Tsefoktam

General characteristics. Structure:

Active ingredient: cefuroxime;

(6R,7R)-3-[(karbomoiloks) marked)]-7-[[(Z) - (furan-2-silt) (metoksiimino) acetyl] amine] - 8-oxo-5-thia-1-azobitsiklo [4.2.0] Oct-2-ene-2-carboxylat sodium salt;

1 bottle contains 0,75 g, 1,5 g of powder of a tsefuroksim of sodium salt sterile anhydrous in terms of tsefuroksy.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the II generation for parenteral use. Works bakteritsidno, breaks synthesis of a cell wall of microorganisms. Has a broad spectrum of activity. Resistant to action of the majority

β-лактамаз, therefore shows activity in relation to many ampicillin - or to amoksitsillinrezistentny strains.

Highly active in the relation:

–  gram-negative aerobes (Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus rettgeri, Providencia spp., Haemophilus influenzae (including ampitsillinrezistentny strains), Haemophilus parainfluenzae (including ampitsillinrezistentny strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including the strains producing a penicillinase), Neisseria meningitidis, Salmonella spp.;

–  gram-positive aerobes (Staphylococcus aureus, Staphylococcus epidermidis (including the strains producing a penicillinase, however excepting metitsilinrezistentny strains), Streptococcus pyogenes (and also other beta and hemolitic streptococci), Streptococcus pneumoniae, Streptococcus of group In (Streptococcus agalactiae), Streptococcus mitis (viridans group), Bordetella pertussis);

– anaerobe bacterias;

–  gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus species);

– gram-positive bacteria (including most Clostridium spp.) and gram-negative bacteria (including Bacteroides spp. і Fusobacterium spp.), Propionibacterium spp.;

– other microorganisms: Borrelia burgdorferi.

Microorganisms not sensitive to a tsefuroksim: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, metitsillinrezistentny strains of Staphylococcus aureus, metitsillinrezistentny strains of Staphylococcus epidermidis, Legionella spp.

Some strains of the microorganisms not sensitive to a tsefuroksim: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp.,    Citrobacter spp., Serratia spp., Bacteroides fragilis.

Pharmacokinetics. After intramuscular introduction in a dose of 0,75 g time of achievement of the maximum concentration in blood serum also makes about 30-45 minutes about 27 mkg/ml. At intravenous administration of 0,75 g and 1,5 g at the end of infusion the maximum concentration, respectively, 50 mkg/ml and 100 mkg/ml.

Contacts proteins of a blood plasma from 33% to 50%. Therapeutic concentration are registered in pleural and synovial liquids, bile, a phlegm, a bone tissue, cerebrospinal fluid (at an inflammation of a meninx), a myocardium, skin and soft tissues. Passes through a placenta, cosecretes with breast milk, gets through GEB at an inflammation of a meninx.

About 85-90% of a dose are removed by kidneys in not changed state in        24 hours (50% are excreted in renal tubules, 50% are filtered in balls).

The elimination half-life at intravenous and intramuscular introductions makes about 70 minutes (at newborns can be by 3-5 times longer).

In 0,75 g of a tsefuroksim 42 mg (1,8 мэкв) sodium contain.

Pharmaceutical characteristics.

Main physical and chemical properties: poroshokbely or almost white color, small it is hygroscopic.

Incompatibility. Pharmaceutical it is incompatible with solutions of aminoglycosides (it is impossible to mix in one syringe).

рН 2,74% of solution of sodium of bicarbonate influence color of solution therefore this solution is not recommended for cultivation of Tsefoktama®. However, in case of need, if the patient receives bicarbonate sodium solution intravenously by infusion, Tsefoktam® can be entered directly into a dropper tube.

