Maxipim

Maxipim is a powder used to make an injection solution.

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Indications Maxipima

Indicated (for adults) to eliminate infectious processes caused by 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 (including infections of the gallbladder and peritonitis);
• gynecological infections;
• in septicemia.

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

In treatment of children:

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

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Release form

It is produced in powder form in bottles of 0.5, 1 or 2 g. Each separate pack contains 1 bottle of medicine.

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Pharmacodynamics

Cefepime inhibits the process of binding enzymes located in the walls of bacterial cells, and also has a wide range of action against many gram-negative and gram-positive microbes. The substance has high resistance to hydrolysis using most b-lactamases, as well as weak affinity for b-lactamases, which are encoded by chromosomal genes. It is able to quickly penetrate into the cells of gram-negative microbes.

The medicine is active against the following bacteria:

Gram-positive aerobic microbes: Staphylococcus aureus and Staphylococcus epidermidis (this also includes their strains capable of producing b-lactamase) and other strains of staphylococci (including Staphylococcus hominis and Staphylococcus saprophyticus). In addition, this also applies to Streptococcus pyogenes (category A streptococci), Streptococcus agalactiae (category B streptococci) and pneumococci (this also includes strains with moderate resistance to penicillin - MIC 0.1-1 μg/ml). This also applies to other b-hemolytic streptococci (categories C, G, F), Streptococcus bovis (category D) and streptococci from the Viridans series. Most strains of enterococci (including, for example, Enterococcus faecalis), as well as staphylococci that exhibit resistance to methicillin, are resistant to most cephalosporins, including cefepime.

Gram-negative aerobic bacteria: pseudomonads, including pseudomonas aeruginosa, pseudomonas putida, and P. stutzeri, as well as klebsiella (klebsiella pneumoniae, klebsiella oxytoca, and K. ozaenae) and E. coli. Also included are enterobacter (including enterobacter cloacae, enterobacter aerogenes, and E. sakazakii), proteus (including proteus mirabilis and proteus vulgaris), Acinetobacter calcoaceticus (such as subsp. anitratus, lwoffi), capnocytophaga spp., and aeromonas hydrophila. In addition, it also covers Citrobacter (including Citrobacter freundii and C. diversus), Campylobacter jejuni, Gardnerella vaginalis, Ducrey's bacillus and Haemophilus influenzae (including strains that produce β-lactamase). It also covers H. parainfluenzae, Legionella, Hafnia alvei, Morgan's bacillus, Moraxella catarrhalis (this list also includes strains that produce β-lactamase), gonococci (this list also includes strains that produce β-lactamase) and meningococci. It also affects Pantoea agglomerans, Providencia spp. (including Providence Rettger and Providence Stewart), Salmonella, Serratia (also Serratia marcescens and S. liquefaciens), Shigella and Yersinia enterocolitica.

However, cefepime has no effect on many strains of Stenotrophomonas maltophilia and Pseudomonas maltophilia.

Affects anaerobic microbes: Bacteroides (including B. melaninogenicus with other microbes inside the oral cavity, which are included in the bacteroides group), Clostridium perfringens, Fusobacterium spp., Mobiluncus, Peptostreptococcus and Veillonella.

Cefepime has no effect on Bacteroides fragilis and Clostridium difficile.

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Pharmacokinetics

Below are the average values of the concentration of the active substance in plasma in healthy adult volunteers (male) after different periods of time (after i.m. and i.v. injection; single dose):

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

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

The average half-life is approximately 2 hours. When healthy volunteers took the drug in a dose of 2 g (with 8-hour intervals between doses) over a period of 9 days, no accumulation of the substance in the body was observed.

