Pefloksatsin-akos

General characteristics. Structure:

Active agent: a pefloksatsina of a mezilat a dihydrate (in terms of пефлоксацин) – 400 mg. Excipients: ascorbic acid, benzyl alcohol, sodium disulphite (sodium metabisulphite), dinatrium эдетат (ethylene diamine tetraacetic acid disodium salt [Trilonum of B]), Natrii hydrocarbonas (sodium bicarbonate), water for injections - to 5 ml.

Pharmacological properties:

Antimicrobic drug of a broad spectrum of activity from group of ftorkhinolon. Has bactericidal effect, blocking DNK-girazu, breaks replication of A-subunit of DNA and RNA and protein synthesis of bacteria.

Concerning gram-negative bacteria affects the cells finding in a stage of rest and division concerning gram-positive bacteria - only on the cells which are in process of mitotic division. It is steady against action β-лактамаз. Possesses a broad spectrum of activity.

Drug is active concerning aerobic gram-negative bacteria: Escherichia coli, Klebsiella spp., an indole - positive and an indole - negative Proteus spp. (including Proteus mirabilis), Enterobacter spp., Helicobacter pylori, Morganella morganii, Yersinia enterocolitica, Vibrio cholerae, Vibrio parahaemolyticus, Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis, Pasteurella multocida, Campylobacter spp., Serratia spp., Citrobacter spp., Salmonella spp., Shigella spp., Haemophilus spp., Neisseria gonorrhoeae; aerobic gram-positive bacteria: Staphylococcus spp., (including, producing and not producing a penicillinase and metitsillinrezistentny), Streptococcus spp. (including Streptococcus pyogenes, Streptococcus agalactiae), Corynebacterium diphtheriae, Listeria monocytogenes; intracellular bacteria: Legionella spp. (including Legionella pneumophila), Brucella spp., Chlamydia spp., Mycoplasma spp.

Are moderately sensitive to drug: Pneumococcus spp. (Streptococcus pneumoniae), Acinetobacter spp., Clostridium perfringens, Pseudomonas spp., Chlamydia trachomatis.

Gram-negative anaerobic bacteria - Bacteroides spp are steady against drug. (except for B.fragilis), Treponema spp., Mycobacterium tuberculosis.

 

Pharmacokinetics. Absorption

After intake пефлоксацин it is quickly absorbed from a GIT. After a single dose in 400 mg of a pefloksatsin in 20 min. 90% of a dose are absorbed, at this Cmax it is reached in 90-120 min. and makes 4 mkg/ml. After repeated introduction of Cmax in a blood plasma - 10 mkg/ml, concentration in a mucous membrane of bronchial tubes - 5 mkg/ml; a ratio between concentration in a mucous membrane and in blood - 100%.

Later in/in introductions of Cmax it is reached within 60 min.

Distribution

Linkng with proteins of plasma makes 25-30%. Vd - 1.5-1.8 l/kg. Pefloksatsin well gets into fabrics and liquids of an organism (a bronchial secret, lungs, a prostate gland, cerebrospinal fluid, peritoneal liquid, a bone tissue, heart, a phlegm, urine, bile). Concentration in the listed above liquids and fabrics of concentration in a blood plasma.

Concentration in cerebrospinal fluid after triple reception in a dose of 400 mg - 4.5 mkg/ml, at increase in a dose up to 800 mg - 9.8 mkg/ml; a ratio between concentration in plasma and liquid - 89%. Concentration in other bodies and fabrics in 12 h after the last reception: a thyroid gland - 11.4 mkg/g, sialadens - 2.2 mkg/g, skin - 7.6 mkg/g, almonds - 9 mkg/g, muscles - 5.6 mkg/g.

Metabolism

It is metabolized in a liver by methylation to a dimetilpefloksatsin (has considerable antibacterial activity), is oxidized to N-oxide and conjugates with glucuronic acid with formation of a pefloksatsina-glucuronide.

Removal

T1/2 after intake makes about 8-10 h, at repeated introduction - 12-13 h; T1/2 in/in introductions of a single dose is later 7.2-13 h, at repeated introduction - 14-15 h. It is removed with urine (60%) and with a stake in not changed look, partially - in the form of metabolites. The maintenance of not changed pefloksatsin in urine in 1-2 h after reception – 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. Coefficient of extraction of a pefloksatsin at a hemodialysis – 23%.

Indications to use:

Treatment of the infectious and inflammatory diseases caused by microorganisms, sensitive to drug:

— infections of kidneys and urinary tract;

— GIT infections (including salmonellosis, typhoid);

— infections of a gall bladder and biliary tract (including cholecystitis, cholangitis, empyema of a gall bladder);

— infections of an abdominal cavity (including intraabdominal abscesses, peritonitis);

— infections of bodies of a small pelvis (including adnexitis, prostatitis);

— infections of bones and joints (including osteomyelitis);

— infections of skin and soft tissues;

— infections of lower parts of respiratory tracts;

— infections of ENT organs (including middle ear, adnexal bosoms of a nose, throat and throat);

— infections of eyes;

— sepsis, septicaemia;

— bacterial endocarditis;

— encephalomeningitis;

— infections of skin and soft tissues;

— gonorrhea;

— clamidiosis;

— prostatitis;

— epididymite;

— venereal ulcer;

— surgical and intrahospital infections;

— prevention of infectious complications after surgical interventions.

Route of administration and doses:

Intravenously kapelno, infusion is carried out within 1 hour. The first dose – 400-800 mg; then - on 400 mg each 12 h. A course of treatment - 1-2 weeks (no more than 4 weeks).

