Hepacef powder for solution for injection 1 g bottle No. 10

Instructions for Gepacef powder for solution for injection 1 g bottle No. 10

Composition

active ingredient: cefoperazone;

1 vial contains cefoperazone sodium salt equivalent to 1.0 g of cefoperazone.

Dosage form

Powder for solution for injection.

Main physicochemical properties: white or white with a yellowish tinge powder, hygroscopic.

Pharmacotherapeutic group

Third generation cephalosporins. ATX code J01D D12.

Pharmacological properties

Pharmacodynamics

The bactericidal effect of the drug Gepacef® is due to the slowing down of the synthesis of the bacterial cell wall.

Gepacef® is active in vitro against a large number of clinically significant microorganisms. At the same time, it exhibits resistance to the action of many beta-lactamases.

The following microorganisms are sensitive to Gepacef®.

Gram-positive microorganisms:

Staphylococcus aureus (penicillinase-producing and non-penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae (previous name – Diplococcus pneumoniae), Streptococcus pyogenes (group A beta-hemolytic streptococci), Streptococcus agalactiae (group B beta-hemolytic streptococci), Streptococcus faecalis (enterococcus), beta-hemolytic streptococci.

Gram-negative microorganisms:

Escherichia coli, Klebsiella genus, Enterobacter genus, Citrobacter genus, Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii (formerly Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri), Providencia genus, Serratia genus (including S. Marcescens), Salmonella and Shigella genera, Pseudomonas aeruginosa and some other Pseudomonas, Acinetobacter calcoaceticus, Neisseria gonorrhoeae (beta-lactamase producing and non-producing strains), Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica.

Anaerobic microorganisms:

Gram-positive and Gram-negative cocci (including the genera Peptococcus, Peptostreptococcus and Veillonella);

Gram-positive rods (including the genera Clostridium, Eubacterium and Lactobacillus);

Gram-negative rods (including the genus Fusobacterium, many strains of Bacteroides fragilis and other members of the genus Bacteroides).

Pharmacokinetics

High levels in blood, bile and urine are achieved after a single administration of the drug. Table 1 shows the drug concentrations in the blood serum of healthy adult volunteers. These data were obtained after a 15-minute intravenous injection of 1, 2, 3 or 4 g of the drug or after a single intramuscular injection of 1 or 2 g of the drug. Probenecid does not affect the level of cefoperazone concentration in the blood.

Mean serum concentrations of cefoperazone (μg/mL) Table 1.

* Time elapsed since drug administration (counting immediately after completion of infusion).

** Results obtained 15 minutes after drug administration.

The half-life of the drug Gepacef® from blood serum is approximately 2 hours, regardless of the route of administration.

Gepacef® reaches therapeutic levels in all body fluids and tissues, including ascitic and cerebrospinal (during meningitis) fluids, urine, bile and gallbladder walls, sputum and lungs, palatine tonsils and sinus mucosa, atrium, kidneys, ureter, prostate, testicles, uterus and fallopian tubes, bones, umbilical cord blood and amniotic fluid.

Gepacef® is excreted in the bile and urine. The concentration of the drug in bile reaches very high levels (usually 1–3 hours after administration) and exceeds similar concentrations in blood serum by 100 times.

The following bile concentrations have been reported: from 66 μg/mL after 30 minutes to 6000 μg/mL after 3 hours after intravenous administration of 2 g of the drug to patients without bile duct obstruction.

After 12 hours after administration of various doses and routes, the increase in the concentration of cefoperazone in the urine of patients with normal renal function reaches an average of 20-30%. The concentration of the drug in the urine of more than 2200 μg / ml was obtained 15 minutes after intravenous administration of 2 g of the drug Gepacef®. After intramuscular administration of 2 g of the drug, the maximum concentration in the urine was approximately 1000 μg / ml.

Repeated administration of Gepacef® does not lead to drug accumulation in healthy volunteers.

Patients with liver dysfunction

In patients with impaired liver function, the serum half-life of the drug increases, but urinary excretion also increases. In patients with renal and hepatic insufficiency, Gepacef® may accumulate in the serum.

Patients with renal impairment

In patients with renal insufficiency, the maximum concentration of the drug in the blood serum, the area under the pharmacokinetic curve, and the serum half-life are the same as in healthy volunteers.

Indication

Treatment of infections caused by microorganisms sensitive to the drug Gepacef®:

Upper and lower respiratory tract infections; Upper and lower urinary tract infections; Peritonitis, cholecystitis, cholangitis and other intra-abdominal infections; Septicemia; Meningitis; Skin and soft tissue infections; Bone and joint infections; Pelvic inflammatory disease, endometritis, gonorrhea and other genital tract infections.

