Pharmacokinetics in children

In neonates up to 2 weeks (premature infants in particular), the plasma half-life is longer and inversely proportional to the age. The following kinetic parameters have been observed in neonates (PNA <4 days):

tmax (hours)	0.8
t½ (hours)	5.8
Cl (ml/min/kg)	1.35
Vd (l/kg)	0.67

The half-life in neonates > 8 days is 1.6 – 3.8 hours [Louvois et al. 1982]. The half-life, the volume of distribution and the clearance in very severely sick children are significantly elevated, which suggests a (higher) loading dose and possibly adjustment of the follow-on doses [Olguin 2008].

Infants > 3 weeks and children have a similar half-life compared to adults (60 - 90 minutes) [SmPC Curocef].

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

Bacterial infections
Intravenous < 1 week and weight at birth < 2000 g [7] [9] 50 mg/kg/day in 2 doses. < 1 week and weight at birth ≥ 2000 g [9] 75 mg/kg/day in 3 doses. 1 week up to 4 weeks and weight at birth < 2000 g [7] [9] 75 mg/kg/day in 3 doses. 1 week up to 4 weeks and weight at birth ≥ 2000 g [9] 100 mg/kg/day in 3 doses. 1 month up to 18 years [9] 100 mg/kg/day in 3 - 4 doses. Max: 4.5 g/day.

Infections (without clinical suspicion of meningitis) caused by microorganisms susceptible at increased exposure ('I')
Intravenous 1 month up to 18 years [26] [27] 150 - 200 mg/kg/day in 3 - 4 doses. Max: 1.500 mg/dose.

Acute tonsillitis, pharyngitis, bacterial sinusitis
Oral ≥ 3 months and < 40 kg [8] 20 mg/kg/day in 2 doses. Max: 250 mg/day. ≥ 40 kg [8] 500 mg/day in 2 doses.

Otitis media, cystitis, uncomplicated infection of skin and soft tissue, Lyme's disease
Oral ≥ 3 months and < 40 kg [8] 30 mg/kg/day in 2 doses. Max: 500 mg/day. ≥ 40 kg [8] 500 - 1.000 mg/day in 2 doses.

Infection in cystic fibrosis
Intravenous 1 month up to 18 years [7] 200 mg/kg/day in 4 - 6 doses. Max: 9 g/day. Alternative: 150 mg/kg/day as a continuous infusion, max 9 g/day

Pyelonephritis
Intravenous Postnatal age < 1 week and ≥ 2000 g [9] 75 mg/kg/day in 3 doses. Postnatal age 1 week up to 4 weeks and ≥ 2000 g [9] 100 mg/kg/day in 3 doses. 1 month up to 18 years [9] 100 mg/kg/day in 3 - 4 doses. Max: 4.5 g/day. Oral 3 months up to 12 years and < 40 kg [8] 30 mg/kg/day in 2 doses. Max: 1 g/day. ≥ 40 kg [8] 500 - 1.000 mg/day in 2 doses.

Prophylaxis for cardiovascular and oesophageal operations
Intravenous 1 month up to 18 years [10] Initial dose: In induction of anaesthesia: 50 mg/kg/dose, once only. Max single dose: 1.5 g/dose. Maintenance dose: After the procedure: 50 mg/kg/dose every 8 hours for 24 hours. Max single dose: 1.5 g/dose.

Prophylaxis in gastrointestinal, orthopaedic and gynaecological surgeries
Intravenous 1 month up to 18 years [9] [12] Initial dose: With induction of anaesthesia: 50 mg/kg/dose, once only. Max: 1.5 g/dose. Maintenance dose: 8 and 16 hours after the surgical procedure: 50 mg/kg/dose, as required. Max: 1.5 g/dose.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2

Adjustment is not required

GFR 30-50 ml/min/1.73 m2

Adjustment is not required

GFR 10-30 ml/min/1.73 m2

100% of normal single dose, the interval between two doses: parenteral administration 12 hours; oral administration: 24 hour.

GFR < 10 ml/min/1.73 m2

100% of normal single dose, the interval between two doses: parenteral administration 24 hours; oral administration: 48 hour.

Clinical consequences

Nephrotoxic symptoms occur primarily at high dosage, in pre-existing renal function disorders and in concomitant treatment with other nephrotoxic substances.

Patients on dialysis

Haemodialysis/peritoneal dialysis (parenteral administration): 100% of the normal dose each time and the interval between two doses: 24 hours. In haemodialysis, administer the dose after dialysis.

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. Mild and moderate hearing impairment occurred in some children after treatment with cefuroxime sodium.

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.
There have been reports of positive H. influenzae in cerebrospinal fluid after 18-36 hours; the relevance of this is unclear. Pseudomembranous colitis may occur during antibiotic use. If pseudomembranous colitis develops, the cefuroxime treatment should be discontinued and an appropriate therapy started. Cefuroxime suspension contains aspartame, which is converted inter alia into phenylalanine and must therefore be used with caution in patients with phenylketonuria.

