Нолицин®

General characteristics. Structure:

Active ingredient: 400 mg of norfloxacin.

Excipients: povidone, sodium carboxymethylstarch, cellulose microcrystallic, silicon dioxide colloid, anhydrous, magnesium stearate, the water purified (for hydration).

Cover: gipromelloza, talc, titanium dioxide, dye sunset yellow, E110 (dye disperse yellow, E110), propylene glycol.

Antimicrobic drug of group of ftorkhinolon of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Effect of norfloxacin is based on prevention of synthesis of DNA in a bacterial cell. The main effect – suppression of activity of DNK-girazy enzyme (topoisomerase II). The last researches showed that the giraza splits DNA chain, and then the complex is formed of fragments of DNA, a hinolon and a giraza. The formed complex interferes with superspiralling of a chain of DNA and changes its space characteristics. Such DNA is not capable to function normally any more. At the following stage such DNA breaks up to small fragments. Antimicrobic action of hinolon is more connected with formation of complexes, than with simple suppression of activity of a giraza.

The resistance caused by natural mutations develops seldom. Enterobacteria seldom become resistant. More often resistance develops at Pseudomonasaeruginosa and Methicillinum resistant strains of stafilokokk. Resistance is not transferred by plasmids. It is result of chromosome mutations bacterial DNK-girazy. Between norfloxacin and other hinolona cross resistance can develop. The strains steady against nalidixic and pipemidinovy acids are susceptible to norfloxacin.

Pharmacokinetics. Norfloxacin is quickly soaked up from digestive tract. At healthy volunteers the maximum concentration in plasma are reached in 1 - 2 hour after intake. Absorption from digestive tract incomplete, 30 - 40% of the accepted dose. "The equilibrium state" is reached within 2 days.

About 15% of norfloxacin contact proteins of plasma. Low extent of linkng with proteins allows drug easily and to get quickly into fabrics and fluid mediums of a human body.

The norfloxacin (50 mg/kg) accepted orally gets through a placental barrier, and its concentration in fabrics of a fruit make about 10% of maternal serumal concentration.

The dose of 400 mg two times a day provides renal concentration from 3,9 to 16,2 mkg/g that is significantly higher than concentration of norfloxacin in blood (by 100 - 300 times). The maximum concentration in urine after reception of a dose of 400 mg are reached in 2 hours and make about 478 mg/l; concentration in a prostate (0,7 – 4,7 mkg/g) are lower, but exceed concentration in blood. Concentration of norfloxacin in bile and in the general bilious channel make from 0,15 to 4,5 mkg/g and from 0,4 to 4 mkg/g, respectively, that 3 - 7 times higher than concentration in blood. High concentration of drug are also found in a liver.

Concentration in a vagina and a uterus after a single dose of 400 mg by 2 - 3 times exceed concentration in blood. Concentration in a phlegm, almonds, ovaries, a wall of a gall bladder, are similar or are slightly lower than concentration in blood.

The maximum concentration of norfloxacin in urine by 100 times exceed MPK90 for the majority of causative agents of infections of urinary tract. Concentration of drug in Calais similarly considerably exceed MPK90 for many intestinal pathogens.

Norfloxacin is removed from an organism with urine, a stake and bile biological time of semi-removal makes 3-4 hours.

In 24 hours after oral administration of 100 - 800 mg of 33 - 39% of the accepted dose it is removed with urine. At reception of higher doses (1600 mg) with urine 47,8% of which 5 - 8% are made by metabolizirovanny drug are removed.

Norfloxacin is removed by glomerular filtering and canalicular secretion.

In small degree (2 - 3%) norfloxacin is also removed with bile. More than 30% of the dose accepted orally are removed with a stake.

At a renal failure of change of pharmacokinetics of norfloxacin depend on extent of damage of kidneys. Despite changes in pharmacokinetics, such as increase in time up to achievement of the maximum concentration, increase in biological time of semi-removal and duration of removal, concentration of norfloxacin in an uric path remain high and allow to treat effectively the corresponding infections.

Preclinical data on safety. At prolonged use of norfloxacin at young animals changes in joint cartilages were observed.

At rats and dogs at introduction of high doses of norfloxacin the crystalluria at pH urine higher than 6 developed.

In researches on animals teratogenic, mutagen or cancerogenic properties of norfloxacin were not revealed.

Indications to use:

The infectious and inflammatory diseases caused by the activators sensitive to drug:

• acute and chronic infectious diseases of urinary tract (urethritis, cystitis, pyelonephritis);
• infections of generative organs: cervicitis, endometritis, chronic bacterial prostatitis;
• gonorrhea is uncomplicated;
• bacterial gastroenteritis (salmonellosis, shigellosis);
• prevention of a recurrence of infections of urinary tract;
• prevention of sepsis at patients with a neutropenia;
• prevention of diarrhea of travelers.

Route of administration and doses:

Nolicin should be accepted, washing down with water. The entire period of treatment needs to be supported by drug a normal diuresis.
Treatment

Inside on an empty stomach (not less than in 1 hour prior to or in 2 hours after food) also wash down with enough liquid.

