Norfloxacin

General characteristics. Structure:

Active ingredient: 400 mg of norfloxacin.

Excipients: cellulose microcrystallic − 143,000 mg; croscarmellose sodium − 36,000 mg; povidone (polyvinylpirrolidone low-molecular) − 12,000 mg; silicon dioxide colloid − 3,000 mg; magnesium stearate − 6,000 mg.

Film cover: [a gipromelloza − 9,000 mg, a hypro rod (hydroxypropyl cellulose) −     3,490 mg, talc − 3,470 mg, titanium dioxide − 1,956 mg, ferrous oxide yellow (ferrous oxide) − 0,084 mg] or [the dry mix for a film covering containing a gipromelloza (50%), a hypro rod (hydroxypropyl cellulose) (19,4%), talc (19,26%), titanium dioxide (10,87%), ferrous oxide yellow (ferrous oxide) (0,47%)] − 18,000 mg.

Antibacterial agent with pronounced bactericidal action.

Pharmacological properties:

Pharmacodynamics. Antibacterial agent from group of ftorkhinolon. Has bactericidal effect. Influences bacterial DNK-girazu enzyme, the providing superspiralling and, thus, stability of DNA of bacteria. Destabilization of a chain of DNA leads to death of bacteria. Possesses a wide range of antibacterial action.

in vitro and in vivo concerning the following microorganisms is active: gram-positive aerobes: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae; gram-negative aerobes: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Salmonella spp., Shigella spp. in vitro concerning the following microorganisms is active: gram-negative aerobes: Citrobacter diversus, Edwardsiella tarda, Enterobacter agglomerans, Haemophilus ducreyi, Klebsiella oxytoca, Morganella morganii, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas fluorescens, Pseudomonas stutzeri; others: Ureaplasma urealyticum.

It is inactive concerning strict anaerobes.

Pharmacokinetics. Norfloxacin quickly, but not completely (30-40%) is soaked up after reception. Food slows down drug absorption. Maximum concentration in a blood plasma is reached in 1-2 hours and makes from 0,8 to 2,4 mkg/ml depending on a dose.

The low size of linkng of norfloxacin with proteins of plasma (10-15%) and high solubility in lipids cause the large volume of distribution of drug and good penetration into bodies and fabrics (a parenchyma of kidneys, ovaries, liquid of seed tubules, a prostate gland, a uterus, abdominal organs and a small pelvis, bile, breast milk). Gets through hematoencephalic and placental barriers.

In 2-3 hours after intake of norfloxacin in a dose of 400 mg concentration in urine exceeds 200 mkg/ml, within 12 hours she is supported at the level of 30 mkg/ml. At urine 7.5 pH solubility of norfloxacin decreases.

In insignificant degree it is metabolized in a liver. The elimination half-life makes 3-4 hours. It is removed by kidneys by glomerular filtering and canalicular secretion. Within 24 hours from the moment of reception of 32% of a dose 5-8% - in the form of metabolites are removed by kidneys in not changed look, with bile about 30% of the accepted dose are allocated.

Indications to use:

The infectious and inflammatory diseases caused by the activators sensitive to norfloxacin:
- infections of urinary tract, including chronic recuring (except the acute and chronic complicated pyelonephritis);
- chronic bacterial prostatitis; 
- gonorrhea is uncomplicated;
- bacterial gastroenteritis (salmonellosis, shigellosis);
- prevention of sepsis at patients with a neutropenia;
- prevention of diarrhea of travelers.

Route of administration and doses:

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

At infections of urinary tract: on 400 mg 2 times a day within 7-10 days, in case of the complicated infection – 10-21 days

At acute uncomplicated cystitis: on 400 mg 2 times a day within 3-7 days.

At a persistent recurrent infection of urinary tract: on 400 mg 2 times a day for up to 12 weeks, with a possibility of a dose decline to 400 mg a day in 4 weeks from the beginning of therapy at sufficient antibacterial efficiency.

At chronic bacterial prostatitis: on 400 mg 2 times a day within 4 weeks.

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

For prevention of diarrhea of travelers: on 400 mg a day in 1 day prior to departure, during the whole time of a travel (no more than 21 day).

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

At uncomplicated gonorrhea: once 800 mg.

More than 30 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 it is lower than 30 ml/min. (or the level of serumal creatinine more than 5 mg / 100 of ml) and to the patients who are on a hemodialysis appoint a full single dose (400 mg) of 1 times a day.

Features of use:

Use at pregnancy and during breastfeeding. Safety of use at pregnancy and during breastfeeding is not studied. Drug is contraindicated at pregnancy. In need of purpose of drug during breastfeeding it is necessary to stop breastfeeding.

During treatment by norfloxacin patients have to receive enough liquid (under control of a diuresis).

In order to avoid formation of crystals of norfloxacin in kidneys it is not necessary to exceed the recommended doses.

During therapy increase in a prothrombin ratio (when carrying out surgical interventions it is necessary to control a condition of system of a blood coagulation) is possible.

