Jurazidim (Ceftazidime)

Jurazidim (Ceftazidime)

Active substance (INN): ceftazidime.

ATC code: J01DA11

Pharmacotherapeutic group:

Antibiotics (group of cephalosporins).

Pharmacological properties

Cephalosporin antibiotic of III generation for parenteral administration. It acts bactericidally. The mechanism of action is caused by an ability of ceftazidime to disorder the synthesis of a cellular wall of microorganisms. It has a wide range of action. Resistant to action of majority of beta-lactamases. Ceftazidime is active to Gram-negative bacteria: Pseudomonas aeruginosa, Pseudomonas spp. (including Pseudomonas pseudomallei), Klebsiella spp. (including Klebsiella pneumoniae), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia spp, Escherichia coli, Enterobacter spp., Citrobacter spp., Serratia spp, Salmonella spp., Shigella spp., Yersinia enterocolitica, Pasteurella multocida, Acinetabacter spp., Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae (including Ampicillin-resistant strains); Gram-positive bacteria: Staphylococcus aureus (the strains sensitive to methicillin), Staphylococcus epidermidis (the strains sensitive to methicillin), Micrococcus spp., Streptococcus pyogencs (beta-hemolytic streptococcus of group A), Streptococcus groups B (Streptococcus agalactiae), Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp., (except for Streptococcus faecalis); anaerobic bacteria: Peptococcus spp., Peptostreptococcus spp.. Streptococcus spp., Propionibacterium spp., Clostridium perfringens, Fusobacterium spp., Bacteroides spp., (many strains of Bacteroides fragilis are resistant). Ceftazidime is not active to methicillin-resistant staphilococci, Streptococcus faecalis and many other Enterococci, Listeria monocytogenes, Campylobacter spp. and Clostridum difficile.

Pharmacokinetics

After the drug administration ceftazidime is distributed quickly in the body and reaches therapeutic concentration in the majority of tissues and bodily liquid media including synovial, pericardiac and peritoneal liquids, bile, sputum and urine. Ceftazidime is also distributed in bones, the myocardium, the gallbladder wall, the skin and soft tissues creating concentrations sufficient for treatment of infectious diseases. It passes through the placenta and releases into the breast milk. Ceftazidime permeates badly through the intact hematoencephalic barrier. In meningitis it is found in therapeutic concentration in the spinal liquid. Its binding (reversible) with plasma proteins makes 15%, a degree of binding with plasma proteins does not depend on the concentration. A bactericidal action is produced by ceftazidime in the unbound form. Following intramuscular drug administration in a dose of 500 mg and 1 g, Cmax is achieved in 1 hour and makes 17 mcg/ml and 39 mcg/ml respectively; in intravenous injection in the same doses of 42 mcg/ml and 69 mcg/ml. Therapeutic concentration of ceftazidime in blood plasma preserves for 8 to 12 hours, and the concentration of 4 mcg/ml is kept within 6 to 8 hours. Vd makes 0.21 to 0.28 l/kg. Ceftazidime also collects in soft tissues, kidneys, lungs, bones, joints and serous cavities. Ceftazidime is not metabolized.Ceftazidime is excreted unchanged with urinemainly via glomerular filtration. Т1/2 in patients with a normal renal function makes 1.8 hour. About 80 to 90% of the ceftazidime dose is excreted within 24 hours. Т1/2 in patients with disturbances of the renal function makes 2.2 hours.

Indications to use

Treatment of infectious and inflammatory diseases (mono or multi-infections) caused with drug-sensitive microorganisms:

  • severe infections (sepsis, hematosepsis, bacteriemia, peritonitis, meningitis, infections in patients with reduced immunity; infections in patients of intensive care units, e.g., infected burns);

  • infections of bones and joints (septic arthritis, osteomyelitis, bacterial bursitis);

  • respiratory infections (acute and chronic bronchitis, infected bronchiectases, pneumonias caused by Gram-negative microorganisms, lung abscess, pleural empyema);

  • infectionsof the urinary tracts (acute and chronic pyelonephritis, pyelitis, prostatitis, cystitis, urethritis/bacterial /renal abscess);

  • infections of the skin and soft tissues (mastitis, wound fevers, dermal ulcers, cellulites, erysipelas, infected burns);

  • infections of the gastrointestinal tract, bile ducts and abdominal cavity (peritonitis, coloenteritis, retroperitoneal abscesses, diverticulitis, inflammation of the small pelvis organs, cholecystitis, cholangitis, gallbladder empyema);

  • gynecologicinfections:

  • infections of the ear, throat and nose (otitis media, sinusitis, mastoiditis);

  • gonorrhea (especially in patients hypersensitive to penicillins).