As a result of metabolism, cefepime is converted into the element N-methylpyrrolidine, and it, in turn, is converted into the substance N-methylpyrrolidine oxide. In this case, the average value of total clearance is 120 ml / minute. Excretion of cefepime is almost completely carried out through regulatory processes in the kidneys - mainly through glomerular filtration (in the kidneys, the average clearance level is 110 ml / minute). In the urine, about 85% of the drug is found (in the form of a constant active substance), in addition, 1% of the substance N-methylpyrrolidine, another approximately 6.8% of the element N-methylpyrrolidine oxide, and also approximately 2.5% of the component epimer cefepime. Synthesis of the drug with plasma protein is less than 19%. This indicator does not depend on the level of serum concentration of the drug.

Tests conducted on people with different degrees of kidney failure have shown that the half-life increases depending on the severity. The average value for severe renal dysfunction in people undergoing dialysis treatment is 13 hours (in the case of hemodialysis) and 19 hours (if peritoneal dialysis is used).

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Dosing and administration

Before using the medicine, a skin test for sensitivity reaction is required.

The standard adult dose is 1 g, administered intravenously or intramuscularly at 12-hour intervals. The course of treatment often lasts 7-10 days, but severe infections may require longer therapy.

However, the methods of administration and doses vary in relation to the sensitivity of pathogenic microbes, the severity of the infectious process, and also the renal function of the patient. Below are recommendations for adult dosages of Maxipim:

• infectious processes in the urinary tract (moderate or mild severity) – 0.5-1 g intramuscularly or intravenously every 12 hours;
• other infections (moderate or mild severity) – 1 g intramuscularly or intravenously every 12 hours;
• severe forms of infections – 2 g every 12 hours;
• very severe forms of infections, as well as those that can be life-threatening – 2 g every 8 hours.

To prevent infection after surgery, 2 g of solution should be administered for half an hour 1 hour before the procedure (for adults). After the procedure is complete, another 0.5 g of metronidazole should be added intravenously. It should be noted that metronidazole should not be administered together with Maxipim. Before using metronidazole, the infusion system should be flushed.

For long-term operations (more than 12 hours), 12 hours after the first dose, it is necessary to administer an equal dose of Maxipim again, also followed by the use of metronidazole.

In the presence of functional renal disorders (and also if the CC indicator is less than 30 ml/minute), the drug dose must be adjusted. For adults, they will be as follows:

• CC rate 30-50 ml/minute – 2 g every 12 or 24 hours; 1 g every 24 hours; 0.5 g every 24 hours;
• CC level 11-29 ml/minute – 2 g every 24 hours; 1 g every 24 hours; 0.5 g every 24 hours;
• CC level less than 10 ml/minute – 1 g every 24 hours; 0.5 g every 24 hours; 0.25 g every 24 hours;
• for hemodialysis – 0.5 g every 24 hours.

As a result of hemodialysis, approximately 68% of the drug is eliminated from the body in 3 hours. After each procedure, the drug must be administered again in doses equal to the initial amount. In the case of constant peritoneal dialysis procedures (outpatient), it is allowed to administer the solution in standard initial doses - 0.5, 1 or 2 g (depending on the severity of the infectious process) at intervals of 48 hours.

The drug can be administered to infants aged 1-2 months only for vital indications - the dose is 0.3 g / kg every 8 or 12 hours (depending on the severity of the infectious process). It is necessary to constantly monitor the condition of children receiving the drug, whose weight is less than 40 kg.

Children with functional kidney disorders require a lower dosage or longer intervals between procedures.

For children over 2 months, the highest dose cannot be higher than the recommended adult dose. For children weighing less than 40 kg (with uncomplicated or complicated infectious processes in the urinary tract (including pyelonephritis), as well as with pneumonia, uncomplicated skin infections and empirical therapy for neutropenic fever), the recommended dosage is 0.5 g / kg every 12 hours. For children with bacterial meningitis or neutropenic fever - every 8 hours.

Dose sizes for children weighing over 40 kg are similar to those for adults.

The medicine is administered intravenously or by deep intramuscular injection. In the second case, you should choose a body area with a large muscle - for example, the gluteal muscle; its outer upper quadrant.

