Cefoperus^® (Powder) Instructions for Use

Marketing Authorization Holder

Sintez PJSC (Russia)

ATC Code

J01DD12 (Cefoperazone)

Active Substance

Cefoperazone (Rec.INN registered by WHO)

Dosage Forms

	Cefoperus®	Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1, 5 or 10 pcs.
		Powder for preparation of solution for intravenous and intramuscular administration 2 g: vial 1, 5 or 10 pcs.
		Powder for preparation of solution for intravenous and intramuscular administration 500 mg: vial 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

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

Vials (1) – cardboard packs.
Vials (5) – cardboard packs.
Vials (10) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin antibiotic of the third generation for parenteral administration. It acts bactericidally by disrupting the synthesis of the microbial cell wall. It has a broad spectrum of action.

Active against gram-positive microorganisms Staphylococcus aureus and Staphylococcus epidermidis (strains producing and not producing penicillinase), Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic strain group A), Streptococcus agalactiae (beta-hemolytic strain group B), Enterococcus faecalis, other strains of beta-hemolytic Streptococcus spp.; gram-negative microorganisms Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae), Enterobacter spp., Citrobacter spp., Haemophilus influenzae (strains producing and not producing β-lactamases), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp. (including Providencia rettgeri), Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., Pseudomonas spp. (including Pseudomonas aeruginosa), some strains of Acinetobacter spp., Neisseria gonorrhoeae (strains producing and not producing β-lactamases), Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica; anaerobic microorganisms: gram-positive and gram-negative cocci (including Peptococcus spp., Peptostreptococcus spp., Veillonella spp.), gram-positive spore-forming and non-spore-forming anaerobes (Clostridium spp., Eubacterium spp., Lactobacillus spp.) and gram-negative (including Fusobacterium spp., Bacteroides spp. /including Bacteroides fragilis/, Prevotella spp.).

Pharmacokinetics

Absorption

T_max after intramuscular administration is 1-2 hours, after intravenous administration – at the end of the infusion, C_max after intramuscular administration of the drug at a dose of 1 g is 65-75 µg/ml, at a dose of 2 g – 97 µg/ml; after a single intravenous administration at doses of 1 g, 2 g, 3 g and 4 g, C_max is 153 µg/ml, 252 µg/ml, 340 µg/ml, 506 µg/ml, respectively. C_max in urine after intramuscular and intravenous administration at a dose of 2 g is 1000 µg/ml and more than 2200 µg/ml, respectively.

Distribution

Plasma protein binding is 82-93%. It reaches therapeutic concentrations in peritoneal, ascitic fluid and cerebrospinal fluid (in meningitis), urine, bile, gallbladder wall, lungs, sputum, palatine tonsils and sinus mucosa, atria, kidneys, ureters, prostate, testicles, uterus, fallopian tubes, bones, umbilical cord blood and amniotic fluid. V_d is 0.14-2 l/kg.

Elimination

T_1/2 is 1.6-2.4 hours, regardless of the route of administration, 2.8-4.2 hours – during hemodialysis, 2.2 hours – in newborns and children from 2 months to 11 years. It is excreted in bile – 70-80%, by the kidneys – 20-30% unchanged.

Pharmacokinetics in special clinical cases

In patients with impaired liver function and biliary obstruction, T_1/2 is 3-7 hours, urinary excretion is 90% or more. Even with severe liver damage, therapeutic concentrations are achieved in bile, and T_1/2 is prolonged only by 2-4 times.

In patients with renal-hepatic insufficiency, Cefoperazone may accumulate.

Indications

• Infections of the upper and lower respiratory tract;
• Urinary tract infections;
• Abdominal infections (peritonitis, cholecystitis, cholangitis);
• Sepsis;
• Meningitis;
• Skin and soft tissue infections;
• Bone and joint infections;
• Infectious and inflammatory diseases of the pelvic organs (endometritis, gonorrhea and other genital tract infections).

Prevention of infectious complications after abdominal, gynecological, cardiovascular and orthopedic surgeries.

ICD codes

Dosage Regimen

The drug is administered intramuscularly and intravenously (bolus or drip).

Adults are prescribed the drug at a daily dose of 2-4 g, 2 times/day. In severe infections, the dose may be increased to 12 g/day: 2-4 g every 8 hours or 3-6 g every 12 hours. Treatment may be started before the results of microorganism susceptibility testing are available.

For uncomplicated gonococcal urethritis – intramuscularly at a dose of 500 mg once.

For prevention of postoperative complications – intravenously, 1 g or 2 g 30-60 minutes before the start of surgery, with repetition every 12 hours (in most cases for no more than 24 hours). In surgeries with an increased risk of infection (e.g., colorectal surgery), or if the resulting infection can cause particularly great harm (e.g., open-heart surgery or joint replacement), prophylactic use of the drug may continue for 72 hours after completion of the surgery.

Patients with renal-hepatic insufficiency are prescribed no more than 2 g/day. Patients with glomerular filtration rate below 18 ml/min, or serum creatinine content more than 3.5 mg/ml – no more than 4 g/day.

