Пефлоксабол®

General characteristics. Structure:

Acting вещесвто: 400 mg of a pefloksatsin of a mezilat a dihydrate (in terms of пефлоксацин).
Vspomogaatelny substances: the dextrose is anhydrous, dinatrium эдетат, water for injections.
 
Synthetic antimicrobic drug of a broad spectrum of activity from group of monoftorkhinolon.

Pharmacological properties:

Pharmacodynamics. Пефлоксабол® is synthetic antimicrobic drug from group of monoftorkhinolon. Works bakteritsidno, inhibiting DNK-girazu enzyme and replication of bacterial DNA; also breaks replication of A-subunit of RNA and protein synthesis by a bacterial cell. Causes an eradikation of gram-negative bacteria as being in a division phase, and in a resting phase. The bactericidal effect concerning gram-positive bacteria extends only to the cells which are in process of mitotic division. The post-antibiotic effect is characteristic.

Пефлоксабол® possesses a wide range of antimicrobic action. It is active concerning gram-positive cocci: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus (activity concerning Streptococcus spp., including S. pneumoniae, Enterococcus spp., low and clinically it is not significant); gram-negative cocci and bacteria: Acinetobacter spp. (are moderately sensitive), Aeromonas spp., Campylobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis (is moderately sensitive), Haemophilus ducreyi, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis, Morganella spp., Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurela multocida, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Salmonella spp., Serratia spp., Shigella spp., Vibrio spp., Yersinia spp.; intracellular microorganisms: Chlamydia spp., Chlamydophila pneumoniae, Legionella spp., Mycoplasma spp. (are moderately sensitive).

Does not collapse beta lactamelements, affects many strains steady against penicillin, cephalosporins and aminoglycosides.

Are insensitive to Pefloksabolu®: Staphylococcus spp strains., steady against Methicillinum, listeriya, gram-negative anaerobe bacterias (Bacteroides fragilis, Bacteroides spp., Prevotella spp., Fusobacterium spp.), Clostridium spp., Treponema spp., Mycobacterium tuberculosis.

Pharmacokinetics. The maximum concentration (Cmax) in blood serum after single infusion of 400 mg of a pefloksatsin is observed in 60 min. and makes 4 mkg/ml; therapeutic concentration are maintained during 12-15 h. After repeated infusions of Cmax in serum reach 10 mkg/ml. 25-30% of the entered dose contact proteins of a blood plasma. Quickly gets and it is well distributed in many bodies, fabrics and liquids of an organism.
 
Therapeutic the significant concentration exceeding concentration in blood serum are observed in saliva, a phlegm, aorta valves, the mitral valve, a myocardium, bones, a mucous membrane and a wall of intestines, peritoneal liquid, pancreatic juice and tissue of a pancreas (including nekrotizirovanny), a wall of a gall bladder, bile, a prostate, semen. The volume of distribution is equal to 1,5-1,8 l/kg.

Gets through a blood-brain barrier: after triple introduction of 400 mg of a pefloksatsin of concentration in liquor make 4,5 mkg/ml, at increase in a dose up to 800 mg - 9,8 mkg/ml; a ratio between concentration of drug in a blood plasma and liquor - 89%. Concentration in other bodies and fabrics in 12 h after the last introduction: a thyroid gland - 11,4 mkg/g, sialadens - 2,2 mkg/g, skin - 7,6 mkg/g, a mucous membrane of a nasopharynx - 6 mkg/g, almonds - 9 mkg/g, muscles - 5,6 mkg/g. The elimination half-life (Т½) is equal to 7,2-13 h (at single infusion) and 14-15 h - at repeated introduction.

Part from the entered dose is metabolized in a liver with formation of the following metabolites: N-dimetilpefloksatsina (norfloxacin which has considerable antibacterial activity), pefloksatsin-N-oxide and a pefloksatsin-glucuronide. 50-60% of the entered dose are removed by kidneys as not changed look, and in the form of metabolites; 30% are excreted with bile in an intestines gleam (also partially in not changed look, partially - in the form of active metabolites (norfloxacin)).

Content of not changed drug in urine in 1-2 h after introduction - 25 mkg/ml, in 12-24 h - 15 mkg/ml. Not changed пефлоксацин and its metabolites are found in urine during 84 h after the last administration of drug. Badly gives in to dialysis: coefficient of extraction of a pefloksatsin at a hemodialysis - less than 23%.

Indications to use:

Antibacterial therapy of the following infections caused by sensitive microorganisms: infections of the central nervous system (the bacterial meningitis caused by meningokokka or gram-negative bacteria, including postoperative or posttraumatic); upper respiratory tract infections and ENT organs (acute and chronic sinusitis, mastoiditis); lower respiratory tract infections (acute and the exacerbation of chronic bronchitis, a bronchoectatic disease, extra hospital and hospital pneumonia caused by gram-negative bacteria or intracellular activators); infections of an abdominal cavity (cholecystitis, cholangitis, treatment and prevention of infectious complications of acute destructive pancreatitis, local and widespread peritonitis, including postoperative); the complicated and uncomplicated infections of kidneys and urinary tract (acute and an exacerbation of chronic pyelonephritis, infectious complications after urinary tract operations); infections of bodies of a small pelvis at women (a pelviperitonitis, a salpingo-oophoritis, tubo-ovarian abscess, an endometritis, a bartholinitis); infections of reproductive system at men (an orchitis, an orchiepididymitis, prostatitis); infections of soft tissues; infections of bones and joints; sepsis; infections, sexually transmitted (gonorrhea, urogenital clamidiosis); bacterial infections of digestive tract, including эшерихиоз, shigellosis, cholera, salmonellosis, typhoid, paratyphus of A, B, C, иерсиниоз.

