Perth Children’s Hospital

Children’s Antimicrobial Management

Program (ChAMP)

MONOGRAPH

Benzathine Benzylpenicillin (Benzathine Penicillin G)

Monograph - Paediatric
Scope (Staff): Medical, Pharmacy, Nursing
Scope (Area): Perth Children’s Hospital (PCH)

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This document should be read in conjunction with this DISCLAIMER

QUICKLINKS

Dosage/Dosage
Administration Compatibility Monitoring
Adjustments

DRUG CLASS

Penicillin-Narrow Spectrum.(1)
INDICATIONS AND RESTRICTIONS
 Benzathine benzylpenicillin is predominantly used in the treatment and secondary prevention
of acute rheumatic fever/rheumatic heart disease and in the treatment of infections
susceptible to prolonged, low concentrations of benzylpenicillin (e.g. early or latent syphilis).(1)
 It may also be used in the treatment of impetigo and Group A Streptococcal
Tonsillitis/Pharyngitis.(2, 3)
 Benzathine benzylpenicillin may also be used as a second line agent for invasive Group A
Streptococcal (iGAS) contacts unable to tolerate oral antibiotics.
IM: Unrestricted (green) antibiotic
 This is not a restricted agent. Follow standard ChAMP guidelines where appropriate.

CONTRAINDICATIONS

 Benzathine benzylpenicillin is contraindicated in patients with a history of high risk allergy to

penicillins. (1, 3)
 Benzathine Benzylpenicillin Monograph - Paediatric

PRECAUTIONS

 Benzathine benzylpenicillin may be prescribed in selected patients with high risk allergy to
another Beta-lactam sub-class (e.g. some cephalosporins, carbapenems) in discussion with
immunology.(3, 4)
 In patients with a previous low risk allergy to benzathine benzylpenicillin or another penicillin
(delayed rash [>1hr after initial exposure] without mucosal or systemic involvement) the risk of
subsequent reaction is low. Re-challenge may be acceptable in discussion with immunology.
 Care must be taken with intramuscular administration of benzathine benzylpenicillin to avoid
intravenous or intra-arterial administration or injection in or near major peripheral nerves or
blood vessels due to the risk of neurovascular damage.(1, 4, 5)
FORMULATIONS
Listed below are products available at PCH, other formulations may be available, check with
pharmacy if required:

 Benzathine benzylpenicillin tetrahydrate 1,200,000 units/2.3mL in aqueous suspension (Bicillin

L-A®), pre-filled syringe for IM injection.
Note:
 In 2019 the manufacturer updated the labelling and packaging of benzathine benzylpenicillin to
include the tetrahydrate salt and describe the active ingredient in ‘units’ rather than ‘mg’. There
was no change to the contents of the product.
 Imprest location: Formulary One
DOSAGE & DOSAGE ADJUSTMENTS

Doses of benzathine benzylpenicillin should be expressed as units only.

Neonates (less than 30 days of age):
 Not routinely used in neonates except in cases of congenital syphilis, refer to Neonatal
Medication Protocols or contact Infectious Disease or Clinical Microbiology consultants for
advice
Congenital Syphilis (less than 30 days of age):
 Low-risk infants <3kg: contact Infectious Diseases for advice, benzyl penicillin may be
appropriate.
 Low-risk infants ≥3kg: 50,000 units/kg IM as a single dose(6, 7)
 High-risk: treatment with IV benzylpenicillin required.(6)
Children:
Impetigo (>1 month to 18 years):
In remote Indigenous communities S. pyogenes is usually the pathogen, even if S. aureus is
isolated.(2)
 <10kg 450,000 units IM (0.9mL) as a single dose
 10 to <20kg 600,000 units IM (1.2mL) as a single dose
 ≥20kg 1,200,000 units IM (2.3mL) as a single dose(8)