During treatment by norfloxacin it is necessary to avoid impact of a direct sunlight.

Norfloxacin, as well as other ftorkhinolona, can cause a tendinitis and ruptures of sinews, especially with the following risk factors: the age is more senior than 60 years, reception of glucocorticosteroids, transplantation of a kidney, heart or lung, the increased physical activity, a chronic renal failure, damage of sinews in the anamnesis (including a pseudorheumatism). These phenomena can arise also in several months after completion of administration of drug. At the first signs of a tendinitis or a rupture of a sinew it is necessary to stop reception of norfloxacin and to see a doctor.

During therapy norfloxacin recommends to avoid excessive exercise stresses.

Norfloxacin can reduce a threshold of convulsive readiness and cause spasms. In case of developing of spasms use of drug is stopped.
Ftorkhinolona can also stimulate the central nervous system, causing a tremor, toxic psychoses, concern, confusion of consciousness and a hallucination, increase in intracranial pressure.

Norfloxacin is not effective at syphilis.

Use of norfloxacin can lead to development of the pseudomembranous colitis caused by Clostridium difficile. In this case it is necessary to cancel drug and to appoint the corresponding treatment (use of Vancomycinum inside or metronidazole). Use of the drugs braking an intestines peristaltics is contraindicated.

At the patients applying ftorkhinolona, including norfloxacin cases of the touch and sensomotor axonal polyneuropathy affecting small and (or) large axons, and leading to paresthesia, a giposteziya, a dizesteziya and weakness are registered. Symptoms can soon be shown after the beginning of use and to be irreversible. If at the patient neuropathy symptoms, including pain, burning, a pricking, numbness and (or) weakness or other disturbances of sensitivity, including tactile, painful, temperature, vibration sensitivity and feeling of situation develop, norfloxacin needs to be cancelled immediately. At use of norfloxacin it was reported about cases of development of cholestatic hepatitis. The patient should be informed that in case of symptoms of an abnormal liver function (anorexia, jaundice, urine darkening, an itch, an abdominal pain) it is necessary to see a doctor before continuing treatment by norfloxacin.

In certain cases after the first use of drug hypersensitivity and allergic reactions can develop what it is necessary to inform the doctor immediately on. Very seldom even after the first use of drug anaphylactic reactions can progress to a life-threatening acute anaphylaxis. In these cases treatment by norfloxacin it is necessary to cancel and hold necessary medical events (including antishock).

Influence on ability of control of vehicles and mechanisms. 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. It is necessary to take potentiality of development of such side effects into account as dizziness, drowsiness and visual disturbances. At emergence of the described undesirable phenomena it is necessary to refrain from performance of the specified types of activity.

Side effects:

From the alimentary system: a loss of appetite, dyspepsia, nausea, vomiting, an abdominal pain, anorexia, diarrhea, a lock, rectum pain or an anus, a meteorism, dryness of a mucous membrane of an oral cavity, heartburn, bitter smack in a mouth, an ulceration of a mucous membrane of an oral cavity, an anus itch, pseudomembranous colitis (at prolonged use), hepatitis, jaundice, including cholestatic, pancreatitis, stomatitis, a liver failure (including with a lethal outcome).

From an urinary system: renal colic, glomerulonephritis, dysuria, polyuria, urethral bleedings, intersticial nephrite, renal failure.

From a nervous system: headache, dizziness, ataxy, faint, sleeplessness, hallucinations, peripheral neuropathy, feeling of a pricking of fingers, hypesthesia, mental disturbances (including confusion of consciousness), drowsiness, alarm, depression, sleep disorder, spasms, myoclonia, tremor, syndrome to Giyenna-Barra, fatigue, concern, irritability, sensation of fear, paresthesia.

From cardiovascular system: myocardial infarction, tachycardia, arrhythmias, ventricular arrhythmia, including pirouette type, lowering of arterial pressure, vasculitis, lengthening of an interval of QT.

From a musculoskeletal system: an arthralgia, tendinites, ruptures of sinews (usually in case of a combination with the promoting factors), a bursitis, puffiness of brushes and feet, a myasthenia aggravation, a spasm of muscles.

From system of a hemopoiesis: eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, hemolitic anemia.

Allergic reactions: anaphylactoid reactions, rash, a skin itch, a small tortoiseshell, hypostases, a Quincke's disease, an asthma, a vasculitis, arthritis, an artalgiya, a mialgiya, a toxic epidermal necrolysis, a leykotsitoklastichesky vasculitis, medicinal rash with an eosinophilia and system symptomatology (DRESS syndrome).

From integuments: malignant exudative erythema (Stephens-Johnson's syndrome), multiformny erythema, exfoliative dermatitis, photosensitization.

Laboratory indicators: increase in activity of "hepatic" transaminases, alkaline phosphatase, lactate dehydrogenase, creatine kinase; proteinuria; decrease in a hematocrit and hemoglobin; increase in concentration of urea in blood, a hypercreatinemia, a glucosuria, a crystalluria, an albuminuria.