Preparation of solution for infusion: contents of one ampoule (400 mg = 5 ml of a concentrate) dissolve 5% of solution of a dextrose in 250 ml. As solvent it is impossible to use the solution of sodium of chloride or any solvent containing chlorine ions!  

For prevention of infectious complications in surgery recommend in/in administration of drug in a dose 400-800 mg for 1 h before carrying out operation.

For patients with liver diseases the single dose for in/in drop introductions makes 8 mg/kg of body weight; infusion duration - 1 h. Frequency of performing infusions at patients with jaundice - 1 time in 24 h; patients with ascites have 1 time in 36 h; at patients with jaundice and ascites - 1 time in 48 h. 

To patients with renal failures (at clearance of creatinine it is lower than 20 ml/min.) the single dose has to make 50% of an average dose at frequency rate of appointment 2 times a day or a full single dose enter 1 time a day. To elderly people the dose of drug is reduced approximately on 1/3. 

Owing to equivalence of doses at intake and in introduction, drug can be used for performing consecutive therapy (the course begun in/in introductions continue by intake).

Features of use:

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

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

Owing to a possible photosensitization during treatment of Pefloksatsinom-AKOS it is necessary to avoid Uv-radiation.

At a serious illness of a liver and kidneys correction of the mode of dosing is required.

At emergence in time or after treatment of Pefloksatsinom-AKOS of heavy and long diarrhea it is necessary to exclude pseudomembranous colitis (at the same time immediate drug withdrawal and purpose of the corresponding therapy is required).

Influence on ability to driving of motor transport and control of mechanisms

At use of drug it is necessary to abstain from the occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From TsNS: depression, headache, dizziness, sleeplessness, increased fatigue, increase in convulsive activity, concern, excitement, tremor; seldom - spasms.

From the alimentary system: nausea, vomiting, diarrhea, abdominal pains, anorexia, meteorism, pseudomembranous colitis, tranzitorny increase in activity of hepatic transaminases, cholestatic jaundice, hepatitis, liver necrosis.

From an urinary system: crystalluria; seldom - a glomerulonephritis, a dysuria.

From system of a hemopoiesis: a leukopenia, a neutropenia, thrombocytopenia (at doses of 1.6 g/days), an agranulocytosis, an eosinophilia.

Allergic reactions: skin rash, skin itch, small tortoiseshell, dermahemia, photosensitization; seldom - a Quincke's edema, a bronchospasm, an arthralgia.

Others: tachycardia, mialgiya, tendinitis, rupture of sinews, candidiasis.

Local reactions: phlebitis.

Interaction with other medicines:

Simultaneous use of Pefloksatsina-AKOS and beta лактамных antibiotics prevents development of resistance at treatment of a staphylococcal infection

At simultaneous use of Pefloksatsina-AKOS with aminoglycosides, piperatsilliny, azlotsilliny, the ceftazidime notes a synergism of antibacterial action (including concerning a pyocyanic stick).

At simultaneous use of Pefloksatsina-AKOS and indirect anticoagulants decrease in a prothrombin ratio is noted (therefore in need of purpose of this combination it is necessary to control a pattern of peripheral blood).

Pharmacokinetic interaction

Absorption of a pefloksatsin is slowed down at a concomitant use with the antacids containing aluminum hydroxide and magnesium hydroxide.

The concomitant use of a pefloksatsin and Cimetidinum leads to decrease in the general clearance and increase in an elimination half-life of a pefloksatsin, but does not change the volume of distribution and renal clearance.

Pefloksatsin-AKOS slows down metabolism of theophylline in a liver that leads to increase in concentration of theophylline in plasma and in TsNS (therefore in need of purpose of this combination it is necessary to reduce a theophylline dose).

The drugs blocking canalicular secretion slow down removal of a pefloksatsin.

Pharmaceutical interaction

Pefloksatsin it is impossible to mix with the solutions containing chlorine ions in order to avoid loss of a deposit.

It is incompatible with heparin.

Contraindications:

— epilepsy;

— hemolitic anemia;

— insufficiency glyukozo-6-fosfatdegidrogenazy;

— pregnancy;

— lactation (breastfeeding);

— children's and teenage age up to 18 years;

— hypersensitivity to ftorkhinolona.

With care appoint drug at atherosclerosis of vessels of a brain, disturbance of cerebral circulation, organic lesions of TsNS, a convulsive syndrome of an unspecified etiology.

 

Use of drug PEFLOKSATsIN-AKOS at pregnancy and feeding by a breast
Drug is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding).

 

Use at abnormal liver functions
Patients with abnormal liver functions require correction of the mode of dosing. At insignificant disturbances drug is appointed on 400 mg 2, at more expressed disturbances - each 36 h, at a serious illness of a liver the interval between introductions is extended to 2 Course of treatment - no more than 30 days.

 

Use at renal failures
To patients with renal failures (at KK less than 20 ml/min.) the single dose makes 50% of an average dose at frequency rate of appointment 2, or the full single dose is entered by 1 times/days.

 

Use for children
Drug is contraindicated to children and teenagers up to 18 years.

Overdose:

Now about cases of overdose of the drug Pefloksatsin-AKOS it was not reported.

At accidental overdose appoint symptomatic therapy. If necessary carry out a hemodialysis and peritoneal dialysis. There is no specific antidote.

Storage conditions:

List B. Drug should be stored in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C. A drug period of validity in the form of tablets - 3 years, in the form of solution for infusions - 2 years.

Issue conditions:

According to the recipe

Packaging:

5 ml - ampoules (5) - packs cardboard.
5 ml - ampoules (10) - packs cardboard.