Мегасеф®

General characteristics. Structure:

Active ingredient: 250 mg or 750 mg of sterile sodium salt of a tsefuroksim, to an equivalent anhydrous tsefuroksim,

Excipient: solvent - water for injections: 2 ml in an ampoule - for a dosage of 250 mg and 6 ml in an ampoule - for a dosage of 750 mg.

Antibiotic of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Мегасеф® – a tsefalosporinovy antibiotic of the second generation of a broad spectrum of activity. Has bactericidal effect at the expense of inhibition of synthesis of a cell wall of bacteria. Мегасеф® acetylates membrane-bound transpeptidases, breaking, thus, the cross stitching of peptido-glycanes necessary for ensuring durability and rigidity of a cell wall. Мегасеф® it is steady against action of many bacterial beta лактамаз therefore it is active concerning the majority of the types steady against penicillin and amoxicillin.

Мегасеф® it is active concerning the following microorganisms:

- gram-negative bacteria: Escherichia coli, Haemophilus influenzae (including the types producing beta lactamelements), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including the types producing beta lactamelements), Neisseria gonorrhoeae (including the types producing beta lactamelements), Salmonella spp., Shigella spp., Proteus mirabilis, Enterobacter spp.

- gram-positive bacteria: Staphylococcus aureus (including the types producing beta lactamelements), Streptococcus pneumoniae, Streptococcus pyogenes.

- certain types of enterococci, for example Enterococcus faecalis, are steady against a tsefuroksim.

- anaerobe bacterias: Peptococcus spp., Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Fusobacterium spp.

Pharmacokinetics. After an intramuscular injection of 750 mg of a tsefuroksim average peak concentration in serum (Cmax) makes 27 mkg/ml. It reaches concentration in plasma (tmax) approximately in 45 minutes.

The elimination half-life (t1/2) after an intramuscular or intravenous injection makes about 80 minutes. About 50% of a tsefuroksim contact serum protein. Tsefuroksim is found in the volumes exceeding the maximum effective concentration in pleural liquid, intra joint liquid, bile, saliva, bones and in liquid of chambers of the eye.

About 89% of a dose of a tsefuroksim are allocated with kidneys without changes during 8 h that results in high concentration in urine. Tsefuroksim gets through a placenta, breast milk and a blood-brain barrier in case of meningitis.

Indications to use:

- acute bronchitis, exacerbation of chronic bronchitis, bacterial pneumonia, абцесс lungs;

- otitis, sinusitis, tonsillitis, pharyngitis;

- acute and chronic pyelonephritis, cystitis, urethritis, symptomless bacteriuria;

- infections of skin and soft tissues, including erysipelatous inflammation, wound fevers;

- osteomyelitis, septic arthritis;

- inflammatory diseases of bodies of a small pelvis;

- gonorrhea;

- peritonitis;

- septicaemia;

- meningitis;

- endocarditis;

- prevention of infectious complications at abdominal organs operations, a basin, heart, lungs, a gullet and vessels, at orthopedic operations.

Route of administration and doses:

Adults and children weighing more than 40 kg. At infections of moderate severity recommends intramusculary or intravenously 750 mg 3 times a day.

At heavy infections – intravenously 1,5 g 3 times a day. If necessary the interval between injections can be reduced to 6 h; a daily dose of drug – 3 - 6 g. The course of treatment makes 5 – 10 days.

At some infections use of drug on 0,75-1 g 2 times a day is more effective. The course of treatment makes 5 – 10 days. Further use of the tableted ^{Megasef® form} is possible.

Children with body weight less than 40 kg. The recommended dose of drug of 30-100 mg/kg a day in 3-4 introductions. For the majority of infections the optimum daily dose makes 60 mg/kg.

The newborn (1 month) appoint 30-100 mg/kg a day in 2-3 introductions.

Pneumonia. At pneumonia recommend to administer the drug on 1,5 g or 2 times a day (intramusculary or intravenously) during 48-72 h. Further use of the tableted ^{MEGASEF® form} in a dose of 500 mg 2 times a day within 7-10 days is possible.

Gonorrhea. At gonorrhea drug appoint in a dose 1,5 g once in the form of the 1st injection or in the form of 2 injections on 750 mg entered into both buttocks.

Meningitis. At meningitis to adults and children with body weight more than 40 kg are appointed on 3 g in/in each 8 h. To children with body weight less than 40 kg appoint 150-250 mg/kg/days in/in in 3-4 introductions. At achievement of optimum therapeutic effect it is possible to reduce a dose of drug to 100 mg/kg/days intravenously.

The newborn appoint drug in an initial dose of 100 mg/kg/days intravenously. At achievement of optimum therapeutic effect it is possible to reduce a dose to 50 mg/kg/days intravenously.

For prevention of infectious complications at abdominal, pelvic and orthopedic operations of drug enter intravenously in a dose 1,5 g along with introduction anesthesia. If necessary additional administrations of drug intramusculary in a dose of 750 mg in 8 and 16 h are possible. At heart, lungs, gullet operations and vessels enter 1,5g drug intravenously with anesthesia induction, then enter 750 mg 3 times a day for the subsequent 24-48 h.

Renal failure. At a renal failure the reduced dose has to be applied. The dosage has to be defined by extent of renal disturbances and sensitivity of a microorganism.

