Tazidem

Ceftazidime pentahydrate.

Each vial contains Ceftazidime (as pentahydrate) with sodium carbonate, USP 1g.

Pharmacology: Pharmacokinetics: Ceftazidime is given by injection as the sodium salt or in solution with arginine. Mean peak plasma concentrations of 17 and 39 mcg/mL have been reported about 1 hour after intramuscular doses of 0.5 and 1g of ceftazidime, respectively. Five minutes after intravenous bolus injections of 0.5, 1, and 2g of ceftazidime, mean plasma concentrations of 45, 90, and 170 mcg/mL, respectively, have been reported. The plasma half-life of ceftazidime is about 2 hours, but this is prolonged in patients with renal impairment and in neonates. Clearance may be enhanced in patients with cystic fibrosis. It is about 10% bound to plasma proteins.
Ceftazidime is widely distributed in body tissues and fluids; therapeutic concentrations are achieved in the CSF when the meninges are inflamed. It crosses the placenta and is distributed into breast milk.
Ceftazidime is passively excreted in bile, although only a small proportion is eliminated by this route. It is mainly excreted by the kidneys, almost exclusively by glomerular filtration; probenecid has little effect on the excretion. About 80 to 90% of a dose appears unchanged in the urine within 24 hours. It is removed by haemodialysis and peritoneal dialysis.

Susceptible organisms: Methicillin-susceptible Staphylococcus aureus, Methicillin-susceptible Staphylococcus epidermidis, Micrococcus, Streptococcus pyogenes (Group A beta (β) hemolytic), Streptococcus agalactiae (Group B), Streptococcus viridans, Streptococcus (Except Enterococcus), Streptococcus pneumoniae, Pseudomonas spp. (Pseudomonas aeruginosa), Klebsiella spp (Klebsiella pneumonia, etc.), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Proteus Providencia rettgeri, Providencia, Escherichia coli, Enterobacter spp., Citrobacter spp., Serratia spp., Salmonella spp., Shigella spp., Yersinia enterocolitis, Pathogenic bacterium of animal pasteurellosis, Acinetobacter, Neisseria gonorrhoeae, Neisseria meningitidis, Hemophilus influenzae (including Ampicillin-resistant strains), Parainfluenza virus (including Ampicillin-resistant strains), Peptococcus, Peptostreptococcus, Propionibacterium, Clostridium perfrigens, Fusobacterium, Bacteroid (except Bacteroides fragilis).
Uses: Sepsis, Meningitis; Pneumonia, Pleuritis, Emphysema, Pulmonary abscess, Bronchiectasis (in infection), Bronchitis, Pulmonary infection in patients with cystic fibrosis; Otitis media, Malignant external otitis, Mastoiditis, Sinusitis, Severe infection in ear or throat part; Pyelonephritis, Prostatitis, Cystitis, Urethritis; Erysipelas, Abscess, Secondary infection after trauma or burn, Mastitis, Dermal ulcer; Cholangitis, Cholecystitis, Empyema of gallbladder, Intra-abdominal abscess, Peritonitis, Diverticulitis, Enterocolitis, Pelvic infection; Osteomyelitis, Ostitis, Septic arthritis, Infectious bursitis; Severe infections in the immunocompromised patient, Severe infection including burn infection, Infection due to hemodialysis or Intraperitoneal dialysis, Infection associated with CAPD.

This drug is administered by intravenous injection/infusion or intramuscularly. Dosage depends upon the severity of infection, condition and upon the age, body weight and renal function of the patient.
The guidelines for amount of diluents are listed in Table: (See Table 1.)

Click on icon to see table/diagram/image

Ceftazidime is less stable in Sodium bicarbonate Injection than in other IV fluids. It is not recommended as a diluent.
Adult: The usual adult dosage is 0.5g to 2g administered intravenously or intramuscularly 2 or 3 times daily. In most infections, 1g is administered intravenously or intramuscularly every 8 hours or 2g is administered every 12 hours.
Urinary tract infections or moderate infection: The usual adult dosage is 0.5g to 1g administered intravenously or intramuscularly every 12 hours.
Very severe infections particularly in immunocompromised patients including those with neutropenia: 2g is administered intravenously or intramuscularly every 8 hours to 12 hours.
Cystic fibrosis: In Fibrocystic adults with pseudomonal lung infections, 100-150 mg/kg/day in 3 divided doses. In adults with normal renal function 9g/day has been used without ill effect.
Infants and Children (≥2 months): 30-100 mg/kg/day in 2 or 3 divided doses. Doses up to 150 mg/kg/day (maximum 6g/day) in three divided doses may be given to infected immunocompromised or fibrocystic children or children with meningitis.
Neonates (0-2 months: 25-60 mg/kg/day in 2 divided doses. In neonates the serum half life of ceftazidime can be 3-4 times that in adults.
Use in the Elderly: In view of the reduced clearance of ceftazidime in acutely ill elderly patients, the daily dosage should not normally exceed 3g, especially in those over 80 years of age.
Impaired Renal Function: In patients with impaired renal function (glomerular filtration rate [GFR] <50 mL/min), it is recommended that the dosage of ceftazidime be reduced to compensate for its slower excretion. In patients with suspected renal insufficiency, an initial loading dose of 1g of Ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dosage. The recommended dosage is presented in Table: (See Table 2.)