From sense bodys: illegibility of visual perception, decrease/hearing loss, sonitus, diplopia, dysgeusia.

Others: dorsodynia, stethalgia, dysmenorrhea, fever, candidiasis, including vaginas, hyperhidrosis, adynamy, hypostases, erythema, fever.

Other side effects at reception of hinolon: albuminuria, kandiduriya, tsilinduriya, dysphagy, hyperglycemia, hypercholesterolemia, hyperpotassemia, gipertriglitseridemiya, hamaturia, liver necrosis, hypoglycemia, nystagmus, postural hypotension, lengthening of a prothrombin time.

Interaction with other medicines:

At simultaneous use of norfloxacin and theophylline it is necessary to control concentration of theophylline in a blood plasma and to adjust its dose as norfloxacin reduces clearance of theophylline by 25%, and development of the corresponding undesirable side effects can be observed.

Simultaneous use of norfloxacin and the drugs causing lengthening of an interval of QT (for example, цизаприд, the tricyclic and tetracyclic antidepressants, the antiarrhytmic drugs IA and III of classes, neuroleptics, macroleads, antifungal drugs derivative of an imidazole, some antihistaminic drugs, including астемизол, терфенадин, эбастин, etc.), has to be carried out under careful medical observation.

Norfloxacin reduces effect of nitrofurans.

Norfloxacin can strengthen therapeutic effect of cyclosporine and warfarin. In some cases at use of norfloxacin with cyclosporine increase in concentration of serumal creatinine therefore at such patients control of this indicator is necessary was observed.
Simultaneous use of norfloxacin and the antiacid means containing aluminum hydroxide or magnesium, and also the drugs containing iron, zinc (including polyvitamins), сукральфат, диданозин (tablets and solution for intake for children), reduces norfloxacin absorption (the interval between their reception has to be not less than 2 hours).

Simultaneous use with the medicines reducing a threshold of convulsive readiness (including with nonsteroid antiinflammatory medicines), can lead to development of spasms.

In vitro norfloxacin inhibits CYP1A2 that can lead to increase in concentration of its substrates in blood (for example, caffeine, clozapine, ропинирол, такрин, theophylline, тизанидин).

Simultaneous use of norfloxacin with glucocorticosteroids can promote increase in risk of tendinites and cases of a rupture of sinews.

Norfloxacin can strengthen therapeutic effect of hypoglycemic drugs (sulphonylurea derivatives). At a concomitant use with Glibenclamidum development of a heavy hypoglycemia is possible.

Probenetsid can reduce norfloxacin excretion.

The concomitant use of norfloxacin with the drugs having potential ability to lower arterial pressure can cause its sharp decrease. In this regard in such cases, and also at simultaneous introduction with barbiturates and other medicines for the general anesthesia, it is necessary to control the heart rate, arterial pressure and indicators of the electrocardiogram

Contraindications:

- hypersensitivity to norfloxacin, components of drug and other drugs of group of hinolon; 
- the tendinites, a tendovaginitis, ruptures of sinews connected with reception of ftorkhinolon including in the anamnesis;
- myasthenia;
- deficit glyukozo-6-fosfatdegidrogenazy;
- pregnancy and period of breastfeeding;
- age up to 18 years.

With care:
- atherosclerosis of vessels of a brain; 
- the age is more senior than 60 years;
- a concomitant use of glucocorticosteroid drugs, the medicines extending QT interval (the antiarrhytmic drugs IA and III of classes, tricyclic and tetracyclic antidepressants, neuroleptics, macroleads, antifungal drugs derivative of an imidazole, some antihistaminic drugs, including астемизол, терфенадин, эбастин);
- a state after transplantation of a kidney, heart, a lung;
- disturbance of cerebral circulation (in the anamnesis);
- organic diseases of the central nervous system;
- mental disturbances in the anamnesis;
- epilepsy, epileptic syndrome; 
- renal/liver failure;
- hepatic porphyria; 
- diabetes mellitus;
- syndrome of inborn lengthening of an interval of QT;
- heart diseases (heart failure, myocardial infarction, bradycardia);
- electrolytic imbalance (for example, hypopotassemia, hypomagnesiemia);
- at women;
- a concomitant use of barbiturates and medicines for the general anesthesia;
- a concomitant use of the medicines reducing arterial pressure.

Overdose:

Symptoms: at overdose emergence of the following symptoms is possible: nausea, vomiting, diarrhea; in hard cases - dizziness, drowsiness, "cold" sweat, spasms, a bloated face without change of the main hemodynamic indications.

Treatment: a gastric lavage, adequate hydration therapy with an artificial diuresis and symptomatic therapy. Inspection and observation in a hospital within several days is required. There is no specific antidote.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 400 mg. 5, 10 or 20 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 10 or 20 tablets in bank from polyethylene of high density. 2 or 4 blister strip packagings on 5 tablets, 1 or 2 planimetric cell
packagings on 10 tablets, 1 blister strip packaging on 20 tablets or one bank together with the instruction on a medical use in a pack from a cardboard.