Maxycef^® (Powder) Instructions for Use

Marketing Authorization Holder

PFC Prebend, LLC (Russia)

ATC Code

J01DE01 (Cefepime)

Active Substance

Cefepime (Rec.INN registered by WHO)

Dosage Forms

	Maxycef®	Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1 or 5 pcs. in a set with solvent or without it
		Powder for preparation of solution for intravenous and intramuscular administration 500 mg: vial 1 or 5 pcs. in a set with solvent or without it

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Excipients: arginine 0.365 g.

Solvent water for injections (5 ml).

1 g – Glass vials with a capacity of 10 ml (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Excipients: arginine 0.73 g.

Solvent water for injections (5 ml).

1 g – Glass vials with a capacity of 10 ml (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
1 g – Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Fourth generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

An antibiotic from the group of fourth generation cephalosporins. It acts bactericidally by disrupting the synthesis of the microbial cell wall (inactivates the transpeptidase enzyme). It quickly penetrates through the membrane of gram-negative bacteria; has a high affinity for penicillin-binding proteins or bacterial transpeptidases.

It has a broad spectrum of activity against gram-positive and gram-negative bacteria, strains resistant to aminoglycosides and/or third-generation cephalosporin antibiotics. It is highly resistant to hydrolysis by most beta-lactamases. Maxycef^®is active against the following microorganisms: gram-positive aerobes: Staphylococcus aureus and Staphylococcus epidermidis (only methicillin-sensitive strains), Staphylococcus hominis, Staphylococcus saprophyticus, other strains of Staphylococcus spp.; Streptococcus pyogenes (serogroup A); Streptococcus agalactiae (serogroup B); Streptococcus pneumoniae, including strains of pneumococci resistant to penicillin; and other beta-hemolytic Streptococcus spp. (serogroups C, G, F), Streptococcus bovis (serogroup D), Streptococcus viridans; gram-negative aerobes: Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; gram-negative aerobes Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas stutzeri); Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae); Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans and Enterobacter sakazakii); Proteus spp. (including Proteus mirabilis and Proteus vulgaris); Acinetobacter calcoaceticus (Acinetobacter anitratum, Acinetobacter calcoaceticus subsp. bvoff); Aeromonas hydrophila; Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii); Campylobacter jejuni, Campylobacter vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including beta-lactamase-producing strains); Haemophilus parainfluenzae, Hafnia alvei, Legionella spp.; Morganella morganii; Moraxella catarrhalis (including beta-lactamase-producing strains); Neisseria gonorrhoeae (including beta-lactamase-producing strains); Neisseria meningitidis, Providencia spp. (including Providencia rettgeri, Providencia Stuartii); Salmonella spp.; Serratia spp. (including Serratia marcescens, Serratia liquefaciens); Shigella spp.; Yersinia enterocolitica; anaerobes: Clostridium perfringens; Fusobacterium spp.; Mobil uncus spp.; Peptostreptococcus spp.; Veillonella spp., Propionibacterium spp.

Pharmacokinetics

Bioavailability is 100%. Time to reach C_max after intravenous and intramuscular administration in a dose of 0.5 g is at the end of infusion and after 1-2 hours, respectively. C_max with intramuscular administration in doses of 0.5 g and 1 g is 14 µg/ml and 30 µg/ml, respectively; with intravenous administration in doses of 0.5 g and 1 g is 39 µg/ml and 82 µg/ml, respectively; time to reach average therapeutic concentration in plasma is 12 hours; average therapeutic concentration with intramuscular administration is 0.2 µg/ml, with intravenous administration is 0.7 µg/ml. High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucous secretion, sputum, prostate gland, appendix and gallbladder. V_d is 0.25 l/kg, in children from 2 months to 16 years – 0.33 l/kg. Plasma protein binding is 20%.

It is metabolized in the liver and kidneys by 15%. T_1/2 is 2 hours, total clearance is 120 ml/min, renal clearance is 110 ml/min. It is excreted by the kidneys (by glomerular filtration unchanged – 85%), with breast milk. T_1/2 during hemodialysis is 13 hours, during continuous peritoneal dialysis is 19 hours.

Indications

Bacterial infections caused by susceptible microorganisms

• Pneumonia (moderate and severe), caused by Streptococcus pneumoniae (including cases associated with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.;
• Febrile neutropenia (empirical therapy);
• Complicated and uncomplicated urinary tract infections (including pyelonephritis), caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis;
• Uncomplicated skin and soft tissue infections, caused by Staphylococcus aureus (only methicillin-sensitive strains), Streptococcus pyogenes;
• Complicated intra-abdominal infections (in combination with metronidazole), caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis;
• Prevention of postoperative infection.

ICD codes

Dosage Regimen

Adults and adolescents over 16 years or children weighing more than 40 kg intravenous infusion (over at least 30 minutes) or intramuscular (only for complicated or uncomplicated urinary tract infections of mild and moderate severity caused by E.coli).

Pneumonia (moderate and severe), caused by Streptococcus pneumoniae (including cases associated with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.: intravenous 1-2 g every 12 hours for 10 days.

Febrile neutropenia (empirical therapy): intravenous 2 g every 8 hours for 7 days or until resolution of neutropenia.

Complicated or uncomplicated urinary tract infections of mild and moderate severity, caused by E.coli, Klebsiella pneumoniae, Proteus mirabilis: intravenous or intramuscular (only for infections caused by E.coli) 0.5-1 g every 12 hours for 7-10 days.

Severe complicated or uncomplicated urinary tract infections (including pyelonephritis), caused by E.coli or Klebsiella pneumoniae: intravenous 2 g every 12 hours for 10 days.