Interactions

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

First-generation cephalosporins
	Cefazolin Related Medicines Menu">	J01DB04
	Cephalexin Related Medicines Menu">	J01DB01

Third-generation cephalosporins
	Cefixim Related Medicines Menu">	J01DD08
	Cefotaxime (as the sodium salt) Related Medicines Menu">	J01DD01
	Ceftazidim + Avibactam Related Medicines Menu">	J01DD52
	Ceftazidime Related Medicines Menu">	J01DD02
	Ceftriaxone Related Medicines Menu">	J01DD04

Carbapenems
	Meropenem Related Medicines Menu">	J01DH02

References

1. GlaxoSmithKline GmbH & Co. KG, SmPC Elobact (16468.00.00 / 16468.01.00 / 16468.02.00 / 16468.00.01), 01/2016
2. de Louvois J, et al, Cefuroxime in the treatment of neonates, Arch Dis Child., 1982, 57, 59-62
3. Gooch WM 3rd, et al, Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media, Pediatr Infect Dis J., 1996, 15, 157-64
4. Nelson JD, Cefuroxime: a cephalosporin with unique applicability to pediatric practice, Pediatr Infect Dis, 1983, 2, 394-6
5. No authors listed, Cefuroxime in pediatric practice. Committee on Infectious Diseases and Immunization, Canadian Paediatric Society, Can Med Assoc J, 1984, 13, 877, 880
6. Scholz H, Streptococcal-A tonsillopharyngitis: a 5-day course of cefuroxime axetil versus a 10-day course of penicillin V. results depending on the children\'s age, Chemotherapy, 2004, 50, 51-4
7. Vuori-Holopainen E, et al, Narrow- versus broad-spectrum parenteral anatimicrobials against common infections of childhood: a prospective and randomised comparison between penicillin and cefuroxime, Eur J Pediatr., 2000, 159, 878-84
8. Hartwig NG, et al, Vademecum Pediatrische Antimicrobiele Therapie, 3e editie, 2005
9. GlaxoSmithKline BV, SPC Zinnat (RVG 13225) 02-02-2019, www.geneesmiddeleninformatiebank.nl
10. Fresenius Kabi Nederland BV, SmPC cefuroxim ( RVG 35183) 21-11-2018, www.geneesmiddeleninformatiebank.nl
11. Knoderer CA et al., Efficacy of limited cefuroxime prophylaxis in pediatric patients after cardiovascular surgery., Am J Health Syst Pharm, 2011, May 15;68(10), 909-14
12. Olguín HJ et al, Effect of severity disease on the pharmacokinetics of cefuroxime in children with multiple organ system failure. , Biol Pharm Bull, 2008, Feb;31(2):, 316-20
13. Bratzler, DW, et al., Clinical practice guidelines for antimicrobial prophylaxis in surgery, 2013, 14(1), 73-156
14. Fresenius Kabi Deutschland GmbH, SmPC Cefuroxim Fresenius 250 mg Pulver zur Herstellung einer Injektionslösung (38985.00.00), 02/2016
15. Ratiopharm GmbH, SmPC Cefuroxim-ratiopharm 125 mg/ 5 ml TS (37162.00.01), 08/2015
16. Aristo Pharma GmbH, SmPC Cefurax 125 mg/5 ml Granulat zur Herstellung einer Suspension zum Einnehmen (53800.00.00), 01/2013
17. Basics GmbH, SmPC Cefurox Basics 125 mg/ 5 ml (53137.00.00), 08/2015
18. Hexal AG, SmPC CefuHEXAL 125 mg/ 5 ml Trockensaft (37164.00.01), 03/2016
19. Ratiopharm GmbH, SmPC Cefuroxim-ratiopahrm 250 / 500 mg Filmtabletten (70940.00.00 / 70941.00.00), 04/2016
20. STADApharm GmbH, SmPC Cefuroxim STADA 250 / 500 mg Tabletten (49168.01.00 / 49168.02.00), 03/2017
21. Fresenius Kabi Deutschland GmbH, SmPC Cefuroxim Fresenius 1500 mg Pulver zur Herstellung einer Infusionslösung (34838.00.00), 02/2016
22. Ratiopharm GmbH, SmPC Cefuroxim-ratiopharm p.i. (38981.00.00 / 38981.01.00 / 38984.00.00), 07/2015
23. Fresenius Kabi Deutschland GmbH, SmPC Cefuroxim Fresenius 750 mg Pulver zur Herstellung einer Injektionslösung (38985.01.00), 02/2016
24. Fresenius Kabi Deutschland GmbH, SmPC Cefuroxim Fresenius 1500 mg Pulver zur Herstellung einer Injektionslösung (38987.00.00), 02/2016
25. Hikma Pharma GmbH, SmPC Cefuroxim Hikma 750 / 1500 mg, Pulver zur Herstellung einer Injektions- oder Infusionslösung (6128154.01.00 / 6128154.02.00), 03/2014
26. European Committee on Antimicrobial Susceptibility Testing - EUCAST, Clinical breakpoints - breakpoints and guidance, https://www.eucast.org/clinical_breakpoints, Jan2, 2023
27. Dutch Working Party on Antibiotic Policy (SWAB) - Special Interest Group Pediatrics, Expert opinion on high dosing for infections caused by microorganisms susceptible to increased doses., Dec 6, 2022

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