  • infections due to hemodialysis and peritoneal dialysis as well as continuous out-patient peritoneal dialysis;

  • prevention of infectious complications in prostate surgery (transurethral resection).

Ceftazidime can be used without combination to other anti-infectives as the first choice drug until data on sensitivity of microorganisms are obtained. Ceftazidime can be used in combination with aminoglycosides and a majority of other antibiotics resistant to beta-lactamase effects. Ceftazidime can be used in combination with other antibiotics in anaerobic infections if the presence of Bacteriodes fragilis is suggested.

Administration and dosage

Ceftazidime is intended only for parenteral administration. A dose is determined individually depending on severity of a disease course, a kind of an originator, age, body weight and a renal function. The drug is administered intravenously or deep intramuscularly into the region of the top external quadrant of the greater cluneal muscle or into the region of the lateral part of the femur. A solution of ceftazidime can be injected directly into a vein or a tube of an infusional system. Adults are prescribed 1 to 6 g daily intravenously or intramuscularly; frequency rate of administration is 2-3 times a day. In infections of the urinary tracts 0.5-1 g each 12 hours is prescribed. In majority of infections the dose of 1 g each 8 hours or 2 g each 12 hours proves effective.In a severe course of a disease, especially in patients with lowered immunity including those with neutropenia, 2 g should be prescribed each 8 or 12 hours or 3 g each 12 hours. To patients with mucoviscidosis and pulmonary infections caused by pseudomonads the drug is prescribed in a dose of 100-150 mg/kg daily; a frequency rate of administration is 3 times daily. In severe or threatening to life infections the drug is administered intravenously 2 g each 8 hours. In infections of bones and joints the drug is prescribed intravenously 2 g each 12 hours. To prevent infectious complications in prostate surgery the drug is administered in a dose of 1 g prior to anesthesia induction. The second dose is administered during the catheter removal. The maximal daily dose for adults is 6 g. Considering lowered clearance of ceftazidime, elderly patients, especially those over 80, should be prescribed the drug in a dose of not more than 3 g daily. To children over 2 months the drug is prescribed in a dose of 30-100 mg/kg daily; a frequency rate of administration is 2-3 times a day. Children with lowered immunity and those with mucoviscidosis or meningitis should be prescribed about 150 mg/kg daily (maximum 6 g in a day); a frequency rate of injections is 3 times daily. Newborns and infants under 2 months should be prescribed a dose of 25-60 mg/kg a day; a frequency rate of injections is 2 times day. In adults with renal insufficiency (including patients on hemodialysis), the dose should be reduced after an initial loading dose of 1 g depending on creatinine clearance.

Creatinineclearance

Dose

Over 50 ml/mines
(0.83 ml/sec)

Mean recommended dose

35-50 ml/min
(0.52-0.83 ml/sec)

1 g each 12 hours

16-30 ml/min
(0.27-0.5 ml/sec)

1 g each 24 hours

6-15 ml/min
(0.1-0.25 ml/sec)

0.5 g each 24 hours

Less than 5 ml/mines
(0.08 ml/sec)

0.5 g each 48 hours

Patients on hemodialysis

1 g after each session

Patients on peritoneal dialysis

0.5 g each 24 hours

 

