Maksipim

Maxipim is the powder used to make the injection solution.

[1], [2], [3]

Indications of the maxipima

It is shown (by adults) for elimination of infectious processes provoked by a microflora, sensitive to the action of drugs:

• in the respiratory system (such as pneumonia or bronchitis);
• in the subcutaneous layer and skin;
• intra-abdominal infectious processes (among such infections are ZHVP, as well as peritonitis);
• Gynecological infections;
• with septicemia.

It is also used in the empirical treatment of febrile fever and in the prevention of complications arising after operations in the intra-abdominal area.

When treating children:

• pneumonia, septicemia;
• infectious processes in the urinary tract (among such pyelonephritis);
• subcutaneous and skin infections;
• empirical form of treatment of febrile fever;
• bacterial form of meningitis.

[4], [5], [6]

Release form

Produced in powder form in 0.5-ml vials, and also 1 or 2 g. Inside a separate pack contains 1 vial of medicine.

[7]

Pharmacodynamics

Cefepime inhibits the binding of enzymes present in the walls of bacterial cells, and also has a wide range of influences in relation to a multitude of gram-negative and gram-positive microbes. The substance has a high resistance to hydrolysis using most β-lactamases, as well as a weak affinity for β-lactamases, which are encoded by chromosomal genes. It is able to quickly pass into the cells of gram-negative microbes.

The drug has activity against such bacteria:

Gram-positive aerobic microbes: Staphylococcus aureus and epidermal staphylococcus (also include their strains that can produce b-lactamase) and other strains of staphylococci (Staphylococcus hominis and staphylococcus saprophytic among them). In addition, it is also relatively streptococcus pyogenic (streptococcus from category A), streptococcus agalactia (streptococcus from category B) and pneumococcus (this includes strains with an average resistance of penicillin - an MIC of 0.1-1 μg / ml). It also applies to other b-hemolytic streptococci (from categories C, G, F), Streptococcus bovis (category D) and streptococcus from the Viridans series. Most of the strains of enterococci (among them, for example, enterococcus fecal), as well as staphylococci that demonstrate resistance to methicillin, are resistant to most cephalosporins, including cefepime.

Gram-negative aerobic bacteria: pseudomonads, including Pseudomonas aeruginosa, pseudomonas pathidae and P. Stutzeri, and in addition Klebsiella (Klebsiella pneumonia, Klebsiella Oxytoca and K. Ozaenae) and Escherichia coli. Also included are Enterobacter (among them enterobacter pylori, Enterobacter anogenes and E. Sakazakii), Proteus (among them Proteus mirabilis and vulgar proteus), Acinetobacter calcoaceticus (such as subsp.Anitratus, lwoffi), Capnocytophaga spp. And hydrophilic aeromonas. Together with this, also tsitrobakter (this includes citrobacter frowni and C. Diversus), Campylobacter vaginitis, Gardnerella vaginalis, Ducrea stick and hemophilic rod (this includes strains that produce β-lactamase). The effect is on H. Parainfluenzae, Legionella, Hafnia alvei, Morgana bacterium, Moraxell cataralis (in this list also strains that produce β-lactamase), gonococci (here also strains that produce β-lactamase) and meningococci are included. In addition, it affects Pantoea agglomerans, Providencia spp. (among them the Providence of Rettger and Stewart's Providence), Salmonella, Serrations, (also on the serration of the Marceses and S. Liquefaciens), Shigella and Yersinia enterocolitis.

In this case, cefepime has no effect on many strains of Stenotrophomonas maltophilia and Pseudomonas maltophilia.

Affects anaerobic microbes: bacteroides (among them B. Melaninogenicus with other microbes inside the oral cavity that form part of the bacteroids group), clostridium perfringence, Fusobacterium spp., Mobiluncus, peptostreptococcus and Veyllonella.

Cefepime does not affect the bacteroids of fraugilis and clostridium difffile.

[8], [9], [10], [11]

Pharmacokinetics

Below are the average values of the concentration of the active substance inside the plasma in healthy adult volunteers (male) after different periods of time (after IM and / or injection, once):

