Decefim (Powder) Instructions for Use

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

ATC Code

J01DE01 (Cefepime)

Active Substance

Cefepime (Rec.INN registered by WHO)

Dosage Forms

	Decefim	Powder for preparation of solution for intravenous and intramuscular administration 0.5 g: vial 1, 5, 10, 15, 25, 50 or 100 pcs.
		Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1, 5, 10, 15, 25, 50 or 100 pcs.
		Powder for preparation of solution for intravenous and intramuscular administration 2 g: vial 1, 5, 10, 15, 25, 50 or 100 pcs.

Dosage Form, Packaging, and Composition

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

Excipients: arginine – 0.365 g.

Vials – cardboard packs.
Vials (10) – cardboard packs.
Vials (15) – cardboard packs.
Vials (25) – cardboard packs.
Vials (50) – cardboard packs.
Vials (100) – cardboard packs.
Vials 1-100 pcs. – cardboard boxes (for hospitals).

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

Excipients: arginine – 0.73 g.

Vials – cardboard packs.
Vials (10) – cardboard packs.
Vials (15) – cardboard packs.
Vials (25) – cardboard packs.
Vials (50) – cardboard packs.
Vials (100) – cardboard packs.
Vials 1-100 pcs. – cardboard boxes (for hospitals).

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

Excipients: arginine – 1.46 g.

Vials – cardboard packs.
Vials (10) – cardboard packs.
Vials (15) – cardboard packs.
Vials (25) – cardboard packs.
Vials (50) – cardboard packs.
Vials (100) – cardboard packs.
Vials 1-100 pcs. – cardboard boxes (for hospitals).

Clinical-Pharmacological Group

Fourth generation cephalosporin

Pharmacotherapeutic Group

Systemic antibacterial agents; other beta-lactam antibacterial agents; fourth-generation cephalosporins

Pharmacological Action

Cefepime is a fourth-generation cephalosporin antibiotic for parenteral administration. It exerts a bactericidal effect by disrupting the synthesis of the microbial cell wall.

It is active against most gram-negative bacteria, including those producing beta-lactamases, including Pseudomonas aeruginosa. It is more active than third-generation cephalosporins against gram-positive cocci.

It is not active against Enterococcus spp., Listeria spp., Legionella spp., and some anaerobic bacteria ( Bacteroides fragilis, Clostridium difficile).

Cefepime is characterized by high stability against various plasmid and chromosomal beta-lactamases.

Pharmacokinetics

Plasma protein binding is less than 19% and does not depend on the serum concentration of cefepime.

Therapeutic concentrations of cefepime are found in urine, bile, peritoneal fluid, blister exudate, bronchial mucous secretion, sputum, prostate tissue, appendix, gallbladder, and cerebrospinal fluid in meningitis.

In healthy individuals, no accumulation in the body was observed after intravenous administration of cefepime at a dose of 2 g every 8 hours for 9 days.

The mean elimination half-life (T_1/2) is about 2 hours, and the mean total clearance is 120 ml/min. Cefepime is excreted by the kidneys, mainly by glomerular filtration (mean renal clearance is 110 ml/min). Approximately 85% of the administered cefepime is found unchanged in the urine.

In patients aged 65 years or older with normal renal function, the renal clearance value is lower than in younger patients.

In patients with impaired renal function, the T_1/2 is increased. In patients with severe renal impairment requiring hemodialysis, the mean T_1/2 is 13 hours, and during peritoneal dialysis, it is 19 hours.

The pharmacokinetics of cefepime are unchanged in patients with impaired liver function and cystic fibrosis.

The age and sex of patients did not significantly affect the total body clearance and volume of distribution (V_d) when adjusted for body weight. No accumulation was noted when cefepime was administered at a dose of 50 mg/kg every 12 hours, and when administered at the same dose every 8 hours at steady state, C_max, AUC, and T_1/2 increased by approximately 15%.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms susceptible to cefepime: lower respiratory tract infections (including pneumonia and bronchitis), urinary tract infections (both complicated and uncomplicated), skin and soft tissue infections, intra-abdominal infections (including peritonitis and biliary tract infections), gynecological infections, septicemia, neutropenic fever (as empirical therapy), bacterial meningitis in children.

Prevention of infections during abdominal surgical operations.

ICD codes

Dosage Regimen

Determine the dosage individually based on the sensitivity of the pathogen, severity of the infection, patient’s age, and renal function.