The doses given in the table are rough. This category of patients is recommended to monitor a level of ceftazidime in blood serum which should not exceed 40 mg/ml. A half-life period of ceftazidime during carrying out of hemodialysis makes 3-5 hours. A relevant drug dose should be repeated in the end of each dialysis procedure. In peritoneal dialysis the drug can be included into dialysis liquid in a dose of 125mi to 250 mg per 2 l of dialysis liquid. For intramuscular administration, 0.5 g of the drug is dissolved in 1.5 ml, 1.0 g in 3 ml of water for injections. For intravenous injection, 0.5 g of the drug is dissolved in 5.0 ml, 1.0 g in 10 ml of water for injections. To prepare an infusion solution, the solution obtained at dissolution of the drug is dissolved additionally in 50-100 ml of one of the solutions listed: a 0.9% isotonic solution of sodium chloride for injections, Ringer solution, 5 and 10% glucose (dextrose) solutions, a 5% solution of glucose with a 0.9% solution of sodium chloride. Only a fresh solution should be used for infusion.Side effect The alimentary system:diarrhea, nausea, vomiting, constipation, abdominal pains, transitional rise in a hepatic transaminase activity, LDG, GGT and AP; seldom: stomatitis, colitis (including pseudomembranous one). The hematopoietic system:eosinophilia, very rare: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, lymphocytosis. The central and peripheral nervous system:headaches, vertigo, paresthesias, disturbance of taste sensations; in patients with renal insufficiency wrong adjustment of a dose may result in tremor, cramps, encephalopathy. Allergic responses:rash, urticaria, fever, itching, eosinophilia; very seldom: bronchospasm, fall in BP, Quincke's disease; in some cases: multiform erythema, Stevens-Johnson's syndrome and toxic epidermal necrolysis. Local reactions: in intravenous injection: phlebitis, thrombophlebitis; in intramuscular administration: tenderness in the site of injection. Other:a positive Coombs test without hemolysis, transitional rise in the serum creatinine level. Effects caused by a biological action: superinfection (candidiasis, including that of vaginal mucosa).

Contraindications

Hypersensibility to ceftazidime, cephalosporins.

Drug interaction

In simultaneous administration of cephalosporin antibiotics with drugs producing nephrotoxic effects, probability of development of by-effects on kidneys, especially in patients with previous diseases of kidneys or impairment of their function, increases. It is not allowed to mix ceftazidime and aminoglycoside antibiotics in one container since it results in an appreciable mutual inactivation. Vancomycin is incompatible with ceftazidime due to sedimentation. If it is necessary to administer the drugs through one tube, a system or a device for an intravenous injection should be washed carefully. Caution should be used in simultaneous administration of the drug and loop diuretics.

Overdose

Symptoms:vertigo, paresthesias, headaches, cramps, deviations in results of laboratory tests. Treatment:if necessary, symptomatic therapy is undertaken, hemodialysis is effective in severe cases. No specific antidote is available.

Special warnings

Prior to the beginning of therapy with the use of ceftazidime it is necessary to establish that the patient has no history of hypersensibility responses to ceftazidime, cephalosporin antibiotics and penicillin or other drugs. Ceftazidime should be prescribed with extra care to patients with past history of allergic responses to penicillin antibiotics or other antibiotics resistant to an action of beta-lactamases. Should an allergic response to ceftazidime develop, the drug should be discontinued immediately. In development of hypersensitivity responses utilization of adrenaline, hydrocortisone, antihistamine drugs and carrying out of other emergency actions can be indicated. Long-term use of antibiotics of a wide spectrum of action including ceftazidime can result in increased growth in resistant microorganisms (for example, Candida Enterococcus), and discontinuation of treatment or carry out a relevant therapy may be required. During treatment it is necessary to evaluate the state of a patient continuously. Similar to utilization of other antibiotics of a wide spectrum of action from the group of penicillins and cephalosporins, some sensitive strains of Enterobacter can become resistance during treatment with ceftazidime. Therefore, if it is necessary, periodical testing of microorganism sensitivity should be carried out during treatment of infections caused with Enterobacter. In renal insufficiency ceftazidime doses are decreased in conformity with a degree of disturbance in the renal function. If doses are adjusted wrong, neurologic disturbances may occur. Ceftazidime does not affect results of enzymatic methods of glucose determination in urine, but to some extent it can influence results of tests with restoration of copper (Benedict, Felish, Cleanitest). Ceftazidime does not influence results of creatinine measurement in the test with alkaline phosphatase. Ceftazidime should be prescribed with especial caution and careful weighing of possible benefits and potential risks to patients with past history of bleedings and GIT diseases (especially in nonspecific ulcerative colitis). Utilization of cephalosporins decreases synthesis of vitamin K due to suppression of intestinal microflora. It can result in a fall in a level of vitamin K-dependent blood coagulation factors and in rare cases in prothrombinopenia and bleedings. A risk of development of bleedings rises considerably in elderly patients, in a severe general state or in weakened patients, in hepatic insufficiency and malnutrition. Utilization of ceftazidime during pregnancy and lactation is possible in cases when an expected benefit of therapy for mother exceeds a potential risk for a fetus. If it is necessary to prescribe the drug to newborns and children under 1 month, it is necessary to evaluate carefully an expected benefit and a potential risk of ceftazidime utilization.

Product form

Powder, 0.5 or 1.0 g in vials

Storage conditions

To be kept in a dry protected from light place at room temperature

Shelf life

3 years