Cefpar (Powder) Instructions for Use

Marketing Authorization Holder

Rusyurapharm, LLC (Russia)

ATC Code

J01DD12 (Cefoperazone)

Active Substance

Cefoperazone (Rec.INN registered by WHO)

Dosage Forms

	Cefpar	Powder for preparation of solution for intramuscular and intravenous administration 1 g: vial 1 or 50 pcs.
		Powder for preparation of solution for intramuscular and intravenous administration 2 g: vial 1 or 50 pcs.
		Powder for preparation of solution for intramuscular and intravenous administration 500 mg: vial 1 or 50 pcs.

Dosage Form, Packaging, and Composition

Vials (1) – cardboard packs.
Vials (50) – cardboard boxes.

Vials (1) – cardboard packs.
Vials (50) – cardboard boxes.

Vials (1) – cardboard packs.
Vials (50) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin semi-synthetic broad-spectrum antibiotic of the third generation. It exerts a bactericidal effect by inhibiting the synthesis of the microbial cell wall: it acetylates membrane-bound transpeptidases, thereby disrupting the cross-linking of peptidoglycans necessary for ensuring the strength and rigidity of the cell wall.

Active against

• Gram-positive microorganisms: Staphylococcus aureus (penicillinase-producing and non-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic group A streptococcus), Streptococcus agalactiae (beta-hemolytic group B streptococcus), Streptococcus faecalis;
• Gram-negative microorganisms: Escherichia coli, Klebsiella spp. (including Klebsiella pneumonia), Enterobacter spp., Citrobacter spp., Haemophilus influenzae (beta-lactamase-producing and non-producing strains), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Serratia marcescens, Salmonella spp. and Shigella spp., Pseudomonas spp., including Pseudomonas aeruginosa, some strains of Acinetobacter spp., Neisseria gonorrhoeae (beta-lactamase-producing and non-producing strains) and Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica;
• Anaerobic microorganisms: gram-positive cocci (including Peptococcus spp., Peptostreptococcus spp.), gram-positive spore-forming and non-spore-forming anaerobes (Clostridium difficile, Eubacterium spp., Lactobacillus spp.) and gram-negative rods (including Fusobacterium spp., some strains of Bacteroides fragilis, and other Bacteroides spp.).

Pharmacokinetics

T_max after intramuscular administration is 1-2 hours; after intravenous administration – at the end of the infusion. C_max in serum after intramuscular administration of 0.25 g and 0.5 g of cefoperazone is 22 µg/ml and 33 µg/ml, respectively. C_max after intravenous administration of 1 g and 2 g of the drug is 153 µg/ml and 252 µg/ml, respectively.

Plasma protein binding is 82-93%.

Cefoperazone reaches therapeutic concentrations in body tissues and fluids: ascitic, peritoneal, synovial fluid, urine, bile and gallbladder walls, lungs, sputum, palatine tonsils, sinus mucosa, atria, kidneys, ureters, prostate, testes, uterus, fallopian tubes, bones, umbilical cord blood, amniotic fluid, as well as in cerebrospinal fluid (in meningitis). In small concentrations, Cefoperazone can be detected in breast milk.

Volume of distribution 0.14 – 2 L/kg. T_1/2 averages 2 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. Excreted in active form (less than 1% metabolized) 70-80% with bile, 20-30% – by the kidneys. In patients with impaired liver function and biliary obstruction, T_1/2 is 3-7 hours, renal excretion is 90% or more. Even with severe liver damage, therapeutic concentrations are achieved in the bile, and T_1/2 is prolonged only 2-4 times. In patients with renal-hepatic insufficiency, accumulation may occur.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug

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

Prevention of infectious complications in abdominal, gynecological and traumatological operations, as well as in cardiovascular surgery.

ICD codes

Dosage Regimen

Intravenously (drip, bolus), intramuscularly.

For adults the average daily dose of cefoperazone is 2-4 g, administered in equal parts every 12 hours. In severe infections, the daily dose can be increased to 8 g, also administered in equal parts every 12 hours. No complications were identified when cefoperazone was administered at a daily dose of 12 g and even 16 g, divided into equal doses every 8 hours. Treatment can be started before the results of the study of microorganism sensitivity are obtained.

For uncomplicated gonococcal urethritis, a single intramuscular injection of 500 mg of the drug is recommended.

For the prevention of postoperative complications – 1 g or 2 g IV 30-90 minutes before the start of surgery. The dose can be repeated every 12 hours, however, in most cases, for no more than 24 hours.

In operations with an increased risk of infection (for example, colorectal surgery), or if the resulting infection is particularly dangerous (for example, in open-heart surgery or joint replacement), prophylactic use may continue for 72 hours after completion of the operation. Patients with impaired renal function are prescribed the usual daily dose (2-4 g). In patients whose glomerular filtration rate is below 18 ml/min or serum creatinine level is above 3.5 mg/dl, the daily dose should not exceed 4 g.

In patients with severe liver dysfunction, pronounced biliary tract obstruction, the daily dose of the drug should not exceed 2 g. In patients with renal-hepatic insufficiency, the concentration of cefoperazone in the blood should be monitored and the dose adjusted if necessary.

Use in children

In children, the daily dose of cefoperazone is 50-200 mg/kg of body weight, administered in equal parts in two doses (every 12 hours) or more if necessary. The maximum daily dose is 12 g.

