Максицеф®

General characteristics. Structure:

Active ingredient: 0,5 g or 1,0 g of a tsefepim of a hydrochloride of monohydrate (in terms of tsefepy).

Excipient: L-arginine.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the IV generation for parenteral use. Possesses a broad spectrum of activity concerning gram-positive and gram-negative bacteria, including strains, resistant to aminoglycosides and/or cephalosporins III of generation, and also other antibiotics. Works bakteritsidno, breaking the final stages of synthesis of a cell wall of bacteria (enzyme inactivates transpeptidase). Quickly gets through an external membrane of gram-negative bacteria; has high affinity to penitsillinsvyazyvayushchy proteins, or bacterial transpeptidases. Высокоустойчив to hydrolysis by the majority beta лактамаз.

Максицеф® in vivo and in vitro concerning gram-positive aerobes is active: Staphylococcus aureus (only metitsillinochuvstvitelny strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A), Streptococcus viridans; gram-negative aerobes: Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.

In vitro is active (but the clinical importance is unknown) concerning gram-positive aerobes: Staphylococcus epidermidis (only metitsillinochuvstvitelny strains), Staphylococcus saprophyticus, Streptococcus agalactiae (group B); gram-negative aerobes: Acinetobacter lwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including the strains producing beta lactamazu), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including the strains producing beta lactamelements), Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens.

Majority of strains of Enterococcus spp., including Enterococcus faecalis, metitsillinorezistentny staphylococcus, Stenotrophomonas (earlier known as Xanthomonas maltophilia and Pseudomonas maltophilia), are not sensitive Clostridium difficile to a tsefepim.

Secondary resistance of microorganisms to Maksitsefu® develops slowly.

Pharmacokinetics. After intravenous infusion of a tsefepim in a dose of 0,5 g, 1 g the maximum concentration (Cmax) make 39,1 mg/l and 81,7 mg/l, respectively. In an hour after infusion of 0,5 g and 1 g of concentration in plasma decrease almost twice and make 21,6 mg/l, 44,5 mg/l, respectively. In 8 hours plasma contains 1,4 mg/l, 2,4 mg/l of a tsefepim, and in 12 hours - 0,2 mg/l and 0,6 mg/l, respectively.

Bioavailability at intramuscular introduction (in oil) makes 100%. Cmax after an injection in oil in doses of 0,5 g and 1 g in an interval between the first and second hours after introduction make 12,5 mg/l and 26,3 mg/l, respectively. In 12 hours after an injection of a tsefepim in oil in doses of 0,5 g and 1 g of concentration in plasma decrease to 0,7 mg/l and 1,4 mg/l, respectively.

Distribution volume - 0,25 l/kg, at children from 2 months to 16 years is 0,33 l/kg. Extent of linkng with proteins of plasma makes, on average, 20% also do not depend on concentration of a tsefepim in blood.

Later in/in and introductions in oil high concentration are defined in urine, bile, peritoneal liquid, intersticial fabric and liquid, skin, hypodermic cellulose, a mucous secret of bronchial tubes, lungs, a phlegm, a prostate, an appendix and a wall of a gall bladder. In insignificant concentration tsefepy gets into breast milk (about 0,5 mg of a tsefepim on 1 l of maternal milk).

The elimination half-life (Т½) makes about 2 hours. At patients with a renal failure in view of the slowed-down excretion of a tsefepim Т½ raises that demands correction of doses and modes of introduction.

About 15% of the entered dose are metabolized in a liver with formation of N-metilpirrolidina which quickly is oxidized to oxide N-metilpirrolidina. 85% of the entered dose are removed in an invariable look through kidneys; other part - in the form of metabolites, generally N-metilpirrolidina, N-metilpirrolidina of oxide and an epimer of a tsefepim.

Indications to use:

The bacterial infections caused by microorganisms, sensitive to a tsefepim:
- lower respiratory tract infections, including medium-weight and heavy pneumonia, bronchitis;
- intraabdominal infections (in a combination with metronidazole), including peritonitis, abscess of an abdominal cavity, an infection of biliary tract, infectious complications of pancreatitis;
- infectious and inflammatory diseases of bodies of a small pelvis at women;
- the uncomplicated and complicated infections of urinary tract, including pyelonephritis, a pyelitis;
- infections of skin and soft tissues;
- febrile neutropenia (empirical therapy);
- sepsis.

Route of administration and doses:

Intravenously (in/in), intramusculary (in oil).
Adults and children with body weight more than 40 kg with normal function of kidneys.
Intravenously (in/in) in the form of infusion by duration not to exchange of 30 min. or intramusculary (in oil).

