Metronidazole-ACOS, 5 mg/ml 100 ml

Metronidazole – Akos is an antimicrobial, antiprotozoal.

A 5-nitroimidazole derivative. Mechanism of action consists in biochemical reduction of 5-nitrogroup by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitrogroup interacts with the DNA of the microbial cell, inhibiting the synthesis of their nucleic acids, which leads to the death of the bacteria.

It is active against Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp, as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides vulgatus), Fusobacterium spp, Veillonella spp., Prevotella (P.bivia, P.buccae, P.disiens) and some gram-positive anaerobic microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.) The MPC for these strains is 0.125-6.25 µg/ml.

In combination with amoxicillin it shows activity against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

Metronidazole is insensitive to aerobic microorganisms and some anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against common aerobes.

It increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like action), stimulates reparative processes.

Pharmacokinetics

The absorption is high; bioavailability if taken orally is not less than 80%. It has high penetrating capacity, reaching bactericidal concentrations in most body tissues and fluids, including lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk; passes through the BBB and placental barrier. Distribution volume in adults is approximately 0.55 L/kg, in infants 0.54-0.81 L/kg. Cmax when taken orally is reached after 1 to 3 hours and is 6 to 40 mcg/ml, depending on the dose. Binding to plasma proteins is 10-20%. Cmax in serum after 1 hour is 35.2 µg/ml, after 4 hours – 33.9 µg/ml, after 8 hours – 25.7 µg/ml; Cmin during subsequent administration – 18 µg/ml. Time of reaching Cmax is 30-60 minutes, therapeutic concentration is maintained for 6-8 hours. With normal bile formation, the concentration of metronidazole in bile after IV administration may be significantly higher than in plasma.

In the body about 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

The T1/2 in normal liver function is 8 h (6 to 12 h), in alcoholic liver damage is 18 h (10 to 29 h); in neonates born at 28-30 weeks gestation is approximately 75 h, 32-35 weeks – 35 h and 36-40 weeks – 25 h respectively. It is excreted by the kidneys 60-80% (20% unchanged), through the intestines 6-15%. Renal clearance is 10.2 ml/min.

Indications

Active ingredient

Composition

Active substances:

metronidazole 5 mg;

Associate compounds:

sodium chloride,

citric acid monohydrate,

sodium hydrophosphate,

water for injection

How to take, the dosage

Intravenous

Adults and children over 12 years of age in an initial dose of 0.5-1 g by IV drip (infusion duration 30-40 minutes), then every 8 hours 500 mg at a rate of 5 ml/min. If tolerated well, after the first 2-3 infusions, switch to jet injection. The course of treatment is 7 days. If necessary, intravenous infusion is continued for a longer period. Maximal daily dose is 4 g. If indicated, switch to oral maintenance dosage of 400 mg 3 times daily. For children under 12 years old a single dose of 7.5 mg/kg is prescribed according to the same regimen.

In purulent-septic diseases one course of treatment is carried out.

For prophylactic purposes in adults and children over 12 years old by intravenous drops – 0.5-1 g before surgery, on the day of surgery and the next day – 1.5 g per day (500 mg every 8 hours). After 1-2 days switch to oral supportive therapy. For patients with chronic renal insufficiency and creatinine’s Cl less than 30 ml/min and/or with hepatic insufficiency maximal daily dose is not more than 1 g, the dose should be taken 2 times a day.

As a radiosensitizer it is administered by intravenous drop at the rate of 160 mg/kg or 4-6 g/m2 0.5-1 hour before the start of irradiation; it is carried out before each session of irradiation during 1-2 weeks. Metronidazole is not used during the remaining period of radiotherapy. The maximum single dose is not more than 10 g, the course dose is 60 g. Drip administration of 5% dextrose solution, hemodase or 0.9% sodium chloride solution is used to relieve intoxication caused by radiation.

Interaction

Metronidazole for IV administration is not recommended for mixing with other drugs.

It enhances the effect of indirect anticoagulants, which leads to prolongation of prothrombin formation time.

Similar to disulfiram causes ethanol intolerance. Concomitant use with disulfiram may lead to the development of various neurological symptoms (interval between prescriptions – at least 2 weeks).

Cimetidine inhibits metabolism of metronidazole, which may increase its serum concentrations and increase the risk of side effects.

The concomitant administration of drugs stimulating enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) may accelerate elimination of metronidazole, resulting in lower plasma concentrations.

Concomitant use with lithium preparations may increase the plasma concentration of the latter and lead to intoxication symptoms.

It is not recommended to combine with nondepolarizing myorelaxants (vecuronium bromide).

Sulfonamides increase the antimicrobial effects of metronidazole.

Special Instructions

Ethanol intake is contraindicated during treatment (development of disulfiram-like reaction is possible: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).

In long-term therapy, blood counts should be monitored.

If leukopenia develops, the possibility of continuing treatment depends on the risk of developing an infectious process.

The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires discontinuation of treatment.

May immobilize treponemes and lead to a false-positive Nelson’s test.

Darkens urine.

When treating trichomonas vaginitis in women and trichomonas urethritis in men it is necessary to refrain from sexual intercourse. The simultaneous treatment of sexual partners is mandatory. The treatment does not stop during menstruation. After the therapy of trichomoniasis should be tested for three consecutive cycles before and after menstruation.

After treatment of giardiasis, if symptoms persist, three stool tests should be performed after 3-4 weeks at intervals of several days (in some successfully treated patients, lactose intolerance caused by the infestation may persist for weeks or months, resembling the symptoms of giardiasis).

Contraindications

Hypersensitivity, leukopenia (including in anamnesis), organic CNS lesions (including epilepsy), hepatic insufficiency (in case of high doses), I trimester of pregnancy, breast-feeding.

With caution – in the second and third trimesters of pregnancy, renal/liver failure.

Side effects

Digestive system disorders: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, metallic taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis.

Nervous system disorders: dizziness, impaired coordination of movements, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, seizures, hallucinations, peripheral neuropathy.

Allergic reactions: urticaria, skin rash, skin hyperemia, nasal congestion, fever, arthralgia.

Urogenital system disorders: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine red-brown.

Local reactions: thrombophlebitis (pain, redness or swelling at the injection site).

Others: neutropenia, leukopenia, flattening of the T wave on the ECG.

Pregnancy use

It is contraindicated in the first trimester of pregnancy; with caution – in the II and III trimesters of pregnancy.

In lactation it is recommended to stop breastfeeding.

Similarities