Dosage ^{of Megasef®} for injections the adult with a renal failure:

Clearance of creatinine (ml/min.)	Dose (mg)	Frequency
> 20	750 – 1500	Each 8 h
10 – 20	750	Each 12 h
<10	750	Each 24 h

Patients with a renal failure, being on continuous a hemodialysis with use of the arteriovenous shunt or on haemo filtering of high speed in intensive care units, ^Megasef®. appoint in a dose 750 g 2 times a day. For the patients who are on haemo filtering of low speed appoint the doses recommended at a renal failure.

Rules of preparation of solutions for parenteral administration. For in oil or in/in injections add water for injections (according to the table), carefully stir up before formation of suspension.

For introduction in oil:

Dose	Amount of water for injections
750 mg	3 ml

For in/in introductions:

Dose	Amount of water for injections
250 mg	3 ml
750 mg	6 ml

Jet in/in introduction – slowly within 3-5 minutes. For continuous infusional to introductions, ^{MEGASEF® solution} it is possible to add to the following infusion solutions: solution of sodium of chloride of 0,9%, solution of a dextrose of 5% and 10%.

Features of use:

At patients with hypersensitivity to penicillin allergic reactions to antibiotics of group of cephalosporins are possible; such patients should appoint cephalosporins with care.

High doses of cephalosporins have to be appointed with care at the expressed renal failures, and also to the patients receiving the accompanying treatment by strong diuretics as furosemide and aminoglycosides, the risk of nephrotoxic effects increases.

Patients with digestive tract diseases (especially at colitis) should apply with care.

At emergence of allergic reaction it is necessary to stop administration of drug.

Pregnancy and period of a lactation. Use in II and III trimesters of pregnancy, and also in the period of a lactation perhaps in cases when the estimated advantage of therapy for mother exceeds potential risk for a fruit. Tsefuroksim is allocated with breast milk therefore during treatment by drug it is necessary to stop breastfeeding.

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms. Drug does not influence ability to manage the vehicle and work with potentially dangerous mechanisms.

Side effects:

- thrombophlebitis (at intravenous administration), morbidity in the place of an injection (at intramuscular introduction);

- gastrointestinal disturbances (glossites, nausea, vomiting, diarrhea, heartburn, abdominal pains);

- passing increase in activity of hepatic transaminases, increase in the general bilirubin in blood, cholestatic jaundice, hepatitis, pseudomembranous colitis;

- hypersensitivity manifestations (insignificant urtikariya, skin rashes, a skin itch and joint pains) which are more often observed at patients with the established hypersensitivity an eosinophilia, a Quincke's edema, a mnogoformny erythema;

- Stephens's syndrome – Johnson, a toxic epidermal necrolysis;

- "medicinal" fever, anaphylaxis, bronchospasm;

- a leukopenia, a neutropenia, thrombocytopenia, hemolitic anemia, an agranulocytosis, an eosinophilia, a prothrombinopenia (at prolonged use in high doses);

- intersticial nephrite (with increase in level of creatinine, nitrogen, urea);

- spasms, decrease in hearing.

Isolated cases:

- dizziness, breath difficulty, hearing disorder, spasms;

- candidiasis of an oral cavity and vagina at prolonged use.

Interaction with other medicines:

Use of a method of a glyukozoksidaza or hexokinase when determining level of glucose in a blood plasma at the patients receiving tsefuroksy is recommended. False positive reactions to availability of glucose in urine in tests with copper recovery can take place (Benedikta, Fekhlinga, Klinitest). For definition of a glucosuria it is necessary to use fermental tests. Nevertheless, it does not cause false positive results as some other cephalosporins. Positive forward reaction of Koombs is also possible.

Tsefuroksim, suppressing an indestinal flora, interferes with vitamin K synthesis. Therefore at simultaneous use with the drugs reducing aggregation of thrombocytes (non-steroidal anti-inflammatory drugs, salicylates, Sulfinpyrazonum) the risk of development of bleedings increases. For the same reason at simultaneous use with anticoagulants strengthening of anticoagulating action is noted.

At simultaneous use of a tsefuroksim in high doses with loopback diuretics (furosemide) and aminoglycosides canalicular secretion is slowed down, the renal clearance decreases, concentration in plasma increases and the elimination half-life of a tsefuroksim increases that increases risk of emergence of nephrotoxic effects.

Co-administration of a probenetsid with tsefuroksimy slows down canalicular secretion, increases peak concentration in serum approximately for 40% and increases an elimination half-life approximately by 30%.

Combined use of a tsefuroksim with ampicillin, gentamycin, Kanamycinum, streptomycin, Tobramycinum, Acidum etacrynicum strengthens risk of a renal failure.

Contraindications:

- hypersensitivity to a tsefuroksim and other cephalosporins;

- bleedings and diseases of digestive tract;

- first trimester of pregnancy.

Overdose:

Symptoms - spasms.

Treatment: hemodialysis and peritoneal dialysis.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

On 250 mg or 750 mg of active agent are placed in a bottle from transparent glass corked by rubber bungs and pressed out by aluminum caps with protective plastic covers. On a bottle paste the self-adhesive label.

On 1 bottle with drug and on 1 ampoule with solvent of 2 ml (for a dosage of 250 mg) or 6 ml (for a dosage of 750 mg) together with the application instruction in the state and Russian languages place in a cardboard box.