Pharmacokinetics in children

The study by Nahata et al. (N=9, age 10 months – 10 years) shows that the elimination half-life of cefazolin in children averages 1.68 ± 0.55 hours. The total clearance and the apparent volume of distribution are 1.43 ± 0.54 ml/min/kg and 0.08 ± 0.03 l/kg respectively.
The study by Deguchi et al. shows that the percentage of the free fraction of cefazolin varies widely in neonates. The volume of distribution in neonates is 0.21–0.37 l/kg.
 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

Dose adjustments <14 years
Cl 40 - 70 mL/min: Start with normal single dose, continue at 60 % of daily dose with divided in 2 doses with dosing interval of 12 hours 
Cl 20 - 40 mL/min: Start with normal single dose, continue at 25 % of daily dose with divided in 2 doses with dosing interval of 12 hours 
Cl < 20 mL/min: Start with normal single dose, continue at 10 % of daily dose,  with dosing interval of 24hours 

Dose adjustments ≥ 14 years
Cl 35 - 54 mL/min: Normal daily dose (no dose adjustment), dosing interval at 8 hours
Cl 10 - 34 mL/min: Start with normal single dose, continue at  50% of normal daily dose, dosing interval at 12 hours
Cl < 10 mL/min: Start with normal single dose, continue at  50% of normal daily dose, dosing interval at 18-24 hours

[SmPC Cefazolin Fresenius]

Clinical consequences

Nephrotoxic symptoms (renal function disorder, tubular necrosis, interstitial nephritis) occur primarily at high dosages, in pre-existing renal function disorders and in concomitant treatment with other nephrotoxic substances. Convulsions can occur at very high doses. The time above the MIC determines the effect.

Patients on dialysis

No data known

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Thrombophlebitis, fever, nausea, vomiting, diarrhoea, obstipation, abnormal blood counts, temporarily elevated liver enzymes.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Cephalosporins can in general be given to patients who are hypersensitive to penicillin, although cross-reactions have been reported. Special care is indicated in patients who previously had anaphylactic responses to penicillins. Pseudomembranous colitis may occur during antibiotic use. If pseudomembranous colitis develops, the cefazolin treatment should be discontinued and an appropriate therapy started. In long-term use, checks of the blood counts and hepatic and renal function are desirable.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIBACTERIALS FOR SYSTEMIC USE

OTHER BETA-LACTAM ANTIBACTERIALS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

1. Hartwig NC, et al, Vademecum pediatrische antimicrobiële therapie, 2005
2. Deguchi Y, et al, Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts, J Pharm Sci, 1988, 77, 674-8
3. Haessler D, et al, Antibiotic prophylaxis with cefazolin and gentamicin in cardiac surgery for children less than ten kilograms, J Cardiothorac Vasc Anesth, 2003, 17, 221-5
4. Maher KO, et al, A retrospective review of three antibiotic prophylaxis regimens for pediatric cardiac surgical patients, Ann Thorac Surg, 2002, 74, 1195-200
5. Nahata MC, et al, Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery, Eur J Drug Metab Pharmacokinet., 1991, 16, 49-52
6. Eurocept International B.V., SPC Kefzol (RVG 06836) 30-01-2019, www.geneesmiddelinformatiebank.nl
7. Bratzler DW et al. , Clinical practice guidelines for antimicrobial prophylaxis in surgery. , Surg Infect (Larchmt). , 2013 , Feb;14(1), 73-156
8. Lorrot M et al. , Antibiotic therapy of bone and joint infections in children: proposals of the French Pediatric Infectious Disease Group. , Arch Pediatr. , 2017, 24(12S):S36-S41, DOI: 10.1016/S0929-693X(17)30517-1
9. DeRonde KJ et al. , Management of Pediatric Acute Hematogenous Osteomyelitis, Part I: Antimicrobial Stewardship Approach and Review of Therapies for Methicillin-Susceptible Staphylococcus aureus, Streptococcus pyogenes, and Kingella kingae, Pharmacotherapy, 2018, 38(9):947-966, doi:10.1002/phar.2160
10. Woods CR, Bradley JS, Chatterjee A, et al. , Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics. , J Pediatric Infect Dis Soc., 2021, 10(8):801-844., DOI: 10.1093/jpids/piab027
11. Pio, L., et al., Antibiotic prophylaxis in children undergoing abdominal surgery for neoplastic diseases., Infez Med, 2018, 26 (2), 122-125
12. Salvador E, et al. , Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus. , Clin Microbiol Infect., 2021, Mar;27(3), 413-419

Changes

Therapeutic Drug Monitoring

Overdose