Onetazid

White crystalline powder, filled in clear glass sealed vials.
Each vial contains: Ceftazidime, USP (as pentahydrate) equivalent to Anhydrous Ceftazidime 1 g.

Pharmacotherapeutic group: Anti-bacterials for systemic use. Third-generation cephalosporins.
Pharmacology: Pharmacodynamics: Mechanism of action: Ceftazidime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
PK/PD relationship: For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval that the unbound concentration remains above the minimum inhibitory concentration (MIC) of Ceftazidime for individual target species (i.e. %T>MIC).
Mechanism of Resistance: Bacterial resistance to Ceftazidime may be due to one or more of the following mechanisms: Hydrolysis by beta-lactamases. Ceftazidime may be efficiently hydrolysed by extended-spectrum beta-lactamases (ESBLs), including the SHV family of ESBLs and AmpC enzymes that may be induced or stably derepressed in certain aerobic Gram-negative bacterial species.
Reduced affinity of penicillin-binding proteins for Ceftazidime.
Outer membrane impermeability, which restricts access of Ceftazidime to penicillin binding proteins in Gram-negative organisms.
Bacterial efflux pumps.
Pharmacokinetics: Absorption: After intramuscular administration of 500 mg and 1 g of ceftazidime, peak plasma levels of 18 and 37 mg/L respectively are achieved rapidly. Five minutes after intravenous bolus injection of 500 mg, 1 g or 2 g, plasma levels are 46, 87 and 170 mg/L, respectively. The kinetics of ceftazidime are linear within the single dose range of 0.5 to 2 g following intravenous or intramuscular dosing.
Distribution: The serum protein binding of Ceftazidime is low at about 10%. Concentrations in excess of the MIC for common pathogens can be achieved in tissues such as bone, heart, bile, sputum, aqueous humour, synovial, pleural and peritoneal fluids. Ceftazidime crosses the placenta readily, and is excreted in the breast milk. Penetration of the intact blood-brain barrier is poor, resulting in low levels of Ceftazidime in the CSF in the absence of inflammation. However, concentrations of 4 to 20 mg/L or more are achieved in the CSF when the meninges are inflamed.
Biotransformation: Ceftazidime is not metabolised.
Elimination: After parenteral administration plasma levels decrease with a half-life of about 2 hrs. Ceftazidime is excreted unchanged into the urine by glomerular filtration; approximately 80 to 90% of the dose is recovered in the urine within 24 hrs. Less than 1% is excreted via the bile.

For the treatment of suspected or documented susceptible Pseudomonas aeruginosa infections, and infections due to susceptible aerobic, gram-positive organisms, including lower respiratory tract, skin, soft tissue, abdominal, bone and joints, and urinary tract infections.

See Tables 1 and 2.

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Overdose can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment. Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal dialysis.

Hypersensitivity to Penicillin or Cephalosporins.

Hypersensitivity: As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with Ceftazidime must be discontinued immediately and adequate emergency measures must be initiated.
Pseudomembranous colitis: Antibacterial agent-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial agents, including Ceftazidime, and may range in severity from mild to life-threatening.
Renal function: Concurrent treatment with high doses of cephalosporins and nephrotoxic medicinal products such as aminoglycosides or potent diuretics (e.g., furosemide) may adversely affect renal function.
Overgrowth of non-susceptible organisms: Prolonged use may result in the overgrowth of non-susceptible organisms (e.g., Enterococci, fungi) which may require interruption of treatment or other appropriate measures. Repeated evaluation of the patient's condition is essential.

Patients with known hypersensitivity to penicillins.
Patients with a personal or familial history of allergy such as bronchial asthma, rash and urticaria.
Patients with severe renal dysfunction.
The elderly, patients with malnutrition, and those with disorder of general condition (Since vitamin K deficiency may occur, observe closely).
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation section for further information.
Use in the Elderly: Decrease dose in case of renal impairment.

Use with caution.
Use in pregnancy and nursing mothers: Because safety to pregnant women is not established, this drug should be used in these only if dearly needed.
Low concentrations of Ceftazidime are excreted in human milk. Caution should be exercised when it is administered to a nursing woman.

Gastrointestinal: diarrhea, abdominal pain, vomiting and nausea.
Hypersensitivity: rash, urticaria, pruritis, Stevens Johnson Syndrome.
Shock: may occur, especially in patients, who show hypersensitivity with this drug.
Hepatic: Slightly increase in SGOT, SGPT and alkaline phosphatase.
Renal: Slight increase in serum creatinine.
Central nervous system: headache or dizziness.
Hematology: Leukopenia, thrombocytopenia, eosinophilia, prolongation of prothrombin time (rarely).
Other: candidiasis, vaginitis.

With aminoglycoside or diuretic: Risk of nephrotoxicity.
Chloramphenicol causes antagonistic effect with Ceftazidime, therefore, concomitant use of these medications should be avoided.

Instruction for reconstitution: Ceftazidime may be used by IV, IM or infusion in 3-5 minutes.
Intramuscular Administration: Dissolve drug in Sterile Water for Injection or Lidocaine hydrochloride solution (0.5% or 1%) with concentration approximate 250 mg/mL.
Intravenous Administration: Dissolve drug in Sterile Water for Injection, Sodium chloride 0.9% or Dextrose 5% solution with concentration approximate 100 mg/mL.
Intravenously by infusion: Dissolve drug in Sterile Water for Injection, Sodium chloride 0.9% or Dextrose 5% solution with concentration approximate 10 mg-20 mg/mL.

Store at temperatures not exceeding 30°C. Protect from light and moisture.

Cephalosporins

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

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