It is applied to an antibiotikoprofilaktika of postoperative it is purulent - septic complications in urology, abdominal surgery and gynecology.

Route of administration and doses:

Пефлоксабол® it is entered in the way in drop infusion lasting not less than 60 min.

The first dose - 800 mg. Then on 400 mg each 12 hours.

Patients with an abnormal liver function on 400 mg have each 24 hours. At more expressed disturbances enter 400 mg each 36 hours. At heavy pathology of a liver (jaundice and ascites) the interval between introductions is extended to 2 days.

At patients with the expressed renal failures (clearance of creatinine less than 10 ml/min.) and being on a hemodialysis on 400 mg each 24 hours.

Duration of treatment is defined by localization and weight of an infection.

At the initial stages of treatment Pefloksabol can parenterally be applied; after achievement of positive dynamics and in the presence of indications for continuation of therapy pass to reception of a peroral form of drug.

For prevention of infectious complications in surgical practice recommend to enter 400 - 800 mg of drug for an hour before operation.

Features of use:

At multi-infections, at perforative processes in an abdominal cavity, at infections of bodies of a small pelvis combine with medicines, active concerning anaerobe bacterias (metronidazole, clindamycin).

During treatment patients have to receive a large amount of liquid (for prevention of a crystalluria).

As well as at therapy by other ftorkhinolona, owing to a possible photosensitization it is recommended to avoid long influence of direct sunshine or ultraviolet radiation.

Patients with a serious illness of a liver and kidneys require dose adjustment in proportion to a damage rate.

At emergence in time or after treatment pefloksatsiny heavy and long diarrhea it is necessary to exclude development of pseudomembranous colitis (immediate drug withdrawal and purpose of the corresponding treatment is required).

Side effects:

From a nervous system and sense bodys: a depression, a headache, dizziness, increased fatigue, sleeplessness, increase in convulsive readiness, feeling of concern, excitement, a tremor, it is very rare - spasms.

From bodies of digestive tract: nausea, vomiting, diarrhea, tranzitorny increase in activity of "hepatic" transaminases, cholestatic jaundice, hepatitis.

From urinogenital system: a crystalluria, it is rare - a glomerulonephritis, a dysuria.

Allergic reactions: skin rash, a skin itch, a small tortoiseshell, a dermahemia, it is rare - phototoxic reactions, a Quincke's edema, a bronchospasm, arthralgias.

From system of blood and bodies of a hemopoiesis: leukopenia, neutropenia, thrombocytopenia, agranulocytosis, eosinophilia.

Others: tachycardia, mialgiya, tendinitis, candidiasis, lengthening of an interval of Q-T.

Local reactions: phlebitis.

Interaction with other medicines:

Antibiotics: combinations of a pefloksatsin with aminoglycosides possess sinergidny action concerning gram-negative aerobic bacteria, including P.aeruginosa that allows to reduce a dose of aminoglycosides and to reduce probability them from - and nephrotoxicity. Sinergidny and additive effects are reached at a combination of a pefloksatsin with a beta laktamnymi antibiotics, fosfomitsiny and rifampicin.

Pefloksatsin reduces metabolism of theophylline in a liver that leads to increase in concentration of theophylline in plasma and the central nervous system. In order to avoid development of intoxication the dose of theophylline needs to be reduced.
Reduces a prothrombin ratio. During treatment pefloksatsiny at the patients accepting indirect anticoagulants constant control of a picture of blood is necessary.

Cimetidinum and other inhibitors of a microsomal oxidation increase an elimination half-life of a pefloksatsin, reduce the general clearance, but do not influence the volume of distribution and renal clearance.

Пефлоксабол®, solution for infusions, it is impossible to mix with the solutions containing chlorine ions.

Contraindications:

Hypersensitivity to ftorkhinolona, children's age up to 18 years, the period of pregnancy and a lactation, to patients with deficit of a glyukozo-6-phosphate-dehydrogenase.

With care appoint to patients with neurologic frustration (epilepsy, a convulsive syndrome of an unspecified etiology, crushing organic lesions of the central nervous system, disturbance of cerebral circulation); heavy renal and/or hepatic insufficiency.

Overdose:

Symptoms: confusion of consciousness, spasm, diskoordination of movements.
Treatment: the specific antidote is unknown. Symptomatic therapy, if necessary - a hemodialysis and peritoneal dialysis is recommended.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. Freezing is not allowed.

Issue conditions:

According to the recipe

Packaging:

100 ml of drug in bottles or bottles glass with a capacity of 100 ml. 1 bottle (bottle) together with the application instruction is placed in a pack from a cardboard.