Prevention of postoperative complications during abdominal, gynecological, cardiovascular and orthopedic surgeries.

Contraindication

Hypersensitivity to cefoperazone or to any of the cephalosporin antibiotics.

Interaction with other medicinal products and other types of interactions

Alcohol

It has been reported that alcohol consumption during treatment with the drug and even 5 days after the last administration of cefoperazone caused a disulfiram-like reaction, characterized by flushing, increased sweating, headache and tachycardia. Similar reactions have also occurred after taking other cephalosporins, so patients should be warned against drinking alcoholic beverages during treatment with cefoperazone. Patients requiring oral or parenteral artificial nutrition should avoid the use of solutions containing ethanol.

Interactions affecting laboratory test results

A false-positive urine reaction to glucose may occur when testing with Benedict's or Fehling's solutions.

Application features

Hypersensitivity

Serious hypersensitivity reactions (anaphylactic reactions), sometimes fatal, have been reported in patients receiving beta-lactam or cephalosporin drugs, including cefoperazone. These reactions occurred more frequently in patients with a history of hypersensitivity reactions to multiple allergens.

Before prescribing cefoperazone, careful inquiry should be made regarding previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. This drug should be administered with caution to patients with known penicillin sensitivity.

Antibiotics should be prescribed with caution to patients who have previously had any form of allergy, especially drug allergies.

If an allergic reaction occurs, the drug should be discontinued and appropriate treatment should be instituted. Serious anaphylactic reactions require immediate emergency administration of adrenaline. Oxygen, intravenous corticosteroids, and airway management, including intubation, should be considered if necessary.

Severe skin reactions, sometimes fatal, such as toxic epidermal necrolysis, Stevens-Johnson syndrome and exfoliative dermatitis, have been reported in patients receiving cefoperazone. If a severe skin reaction occurs, cefoperazone therapy should be discontinued and appropriate treatment initiated (see section 4.8).

Use in patients with liver dysfunction

Cefoperazone is largely excreted in the bile. In patients with liver disease and/or biliary obstruction, the serum half-life of cefoperazone is prolonged and renal excretion of the drug in the urine is increased. Even in severe liver dysfunction, therapeutic concentrations of cefoperazone are achieved in the bile, and the half-life increases only 2–4 times.

General warnings

Cases of serious bleeding, including fatal cases, have been reported with the use of cefoperazone.

Patients at risk include patients with restricted nutrition, malabsorption, and patients on prolonged parenteral (intravenous) nutrition. Such patients should be monitored for signs of bleeding, thrombocytopenia, and hypoprothrombinemia. In the event of prolonged bleeding without other causes identified, cefoperazone should be discontinued.

As with other antibiotics, prolonged use of cefoperazone may lead to increased growth of resistant microflora, therefore, during treatment, patients should be carefully monitored. As with any potent systemic drug, during long-term therapy with cefoperazone, periodic examinations are recommended to detect possible functional disorders of body systems, in particular the kidneys, liver and hematopoietic system. Such examinations are especially important in newborns, in particular premature and other infants.

difficile produces toxins A and B, which contribute to the development of CDAD. C. difficile strains with overproduction of toxins are associated with increased morbidity and mortality because the infections they cause may be resistant to antimicrobial therapy and may require colectomy. CDAD should be suspected in all patients who present with diarrhea after antibiotic use. A careful history is necessary, as CDAD has been reported to occur more than 2 months after antibiotic use.

If the patient is on a low-sodium diet, it should be noted that Gepacef® contains 34 mg of sodium.

Ability to influence reaction speed when driving vehicles or other mechanisms

Experience with the clinical use of cefoperazone indicates that the drug is unlikely to affect the patient's ability to drive or operate machinery.

Use during pregnancy or breastfeeding

Pregnancy

Animal reproduction studies at doses 10 times the human dose have shown no evidence of impaired fertility or teratogenicity. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, the drug should be used during pregnancy only if clearly indicated.

Breastfeeding period

Only small amounts of cefoperazone pass into breast milk. Although cefoperazone does not pass into breast milk, caution should be exercised when administering the drug during breastfeeding.

Method of administration and doses

The drug is administered intravenously or intramuscularly.

Adults.

The usual adult dose is 2–4 g/day, administered every 12 hours in equally divided doses. In particularly severe infections, the dose may be increased to 8 g/day, administered every 12 hours in equally divided doses. No complications have been observed with Gepacef® administered at a daily dose of 12–16 g in 3 divided doses (8 hours apart). Treatment with the drug may be initiated before the results of susceptibility testing of microorganisms are available.

