COMPOSITION :
Ceftazidime pentahydrate Powder for Injection 1 g, each vial contains : Ceftazidime pentahydrate with Sodium carbonate equivalent to Ceftazidime 1 g.
DESCRIPTIONS :
Ceftazidime pentahydrate contains Ceftazidime pentahydrate with Sodium carbonate (equivalent to Ceftazidime) available in powder for injection 1 g.
INDICATIONS :
For the treatment of serious infections caused by susceptible organism.
Because of its broad antibacterial spectrum, Ceftazidime may be used alone in emergency cases pending sensitivity test results. In meningitis, it is recommended that the results of a sensitivity test are known before treatment with Ceftazidime as a single agent.
Ceftazidime may be used for infections caused by organisms resistant to other antibiotics, including Aminoglycosides and many Cephalosporins. When appropriate, however, it may be used safely in combination with an Aminoglycoside or other β-lactam antibiotic for example in the presence of severe neutropenia or with an antibiotic active against anaerobes when the presence of Bacteroides fragilis is suspected (see Precautions). Indications include severe infection as follows :
- In general : Septicaemia, bacteremia, peritonitis, meningitis, infections in immunosuppressed patients with haemotological or solid malignancies and in patients in ICU with spesific problems for example, infected burns.
- Lower respiratory tract infections : Pneumonia, bronchopneumonia, infected pleurisy, empyema, lung abscess, infected bronchiectasis and in lung infections in patients with cystic fibrosis.
- Urinary tract infections : Acute and chronic pyelonephritis, pyelitis, prostatitis and renal abscess.
- Skin and soft tissue infections : Erysipelas, abscesses, cellulitis, infected burns and wounds, mastitis, skin ulcers.
- Biliary and abdominal infections : Cholangitis, cholecystitis, empyema of gallbladder, intra-abdominal abscesses, peritonitis, diverticulitis and pelvic inflammatory disease.
- Bone and joint infections : Osteitis, osteomyelitis, septic arthritis, infected bursitis.
- Dialysis : Infections associated with haemo- and peritoneal dialysis and with Continuous Ambulatory Peritoneal Dialysis (CAPD).
DOSAGE AND ADMINISTRATIONS :
Dosage :
Ceftazidime is to be used by the parenteral route, the dosage depending upon the severity, sensitivity and type of infection and the age, weight and renal function of the patient.
- Adults :
The adult dosage range for Ceftazidime is 1 to 6 g per day, for instance, 500 mg, 1 g or 2 g given 12 or 8-hourly by IV or IM injection. In urinary tract infections and in many less serious infections, 500 mg or 1 g 12 hourly is usually adequate. In the majority of infections, 1 g 8-hourly or 2 g 12-hourly should be given. In very severe infections, 2 g 8 or 12 hourly should be administered. Individual doses in excess of 1 g should be administered intravenously. In very severe infections, especially in immunocompromised patients, including those with neutropenia, 2 g 8 or 12-hourly should be administered.
- Cystic fibrosis :
In fibrocystic adults with normal renal function who have pseudomonal lung infections, high doses of 100 – 150 mg/kgBW/day in 3 divided doses should be used. In adult with normal renal function, 9 g/day has been used safety.
- Infants and children :
The usual dosage range for children aged over 2 months is 30 to 100 mg/kgBW/day, given as two or three divided doses. Doses up to 150 mg/kgBW/day (maximum 6 g daily) in three divided doses may be given to infected immunocompromised or fibrocystic children or children with meningitis.
- Neonates and infants up to 2 months of age :
A dose of 25 to 60 mg/kgBW/day given as two divided doses has proved to be effective. In neonate the serum half-life of Ceftazidime can be 3 or 4 times that in adults.
- Dosage in impaired renal function :
Ceftazidime is excreted by the kidneys almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function it is recommended that the dosage of Ceftazidime should be reduced to compensate for its slower excretion, except in mild impairment, i.e., glomerular filtration rate (GFR) > 50 ml/minute. In patients with suspected renal insufficiency, an initial loading dose of 1 g of Ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose. Recommended maintenance doses are shown below :
RECOMMENDED MAINTENANCE DOSES OF CEFTAZIDIME
IN RENAL SUFFICIENCY
| Creatinine
clearance (ml/min) |
Serum creatinine* µmol/l (mg/dl) | Recommended
Unit dose of Ceftazidime (gram) |
Frequency of administration
(hourly) |
| 50 – 31
30 – 16 15 – 6 < 5 |
150 – 200 (1.7 – 2.3)
200 – 350 (2.3 – 4) 350 – 500 (4 – 5.6) > 500 (> 5.6) |
1.0
1.0 0.5 0.5 |
12
24 24 48 |
*These values are guide-lines and may not accurately predict renal function in all patients especially in the elderly in whom the serum creatinine concentration may overestimate renal function.
In patients with severe infections, especially in neutropenics who would normally receive 6 g of Ceftazidime daily, were it not for renal insufficiency, the unit dose given in the table above may be increased by 50% or the dosing frequency increased appropriately. In such patients it is recommended that Ceftazidime serum levels should be monitored and trough levels should not exceed 40 mg/l.
