Vicef^® (Powder) Instructions for Use

Marketing Authorization Holder

PFC Prebend, LLC (Russia)

ATC Code

J01DD02 (Ceftazidime)

Active Substance

Ceftazidime (Rec.INN registered by WHO)

Dosage Forms

	Vicef®	Powder for preparation of solution for intravenous and intramuscular administration 0.5 g: vial 1 or 5 pcs. in a set with solvent or without it
		Powder for preparation of solution for intravenous and intramuscular administration 1 g: vial 1 or 5 pcs. in a set with solvent or without it
		Powder for preparation of solution for intravenous and intramuscular administration 2 g: vial 1 or 5 pcs. in a set with solvent or without it

Dosage Form, Packaging, and Composition

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

Excipients: sodium carbonate.

Solvent: water for injections (5 ml).

Glass vials with a capacity of 10 ml (1) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (2) – cardboard packs.

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

Excipients: sodium carbonate.

Solvent: water for injections (5 ml).

Glass vials with a capacity of 10 ml (1) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (2) – cardboard packs.

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

Excipients: sodium carbonate.

Solvent: water for injections (5 ml).

Glass vials with a capacity of 10 ml (1) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Glass vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) – contour cell packs (1) – cardboard packs.
Glass vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (2) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Ceftazidime is an antibacterial drug from the group of third generation cephalosporins, has a broad spectrum and acts bactericidally, disrupts the synthesis of the microbial cell wall, and is resistant to the action of most beta-lactamases.

The drug is active against gram-negative microorganisms: Haemophilus influenzae, Neisseria gonorrhoeae and other Neisseria spp. and most representatives of the Enterobacteriaceae family (Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and other Klebsiella spp., Morganella morganii and other Morganella spp., Proteus mirabilis (including indole-positive), Proteus vulgaris and other Proteus spp., Providencia rettgeri and other Providencia spp. and Serratia spp.), Acinetobacter spp., Haemophilus parainfluenzae (including strains resistant to ampicillin), Pasteurella multocida, Salmonella spp., Shigella spp., Yersinia enterocolitica.

Ceftazidime has the highest activity among third generation cephalosporins against Pseudomonas aeruginosa and nosocomial infections.

The drug is active against gram-positive bacteria: Micrococcus spp., Streptococcus aureus, Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pyogenes group A, Streptococcus viridans and other Streptococcus spp. (excluding Streptococcus faecalis); strains sensitive to methicillin: Staphylococcus aureus, Staphylococcus epidermidis.

Ceftazidime is active against anaerobic bacteria: Bacteroides spp. (most strains of Bacteroides fragilis are resistant), Clostridium perfringens, Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.

The drug is not active against methicillin-resistant strains of Campylobacter spp., Chlamydia spp., Clostridium difficile, Enterococcus spp., Listeria monocytogenes and other Listeria spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis.

Pharmacokinetics

After administration, the drug is rapidly distributed in the human body and reaches therapeutic concentrations in most tissues and fluids, including synovial, pericardial and peritoneal fluid, as well as in bile, sputum and urine.

Distribution also occurs in bones, myocardium, gallbladder, skin and soft tissues in concentrations sufficient for the treatment of infectious diseases, especially during inflammatory processes that enhance drug diffusion.

It penetrates poorly through the intact blood-brain barrier, but the therapeutic level achieved by the drug in the cerebrospinal fluid is sufficient for the treatment of meningitis.

It reversibly binds to plasma proteins (less than 15%), and it has a bactericidal effect only in the free form. The degree of protein binding does not depend on concentration. C_max after intramuscular administration of 0.5 g or 1 g after one hour is 17 µg/ml and 39 µg/ml, respectively, after intravenous administration, respectively, 42 µg/ml and 69 µg/ml.

T_max after intramuscular administration is 1 hour, after intravenous administration – by the end of the infusion.

A drug concentration of 4 µg/ml is maintained for 6-8 hours.

The therapeutic concentration in blood plasma is maintained for 8-12 hours.

T_1/2 with normal renal function is 1.8 hours; with impaired function – 2.2 hours.

V_d is 0.21-0.28 l/kg.

The drug accumulates in soft tissues, kidneys, lungs, bones and joints, and serous cavities.

The drug is not metabolized in the liver; impaired liver function does not affect the pharmacodynamics and pharmacokinetics of the drug.

The dose in such patients remains usual.

It is excreted unchanged by the kidneys up to 80-90% (70% of the administered dose is excreted in the first 4 hours) within 24 hours by glomerular filtration and tubular secretion equally.

