraenteric  amebiasis, including  hepatic amoebiasis,  intestinal amebiasis (amebic dysentery),  trichomoniasis, hiardiasis, balantidiasis, lambliasis,  cutaneous  leishmaniasis,  trichomonal vaginitis, trichomonal urethritis. Infections, induced by Bacteroides spp. (including В. fragilis, В. distasonis, В. ovatus, В. thetaiotaomicron, В. vulgatus): infections of bones and joints, infections of central nervous center (CNC), including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lungs’ abscess. Infections, induced by Bacteroides kinds, including В. fragi1is group, C1ostridium, Peptococcus and Peptostreptococcus kinds: abdominal infections (peritonitis, liver abscess), pelvis infections (endometritis, endomyometritis, abscess of  Fallopian tubes and ovaries, infections of vagina fornix after surgical operations), infections of skin and soft tissues, sepsis. Pseudo membranous colitis (connected with antibiotics use). Gastritis or duodenal ulcer, connected with Helicobacter pylori, alcoholism. Prophylaxis of post-operational complications (especially operations on colon in peri-rectal area, appendectomy, gynaecological operations). Radiation therapy of patients having edemas – as radio sensitizing drug, in case when resistance of edema is caused by hypoxemia in edema’s cells.

Method of application and dosage

Adults and children over 12 years it is introduced i/v drop-by-drop with initial dose 0,5-1g (duration of infusion ­30-40 minutes), and then, every 8 hours by 500 mg with the speed of 5 ml/min. At good tolerance after 2-3 infusions stream introduction should be initiated. Treatment course – 7 days. If necessary, i/v introduction is to be continued within longer period. Maximum daily dose - 4 g. By instruction supporting receiving is initiated in the dose by 400 mg 3 times/day. Children at the age of 12 years old – by the same scheme, single dose ­7,5 mg/kg. At pyoinflammatory diseases 1 course of treatment is usually implemented. In prophylactic purposes adults and children over 12 years old are administrated i/v streamly by 0,5-1 g the day before operation, at the day of operation and next day – 1,5 g/day (by 500 mg every 8 hours). In 1-2 days supporting therapy is initiated. Patients with chronic renal failure (CRF) and creatinine clearance (CC) less than 30 ml/minute and/or hepatic failure, maximum daily dose – not more than 1 g, receiving order - 2 times per day. As radio sensitizing drug it is introduced i/v drop-by-drop, taking 160 mg/kg or 4-6 g/sq.m of body surface 0,5-1 hour before beginning of radiation. It is used before each session of radiation within 1-2 weeks. In the rest period of radiation therapy metronidazole is not used. Maximum single dose should not exceed 10 g, course - 60 g. For intoxication removing, caused by radiation, drop-by-drop introduction of glucose solution or isotonic solution of chloride sodium is used.

Adverse effects

Digestive system:diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, “metallic” taste in the mouth, glossitis, stomatitis, pancreatitis. Nervous system:dizziness, hypotaxia, ataxia, mental confusion, irritability, depression,  increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy. Urogenital system:dysuria, cystitis, polyuria, enuresis, candidosis, coloration of urine to red-brown color. Allergic reactions:nettle rash, skin eruption, hyperemia of skin, stuffiness in nose, fever, arthralgia. Local reactions:trombophlebitis (pain, redness or edema in injection place). Other:hypogranulocytosis, leucopenia, flattening of Т-wave on ECG. Contraindications Hypersensitivity to preparation,  leucopenia (including that in anamnesis), organic lesions of CNS (including epilepsy), renal failure (in case of administration of big doses), pregnancy (I trimester), period of lactation. With care - pregnancy (II-Шtrimester), renal/hepatic failure. Drug interaction Metronidazole for i/v introduction is not recommended to be mixed with other preparations. Preparation enforces the action of indirect anticoagulants, that causes to the increasing of time of prothrombin formation. Being analogous with disulfiram it causes intolerance of ethanol. Simultaneous use with disulfiram can cause to the development of different neurological symptoms (interval between administration – not less than 2 weeks). Cimetidine inhibits metabolism of Metronidazole, that can cause to the increasing of its concentration in blood serum and increasing of risk of adverse effects development. Simultaneous administration of preparations, stimulating ferments of microsomal oxidation in liver (phenobarbital, phenitoin), can intensify elimination of Metronidazole, due to which its concentration in plasma will be reduced. At simultaneous receiving with the lithium preparations concentration of lithium can be increased in plasma and symptoms of intoxication can be increased also. It is not recommended to combine Metronidazole with nondepolarizing muscle relaxants (vecuronium bromide). Sulfanilamides intensify antimicrobial action of Metronidazole. Special instructions During treatment receiving of ethanol is contraindicated (development ofdisulfiram similar reaction is possible: spastic abdominal pains, nausea, vomiting, headache, sudden face flash). In combination with amoxicillin it is not recommended to use at patients younger than 18 years old. At long-term therapy it is necessary to control blood picture. At leucopenia the possibility of treatment prolongation depends on the risk of development of infection process. Occurrence of ataxia, dizziness and any other worsening of neurological status of patients requires cancellation of treatment. Metronidazole can immobilize treponemas and cause false-positive Nilson test. It colors urine to dark color. At treatment of trichomonal vaginitis at women and trichomonal uretritis at men it is necessary to abstain from sex life. Simultaneous treatment of sex partners is mandatory. Treatment should not be stopped during menses. After therapy of trichomoniasis it is necessary to make control test within three regular cycles before and after menses. After treatment of lambliasis, if symptoms still exists, in 3-4 weeks it is necessary to make feces analysis with intervals of several days (At some successfully treated patients, intolerance of lactose, induced by invasion, can be kept within several weeks or months, showing lambliasis symptoms). During lactation it is recommended to stop breast feeding.


Symptoms:nausea, vomiting, ataxia. Treatment:gastric lavage, introduction of absorbent carbon (in case of preparation intake), implementation of hemodialysis. Metronidazole and its metabolites is excreted well during hemoialysis.

Form of issue

Solution for infusions 0,5%, by 100 ml in vials made of polypropylene

Terms of storage

Store in the place protected from light, at the temperature not higher than 250С

Shelf life

2 years.

Prescription preparation

Do not use after expiration of shelf life indicated on the package. Store in the place unavailable for children.