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Drug dosage identifier


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Dose and administration

  1. For congenital Syphillis - 30mg/kg 12 hourly for 10 days.
  2. For severe sepsis and meningitis - 90mg/kg/dose . Max daily dose 300mg/kg/day.

Add an aminoglycoside if tolerance is suspected/confirmed.

Postmenstrual Age (weeks) Postnatal Age (days) Dosing Interval (hr)
≤29  0 to 28 12
>28 8
30 to 36  0 to 14 12
>14 8
37 to 44  0 to 7 12
>7 8
≥45 All 6


  • Directed treatment of neonatal infections caused by susceptible organisms - streptococci (non enterococcal), gonococci.
  • Treatment of meningitis due to susceptible bacterium including GBS (Group B Streptococcus).
  • Treatment of congenital syphillis

Contraindications and precautions

  • Caution in preterm infants, especially extreme immaturity.
  • Caution in infants with liver, renal or gastrointestinal disease.
  • Consider sodium load in renal failure - a dose of 300mg/kg/day provides 0.90 mmol/kg/day of sodium.

Clinical pharmacology

Benzylpenicillin has bacteriostatic/bacteriocidal actions (depending on its concentration) against most gram positive bacteria and gram negative cocci. Also active against some spirochaetes and actinomycetes. Antimicrobial action is through inhibition of cell wall synthesis.

Well absorbed following intramuscular injection. Widely distributed at varying concentrations in body tissues and fluids. Very little passes into the CSF unless the meninges are inflamed. Larger doses are recommended in meningitis.2 Moderate binding (45-65%) to human plasma protein. Rapidly excreted via the kidney, mainly unchanged. Half life 5-6 hours in healthy newly born preterm infants and 2 hours in full term babies > 1-2 weeks old.

Possible adverse effects

  • Venous irritation, soft tissue injury at site of IV injection.
  • Pain, soft tissue injury at site of IM injection.
  • Gastrointestinal disturbance (nausea, vomiting, diarrhoea).
  • Non specific rashes and skin eruptions.
  • Fever, pruritis, urticaria.
  • Seizures with high doses (greater than 400 mg/kg/day) and rapid infusions

Special considerations

  • May give concurrently with aminoglycoside therapy for synergistic effect. Administer separately as intravenous administration may cause inactivation.
  • Adjust dose in suspected renal dysfunction (by lengthening the dosing interval).
  • Sodium content 1.7 mmol/g.


Two RCTs comparing penicillin versus ampicillin in the empiric therapy of extremely low-birth weight neonates at risk of early onset sepsis showed similar effectiveness in change of antibiotics at 72 hours and/or 7 day all-cause mortality.3,4

Management of Benzylpenicillin administration


  • White powder for reconstitution 600 mg/vial.
  • Reconstituted solution is clear, pale, straw coloured.
  • pH 6-7.5. Is inactivated in alkaline solutions.


  • Stat dose is charted on stat page of prescription chart in mg/dose.
  • Maintenance doses are charted on the prescription chart in mg/dose.


Slow IV Infusion

  1. Reconstitute with water to 100mg/ml immediately prior to use.10
Powder Displacement For both Crystapen and Biochemie
Powder space 0.4ml
Water to be added 5.6ml
  600mg in 6.0ml
  1. Shake vigorously. Filter before administration through a Pall 0.2 micron filter.
  2. Does not require further dilution.
  3. Administer IV by infusion over at least 5 minutes.
  4. Compatible with D5W and NS.
  5. Do NOT mix with other drugs, IV solutions, blood or blood products.
  6. Flush line with NS before and after infusion of penicillin.

Intramuscular Injection

Reconstitute with water to 300 mg/ml immediately prior to use.

Powder Displacement For both Crystapen and Biochemie
Powder space 0.4ml
Water to be added 1.6ml
  600mg in 2.0ml
  1. Penicillin reconstituted to 300mg/ml is not suitable for IV administration, due to high osmolality.

Nursing considerations

  1. Observe IV site carefully for extravasation during administration.
  2. Observe for signs of adverse effects.
  3. Observe for hypernatraemia.


  • At room temperature <25°C until reconstitution.
  • Should be used within 1 hour following reconstitution.
  • Is not suitable for storage.


  1. Azimi P.H., Janner D., Berne P. et al. Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of infants treated for congenital syphilis. J Pediatr 1994;124:649-53.
  2. American Academy of Pediatrics. Kimberlin D. W, Brady M.T., Jackson M.A., Long S.S. Eds. 2015 Red Book: Report of the Committee on Infectious Diseases. 30th Ed. Elk Grove Village, IL.
  3. Metsvaht T, Ilmoja ML, Parm U, Maipuu L, Merila M, Lutsar I. Comparison of ampicillin plus gentamicin vs penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis. Acta Paediatr 2010;99:665-72
  4. Metsvaht T, Ilmoja ML, Parm U et al. Ampicillin versus penicillin in the empiric therapy of extremely low-birthweight neonates at risk of early onset sepsis. Pediatr Int. 2011 Dec;53(6):873-80.
  5. Prober CG, Stevenson DK, Binitz WE. The use of antibiotics in neonates weighing less than 1200 gm. Pediatr Infec Dis J 1990; 9:111.
  6. McCracken GH, Ginsburg C, Chrane DF, et al. Clinical pharmacology of penicillin in newborn infants. J Pediatr 1973; 82:692.
  7. The Northern Neonatal Network, Neonatal Formulary BMJ Books, 2nd Edition 1998, p176.
  8. Nursing 97 Drug Handbook Springhouse p 98-9.
  9. Penicillin G sodium Biochemie product enclosure.
  10. Neonatal Pharmacopoeia (2nd ed.). Pharmacy dept. Royal Women's Hospital, Melbourne. 2005

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Document Control

  • Date last published: 31 March 2018
  • Document type: Drug Dosage Guideline
  • Services responsible: ADHB Pharmacy, Neonatology, Paediatric Infectious Diseases
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years