Dose
  
Treatment - Neonatal Intensive Care Drug Manual

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Neonatal Intensive Care Drug Manual
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bet | 102/654 | Sana | 03.01.2022 | Hajmi | 1,5 Mb. | | #14803 |
Dose
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Treatment
Postnatal Age (Days)
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Dose
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Interval
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0─7 days
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25 mg/kg
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12-hourly
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8─28 days
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25 mg/kg
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8-hourly
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≥29 days
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25 mg/kg
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6-hourly
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Prophylaxis of urinary tract infection (UTI)
12.5 (10–15) mg/kg/dose DAILY (maximum dose 125 mg daily).7,8
Prophylaxis around Micturating Cystourethrogram (MCU)
12.5 (10–15) mg/kg/dose 8-hourly for 3 days (day prior, on the day and one day after MCU).10
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Dose adjustment
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Maximum dose
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500 mg
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Total cumulative dose
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Route
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Oral
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Preparation
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Supplied reconstituted by Pharmacy.
If supplied unreconstituted, use water for injection with the volume specified on the packaging for reconstitution.
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Administration
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Shake bottle well before measuring dose.
Prophylactic dose: May be taken with or without food.
Treatment dose: Preferably commence treatment without feeds for faster absorption and higher peak concentrations3
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Monitoring
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Renal, hepatic and haematological function with prolonged use.
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Contraindications
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Hypersensitivity to cephalosporins.
Immediate hypersensitivity or severe reaction to penicillins.
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Precautions
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Use with caution in patients with hypersensitivity or mild adverse reactions to penicillins or carbapenems as cross-reactivity can occur (e.g. rash).
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Drug interactions
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Not applicable.
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Adverse reactions
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Diarrhoea, abdominal pain, vomiting.
Pseudomembranous colitis (rare).
Transient elevation of liver enzymes.
Hypersensitivity: Immediate − urticaria, bronchospasm, anaphylaxis. Delayed − maculopapular rash, fever, eosinophilia.
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Compatibility
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Not applicable.
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Incompatibility
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Not applicable.
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Stability
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Reconstituted solution should be discarded after 14 days.
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Storage
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Store powder below 25°C
Store reconstituted solution between 2 and 8°C
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Special comments
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May cause false positive Coombs test.
Consider increasing dosing interval in significant renal impairment.
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Evidence
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Pharmacokinetics and pharmacodynamics
First-generation cephalosporins are most active against gram-positive cocci, including MSSA and streptococci. They have no activity against enterococci, MRSA, or Listeria. Therapeutic concentrations occur in most tissues, including pleura, synovial fluids, and bone, but not middle ear fluid. First-generation cephalosporins should not be used if bacterial meningitis is possible, due to poor CSF penetration, with or without inflammation.1 Cefalexin is rapidly absorbed in the upper intestine. Distribution to the tissues, other than the spinal fluid and aqueous humour, is rapidly achieved. Cefalexin does not penetrate host cells, which probably accounts for its low incidence of side effects. Binding to human serum proteins is low and there is no measurable metabolism in body fluids. Cefalexin is rapidly cleared from the body by the kidneys. In adults, 70 to 100% of the dose is found in the urine 6–8 h after each dose. The elimination half-life was 0.8 hours in adults.2 In infants and children, following ingestion of a 15 mg/kg dose, mean peak concentrations of cefalexin in serum were achieved at one-half hour (23.4 microgram/mL) in fasting and at one hour (9.0 microg/mL) in non-fasting patients. Administration of drug with milk reduced the mean peak concentration by 60% and the area-under-the-curve value by approximately 40%. The half-life in serum was approximately 60 minutes. Concentrations in tears and saliva were below MIC for many organisms.3 In 40 newborn infants given 15 mg/kg cefalexin every 8 hours the serum concentrations of cefalexin were lower than the average MIC for many of the Gram-negative organisms encountered in the neonatal period. In a second series, in 30 newborn infants who received 50 mg/kg every 12 hours, adequate serum concentrations were achieved. Urinary excretion of cefalexin in 24 hours ranged from 5 to 66% of the total daily dose suggesting 50 to 60% of the administered dose of cefalexin is absorbed by the newborn infant.4 Pharmacokinetic data are lacking in preterm infants.
Efficacy
Trials on cefalexin in treating specific infections in neonates are lacking. Beyond the neonatal age group, American Academy of Pediatrics recommends a cefalexin dosage of 50–100 mg/kg/day in 4 divided doses.5,6
Antimicrobial prophylaxis for UTI: The suggested prophylactic dose of cefalexin ranges from 10–12.5 mg/kg/dose daily.7,8 Due to concerns about bacterial resistance, it is suggested to use cefalexin or amoxicillin (based on culture and susceptibility results) as second-choice antibiotics for prophylaxis beyond 3 months of age.8
Antimicrobial prophylaxis for micturating cystourethrogram (MCUG): NICE Guideline 2007 recommends a 3-day antibiotic course with MCUG taking place on the second day.9 Cefalexin 10–15 mg/kg/dose 8-hourly for 3 days in children aged 2 months to 5 years undergoing MCUG was reported to reduce MCUG-associated UTI in a randomised, controlled trial.10 (LOE:II)
Safety
Non-pruritic rashes occur in 1% to 2.8% of patients and are not a contraindication to future use. True anaphylactic reactions related to cephalosporins are rare, with an estimated risk of 0.0001% to 0.1%. Cephalosporin-induced anaphylaxis is no greater among penicillin-allergic patients according to newer evidence that established that previous rates of cross-reactivity between penicillins and cephalosporins were overestimated.1
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Practice points
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References
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1. Harrison CJ, Bratcher D. Cephalosporins: a review. Pediatr Rev. 2008;29:264-7.
2. Griffith RS. The pharmacology of cephalexin. Postgrad Med J. 1983;59 Suppl 5:16-27.
3. McCracken GH, Jr., Ginsburg CM, Clahsen JC, Thomas ML. Pharmacologic evaluation of orally administered antibiotics in infants and children: effect of feeding on bioavailability. Pediatrics. 1978;62:738-43.
4. Boothman R, Kerr MM, Marshall MJ, Burland WL. Absorption and excretion of cephalexin by the newborn infant. Arch Dis Child. 1973;48:147-50.
5. Paintsil E. Update on recent guidelines for the management of urinary tract infections in children: the shifting paradigm. Curr Opin Pediatr. 2013;25:88-94.
6. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128:595-610.
7. Baracco R, Mattoo TK. Diagnosis and management of urinary tract infection and vesicoureteral reflux in the neonate. Clin Perinatol. 2014;41:633-42.
8. NICE Guidelines. Urinary tract infections. Antimicrobial prescribing. 31 October 2018. https://www.nice.org.uk/guidance/ng112/chapter/Recommendations#treatment-for-children-and-young-people-under-16-years-with-recurrent-uti.
9. NICE Guidelines. Urinary tract infection in under 16s: diagnosis and management. 22 August 2007. https://www.nice.org.uk/guidance/cg54/chapter/Recommendations#imaging-tests
10. Sinha R, Saha S, Maji B, Tse Y. Antibiotics for performing voiding cystourethrogram: a randomised control trial. Arch Dis Child. 2018;103:230-4.
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Original version Date: 16/12/2020
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Author: NeoMed Consensus Group
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Current Version number: 3
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Version Date: 16/12/2020
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Risk Rating: Low
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Due for Review: 16/12/2025
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Approved by: DTC
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Approval Date: TBA
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