Pimocev-AG (Powder) Instructions for Use

Marketing Authorization Holder

Altegra, JSC (Russia)

ATC Code

J01DE01 (Cefepime)

Active Substance

Cefepime (Rec.INN registered by WHO)

Dosage Forms

	Pimocev-AG	Powder for preparation of solution for intravenous and intramuscular administration 500 mg
		Powder for preparation of solution for intravenous and intramuscular administration 1000 mg
		Powder for preparation of solution for intravenous and intramuscular administration 2000 mg

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration

500 mg – vials – cardboard packs – By prescription

Powder for preparation of solution for intravenous and intramuscular administration

1000 mg – vials – cardboard packs – By prescription

Powder for preparation of solution for intravenous and intramuscular administration

2000 mg – vials – cardboard packs – By prescription

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, such as 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 approximately 2 hours, and the mean total clearance is 120 ml/min. Cefepime is excreted by the kidneys, primarily 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, while administration at the same dose every 8 hours resulted in an approximately 15% increase in C_max, AUC, and T_1/2 at steady state.

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.

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

For adults with normal renal function (creatinine clearance > 60 mL/min), use a dose of 500 mg to 2 g every 12 hours. For severe infections, including neutropenic fever, administer 2 g every 8 hours.

For pediatric patients over 2 months of age, administer 50 mg/kg per dose. Use a dosing interval of every 12 hours for most infections. For febrile neutropenia, use a dosing interval of every 8 hours.

Adjust the dosage for all patients with renal impairment. Calculate the creatinine clearance (CrCl) to determine the maintenance dose and frequency.

For a CrCl of 30 to 60 mL/min, use a maximum dose of 2 g every 24 hours or 1 g every 12 hours. For a CrCl of 10 to 30 mL/min, use a maximum dose of 2 g every 24 hours or 500 mg every 12 hours. For a CrCl of less than 10 mL/min, use a maximum dose of 1 g every 24 hours.

Administer an additional dose after hemodialysis. For patients on continuous ambulatory peritoneal dialysis, administer a 1 g loading dose followed by 500 mg every 24 hours.

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

Reconstitute the powder with an appropriate volume of diluent as specified. For intravenous infusion, further dilute the reconstituted solution in a compatible IV fluid. Infuse over approximately 30 minutes.

Adverse Reactions

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

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

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

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

From the hematopoietic system: anemia may occur.

From laboratory parameters: increased ALT, AST, ALP activity, increased total bilirubin, eosinophilia, increased prothrombin time; rarely – transient 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; rarely – genital itching, nonspecific candidiasis.

Local reactions: with intravenous infusion – phlebitis, 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.

Experimental studies have not revealed any effect on reproductive function or fetotoxic effects of cefepime.

Use in Renal Impairment

In case of renal impairment (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 are similar in adults and children.

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), it is recommended to concomitantly administer an agent active against anaerobes along with cefepime until the pathogen is identified.

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 pseudomembranous colitis should be considered. In such cases, Cefepime should be discontinued immediately and appropriate treatment initiated if necessary.

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

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

Use Cefepime with particular caution in conjunction 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.