Ceftazidime

Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with impaired renal function, the dosage should be reduced.

An initial loading dose of 1 g should be given. Maintenance doses should be based on creatinine clearance:

Table 3. Recommended maintenance doses of Ceftazidime in renal impairment – intermittent infusion:

Adults and children ≥40 kg:

In patients with severe infections the unit dose should be increased by 50% or the dosing frequency increased.

In children the creatinine clearance should be adjusted for body surface area or lean body mass.

Children <40 kg:

* The serum creatinine values are guideline values that may not indicate exactly the same degree of reduction for all patients with reduced renal function.
** Estimated based on body surface area, or measured.

Close clinical monitoring for safety and efficacy is advised.

Table 4. Recommended maintenance doses of Ceftazidime in renal impairment – continuous infusion:

Adults and children ≥40 kg:

Caution is advised in dose selection. Close clinical monitoring for safety and efficacy is advised.

Children <40 kg:

The safety and effectiveness of Ceftazidime administered as continuous infusion in renally impaired children <40 kg has not been established. Close clinical monitoring for safety and efficacy is advised.

If continuous infusion is used in children with renal impairment, the creatinine clearance should be adjusted for body surface area or lean body mass.

There are no study data in patients with severe hepatic impairment. Close clinical monitoring for safety and efficacy is advised.

Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered.

Haemodialysis

The serum half-life during haemodialysis ranges from 3 to 5 h.

Following each haemodialysis period, the maintenance dose of ceftazidime recommended in the below table should be repeated.

Peritoneal dialysis

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 250 mg for 2 litres of dialysis solution).

For patients in renal failure on continuous arterio-venous haemodialysis or high-flux haemofiltration in intensive therapy units: 1 g daily either as a single dose or in divided doses. For low-flux haemofiltration, follow the dose recommended under renal impairment.

For patients on veno-venous haemofiltration and veno-venous haemodialysis, follow the dosage recommendations in the tables 5 & 6 below.

Table 5. Continuous veno-venous haemofiltration dose guidelines:

¹ Maintenance dose to be administered every 12h.

Table 6. Continuous veno-venous haemodialysis dose guidelines:

¹ Maintenance dose to be administered every 12h.

Antibacterial agent-associated colitis and pseudo-membranous colitis have been reported with nearly all anti-bacterial agents, including ceftazidime, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of ceftazidime. Discontinuation of therapy with ceftazidime and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.

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.

Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to ceftazidime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if ceftazidime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.

There are limited amounts of data from the use of ceftazidime in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy embryonal/foetal development, parturition or postnatal development.

Ceftazidime should be prescribed to pregnant woman only if the benefit outweighs the risk.

Ceftazidime is excreted in human milk in small quantities but at therapeutic doses of ceftazidime no effects on the breast-fed infant are anticipated. Ceftazidime can be used during breast-feeding.

Fertility

No data are available.

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use machines.

The most common adverse reactions are eosinophilia, thrombocytosis, phlebitis or thrombophlebitis with intravenous administration, diarrhoea, transient increases in hepatic enzymes, maculopapular or urticarcial rash, pain and/or inflammation following intramuscular injection and positive Coomb’s test.

Data from sponsored and un-sponsored clinical trials have been used to determine the frequency of common and uncommon undesirable effects. The frequencies assigned to all other undesirable effects were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The following convention has been used for the classification of frequency:

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Unknown (cannot be estimated from the available data)

Infections and infestations

Uncommon: Candidiasis (including vaginitis and oral thrush)

Blood and lymphatic system disorders

Common: Eosinophilia, Thrombocytosis

Uncommon: Neutropenia, Leucopenia, Thrombocytopenia

Unknown: Agranulocytosis, Haemolytic anaemia, Lymphocytosis

Immune system disorders

Unknown: Anaphylaxis (including bronchospasm and/or hypotension)

Nervous system disorders

Uncommon: Headache, Dizziness

Unknown: Neurological sequelae¹, Paraesthesia

Vascular disorders

Common: Phlebitis or thrombophlebitis with intravenous administration

Gastrointestinal disorders

Common: Diarrhoea

Uncommon: Antibacterial agent-associated diarrhoea and colitis², Abdominal pain, Nausea, Vomiting

Unknown: Bad taste

Hepatobiliary disorders

Common: Transient elevations in one or more hepatic enzymes³

Unknown: Jaundice

Skin and subcutaneous tissue disorders

Common: Maculopapular or urticarial rash

Uncommon: Pruritus

Unknown: Toxic epidermal necrolysis, Stevens-johnson syndrome, Erythema multiforme, Angioedema, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)⁴

Renal and urinary disorders

Uncommon: Transient elevations of blood urea, blood urea nitrogen and/or serum creatinine

Very rare: Interstitial nephritis, Acute renal failure

General disorders and administration site conditions

Common: Pain and/or inflammation after intramuscular injection

Uncommon: Fever

Investigations

Common: Positive Coombs' test⁵

¹ There have been reports of neurological sequelae including tremor, myoclonia, convulsions, encephalopathy and coma in patients with renal impairment in whom the dose of Ceftazidime has not been appropriately reduced.
² Diarrhoea and colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis.
³ ALT (SGPT), AST (SOGT), LHD, GGT, alkaline phosphatase.
⁴ There have been rare reports where DRESS has been associated with ceftazidime.
⁵ A positive Coombs test develops in about 5% of patients and may interfere with blood cross matching.