For IV bolus administration, the maximum single dose for children is 50 mg/kg, the duration of administration is at least 3-5 minutes. For newborns (<8 days), 50-200 mg/kg of body weight per day is administered in equal parts every 12 hours. Daily doses up to 300 mg/kg have been used without complications in young children and children with severe infections, including bacterial meningitis. The efficacy and safety of use in children to date have not been established.

Intravenous administration

The solution for intravenous administration is prepared ex tempore.

As a solvent, 5% dextrose solution, 10% dextrose solution, 0.9% sodium chloride solution, sterile water for injection can be used. To prepare a solution for IV bolus administration, it is necessary to dissolve 1 g of cefoperazone in 10 ml of sterile water for injection or another compatible solution and administer it over at least 3-5 minutes. For IV bolus administration, the maximum single dose of cefoperazone for adults is 2 g, for children – 50 mg/kg of body weight.

When preparing a solution for IV drip administration, it is recommended to use 5 ml of solvent per 1 g of cefoperazone to facilitate dissolution. The resulting solution is added to the infusion solution (Ringer’s lactate solution, 5% dextrose solution, 0.9% sodium chloride solution) in a volume of 20-100 ml. The duration of administration, depending on the volume of the solution, can range from 10-30 minutes or more.

Intramuscular administration

For the preparation of solutions intended for IM injections, sterile water for injection or 0.9% sodium chloride solution can be used. To dilute 0.5 g of the drug, 2 ml of solvent should be used, 1 g – 4 ml to obtain a final concentration of cefoperazone of 250 mg/ml. To reduce pain during intramuscular injections in cases where it is intended to administer a solution with a concentration of 250 mg/ml or more, it is recommended to use a 2% lidocaine solution for the preparation of the solution (provided that the patient has no hypersensitivity reaction to lidocaine). This solution can be prepared using sterile water for injection in combination with 2% lidocaine solution. The following two-step dilution method is recommended: first add the required amount of sterile water for injection and shake until the cefoperazone powder is completely dissolved, then add the required amount of 2% lidocaine and mix.

IM injection is performed deep into a large muscle (gluteus maximus muscle or anterior thigh surface).

Adverse Reactions

Allergic reactions urticaria, maculopapular rash, fever, eosinophilia, multiforme erythema, skin itching, malignant exudative erythema (Stevens-Johnson syndrome), rarely – Quincke’s edema, anaphylactic shock.

From the gastrointestinal tract nausea, vomiting, diarrhea, pseudomembranous colitis.

Laboratory parameters hypoprothrombinemia, increased prothrombin time, increased activity of “hepatic” transaminases and alkaline phosphatase, transient hypercreatininemia, transient eosinophilia, decreased hematocrit, positive Coombs test.

From the hematopoietic organs anemia, reversible neutropenia (with prolonged use), bleeding.

Local reactions phlebitis (with intravenous administration), pain at the injection site (with intramuscular administration).

Other candidiasis.

Contraindications

• Hypersensitivity to cephalosporins and other beta-lactam antibiotics.

With caution renal-hepatic insufficiency, history of colitis.

Use in Pregnancy and Lactation

Cefoperazone can be used during pregnancy if the intended benefit to the mother outweighs the potential risk to the fetus. When prescribing cefoperazone during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution hepatic insufficiency.

Use in Renal Impairment

With caution renal insufficiency.

Pediatric Use

Use is possible according to the dosing regimen.

Special Precautions

Can be used in combination therapy in combination with other antibiotics.

In patients with hypersensitivity to penicillins, cross-allergic reactions to cephalosporin antibiotics, including Cefoperazone, are possible.

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

During treatment with cefoperazone and for 5 days after its completion, ethanol intake should be avoided, as a disulfiram-like reaction may develop.

In patients with impaired food absorption (for example, those suffering from cystic fibrosis), as well as patients on long-term parenteral nutrition, vitamin K deficiency may occur. Such patients should be monitored for prothrombin time and, if necessary, exogenous vitamin K should be prescribed.

Long-term use may lead to the development of pathogen resistance. In the case of biliary tract obstruction, severe liver disease, or concomitant renal impairment, a dosage regimen adjustment may be required.

Overdose

Symptoms epileptic seizure.

Treatment administration of diazepam, symptomatic therapy.

Drug Interactions

Cefoperazone solution should not be mixed in the same syringe with aminoglycosides due to chemical and physical incompatibility (if combination therapy with these drugs is necessary, Cefoperazone and the aminoglycoside should be administered as sequential fractional intravenous injections using two separate intravenous catheters).

Non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen, indomethacin, ketorolac, etc.), indirect anticoagulants, heparin, thrombolytics, and antiplatelet agents (dipyridamole, alprostadil, etc.) increase the frequency of hypoprothrombinemia development and elevate the risk of bleeding.

Aminoglycosides and “loop” diuretics increase the risk of nephrotoxicity, especially in individuals with renal failure.

When Cefoperazone is co-administered with ethanol, or if the interval between their intake is less than 5 days, a disulfiram-like reaction may occur, manifested as flushing, nausea, vomiting, headache, shortness of breath, tachycardia, decreased blood pressure, and abdominal cramps.

Drugs that reduce tubular secretion increase the concentration of the drug in the blood and slow its elimination.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.