Moderate and severe skin and soft tissue infections, caused by Staphylococcus aureus (only methicillin-sensitive strains), Streptococcus pyogenes: intravenous 2 g every 12 hours for 10 days.

Complicated intra-abdominal infections (in combination with metronidazole), caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis: intravenous 2 g every 12 hours for 7-10 days.

Children from 2 months to 16 years or weighing up to 40 kg – the recommended dosage regimen for all indications (excluding febrile neutropenia) is 50 mg/kg every 12 hours intravenously; for febrile neutropenia – 50 mg/kg every 8 hours. The maximum single dose should not exceed 2 g. The duration of treatment is the same as in adults.

In chronic renal failure, the dose is prescribed depending on the severity of the infection and creatinine clearance (CrCl): more than 60 ml/min – 0.5 g, 1 g or 2 g every 12 hours or 2 g every 8 hours, CrCl 30-60 ml/min – 0.5 g, 1 g or 2 g every 24 hours or 2 g every 12 hours, with CrCl 11-29 ml/min – 0.5 g, 1 g or 2 g every 24 hours, less than 11 ml/min – 0.25 g, 0.5 g or 1 g every 24 hours; continuous ambulatory peritoneal dialysis – 0.5 g 1 g or 2 g every 48 hours. For patients on hemodialysis, 1 g is administered on the 1st day, then 0.5 g every 24 hours for all infections and 1 g every 24 hours for the treatment of febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is advisable to administer Cefepime every day at the same time.

Data on the use of the drug in children with concomitant chronic renal failure are not available, however, given the similarity of pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between administrations) in children is similar to the dosage regimen in adults.

For intravenous administration, dissolve in sterile water for injections, 5% dextrose solution or 0.9% sodium chloride solution; for intramuscular administration – in sterile water for injections with paraben or benzyl alcohol, in 0.5 and 1% lidocaine solution.

Adverse Reactions

Maxycef^® is usually well tolerated. Adverse drug reactions are rare and transient.

Allergic reactions skin rash (including erythematous rashes), itching, fever, anaphylactoid reactions, positive Coombs test, eosinophilia, multiform exudative erythema (including Stevens-Johnson syndrome), rarely – toxic epidermal necrolysis (Lyell’s syndrome).

Local reactions with intravenous administration – phlebitis, with intramuscular administration – redness and pain at the injection site.

Nervous system disorders headache, dizziness, insomnia, paresthesia, feeling of anxiety, confusion, convulsions.

Genitourinary system disorders vaginitis.

Urinary system disorders impaired renal function.

Digestive system disorders diarrhea, nausea, vomiting, constipation, abdominal pain, dyspepsia, pseudomembranous enterocolitis.

Hematopoietic disorders anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, hemolytic anemia, bleeding.

Respiratory system disorders cough.

Cardiovascular system disorders tachycardia, shortness of breath, peripheral edema.

Laboratory parameters decreased hematocrit, increased prothrombin time, increased urea concentration, hypercreatininemia, hypercalcemia, increased activity of hepatic transaminases and alkaline phosphatase, hyperbilirubinemia.

Other sore throat, thoracalgia, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.

Contraindications

• Immediate hypersensitivity to cefepime, L-arginine (including to other cephalosporins, penicillins, other beta-lactam antibiotics);
• Children’s age (under 2 months).

With caution pregnancy, lactation period, gastrointestinal diseases (including in history), especially colitis, severe chronic renal failure

Use in Pregnancy and Lactation

Use with caution during pregnancy and lactation.

Use in Renal Impairment

Use with caution in severe chronic renal failure.

Pediatric Use

Children from 2 months to 16 years or weighing up to 40 kg – the recommended dosage regimen for all indications (excluding febrile neutropenia) is 50 mg/kg every 12 hours intravenously; for febrile neutropenia – 50 mg/kg every 8 hours. The maximum single dose should not exceed 2 g. The duration of treatment is the same as in adults.

The drug is contraindicated in children under 2 months.

Special Precautions

If pseudomembranous colitis with prolonged diarrhea occurs, discontinue use and prescribe vancomycin (orally) or metronidazole.

Cross-hypersensitivity is possible in patients with allergic reactions to penicillins. In case of combined severe renal and hepatic insufficiency, the concentration of the drug in plasma should be regularly determined (dose adjustment is carried out depending on creatinine clearance). During long-term treatment, regular monitoring of peripheral blood, indicators of the functional state of the liver and kidneys is necessary.

For mixed aerobic-anaerobic infection, until the pathogens are identified, a combination with a drug active against anaerobes is advisable.

Patients in whom meningeal dissemination occurs from a removed focus of infection, if meningitis is suspected or the diagnosis of meningitis is confirmed, should be prescribed an alternative antibiotic with proven clinical efficacy for this situation.

Detection of a positive Coombs test, a false-positive urine glucose test is possible.

The prepared solution should be stored for no more than 24 hours at room temperature or for 7 days in the refrigerator. Color change does not affect the activity of the drug.

Overdose

Symptoms (more often occur in patients with chronic renal failure): convulsions, encephalopathy, neuromuscular excitation.

Treatment symptomatic and supportive therapy; hemodialysis.

Drug Interactions

Pharmaceutically incompatible with other antimicrobial drugs and heparin.

Incompatible with metronidazole solution (before administering metronidazole solution for infection prevention during surgical interventions, the infusion system should be flushed from the cefepime solution).

Increases the nephro- and ototoxicity of aminoglycosides.

Potent diuretics (including furosemide) – risk of nephrotoxic action of cefepime.

NSAIDs, by slowing down the excretion of cephalosporins, increase the risk of bleeding.

When co-administered with aminoglycosides, a pronounced synergy of antimicrobial action is observed.

Storage Conditions

List B. In a dry, light-protected place, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.