In isolated hepatic insufficiency, dose reduction is not required if the patient is not receiving the maximum dose, because renal excretion of the drug compensatorily increases to 90% or more.

In children, daily doses are 50-200 mg/kg of body weight in 2 doses (every 12 hours) or more if necessary. Newborns (less than 8 days) are prescribed the drug every 12 hours.

The drug in doses up to 300 mg/kg/day is used without complications in young children and childrenwith severe infections, including bacterial meningitis.

Rules for preparation and administration of the drug

The following solvents can be used to prepare solutions for intramuscular administration: sterile water for injections, 0.9% sodium chloride solution, 0.5% lidocaine hydrochloride solution, which are added to 1 g of cefoperazone in a volume of 3 ml. When administered intramuscularly, the drug is injected deep into the gluteal muscle. Freshly prepared cefoperazone solutions are stored for no more than 24 hours at a temperature from 5°C (41°F) to 25°C (77°F).

For bolus intravenous injection, the maximum single dose of cefoperazone for adults is 2 g, for children 50 mg/kg of body weight, and the duration of administration should be at least 3-5 minutes. The solution for intravenous administration is prepared ex tempore. The following can be used as solvents: 5% dextrose (glucose) solution, 0.9% sodium chloride solution, Ringer’s lactate solution, sterile water for injections.

For drip intravenous administration, 1 g of cefoperazone is dissolved in 5 ml of sterile water for injections, the resulting solution is added to the infusion solution to a concentration of 20-100 mg/ml. The duration of administration depending on the volume of the solution can range from 10 to 30 minutes or more.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea, pseudomembranous colitis, increased activity of hepatic transaminases and alkaline phosphatase.

From the coagulation system bleeding (vitamin K deficiency), hypoprothrombinemia, increased prothrombin time.

From the hematopoietic system anemia, neutropenia.

Laboratory parameters hypercreatininemia.

Allergic reactions: urticaria, maculopapular rash, fever, eosinophilia, multiforme erythema, malignant exudative erythema (Stevens-Johnson syndrome), positive Coombs test.

Local reactions with intravenous administration – phlebitis; with intramuscular administration – pain at the injection site.

Contraindications

• Hypersensitivity to the components of the drug, including other beta-lactam antibiotics.

With caution the drug should be prescribed in renal and/or hepatic insufficiency, colitis (including in the anamnesis), pregnancy, during lactation.

Use in Pregnancy and Lactation

With caution the drug should be prescribed during pregnancy.

If prescribed during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution the drug should be prescribed in hepatic insufficiency.

In isolated hepatic insufficiency, dose reduction is not required if the patient is not receiving the maximum dose, because renal excretion of the drug compensatorily increases to 90% or more.

Use in Renal Impairment

With caution the drug should be prescribed in renal insufficiency.

Patients with renal-hepatic insufficiency are prescribed no more than 2 g/day. Patients with glomerular filtration rate below 18 ml/min, or serum creatinine content more than 3.5 mg/ml – no more than 4 g/day.

Pediatric Use

In children, daily doses are 50-200 mg/kg of body weight in 2 doses (every 12 hours) or more if necessary. Newborns (less than 8 days) are prescribed the drug every 12 hours.

The drug in doses up to 300 mg/kg/day is used without complications in young children and childrenwith severe infections, including bacterial meningitis.

Special Precautions

Cefoperus^® can be used in combination therapy in combination with other antibiotics.

Patients with hypersensitivity to penicillin should be prescribed the drug with great caution.

In cases of biliary obstruction, severe liver disease or concomitant renal impairment, it may be necessary to adjust the dosage regimen.

Long-term use may lead to the development of pathogen resistance.

During the use of the drug, a false-positive reaction to glucose in urine with Benedict’s or Fehling’s solution may occur.

During treatment, one should refrain from taking ethanol, because disulfiram-like reactions may develop (facial skin hyperemia, abdominal and stomach cramps, nausea, vomiting, headache, decreased blood pressure, tachycardia, shortness of breath).

In patients on an inadequate diet or with malabsorption (e.g., cystic fibrosis), as well as patients on prolonged parenteral nutrition, vitamin K deficiency may occur. Such patients should have their prothrombin time monitored; if necessary, they are indicated for exogenous vitamin K administration.

Overdose

Symptoms: epileptic seizure may develop.

Treatment sedative therapy with diazepam.

Drug Interactions

With simultaneous use with ethanol, disulfiram-like reactions may develop.

Indirect anticoagulants, heparin, thrombolytics when used simultaneously with Cefoperus^® increase the risk of hypoprothrombinemia, bleeding.

Aminoglycosides and “loop” diuretics when used simultaneously with Cefoperus^® increase nephrotoxicity, especially in persons with renal insufficiency.

Drugs that reduce tubular secretion increase the concentration of the drug Cefoperus^® in the blood and slow down its excretion.

Pharmaceutical interaction

Pharmaceutically incompatible with aminoglycosides (if combined therapy with cefoperazone and an aminoglycoside is necessary, they are prescribed as sequential fractional intravenous administration of the drugs, using 2 separate intravenous catheters).

Storage Conditions

List B. The drug should be stored in a dry, light-protected place, out of reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

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.