Click on icon to see table/diagram/image

The previously mentioned table as guideline could not be applied to every patient. Particularly in elderly patients, renal function could be overestimated with serum creatinine value. In patient who is receiving 6g/day with neutropenia, the unit dose should be increased by 50% or the dosing frequency increased. In such patients, the ceftazidime serum levels should be monitored and trough levels should not exceed 40 mg/L. When only serum creatinine is available, the following formula may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function: Males: (See equation.)

Click on icon to see table/diagram/image

Females: 0.85 x male value.
In children the creatinine clearance should be adjusted for body surface area or lean body mass.
The serum half-life during haemodialysis ranges from 3 to 5 hours. Following each haemodialysis period the maintenance dose of ceftazidime should be repeated.
Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD). In addition to intravenous use, ceftazidime can be incorporated into the dialysis fluid (usually 125 to 250mg for 2 litres of dialysis solution).

Symptoms: Neurological disorder such as degenerative brain disease, convulsion or coma may occur.
Treatment: Hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body.

Patients with known shock to this drug.
Patients with known hypersensitivity to the cephalosporin group of antibiotics.
The drug should be administered with caution in the following patients:
Patients with a history of hypersensitivity to the drug or cephalosporin antibiotics, but if necessary, the drug can be given with caution.
Patients with a history of hypersensitivity to penicillin-group antibiotics or β-lactam antibiotics.
Patients whose family are susceptible to cause the allergic symptoms such as bronchial asthma, eruption and urticaria, etc.
Patients with severe renal disorder.
Patients who cannot ingest orally, or parenteral patients, elderly patients, patients with systemic bad condition (because avitaminosis K may occur, they should be sufficiently observed).

Prior to the administration, susceptibility to the drug should be tested to prevent manifestation of resistant bacteria, and the duration of therapy should be the minimum needed for the treatment.
Patients should be asked about their condition in order to predict the reaction such as shock and also their previous skin reaction should be tested.
First aid (against anaphylactic shock) should be prepared. After the administration, patient should be observed in a stable state. In the occurrence of allergic reaction, administration should be immediately discontinued. In severe case appropriate therapy such as epinephrine, hydrocortisone or antihistamine is instituted.
Prolonged use of this drug may result in overgrowth of insusceptible bacteria (Candida, Enterococcus).
Although this drug does not inhibit a renal function on the therapeutic dose, it is excreted by the kidney. Therefore, the dose should be appropriately reduced if patients have renal disorder. Neurologic secondary disease has been reported in patients without appropriate dose control.
Prior to this therapy, history of hypersensitivity to Ceftazidime, Cephalosporins, Penicillins and other drugs should be checked.
Like other broad spectrum Cephalosporins or Penicillins, tolerance to susceptible strain such as Enterobacter spp., Serratia spp. should be considered during this therapy.
Use in children: Safety has not been established in premature and newborn.
Use in elderly: In elderly patients, care should be taken in dose selection and patients should be carefully monitored.
1) Because elderly patients are more likely to have decreased renal function, this risk of adverse reactions may be greater.
2) Due to Vitamin K deficiency, bleeding tendency may occur.

Pregnancy: The safety of the use in pregnancy has not been established, therefore the drug should be used during pregnancy only if the expected benefits clearly outweigh the potential risks.
Lactation: Ceftazidime is excreted in human milk. Caution should be exercised when Ceftazidime is administered to a nursing woman.