Indications to use:

The infectious and inflammatory diseases caused by activators, sensitive to drug, including infection of upper and lower respiratory tracts – acute and chronic bronchitis, the infected bronchiectasias, bacterial pneumonia, abscess of lungs, postoperative infections of bodies of a chest cavity; infections of an ear, a throat, a nose – sinusitis, tonsillitis, pharyngitis and average otitis; infections of urinary tract – acute and chronic pyelonephritis, cystitis, a symptomless bacteriuria; infections of soft tissues – cellulitis, an ugly face, wound fevers; infections of bones and joints: osteomyelitis, septic arthritis; inflammatory diseases of bodies of a small pelvis (in obstetrics and gynecology); gonorrhea; other infections – peritonitis, a septicaemia, meningitis; prevention of infections at operations on bodies of a chest and abdominal cavity, bodies of a small pelvis, at cardiovascular and orthopedic operations.

Route of administration and doses:

Before use of drug carry out skin test on hypersensitivity to antibiotics.

Цефоктам® enter only intramusculary and intravenously.

Solvents for dissolution of powder of a tsefuroksim: 5% glucose solution for injections,           10% glucose solution for injections, 0,9% chloride sodium solution for injections, 5% glucose solution s0,9% or 0,45%, or 0, 225% chloride sodium solution for injections, Ringen's solutions, Ringera-laktata, Gartmana, water for injections.

Intramusculary: add 3 ml of water for injections to 0,75 g of drug, carefully stir up a bottle before formation of homogeneous suspension.

Intravenously: dissolve 0,75 g of drug not less, than in 6 ml of water for injections, 1,5 g – in 15 ml of solvent.

For short intravenous infusions (up to 30 minutes) 0,75 g of drug dissolve not less, than in 25 ml of solvent (water for injections, 0,9% solution of sodium of chloride, 5% glucose solution), 1,5 g – in 50 - 100 ml of solvent.

Solvents for intravenous administration: 5% glucose solution for injections, 5% solution of glucose and Ringer's solution lactat for injections, 5% solution of glucose and      0,9% chloride sodium solution for injections, 10% glucose solution for injections, Ringer's solution lactat for injections, 0,9% chloride sodium solution for injections. The received solutions can be entered directly into a vein or into a dropper tube at infusional therapy. In storage time of already ready solutions there can be changes of a saturation of color.

The adult intramusculary or intravenously appoint 0,75 g of drug 3 times a day, at heavier infections – on 1,5 g 3 times a day intravenously. If necessary the interval between injections can be reduced to 6 h. A daily dose of drug –      3-6 g.

To babies and children appoint drug in a dose of 30-100 mg/kg a day for 3 - 4 introductions. For the majority of infections the optimum daily dose makes 60 mg/kg a day.

The newborn appoint 30-100 mg/kg a day for 2-3 introductions. It is necessary to consider that the elimination half-life of a tsefuroksim in the first weeks of life, can be by 3-5 times big, than at adults.

At gonorrhea drug appoint in a dose 1,5 g disposable in the form of one or two injections on 0,75 g which are entered into both buttocks.

At each 8 h meningite:vzroslymnaznachat 3 g intravenously; to babies, detyamnaznachat 150-250 mg/kg the day intravenously divided into 3-4 introductions; the newborn appoint drug in a dose of 100 mg/kg a day intravenously.

For prevention of infections at abdominal, pelvic and orthopedic operations the drug is administered intravenously in an average dose of 1,5 g during an anesthesia. If necessary additional administrations of drug intramusculary in a dose 0,75 in about 8 g and   16 h are possible.

At heart, lungs, gullet operations and vessels the usual dose makes 1,5 g intravenously, entered at a stage of induction of anesthesia which then is supplemented with intramuscular introduction of 0,75 g 3 times a day for the following 24 - 48 h.

At full replacement of a joint of 1,5 g of the powder Tsefoktama® mix with one package of methylmethacrylate cement-polymer before addition of liquid monomer.

Consecutive therapy.

Pneumonia: 1,5 g Цефоктама® 2-3 times a day (intramusculary or intravenously) for 48-72 h with further transition to peroral forms of antibiotics for 7-10 days.

Exacerbation of chronic bronchitis: 0,75 g Цефоктама® 2-3 times a day (intramusculary or intravenously) for 48-72 h with further transition to peroral forms of antibiotics for 5-10 days.