When only serum creatinine is available, the following formula (Cockcroft’s equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function :
Males :
Weight (kg) x (140 – age in years)
Creatinine clearance = ——————————————————
(ml/minute) 72 x serum creatinine (mg/dl)
Females : 0.85 x above value.
To convert serum creatinine in micromole/litre into mg/dl, divided by 88.4.
In children the creatinine clearance should be adjusted for body surface area or lean body mass and the dosing frequency as for adults.
The serum half-life of Ceftazidime during hemodialysis ranges from 3 – 5 hours. The appropriate maintenance dose of Ceftazidime should be repeated following each hemodialysis period.
- Peritoneal dialysis :
Ceftazidime may also be used in peritoneal dialysis and Continuous Ambulatory Peritoneal Dialysis (CAPD). As well as using Ceftazidime IV, it can be incorporated into dialysis fluid (usually 125 – 250 mg for 2 litre of dialysis fluid).
Administration :
Ceftazidime may be given intravenously or by deep intramuscular injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.
Preparation of solution :
IM administration : For 1 g vial, adding 3 ml water for injection.
IV administration : For 1 g vial, adding 10 ml water for injection.
OVERDOSAGE :
Serum levels of Ceftazidime are reduced by dialysis.
CONTRAINDICATION :
Known hypersensitivity to Cephalosporin antibiotics.
WARNINGS AND PRECAUTIONS :
Warnings :
- Careful inquiry should be made for a history of hypersensitivity reactions to Ceftazidime, Cephalosporins, Penicillins, or other drugs.
- Ceftazidime should be given only with special caution to patients with mild type I or immediate hypersensitivity reactions to Penicillin.
- If an allergic reaction to Ceftazidime occurs, discontinue the drug.
- Serious hypersensitivity reactions may require Epinephrine (Adrenaline), Hydrocortisone, antihistamine or other emergency measures.
Precautions :
- High doses of Cephalosporins should be given with caution when administered concurrent with nephrotoxic drugs as Aminoglycoside antibiotics or potent diuretic such as Furosemide, since the combinations are suspected of affecting renal function adversely.
- For all antibiotics eliminated via the kidneys, it is necessary to reduce the dosage according to the degree of reduction in renal function to avoid the clinical consequences of elevated antibiotic levels e.g., convulsions.
- Ceftazidime does not interfere with enzyme-based tests for glycosuria. Slight interference with copper reduction methods (Benedict’s, Fehling’s, Clinitest) may be observed. Ceftazidime does not interfere in the alkaline picrate assay for creatinine.
- The development of a positive Coombs’ test associated with the use of Ceftazidime in about 5% of patients may interfere with the cross-matching of blood.
- Prolonged use of Ceftazidime may result in the overgrowth of nonsusceptible organisms (e.g., Candida, Enterococci) which may require interruption of treatment or adoption of appropriate measures.
- Use in pregnancy and lactation : Should be administered with caution during the early months of pregnancy and in early infancy. Use in pregnancy requires that the anticipated benefit be weighed against the possible risks. Ceftazidime is excreted in human milk in low concentrations and consequently, caution should be exercised when Ceftazidime is administered to a nursing mother.
Pharmaceutical Precautions :
- Solutions of Ceftazidime for injection retain satisfactory potency for 18 hours if store below 25°C or for 7 days if refrigerated (2 – 8)°C. Some increase in the colour of prepared solutions of Ceftazidime for injection may occur during storage.
- Ceftazidime and Aminoglycosides should not be mixed in the same giving set or syringe.
- Precipitation has been reported when Vancomycin has been added to Ceftazidime in solution.
DRUG INTERACTION :
Concomitant administration of nephrotoxic drugs.
ADVERSE REACTIONS :
- Local : Phlebitis or thrombophlebitis with IV administration; pain and/or inflammation after IM injection.
- Hypersensitivity : Maculopapular or urticarial rash, fever, pruritus and very rarely angioedema and anaphylaxis (including bronchospasm and/or hypotension).
- Gastrointestinal : Diarrhea, nausea, vomiting, abdominal pain and very rarely oral thrush or colitis.
Other adverse events which may be related to Ceftazidime therapy or of uncertain aetiology include :
- Genito-urinary : Candidiasis, vaginitis.
- Central nervous system : Headache, dizziness, paraesthesia and bad taste. There have been a few reports of convulsions occurring in patients with renal impairment in whom the dose of Ceftazidime has not been appropriately reduced.
- Laboratory test changes noted transiently during Ceftazidime therapy include : Eosinophilia, positive Coombs’ test without hemolysis, thrombocytosis and slight elevations in one or more of the hepatic enzymes, SGOT, SGPT, LDH, GGT and alkaline phosphatase.
- As with some other Cephalosporins, transient elevation of blood urea, blood urea nitrogen and/or serum creatinine have been observed occasionally. Very rarely, transient leucopenia, neutropenia, thrombocytopenia and lymphocytosis have been seen.
PRESENTATION :
Ceftazidime pentahydrate Powder for Injection 1 g Box, 10 vial @ 1 g
Reg. No. GKL1402350044A1
STORAGE :
STORE BELOW 25ºC AND DRY PLACE, PROTECT FROM LIGHT
Solutions of Ceftazidime for injection retain satisfactory potency for 18 hours if store below 25ºC or 7 days if refrigerated (2 – 8)ºC, residual of solutions should be disposed.
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