At slight and medium-weight infections of urinary tract - 0,5-1 g in/in or each 12 h in oil; at slight and medium-weight infections of other localizations - 1 g in/in or each 12 h in oil; at heavy infections - 2 g in/in each 12 h; at very heavy and life-threatening infections - 2 g in/in each 8 h.

Children from 2 months to 16 years with body weight to 40 kg. The usual recommended dose at the complicated or uncomplicated infections of urinary tract, infections of skin and soft tissues, pneumonia makes 50 mg/kg 2 times a day; at heavy infections and a febrile neutropenia - on 50 mg/kg 3 times a day. The maximum single dose should not exceed 2 g.

The average duration of a course of therapy ^{of Maksitsefom®} makes 7-10 days. At treatment of a febrile neutropenia introduction ^{of Maksitsefa®} is continued by 7 days or to permission of a neutropenia.

Patients with a renal failure. At a renal failure dose adjustment depending on clearance of creatinine is required. The initial dose ^{of Maksitsefa®} has to be same, as well as for patients with normal function of kidneys. The recommended maintenance doses are presented in the table.

Clearance of creatinine, ml/min.	The recommended maintenance doses
> 50	(A usual dose (depending on weight of an infection), adjustment is not required)
	2 g each 8 h	2 g each 12 h	1 g each 12 h	0,5 g each 12 h
30-50	2 g each 12 h	2 g each 24 h	1 g each 24 h	0,5 g each 24 h
11-29	2 g each 24 h	1 g each 24 h	0,5 g each 24 h	0,5 g each 24 h
<10	1 g each 24 h	0,5 g each 24 h	0,25 g each 24 h	0,25 g each 24 h
Patients on hemodialysis *	0,5 g each 24 h	0,5 g each 24 h	0,5 g each 24 h	0,5 g each 24 h

* - For the patients who are on a hemodialysis: in the first days - a load dose of 1 g, then 0,5 g each 24 h at all infections, except a febrile neutropenia at which the maintenance dose makes 1 g each 24 h.

In days of dialysis ^{of Maksitsef®} it is necessary to enter upon termination of the procedure of dialysis. Whenever possible, the drug should be administered every day at the same time.
Data on use of drug for children with the accompanying chronic renal failure (CRF) are absent, however, considering similarity of pharmacokinetics at children and at adults, the dosing mode (reduction of a dose or increase in an interval between introductions) at children with a chronic renal failure is similar to the dosing mode at adults.

Intramuscular introduction. For introduction in oil the sterile ^{powder Maksitsefa®} 0,9% solution of sodium of chloride dissolve in sterile water for injections, 0,5% or 1% hydrochloride lidocaine solution. The following minimum quantities of solvent add directly to a bottle with dry powder of an antibiotic:

	The bottle containing 0,5 g of Maksitsefa®	1,3 ml of solvent
	The bottle containing 1,0 g of Maksitsefa®	2,4 ml of solvent

The received solution, approximate concentration of a tsefepim in which 280 mg/ml, enter deeply intramusculary into body parts with the expressed muscular layer (an upper outside quadrant of a buttock or the lateral surface of a hip). It is recommended to carry out the test for aspiration to avoid undesirable administration of solution in a blood vessel.

Intravenous administration. For in/in jet introductions ^{of Maksitsef®} dissolve in sterile water for injections, 0,9% solution of sodium of chloride or 5% dextrose solution.

The following minimum quantities of solvent add directly to a bottle with dry powder of an antibiotic:

	The bottle containing 0,5 g of Maksitsefa®	5 ml of solvent
	The bottle containing 1,0 g of Maksitsefa®	10 ml of solvent

The received solution, approximate concentration of a tsefepim in which 100 mg/ml, enter in/in slowly, within 3-5 min.; introduction through a special node or port for system injections for in/in infusions is possible if the patient receives liquids parenterally.

For in/in drop introductions of 0,5 g ^{of Maksitsefa®} dissolve in 5 ml, 1 g - in 10 ml of sterile water for injections, 0,9% solution of sodium of chloride or 5% dextrose solution. The received solution is added to the bottle containing 50-100 ml of the compatible infusional environment. Enter through system for in/in infusions within not less than 30 minutes. ^{Maksitsefa® solutions} are compatible from 0,9% solution of sodium of chloride, 5% dextrose solution; the solution for infusions containing 0.45% of sodium of chloride and 5% of a dextrose; the solution for infusions containing 0,9% of sodium of chloride and 5% of a dextrose; 5% dextrose solution in Ringer's solution with a lactate.