The recommended dose for uncomplicated gonococcal urethritis is 500 mg once (intramuscularly).

Intramuscular injection is performed deep into the gluteus maximus muscle or into the anterior surface of the thigh.

Combination therapy.

The broad spectrum of action of Gepacef® allows for monotherapy of most infections. However, the drug can also be used as part of combination therapy with other antibiotics, if indicated. During concomitant treatment with aminoglycosides, it is recommended to monitor renal function. Official recommendations for the use of antibiotics should be taken into account.

Patients with liver dysfunction.

Dosage adjustment may be necessary in cases of bile duct obstruction, severe liver disease, or concomitant renal impairment. If serum concentrations are not monitored, the dose should not exceed 2 g/day.

Patients with renal impairment.

Since the kidneys are not the main route of elimination of Gepacef®, the usual daily dose (2-4 g) can be administered without adjustment to patients with renal impairment. For patients with a glomerular filtration rate below 18 ml/min or a serum creatinine level above 3.5 mg/100 ml, the maximum daily dose is 4 g.

The half-life of Gepacef® from blood serum is slightly reduced during hemodialysis. The drug should be administered after the end of the dialysis procedure.

Patients with impaired liver function and concomitant renal impairment.

In patients with impaired liver function and concomitant renal impairment, serum drug concentrations should be monitored and the dose adjusted if necessary. If serum drug concentrations are not monitored, the dose should not exceed 2 g per day.

Children.

For the treatment of children, Gepacef® should be prescribed in daily doses of 50 to 200 mg per 1 kg of body weight; the dose is administered in 2 injections (every 8–12 hours). The maximum dose should not exceed 12 g per day (see section "Special instructions").

Daily doses of up to 300 mg/kg have been used to treat children with severe infections, including several patients with bacterial meningitis, which did not cause complications.

Newborns.

Newborns (up to 8 days old) should be given the drug every 12 hours.

Intravenous use in children and adults.

For intermittent intravenous infusion, 1 g of Gepacef® (contents of 1 vial) should be dissolved in 20–100 ml of a compatible sterile solution for intravenous injection and administered over 15 minutes to 1 hour. If the solvent is sterile water, no more than 20 ml should be added to the vial with the drug.

For direct intravenous injection, the maximum single dose of Gepacef® for adult patients is 2 g, for children - 50 mg/kg body weight. The drug should be dissolved in a suitable solvent to achieve a final concentration of 100 mg/ml and administered over at least 3-5 minutes.

For antibacterial prophylaxis of postoperative complications, 1 g or 2 g of the drug is administered intravenously 30–90 minutes before the start of the operation. The dose can be repeated every 12 hours, but in most cases - for no more than 24 hours. In operations with an increased risk of infection (for example, operations in the colorectal area) and when infection may be accompanied by severe complications (for example, during open heart surgery or joint replacement), prophylactic use of the drug can continue for 72 hours after the end of the operation.

Intravenous administration.

Sterile Hepacef® powder may be initially reconstituted with any compatible diluent (at least 2.8 ml/g cefoperazone) suitable for intravenous administration. To facilitate reconstitution, it is recommended to use 5 ml of diluent per 1 g of Hepacef®.

Solutions recommended for reconstitution of cefoperazone sodium powder: 5% glucose for injection; 10% glucose for injection; 5% glucose and 0.9% sodium chloride for injection; 0.9% sodium chloride for injection; Normosol-M and 5% glucose for injection; 5% glucose and 0.2% sodium chloride for injection; Normosol-R; sterile water for injection.

After reconstitution, the resulting solution should be diluted with one of the standard solvents for intravenous administration: 5% glucose for injection; 10% glucose for injection; 5% glucose and lactated Ringer's solution for injection; lactated Ringer's solution for injection; 0.9% sodium chloride for injection; 5% glucose and 0.9% sodium chloride; Normosol-M and 5% glucose for injection; Normosol-R; 5% glucose and 0.2% sodium chloride for injection.

Intramuscular injection

Sterile or bacteriostatic water for injection may be used to prepare a solution for intramuscular administration. If a solution with a concentration of 250 mg/ml or higher is to be administered, it is recommended to use lidocaine solution to prepare the solution. Such a solution may be prepared using a combination of sterile water for injection and 2% lidocaine hydrochloride solution, which is approximately equivalent to a 0.5% lidocaine hydrochloride solution.

A 2-step dissolution method is recommended: first add the required amount of sterile water for injection and shake until the Gepacef® powder is completely dissolved, then add the required amount of 2% lidocaine solution and mix.