Duration of both parenteral, and peroral therapy is defined by weight of an infection and a clinical condition of the patient.

The patient with renal failures at clearance of creatinine of 10-20 ml/min. 2 times a day recommend to administer the drug on 0,75 g; at clearance of creatinine less than 10 ml/min. – 0,75 g of 1 times a day. To patients who are on a hemodialysis at the end of each procedure enter 0,75 more g of drug intramusculary or intravenously. In addition to parenteral administration drug can be added to peritoneal dialysis liquid (usually 0,25 g on each 2 liters of dialysis liquid). At a long arteriovenous hemodialysis or bystry haemo filtering drug is appointed on 0,75 g by 2 times a day. At slow haemo filtering it is necessary to adhere to the scheme of doses as for treatment at renal failures.

Features of use:

Use during pregnancy or feeding by a breast.

There are no data on embriotoxity and teratogenic action of a tsefuroksim, however, as at use of other drugs, it has to be appointed with care in the first months of pregnancy. Tsefuroksim is allocated with breast milk therefore use of drug during feeding by a breast should be stopped.

Children.

Drug is used in pediatric practice.

With care appoint drug to newborn, premature children.

 

The patients having allergic reactions to penicillin or other β-laktamny antibiotics in the anamnesis can have hypersensitivity to tsefalosporinovy antibiotics.

Carefully appoint drug to newborn, premature children, patients with the expressed renal failures, at colitis, a reduced blood coagulation, stomach ulcer and a duodenum, to elderly people, patients with a renal failure.

At long use it is recommended to control function of kidneys (especially at use of high doses) and to perform prevention of dysbacteriosis. Tsefalosporinovy antibiotics in high doses should be applied with care at the patients receiving highly active diuretics, such as furosemide or aminoglikozidny antibiotics as there are messages on cases of undesirable influence on function of kidneys at such combination. At patients with a renal failure the dose has to be lowered taking into account expressiveness of a renal failure and sensitivity of the activator.

After elimination of symptoms of a disease treatment should be continued on an extent of 48-72 hours.

During treatment it is impossible to take alcohol.

As well as at other schemes of treatment of meningitis, at several patients is children who were treated tsefuroksimy, cases of a partial hearing loss were registered.

As well as at treatment by other antibiotics, in 18-36 hours after an injection of a tsefuroksim in spinnomozkovy liquid the culture of Haemophilus influenzae was defined. However clinical value of this phenomenon is unknown.

As well as at use of other antibiotics, prolonged use of a tsefuroksim can lead to the overgrowth of insensitive microorganisms (for example, Candida, Enterococci, Clostridium difficile) that can demand the treatment termination.

At use of a tsefuroksim in the mode of consecutive therapy time of transition to oral administration of a tsefuroksim is defined by weight of an infection, a clinical condition of the patient and sensitivity of a microorganism. In the absence of clinical improvement for 72 hours it is necessary to continue parenteral administration of drug.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

There are no messages on influence of drug on speed of response at control of motor transport or other mechanisms.

Side effects:

From the central nervous system and peripheral nervous system: headache, dizziness, spasms.

From bodies of system of feelings: at treatment of meningitis at children the hearing loss of average and weak severity was observed.

From a digestive tract: abdominal pain, nausea, vomiting, diarrhea; cases of pseudomembranous colitis are described.

From a liver and biliary tract: tranzitorny increase in activity of liver enzymes (mainly at patients with the existing liver pathology), tranzitorny increase in level of bilirubin, a cholestasia.

From system of blood: anemia, eosinophilia, leukopenia, neutropenia, thrombocytopenia, hemolitic anemia, decrease in a hematocrit. Cephalosporins have property to be absorbed on a surface of a membrane of red blood cells and to interact with antibodies, causing positive test of Koombs that can influence blood typing and is very rare – hemolitic anemia.

From an urinary system: increase in level of creatinine in blood serum, a blood urea nitrogen, reduction of level of clearance of creatinine.