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Use Maxipima during pregnancy

There have been no tests of the use of the drug in pregnant women, which is why at this time it is allowed to be prescribed only in cases where the potential benefit to the woman is greater than the occurrence of negative consequences in the fetus.

Small amounts of the drug penetrate into breast milk, which is why breastfeeding should be discontinued during treatment.

Contraindications

Main contraindications: hypersensitivity to cefepime or L-arginine, and also to cephalosporins, penicillins or other β-lactam antibiotics. In addition, it is prohibited to prescribe to infants under 1 month.

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Side effects Maxipima

The use of the solution may cause certain side effects:

• manifestations of hypersensitivity: development of urticaria or itching;
• digestive tract organs: the appearance of vomiting, diarrhea, nausea, the development of candidiasis in the mouth, as well as colitis (also its pseudomembranous form);
• CNS organs: occurrence of headaches;
• local manifestations (at the site of drug administration): in the case of the intravenous method - an inflammatory process or phlebitis; in the case of the intramuscular method - the appearance of inflammation or pain;
• Others: development of erythema, vaginitis or fever.

Constipation, respiratory problems, paresthesia, vasodilation, as well as abdominal pain, dizziness, fever, candidiasis and itching in the genital area occur quite rarely.

The development of anaphylaxis or epileptiform seizures is possible in isolated cases.

During post-marketing testing, the following reactions were observed:

• development of renal failure, myoclonus, and encephalopathy (the appearance of hallucinations, loss of consciousness, development of stupor and comatose state);
• development of anaphylaxis (this includes anaphylactic shock), thrombocyto- or neutropenia, transient leukopenia, and agranulocytosis;
• laboratory test data: increased AST with ALT and ALP values, as well as total bilirubin level. In addition, the development of eosinophilia or anemia, increased PTT or PT values, and along with this, a positive result of the direct Coombs test in the absence of hemolysis. A transient increase in the level of serum creatinine or urea nitrogen in the blood is possible, as well as the development of a transient form of thrombocytopenia (these cases are quite rare). In addition, sometimes neutro- or leukopenia of a transient type is observed.

Overdose

If the required dosage is greatly exceeded (especially in people with functional disorders of the kidneys), the symptoms of adverse reactions increase. Among the manifestations of overdose are epileptiform seizures, myoclonus, neuromuscular excitability, and encephalopathy (this includes disorders of consciousness, coma, stupor, and hallucinations).

To eliminate the disorders, it is necessary to stop the administration of the solution and perform treatment aimed at eliminating the disorders. Hemodialysis will speed up the excretion of cefepime, but peritoneal dialysis will not provide the desired result. In case of severe manifestations of allergy (immediate reactions), it is necessary to use adrenaline and other methods of intensive therapy.

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Interactions with other drugs

Combination with high doses of aminoglycosides requires careful monitoring of renal function, as these drugs have potential ototoxic and nephrotoxic effects. Nephrotoxicity has been observed when other cephalosporins are combined with diuretics (such as furosemide).

Maxipim in the range of 1-40 mg/ml is allowed to be combined with the following parenteral drugs: injection solution (0.9%) sodium chloride, injection solution of glucose (5, as well as 10%), injection solution of 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 interactions with other drugs, it is necessary not to mix the solution of Maxipim (as well as most other β-lactam antibiotics) with such drugs as vancomycin, tobramycin sulfate, metronidazole, as well as netromycin sulfate and gentamicin. If treatment with both such solutions is necessary, each of them should be administered separately.

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Storage conditions

The powder must be kept out of reach of children, in a place protected from light. Temperature values – maximum 30°C.

Ready solutions for intravenous and intramuscular injections should be kept in the refrigerator at a temperature of 2-8°C.

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Shelf life

Maksipim is suitable for use within 3 years from the date of powder production. The prepared solution can be stored at room temperature for no more than 24 hours, and if kept in the refrigerator - no more than 7 days.

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