In case of impaired renal function, a dose reduction is recommended.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug

• Severe infections: meningitis, sepsis (septicemia), severe purulent-septic conditions;
• Bone and joint infections: septic arthritis, osteomyelitis, bacterial bursitis;
• Respiratory tract infections: acute and chronic bronchitis, infected bronchiectasis, pneumonia caused by gram-negative bacteria, lung abscess, pleural empyema;
• Urinary tract infections: acute and chronic pyelonephritis, pyelitis, prostatitis, cystitis, urethritis (only bacterial), kidney abscess;
• Skin and soft tissue infections: mastitis, wound infections, skin ulcers, phlegmon, erysipelas, infected burns;
• Gastrointestinal tract, abdominal cavity and biliary tract infections: peritonitis, enterocolitis, retroperitoneal abscess, diverticulitis, pelvic inflammatory disease, cholecystitis, cholangitis, gallbladder empyema;
• Female genital tract infections;
• Ear, throat, nose infections: otitis media, sinusitis, mastoiditis, etc.;
• Gonorrhea (especially with increased sensitivity to antibacterial drugs from the penicillin group).

ICD codes

Dosage Regimen

Intramuscularly (IM) and intravenously (IV).

The dose of the drug is set individually, taking into account the severity of the disease, the location of the infection and the sensitivity of the pathogen, age and body weight, and renal function.

Usual dose for adults and adolescents

For complicated urinary tract infections – IM or IV 250 mg every 12 hours; for uncomplicated pneumonia and skin infections IM or IV 500 mg-1 g every 8 hours; for cystic fibrosis, lung infections caused by Pseudomonas spp. from 30 to 50 mg/kg/day, frequency of administration – 3 times/day (use of a dose up to 9 g/day in such patients did not cause complications); for bone and joint infections IV 2 g every 12 hours; for extremely severe or life-threatening infections IV 2 g every 8 hours.

After an initial loading dose of 1 g, adults with impaired renal function (including patients undergoing dialysis) may require a dose reduction as indicated below

These indicators are approximate.

In such patients, it is recommended to monitor the drug level in the serum, which should not exceed 40 mg/l.

T_1/2 of the drug during hemodialysis is 3-5 hours.

The appropriate dose of the drug should be repeated after each dialysis period.

During peritoneal dialysis, Vicef^® can be included in the dialysis fluid at a dose of 125 mg to 250 mg per 2 liters of dialysis fluid.

Usual dose for children

Children under 1 month of age – IV infusion 30 mg/kg per day (frequency – 2 administrations).

Children from 2 months to 12 years – IV infusion 30 – 50 mg/kg per day (frequency – 3 administrations).

A dose of up to 150 mg/kg/day every 12 hours is prescribed for children with reduced immunity, cystic fibrosis, meningitis. The maximum daily dose for children should not exceed 6 g.

Preparation of solutions

2. Secondary dilution

For IV drip administration, the solution of the drug Vicef^® obtained by the method described above is additionally diluted in 50-100 ml of one of the following solvents intended for IV administration: 0.9% sodium chloride solution, Ringer’s solution, 5%, 10% glucose (dextrose) solution, 5% glucose (dextrose) solution with 0.9% sodium chloride solution, 5% sodium bicarbonate solution.

Use only freshly prepared solution

Adverse Reactions

Allergic reactions urticaria, chills or fever, rash, itching; rarely – bronchospasm, eosinophilia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), angioedema, anaphylactic shock.

From the digestive system : nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, dysbacteriosis, cholestasis; rarely – stomatitis, glossitis, pseudomembranous enterocolitis.

From the hematopoietic organs leukopenia, neutropenia, granulocytopenia, thrombocytopenia, hemolytic anemia, hypocoagulation.

From the urinary system toxic nephropathy (azotemia, increased blood urea), oliguria, anuria.

From the central and peripheral nervous system headache, dizziness, paresthesia, convulsive seizures, encephalopathy, “flapping” tremor.

From laboratory parameters increased activity of hepatic transaminases, alkaline phosphatase; hypercreatininemia, false-positive direct Coombs test, hyperbilirubinemia, false-positive urine reaction for glucose, increased prothrombin time.

Local reactions phlebitis, pain along the vein, pain and infiltration at the site of IM injection.

Other nosebleed, candidal vaginitis, superinfection.

Contraindications

• Hypersensitivity to cephalosporins and penicillins.

With caution patients with a history of allergic reactions to penicillins, since there is a possibility of cross-hypersensitivity between penicillins and cephalosporins; in case of impaired renal function and renal failure; with a history of nonspecific ulcerative colitis, antibiotic-associated (pseudomembranous) colitis; patients with malabsorption syndrome (increased risk of decreased prothrombin activity, especially in persons with severe renal and/or hepatic insufficiency); neonatal period, pregnancy.