Features of use:

When developing diarrhea during treatment of Maksitsefom® it is necessary to show vigilance in view of possible development of pseudomembranous colitis. If the diagnosis an antibiotic - the associated diarrhea or pseudomembranous colitis is established, it is necessary to stop immediately introduction of Maksitsefa® and to appoint the corresponding treatment.

Максицеф® it can be applied in the form of monotherapy before identification of a microorganism activator. At patients with the probable mixed aerobic-anaerobic infection it is possible to begin treatment by Maksitsef in a combination with the drug influencing on anaerobe bacterias.

As well as in case of other antibiotics, use of Maksitsefa® can lead to colonization of insensitive microflora and development of superinfection.
False positive test of Koombs and false positive test result on glucose in urine is possible.

At prolonged treatment regular control of peripheral blood, indicators of a functional condition of a liver and kidneys is necessary.

At use of a tsefepim it is necessary to be careful when driving vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Максицеф® it is usually well transferred. Undesirable medicinal reactions are observed seldom and have tranzitorny character.

Allergic reactions: urticaria, itch, anaphylactoid reactions, fever, multiformny exudative erythema, Stephens-Johnson's syndrome, Lyell's disease. 

From digestive tract: diarrhea, nausea, vomiting, lock, abdominal pain, dyspepsia, pseudomembranous colitis.

From cardiovascular system: pain behind a breast, tachycardia, peripheral hypostases, short wind. 

From respiratory system: cough. 

From the central nervous system: headache, dizziness, sleeplessness, paresthesias, concern, confusion of consciousness, spasm. 

From bodies of a hemopoiesis: thrombocytopenia, leukopenia, including neutropenia; anemia, pancytopenia, bleeding.

Local reactions: phlebitis later in/in introductions, a hyperemia and morbidity in places in oil of injections.  

Changes from laboratory indicators: a hyperbilirubinemia, increase in activity of "hepatic" enzymes - alaninaminotranspherases, aspartate aminotransferases, an alkaline phosphatase, increase in concentration of urea, a giperkreatininemiya, false positive test of Koombs; increase in a prothrombin time.

From bodies of an urinary system: toxic nephropathy. Other: an adynamy, the increased perspiration, a pharyngalgia, a dorsodynia, a vaginitis, orofaringealny candidiasis.

Interaction with other medicines:

"Loopback" diuretics, aminoglycosides, polymyxin B reduce canalicular secretion of a tsefepim, extend Т½ and increase its concentration in blood serum, increasing risk of development of nephrotoxicity.

Pharmaceutical it is incompatible with aminoglycosides (gentamycin, Tobramycinum, amikacin, netilmitsiny), Vancomycinum, metronidazole; it is not necessary to mix these antibiotics in one syringe or one infusional environment; at intravenous administration tsefepy and other antibiotics it is recommended to enter separately, or observing a certain sequence with a certain time interval between injections (infusions), or entering through separate intravenous catheters; before administration of solution of metronidazole it is necessary to wash out infusional system from solution of a tsefepim.

Non-steroidal anti-inflammatory drugs, slowing down removal of cephalosporins, increase risk of development of bleeding.

At simultaneous use with aminoglycosides the expressed synergism of antimicrobic action is observed.

Contraindications:

- hypersensitivity to a tsefepim, L-arginine, other cephalosporins, penicillin, another beta лактамным to antibiotics;
- children's age up to 2 months.

With care appoint the patient with a renal failure (see the Route of administration and doses); at instructions on diseases of a large intestine, especially ulcer colitis.

During pregnancy and a lactation appoint according to "vital" indications. In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: spasms, encephalopathy, excitement.
Treatment: symptomatic and maintenance therapy, hemodialysis.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

0,5 g and 1,0 g of active agent in bottles glass with a capacity of 10 ml, hermetically corked by traffic jams from rubber mix, pressed out by caps aluminum or pressed out by the caps combined (aluminum with safety plastic covers).

Solvent - "Water for injections" in glass ampoules of 5 ml.

1 bottle with drug and the application instruction is placed in a pack from a cardboard. 

1 bottle with drug and 1 ampoule with solvent is packed into a blister strip packaging.

One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug pack into blister strip packagings. One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug complete with 5 ampoules of solvent pack into blister strip packagings. One blister strip packaging with drug, one blister strip packaging with solvent and the application instruction is put in a pack cardboard.