• intravenous administration of 0.5 g of the drug - 38.2 μg / ml (after 30 minutes); 21.6 μg / ml (after 1 hour); 11.6 μg / ml (after 2 hours); 5.0 μg / ml (after 4 hours); 1.4 μg / ml (after 8 hours) and 0.2 μg / ml (after 12 hours);
• intravenous administration of 1 g of the drug - 78.7 μg / ml (after 30 minutes); 44.5 μg / ml (after 1 hour); 24.3 μg / ml (after 2 hours); 10.5 μg / ml (after 4 hours); 2.4 μg / ml (after 8 hours); 0.6 μg / ml (after 12 hours);
• in / in the introduction of 2 g of solution - 163.1 mcg / ml (after half an hour); 85.8 μg / ml (after 1 hour); 44.8 μg / ml (after 2 hours); 19.2 μg / ml (after 4 hours); 3.9 μg / ml (after 8 hours); 1.1 μg / ml (after 12 hours);
• in / m injection of 0.5 g of the drug - 8.2 μg / ml (after half an hour); 12.5 μg / ml (after 1 hour); 12.0 μg / ml (after 2 hours); 6.9 μg / ml (after 4 hours); 1.9 μg / ml (after 8 hours); 0.7 μg / ml (after 12 hours);
• in / m administration of 1 g of drugs - 14.8 mcg / ml (after 30 minutes); 25.9 μg / ml (after 1 hour); 26.3 (after 2 hours); 16.0 μg / ml (after 4 hours); 4.5 μg / ml (after 8 hours); 1.4 μg / ml (after 12 hours);
• in / m administration of 2 g of drugs - 36.1 μg / ml (after 0.5 hours); 49.9 μg / ml (after 1 hour); 51.3 μg / ml (after 2 hours); 31.5 μg / ml (after 4 hours); 8.7 μg / ml (after 8 hours); 2.3 μg / ml (after 12 hours).

Inside the mucus secreted by the bronchi, bile, sputum and urine, and in addition to the appendix, prostate and peritoneal fluid with the gall bladder, drug concentrations of the active drug component are also observed.

The average half-life is approximately 2 hours. When a medication was taken by healthy volunteers in the amount of 2 g (with intervals of 8 hours between administrations), during 9 days the cumulation of the substance inside the body was not observed.

As a result of metabolism, cefepime converts N-methylpyrrolidine into an element, and it, in turn, converts N-methylpyrrolidine oxide into a substance. The average total clearance is 120 ml / minute. Separation of cefepime is almost entirely achieved through regulating processes in the kidneys - mainly through the filtration of glomeruli (in the kidneys the average clearance level is 110 ml / minute). Inside the urine, about 85% of the drug (in the form of a permanent active substance) is found, in addition 1% of the substance N-methylpyrrolidine, about 6.8% of the N-methylpyrrolidine oxide element, and about 2.5% of the ephemeris component of cefepime. The synthesis of the drug with the plasma protein is less than 19%. This indicator does not depend on the level of serum concentration of drugs.

Tests that were conducted in people with different degrees of severity of kidney failure showed that, depending on them, the half-life time increases. The average value for a severe degree of functional renal impairment in people who undergo dialysis treatment is equal to 13 hours (in case of hemodialysis), and also for 19 hours (if peritoneal dialysis is used).

[12], [13], [14], [15]

Dosing and administration

Before using the medication, a skin sensitivity test is required.

The standard size of the adult dose is 1 g, administered by iv or in / m at intervals of 12 hours. Often, the course of treatment lasts 7-10 days, but with severe forms of infection, longer therapy may be required.

But the methods of administration and dose fluctuate with the sensitivity of pathogenic microbes, the degree of severity of the infectious process, and also with the patient's renal function. The following are recommendations for adult dosages Maxipim:

• infectious processes in the urinary ducts (medium or mild severity) - 0.5-1 g by the method IM or I / O every 12 hours;
• other infections (medium or mild severity) - 1 g IM or IV every 12 hours;
• severe forms of infection - 2 g after every 12 hours;
• very serious forms of infections, as well as those that can be life threatening - 2 g after every 8 hours.

To perform prophylaxis against the emergence of infection due to surgery, you need 1 hour before the procedure to enter 2 g of solution for half an hour (for adults). After the process is completed, add 0.5 g of metronidazole intravenously. It should be noted that metronidazole can not be administered together with Maxipim. Before using metronidazole, the infusion system must be rinsed.

For prolonged operations (more than 12 hours) 12 hours after the 1st dosage, it is required to enter an equal dose of Maxipim repeatedly, also with the subsequent use of metronidazole.

In the presence of functional renal disorders (and also, if the QC value is less than 30 ml / minute), dose adjustment of the drug is required. For adults, they will be:

• the QC value is 30-50 ml / minute - 2 g after every 12 or 24 hours; 1 g after every 24 hours; 0.5 g after every 24 hours;
• level of CK 11-29 ml / minute - 2 g after every 24 hours; 1 g after every 24 hours; 0.5 g every 24 hours;
• the level of QC is less than 10 ml / minute - 1 g every 24 hours; 0.5 g every 24 hours; 0.25 g after every 24 hours;
• at a hemodialysis - on 0,5 g after every 24 hours.

As a result of hemodialysis, approximately 68% of the drug is excreted from the body within 3 hours. At the end of each procedure, it is required to enter the drug again at doses equal to the initial size. In the case of permanent peritoneal dialysis (outpatient) procedures, it is allowed to administer the solution at standard starting doses - 0.5, 1 or 2 g (depending on the severity of the infection process) at intervals of 48 hours.

For infants 1-2 months of age, the medication can be administered solely for life indications - the dose is 0.3 g / kg every 8 or 12 hours (depending on the severity of the infection process). It is required to constantly monitor the condition of the children receiving medication, the weight of which is less than 40 kg.