Use in Pregnancy and Lactation

Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution patients with severe hepatic insufficiency.

Use in Renal Impairment

After an initial loading dose of 1 g adults with impaired renal function (including patients undergoing dialysis), a dose reduction may be required, as indicated below

These figures are approximate. In such patients, it is recommended to monitor the drug level in the serum, which should not exceed 40 mg/l.

T_1/2 of the drug during hemodialysis is 3-5 hours. The appropriate dose of the drug should be repeated after each dialysis period. During peritoneal dialysis, the drug Vicef^® can be included in the dialysis fluid at a dose of 125 mg to 250 mg per 2 liters of dialysis fluid.

After an initial loading dose of 1 g adults with impaired renal function (including patients undergoing dialysis), a dose reduction may be required, as indicated below

These figures are approximate. In such patients, it is recommended to monitor the drug level in the serum, which should not exceed 40 mg/l.

T_1/2 of the drug during hemodialysis is 3-5 hours. The appropriate dose of the drug should be repeated after each dialysis period. During peritoneal dialysis, the drug Vicef^® can be included in the dialysis fluid at a dose of 125 mg to 250 mg per 2 liters of dialysis fluid.

Pediatric Use

With caution use the drug in the neonatal period.

Children under 1 month of age – IV infusion 30 mg/kg per day (frequency 2 administrations).

Children from 2 months to 12 years – IV infusion 30 – 50 mg/kg per day (frequency 3 administrations).

A dose of up to 150 mg/kg/day every 12 hours is prescribed for children with reduced immunity, cystic fibrosis, meningitis. The maximum daily dose for children should not exceed 6 g.

Special Precautions

If diarrhea occurs during treatment with Vicef^®, caution should be exercised due to the possible development of pseudomembranous colitis. If the diagnosis of antibiotic-associated diarrhea or pseudomembranous colitis is established, administration of Vicef^® should be discontinued immediately and appropriate treatment should be prescribed. In mild cases, drug withdrawal is sufficient; in more severe cases, restoration of water-electrolyte and protein balance is recommended; if these measures do not help, metronidazole, bacitracin, vancomycin are prescribed.

As with the use of other antibiotics, the use of Vicef^® may lead to colonization with non-susceptible microflora and the development of superinfection.

Overdose

Administration of inadequately high doses of the drug Vicef^® may cause dizziness, paresthesia, headache, convulsive seizures.

Treatment since there is no specific antidote, treatment of overdose with cephalosporin antibiotics is symptomatic and supportive. In case of severe overdose, when conservative therapy is unsuccessful, the concentration of the drug in the blood can be reduced by hemodialysis.

Drug Interactions

Pharmaceutically incompatible with aminoglycosides, heparin, vancomycin. Sodium bicarbonate solution should not be used as a solvent.

Loop diuretics, aminoglycosides, vancomycin, clindamycin reduce the clearance of ceftazidime, thereby increasing the risk of nephrotoxic action.

Pharmaceutically compatible with the following solutions: at concentrations from 1 to 40 mg/ml sodium chloride 0.9%, sodium lactate, Hartmann’s solution, dextrose 5%, sodium chloride 0.225% and dextrose 5%, sodium chloride 0.45% and dextrose 5%, sodium chloride 0.9% and dextrose 5%, sodium chloride 0.18% and dextrose 4%, dextrose 10%, dextran 40 10% in sodium chloride solution 0.9%, dextran 40 10% in dextrose solution 5%, dextran 70 6% in sodium chloride solution, dextran 70 6% in dextrose solution 5%. At concentrations from 0.05 to 0.25 mg/ml Ceftazidime is compatible with intraperitoneal dialysis solution (lactate).

For IM administration, Ceftazidime can be diluted with 0.5% or 1% lidocaine hydrochloride solution. Both components retain activity if Ceftazidime is added to the following solutions (ceftazidime concentration 4 mg/ml): hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in sodium chloride 0.9% solution or dextrose 5% solution, cefuroxime (cefuroxime sodium) 3 mg/ml in sodium chloride 0.9% solution, cloxacillin (cloxacillin sodium) 4 mg/ml in sodium chloride 0.9% solution, heparin 10 IU/ml or 50 IU/ml in sodium chloride 0.9% solution, potassium chloride 10 mEq/L or 40 mEq/L in sodium chloride 0.9% solution. When mixing a solution of ceftazidime (500 mg in 1.5 ml of water for injections) and metronidazole (500 mg/100 ml), both components retain their activity.

Storage Conditions

List B. In a dry place, protected from light, at a temperature not exceeding 25°C (77°F).

Keep out of the reach of children.

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

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.