In the absence of special doctor's instructions the following doses are recommended: on 1 tablet (400 mg) 2 times a day. Duration of treatment from 7 to 14 days, if necessary carry out more prolonged treatment.

At chronic bacterial prostatitis about 400 mg 2 times a day within 4-6 weeks or more are appointed.

At uncomplicated gonorrhea drug is appointed once in a dose by 800 - 1200 mg or 2 times a day on 400 mg within 3-7 days.

At a bacterial gastroenteritis (a shigellosis, a salmonellosis) about 400 mg 2 times a day for up to 5 days are recommended.

For prevention of diarrhea of travelers about 400 mg a day in 1 day prior to departure, during the whole time of a travel and 2 days after its termination (no more than 21 day) are recommended to accept.

For prevention of sepsis at a neutropenia appoint 400 mg 2 times a day up to 8 weeks.

At acute uncomplicated cystitis appoint 400 mg 2 times a day within 3-5 days.

For prevention of recurrent uncomplicated infections of urinary tract at frequent aggravations (more than 3 episodes a year or more than 2 within half a year) drug is appointed on 200 mg (1/2 tablets of Nolicin) of 1 times to night it is long (from 6 months to several years).

 More than 20 ml/min. of correction of the mode of dosing are not required to patients with a renal failure at clearance of creatinine.

At clearance of creatinine less than 20 ml/min. (or the level of serumal creatinine above 5mg/100ml) and to the patients who are on a hemodialysis appoint a half of a therapeutic dose of Nolicin 2 times a day or a full dose of drug of 1 times a day. 

* One day before departure, all the time of a travel and two more days after return however no more than 21 day.

Features of use:

Safety of drug during pregnancy and during feeding by a breast was not proved. Use of drug during pregnancy is justified in urgent cases when the potential advantage for mother exceeds possible risk for a fruit. During treatment by drug feeding by a breast needs to be stopped.

It is necessary to be careful during the driving of the car and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (especially at the simultaneous use of ethanol).

Side effects:

From the alimentary system: a loss of appetite, bitterness in a mouth, nausea, vomiting, an abdominal pain, diarrhea, a pseudomembranous coloenteritis (at prolonged use), increase in activity of "hepatic" transaminases.

From an urinary system: crystalluria, glomerulonephritis, dysuria, polyuria, albuminuria, urethral bleedings, increase in urea and creatinine of a blood plasma.

From a nervous system: headache, dizziness, unconscious states, sleeplessness, hallucinations. At elderly patients are possible: fatigue, drowsiness, concern, irritability, sensation of fear, depression, sonitus.

From cardiovascular system: tachycardia, arrhythmias, lowering of arterial pressure, vasculitis.

Allergic reactions: rash, skin itch, small tortoiseshell, hypostases, malignant exudative erythema (Stephens-Johnson's syndrome).

From a musculoskeletal system: an arthralgia, tendinites, ruptures of sinews (usually in case of a combination with the promoting factors).

From system of a hemopoiesis: eosinophilia, leukopenia, decrease in a hematocrit.

Others: candidiasis.

Interaction with other medicines:

The norfloxacin which is applied along with theophylline or cyclosporine increases their concentration in serum. In the course of therapy it is necessary to control concentration of these substances.

Simultaneous use of norfloxacin and peroral anticoagulants (warfarin) increases their therapeutic effect.

Milk and yogurt (liquid dairy products), an antacid and сукральфат reduce Nolicin absorption. Nolicin needs to be accepted in 1 hour prior to or in 2 hours after the use of dairy products.

If norfloxacin is applied together with the drugs containing iron, aluminum, bismuth, magnesium, calcium or zinc the large not soaking up complexes are formed (quinolone-threw). An antacid, сукралфат, and it is necessary to accept the drugs containing these elements not earlier than in 2 hours after Nolicin reception.

Simultaneous use of hinolon and corticosteroids can increase risk of tendinites and ruptures of sinews.

Strengthening of effects of antidiabetic drugs (sulphonylurea derivatives) at simultaneous use with norfloxacin is noted.
Combined use of norfloxacin and nitrofurantoin leads to reduction of effects of both drugs.

Contraindications:

• hypersensitivity to norfloxacin, components of drug and other hinolona;
• deficit glyukozo-6-fosfatdegidrogenazy;
• children's and teenage age (up to 18 years);
• pregnancy and period of a lactation.

With care: atherosclerosis of vessels of a brain, disturbance of cerebral circulation, epilepsy, epileptic syndrome, renal/liver failure, existence of allergic reaction to acetylsalicylic acid.

Overdose:

The overdose is shown preferential by nausea, vomiting, diarrhea, and in more hard cases – also dizziness, weakness and spasms.

After reception of a large number of tablets the gastric lavage, careful observation of the patient and if necessary – a symptomatic treatment is recommended.

Good hydration and maintenance of an adequate diuresis is of great importance.

Storage conditions:

To protect from influence of moisture and light. To store at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Blisters (aluminum film, PVH/PVDH film): on 10 tablets, in a cardboard pack.

Blisters (aluminum film, PVH/PVDH film): on 20 tablets, in a cardboard pack.