Shock: Rarely shock may occur, should therefore be observed. In the occurrences of dysphoria, mouth allesthesia, wheezing, dizziness, tinnitus or perspiration, the administration should be discontinued and/or appropriate therapy should be instituted.
Hypersensitivity: In the occurrences of rash (erythema, wheal), fever, rarely urticaria, erythema, pruritus, macula, papular erythema, angioedema or anaphylaxis (bronchospasm, hypotension), the administration should be discontinued and/or appropriate therapy should be instituted.
Gastrointestinal: Rarely severe colitis causing hemofecia including pseudomembranous colitis may occur. If abdominal pain and frequent diarrhea occur, appropriate therapy should be instituted such as discontinuance of the administration. Occasionally nausea, vomiting, diarrhea or rarely anorexia, abdominal pain, dry mouth and thrush may also occur.
Respiratory: In the administration of other cephalosporin series antibiotics, interstitial pneumonia accompanying with fever, cough, dyspnea, disorder of chest X-ray and eosinophilia, and PIE syndrome may rarely occur. In the events of symptoms, the administration should be discontinued and/or appropriate therapy including the administration of adrenocortical hormone should be instituted.
Hematologic: Occasionally granulocytopenia, eosinophilia, thrombocytosis, rarely panhematopenia, leukocytopenia, agranulocytosis, hemolytic anemia, lymphocytosis, anemia, neutropenia, thrombocytopenia may occur.
CNS: Occasionally headache, dizziness, rarely paresthesia and dysgeusia may occur. In case that dose is not appropriately reduced to patients who have renal failure, convulsion, tremor, myoclonia or degenerative brain disease may occur.
Skin: Rarely erythema multiforme, Stevens-Johnson syndrome (muco-cutaneous-ocular syndrome) and toxic epidermal necrolysis may occur.
Hepatic: Rarely jaundice, occasionally elevation in liver enzyme value such as ALT, AST, ALP, LDH or γ-GTP (GGT) may occur.
Renal: Occasionally transient elevation of urea in blood and blood urea nitrogen (BUN) and serum creatinine may occur. Rarely severe renal disorder including acute renal failure may occur. Therefore careful observation including periodic examination is required. In the occurrence of adverse reaction, administration should be discontinued and/or appropriate therapy should be instituted.
Reproductive system: Occasionally vaginitis may occur.
Superinfection: Rarely candidiasis and stomatitis may occur.
Avitaminosis: Rarely avitaminosis K (e.g. Hypoprothrombinemia, bleeding tendency) and avitaminosis B group (e.g. glossitis, stomatitis, anorexia, neuritis) may occur.
Others: Phlebitis and thrombotic phlebitis may occur in intravenous injection. Pain and infection may occur in intramuscular injection.

If high dose of cephalosporin is concurrently used with antibiotics such as aminoglycoside or diuretics such as furosemide, renal disorder may be increased. Through clinical experience, it is not considered to make a problem with the recommended dose. There is no evidence to negative effect on renal function in the normal therapeutic dose.
If this drug is concurrently used with chloramphenicol, the possibility of counteraction should be considered.
Like other antibiotics, it may reduce reabsorption rate of estrogen or may reduce effect of oral contraceptives.
Laboratory Test Interferences: Ceftazidime reportedly cause false-positive results in urine glucose determinations using Benedict's reagent, Clinitest, Fehling's solution; however, the glucose determination using Tes-Tape are unaffected by the drug.
Positive direct antiglobulin (Coombs') test results may appear; therefore, it should be cautioned.
This drug may impact on creatinine test using picrate alkali-method.

Cautions on application: 1) A large volume of intravenous administration may cause rarely angioalgia, thrombophlebitis. The preparation of injectable solution, sites and methods of injection are considered with caution and administration should be done as slowly as possible (I.V.).
2) Vancomycin solution exhibits a physical incompatibility when mixed with a number of drugs, including ceftazidime. The likelihood of precipitation with ceftazidime is dependent on the concentrations of vancomycin and ceftazidime present. It is therefore recommended, when both drugs are to be administered by intermittent IV infusion, that they be given separately, flushing the IV lines (with 1 of the compatible IV fluids) between the administration of these 2 agents.
3) All vials of this drug as supplied are under reduced pressure. When ceftazidime is dissolved, carbon dioxide is released and a positive pressure develops.
4) Sodium bicarbonate injection is not used as a diluent.
5) Solutions of this drug should not be added to solutions of aminoglycoside antibiotics.
6) Distal necrosis can occur after inadvertent intra-arterial administration of ceftazidime.
Caution on storage: After reconstitution, this drug is used within 6 hours at temperatures not exceeding 30°C or within 72 hours under refrigeration (2-8°C).
Others: In domestic studies (2001), tolerance to this drug has been reported in 9% of Escherichia coli, 27% of Klebsiella pneumoniae, 44.0% of Enterobacter cloacae, 26% of Serratia marcescens, 21% of Pseudomonas aeruginosa and 65% of Acinetobacter.

Store at temperatures not exceeding 30°C.
Shelf-life: 24 months.

Cephalosporins

J01DD02 - ceftazidime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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