Children with functional disorders of the kidneys need to lower the dosage, or lengthen the intervals between procedures.

For children over 2 months, the highest dose can not be more than the recommended adult. In children weighing less than 40 kg (with uncomplicated or complicated infectious processes in the urinary ducts (among them pyelonephritis), and in addition, with pneumonia, uncomplicated skin infections and with the empirical therapy of neutropenic fever), the recommended dosage is 0.5 g / kg every 12 hours. For children with bacterial meningitis or neutropenic fever - every 8 hours.

Dosage sizes for children weighing 40 kg are similar to adults.

The drug is injected / in a way either by deep injection intramuscularly. In the second case, you should choose a site of the body with a large muscle - for example, gluteus; outer upper quadrant.

[18], [19], [20]

Use of the maxipima during pregnancy

Testing of the use of the drug in pregnant women was not carried out, because of which at this time it is allowed to appoint only in cases where the possible benefits for women are higher than the appearance of the fetus negative consequences.

Small amounts of the drug penetrate into the breast milk, so you need to cancel breastfeeding for the period of treatment.

Contraindications

The main contraindications: the presence of high sensitivity to cefepime or L-arginine, and with it cephalosporins, penicillins or other β-lactam antibiotics. In addition, it is forbidden to appoint babies until the 1st month.

[16], [17]

Side effects of the maxipima

Use of the solution can cause some side effects:

• manifestations of hypersensitivity: the development of urticaria or itching;
• organs of the digestive tract: the appearance of vomiting, diarrhea, nausea, the development of candidiasis in the mouth, and in addition to colitis (also pseudomembranous of its form);
• CNS organs: the onset of headaches;
• local manifestations (at the site of drug administration): in the case of intravenous method - inflammatory process or phlebitis; with the / m method - the appearance of inflammation or pain;
• Other: development of erythema, vaginitis or fever.

Rarely do constipation occur, problems with respiratory function, paresthesia, vasodilation, and in addition abdominal pain, dizziness, fever, candidiasis and itching in the genital area.

It is possible to develop anaphylaxis or epileptiform seizures.

During the postmarketing tests, the following reactions were observed:

• development of kidney failure, myoclonia, as well as encephalopathy (the appearance of hallucinations, loss of consciousness, the development of stupor and coma);
• the development of anaphylaxis (this includes anaphylactic shock), thrombocyto-or neutropenia, transient form of leukopenia, as well as agranulocytosis;
• laboratory test data: increase in AST values from ALT and APF, as well as the general level of bilirubin. In addition, the development of eosinophilia or anemia, an increase in PTT or PTV, and with it a positive result of direct Coombs test in the absence of hemolysis. Perhaps a transient increase in the level of serum creatinine or urea nitrogen inside the blood, as well as the development of transient form of thrombocytopenia (these cases are quite rare). In addition, neutrophilic or leukopenia of the transient type is sometimes observed.

Overdose

With a strong excess of the necessary dosages (especially in people with functional disorders of the kidneys), the symptoms of adverse reactions increase. Among the manifestations of overdose are epileptiform seizures, myoclonia, neuromuscular excitability, and also encephalopathy (it includes disorders of consciousness, coma, stupor and hallucinations).

To remove the violations, you need to stop the administration of the solution and perform treatment aimed at eliminating the disorders. Hemodialysis will accelerate the excretion of cefepime, but peritoneal dialysis will not have the desired result. In case of severe manifestations of allergies (reactions of immediate appearance) adrenaline and other intensive care methods should be used.

[21], [22], [23]

Interactions with other drugs

Combination with large doses of aminoglycosides requires careful monitoring of the kidneys, as these drugs have potentially ototoxic and nephrotoxic effects. Nephrotoxicity was observed when other cephalosporins were combined with diuretics (such as furosemide).

Maxipim in the value of 1-40 mg / ml is allowed to combine with the following parenteral drugs: injection solution (0.9%) sodium chloride, injection glucose (5, and 10%), injection solution 6M sodium lactate, a mixture of glucose solutions (5 %) with sodium chloride (0.9%) and a mixture of injection solutions of glucose (5%) and Ringer's lactate.

To avoid possible interaction with other drugs, it is required not to mix Maxipim's solution (as well as most other β-lactam type antibiotics) with drugs such as vancomycin, tobramycin sulfate, metronidazole, as well as non -romycin sulfate and gentamicin. If it is necessary to treat both of these solutions, each of them should be administered separately.

[24], [25], [26], [27], [28]

Storage conditions

Powder is required to keep out of reach of children, in a place that is closed from penetration of light. Temperature values are a maximum of 30 ° C.

Ready-made solutions for intravenous and / or injection should be kept in a refrigerator at a temperature of 2-8 ° C.

[29]

Shelf life

Maxipim is suitable for use in the period of 3 years from the moment of release of the powder. The prepared solution can be stored at room temperature for no more than 24 hours, and if it is kept in the refrigerator, not more than 7 days.

[30]