Table 2

* The available surplus allows you to select and enter the specified volumes.

Intramuscular injection is performed deep into the gluteus maximus muscle or into the anterior surface of the thigh.

Storage of solutions

Stability

The chemical and physical stability of cefoperazone solutions prepared using the parenteral diluents listed below with the approximate concentrations of cefoperazone indicated ensures the stability of the solution under the specified temperature conditions and storage times. After the specified period, unused solution should be destroyed.

At stable room temperature (15–25°C) for 24 hours, cefoperazone solutions can be stored in the following solvents (approximate concentrations of cefoperazone are given in parentheses): bacteriostatic water for injection (300 mg/mL); 5% glucose for injection (2 mg to 50 mg/mL); 5% glucose for injection and lactated Ringer's solution for injection (2 mg to 50 mg/mL); 5% glucose and 0.9% sodium chloride for injection (2 mg to 50 mg/mL); 5% glucose and 0.2% sodium chloride for injection (2 mg to 50 mg/mL); 10% glucose for injection (2 mg to 50 mg/mL); lactated Ringer's solution for injection (2 mg/mL); 0.5% lidocaine hydrochloride for injection (300 mg/ml); 0.9% sodium chloride for injection (2 mg to 300 mg/ml); Normosol-M and 5% glucose for injection (2 mg to 50 mg/ml); Normosol-R (2 mg to 50 mg/ml); sterile water for injection (300 mg/ml). Reconstituted solutions of Gepacef® can be stored in glass or plastic syringes, glass or flexible plastic containers intended for parenteral solutions.

Solutions of cefoperazone in the following diluents (approximate concentrations of cefoperazone are given in parentheses) may be stored in a freezer (-20 to -10°C) for 3 weeks: 5% glucose for injection (50 mg/mL); 5% glucose and 0.9% sodium chloride for injection (2 mg/mL); 5% glucose and 0.2% sodium chloride for injection (2 mg/mL), or for 5 weeks: 0.9% sodium chloride for injection (300 mg/mL); sterile water for injection (300 mg/mL). Reconstituted solutions may be stored in plastic syringes or flexible plastic containers intended for parenteral solutions.

Thaw the product at room temperature before use. After thawing, any unused solution should be discarded. The solution should not be refrozen.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Children

See section "Method of administration and dosage".

Cefoperazone is effective in children from birth. Large-scale studies involving premature infants and newborns have not been conducted. Therefore, before prescribing cefoperazone to premature infants and newborns, the potential benefits and possible risks of therapy with this drug should be carefully weighed.

In newborns with kernicterus, cefoperazone does not displace bilirubin from its binding sites with blood plasma proteins.

Overdose

Data on the acute toxicity of cefoperazone sodium are limited. The expected manifestations of overdose with the drug are primarily an increase in the side effects characteristic of the drug. It should be taken into account that high concentrations of beta-lactam antibiotics in the cerebrospinal fluid can cause neurological effects and convulsions. Since cefoperazone is removed from the body by hemodialysis, this procedure may accelerate the elimination of the drug if overdose occurs in patients with impaired renal function.

Adverse reactions

The following are the adverse reactions that have been identified and reported during therapy with cefoperazone. The frequency of adverse reactions is indicated according to the classification of the Council of International Organizations for Medical Sciences (CIOMS III): very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency unknown (frequency cannot be estimated from the available data).

From the blood and lymphatic system: very often - decreased hemoglobin level, decreased hematocrit level; often - neutropenia, positive direct antiglobulin Coombs test, thrombocytopenia, eosinophilia; frequency unknown - hypoprothrombinemia; coagulopathy.

Immune system disorders: frequency unknown - anaphylactic shock, anaphylactic reaction, anaphylactoid reaction (including shock), hypersensitivity.

Vascular: often - phlebitis at the catheter connection site; rarely - hemorrhage.

Gastrointestinal: often - diarrhea; infrequently - vomiting; frequency unknown - pseudomembranous colitis.

Hepatobiliary disorders: often - increased ALT, AST, increased blood alkaline phosphatase, jaundice.

Skin and subcutaneous tissue disorders: common: pruritus, urticaria, maculopapular rash; frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis.

General disorders and administration site conditions: uncommon - pain at the injection site, fever.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after a medicinal product has been authorised. This allows for continued monitoring of the risk/benefit balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature of 2 to 8 °C.

Keep out of reach of children.

Packaging

1.0 g per vial, 10 vials per pack.

Vacation category

According to the recipe.

Producer

PJSC "Kyivmedpreparat".

Location of the manufacturer and its business address

Ukraine, 01032, Kyiv, Saksaganskoho St.