From immune system: at prolonged use the overgrowth of insensitive microorganisms, for example Candida is possible.

Allergic reactions: skin rash, itch, small tortoiseshell, medicamentous fever, intersticial nephrite; extremely seldom – an acute anaphylaxis; makulopapulezny rashes, a vasculitis of vessels of skin, an anaphylaxis, a Quincke's disease are occasionally noted.

From skin and hypodermic cellulose: polymorphic erythema, Stephens-Johnson's syndrome and toxic epidermal necrolysis.

Disturbances in an injection site: pain, at intravenous administration – a burning sensation in an injection site, thrombophlebitis.

Interaction with other medicines:

The drugs reducing aggregation of thrombocytes (non-steroidal anti-inflammatory drugs, salicylates, Sulfinpyrazonum) – Tsefoktam®, oppressing an indestinal flora, interferes with vitamin K synthesis as the result – increases risk of development of bleedings.

Anticoagulants – strengthening of anticoagulating action as result – increases risk of development of bleedings.

Diuretics and potentially nefrotoksichny antibiotics (for example, aminoglycosides) – the risk of development of nephrotoxic action increases. In a combination the additive effect meets aminoglikozidny antibiotics, a synergism in certain cases comes to light.

Probenetsid – drug reduces canalicular secretion and reduces renal clearance of Tsefoktama® that leads to increase in its concentration in blood serum.

Oral contraceptives – Tsefoktam® oppresses intestinal microflora, thereby reduces an estrogen reabsorption from intestines therefore action of contraceptives decreases.

At treatment of Tsefoktamom® glucose level in blood and a blood plasma is recommended to be determined by a glyukozooksidazny or geksozokinazny technique.

Цефоктам® does not influence results of enzymatic methods of definition of a glucosuria.

Цефоктам® in insignificant degree can influence use of the techniques which are based on copper recovery (Benedikta, Felinga, Klinitest), however it does not result in pseudo-positive results, as in cases with some other cephalosporins.

Цефоктам® does not influence result of a research of level of creatinine alkaline picrate.

1,5 g of Tsefoktama® dissolved in 15 ml of water for injections can be applied together with metronidazole solution (500 mg / 100 in ml); both drugs keep activity within 24 hours at a temperature below 25 °C.

1,5 g of Tsefoktama® are compatible to 1 g of an azlotsillin (in 15 ml of solvent) or from 5 g (in 50 ml of solvent) within 24 hours at a temperature of 4 °C and 6 watch at a temperature up to 25 °C.

Цефоктам® (5mg/ml) it is possible to store within 24 hours at a temperature of 25 °C of 5% or  10% xylitol solution for injections.

Цефоктам® it is compatible to solutions which contain up to 1% of lidocaine of a hydrochloride. Цефоктам® it is compatible to the majority of the applied solutions for intravenous injections. It keeps the properties for 24 hours at the room temperature.

Stability of Tsefoktama® in 0,9% chloride sodium solution for injections from 5% solution of glucose does not change in the presence of a phosphate sodium hydrocortisone.

Цефоктам® it is also compatible for 24 hours at the room temperature at cultivation in solutions for infusions:

with heparin (10 or 50 PIECES/ml) in 0,9% chloride sodium solution for injections,

with chloride potassium solution (10 or 40 ¼Ý¬ó/l) in 0,9% chloride sodium solution for injections.

Contraindications:

Hypersensitivity to tsefalosporinovy antibiotics.

Bleedings and disease of a digestive tract in the anamnesis, including nonspecific ulcer colitis.

Overdose:

The overdose by cephalosporins can lead to development of symptoms of irritation of a brain therefore development of spasms is possible.

Treatment. Use of anticonvulsants, protection of respiratory tracts, ensuring ventilation and perfusion, control and support at the necessary level of the vital indicators, gases and electrolytes of blood, haemo - and peritoneal dialysis.

Storage conditions:

Period of validity. 2 years. To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 0,75 g, 1,5 g in a bottle. On 1 or 5 bottles in a pack.