Administer intramuscularly or intravenously. Use the intravenous route for severe or life-threatening infections, particularly when shock is threatened.

For adults with normal renal function, use a dose of 0.5-2 g every 12 hours. For severe infections, including those caused by Pseudomonas aeruginosa, increase the frequency to every 8-12 hours.

For pediatric patients over two months of age, administer 50 mg/kg per dose. Repeat the dose every 12 hours. For febrile neutropenia, use a dose of 50 mg/kg every 8 hours.

Adjust the dosage for patients with renal impairment. For a creatinine clearance of 30-60 mL/min, use a maximum of 2 g daily. For a clearance of 11-29 mL/min, use a maximum of 1 g daily. For a clearance of less than 10 mL/min, use a maximum of 0.5 g daily.

Administer intravenous infusions over approximately 30 minutes.

For surgical prophylaxis, administer a 2 g single dose intravenously 60 minutes before the procedure.

Reconstitute the powder with an appropriate volume of Sterile Water for Injection, 0.9% Sodium Chloride, or other compatible diluent. Shake well until the solution is clear.

Do not mix the reconstituted solution with solutions containing aminoglycosides in the same container. Administer such concomitantly used drugs separately.

Adverse Reactions

From the digestive system: diarrhea, nausea, vomiting, colitis (including pseudomembranous colitis) may occur; rarely – abdominal pain, constipation, taste alteration.

Allergic reactions: rash, itching, urticaria may occur; rarely – anaphylactic reactions.

From the central and peripheral nervous system: headache may occur; rarely – dizziness, paresthesia; in some cases – seizures.

Dermatological reactions: rarely – skin redness. Most often in children – rash.

From the hematopoietic system: anemia may occur.

From laboratory test parameters: increased activity of ALT, AST, ALP, increased total bilirubin, eosinophilia, increased prothrombin time may occur; rarely – temporary increase in blood urea nitrogen and/or serum creatinine, transient thrombocytopenia, transient leukopenia and neutropenia; frequently – positive Coombs’ test without hemolysis.

Other: fever, vaginitis, erythema may occur; rarely – genital itching, nonspecific candidiasis.

Local reactions: with intravenous infusion, phlebitis may occur, rarely – inflammation; with intramuscular injection, inflammation or pain may occur.

Contraindications

Hypersensitivity to cefepime or L-arginine, as well as to cephalosporin antibiotics, penicillins, or other beta-lactam antibiotics.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of cefepime use during pregnancy have not been conducted; use is possible only under medical supervision.

Cefepime is excreted in breast milk in very low concentrations. Use with caution during lactation.

In experimental studies, no effect on reproductive function and no fetotoxic effects of cefepime were identified.

Use in Renal Impairment

In case of impaired renal function (creatinine clearance less than 30 ml/min), adjustment of the dosage regimen is necessary. The initial dose of cefepime should be the same as for patients with normal renal function. Maintenance doses are determined depending on creatinine clearance values or serum creatinine concentration.

Pediatric Use

The safety and efficacy of cefepime use in children under 2 months of age have not been established. For children over 2 months of age, use is possible according to the dosage regimen. For children with impaired renal function, the same dosage adjustments are recommended as for adults, since the pharmacokinetics of cefepime in adults and children are similar.

Special Precautions

When used in patients at increased risk of infection due to mixed aerobic/anaerobic flora (including cases where one of the pathogens is Bacteroides fragilis), until the pathogen is identified, it is recommended to prescribe a drug active against anaerobes concomitantly with cefepime.

Use with caution in patients at risk of developing allergic reactions, especially to medications.

If allergic reactions develop, Cefepime should be discontinued.

In case of serious immediate hypersensitivity reactions, the use of epinephrine (adrenaline) and other forms of supportive treatment may be required.

If diarrhea occurs during treatment, the possibility of developing pseudomembranous colitis should be considered. In such cases, Cefepime should be discontinued immediately and appropriate treatment instituted if necessary.

If superinfection develops, Cefepime should be discontinued immediately and appropriate treatment instituted.

The safety and efficacy of cefepime use in children under 2 months of age have not been established.

Use Cefepime with particular caution concomitantly with aminoglycosides and “loop” diuretics.

Drug Interactions

Pharmaceutical interaction is possible when cefepime solution is administered simultaneously with solutions of metronidazole, vancomycin, gentamicin, tobramycin sulfate, and netilmicin sulfate.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.