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 Benzathine Benzylpenicillin Monograph - Paediatric
Presumed Streptococcus pyogenes (>1 month to 18 years): (Group A Streptococcus)
tonsillitis or pharyngitis, scarlet fever:
 <10kg 450,000 units IM (0.9mL) as a single dose
 10 to <20kg 600,000 units IM (1.2mL) as a single dose
 ≥20kg 1,200,000 units IM (2.3mL) as a single dose(8)
Rheumatic fever (>1 month to 18 years):
Acute episode:
 < 20kg: 600,000 units IM (1.2mL) as a single dose
 ≥ 20kg: 1,200,000 units IM (2.3mL) as a single dose.(8)
Prevention of recurrence:
 < 20kg: 600,000 units IM (1.2mL) every 3 to 4 weeks for 5 to 10 years.
 ≥ 20kg: 1,200,000 units IM (2.3mL) every 3 to 4 weeks for 5 to 10 years. (8)
 Duration of antibiotic prophylaxis for prevention of rheumatic fever recurrence depends on
patient factors such as age, likelihood of ongoing exposure to S. pyogenes and time since last
episode of acute rheumatic fever refer to: The 2020 Australian guideline for prevention,
diagnosis and management of acute rheumatic fever and rheumatic heart disease (3 rd edition).
Syphilis (>1 month to 18 years):
 50,000 units/kg given IM (to a maximum of 2.4 million units) as a single dose.(9-11)
 Early latent syphilis requires a single dose, for late latent syphilis, 3 doses given at one week
intervals is required. Contact Infectious Diseases for advice.(9, 10)
Dosing in Overweight and Obese Children: Dose based on measured body weight
Renal impairment:
 Excretion of benzathine benzylpenicillin is delayed in renal impairment and it should be used
with caution in patients requiring repeat dosing. There are no recommendations regarding
dose reduction in renal impairment.(2, 5)
 eGFR calculator (Google Chrome®)
Hepatic impairment:
 No dosage adjustment is necessary in hepatic impairment. (10)
RECONSTITUTION & ADMINISTRATION
Benzathine benzylpenicillin may be administered with lidocaine. It is reported to
(8)
significantly reduce pain during injection and in the first 24 hours after injection.

 Benzathine benzylpenicillin must only be administered via intramuscular injection into the
mid-lateral aspect of the thigh (preferred in children) or upper, outer quadrant of the buttock. (3)
 It should be administered at a slow, steady rate preferably over 2-3 minutes to avoid blockage
of the needle and to minimise pain.(4) The injection site should be rotated for subsequent
doses.(4)
 After insertion of the needle, aspiration is recommended and the barrel should be observed
for any blood or discolouration. If there is any discolouration, the needle should be withdrawn

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 Benzathine Benzylpenicillin Monograph - Paediatric
and the syringe discarded.(5)
 Stop injection immediately if there is severe pain at the injection site.(4)
The pain of administration can be reduced by;
 Allowing the alcohol from the alcohol swab to dry before injection
 Applying pressure with thumb for 10 seconds before injection
 Warming the syringe to room temperature immediately prior to the injection
 Using a 21 gauge needle.(4, 8)
Administering Benzathine Benzylpenicillin with Lidocaine(8):
Equipment:
 Pre-filled Benzathine Benzylpenicillin syringe
 3 mL syringe
 2 drawing-up needles
 21G needle
Preparation:
1. Attach a drawing-up needle to a 3 mL syringe.
2. Draw the required contents of Benzathine Benzylpenicillin from the pre-filled syringe into the
3mL syringe (2.3 mL for 1,200,000-unit dose and 1.2 mL for 600,000-unit dose).
3. Using a new needle, draw up 0.5 mL of lidocaine 1% into the tip of the 3mL syringe.
4. Avoid mixing to keep the lidocaine in the tip of the syringe.
5. Push plunger up carefully to remove any air in the syringe.
6. Remove the drawing-up needle.
7. Attach IM needle (e.g. 21 gauge) to the syringe to administer injection.

 Note: Lidocaine is contraindicated in people with a known hypersensitivity to local

anaesthetics of the amide type; second or first degree heart block. (8)
COMPATIBILITY (LIST IS NOT EXHAUSTIVE)

 Not applicable: Benzathine benzylpenicillin must only be administered via intramuscular

injection.(1, 4)

MONITORING

 In patients being treated for syphilis and other spirochete infections monitor for Jarisch-
Herxheimer reaction (fever, chills, headache, hypotension and flare-up of lesions lasting for 12-
24 hours). Consideration should be given to the use of prednisolone to minimise the likelihood
of this in patients where this could be dangerous (i.e. cardiovascular syphilis or
neurosyphilis).(1)

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ADVERSE EFFECTS

Caution: Inadvertent intravascular administration may result in neuromuscular damage, seizures,

cardiac arrest and/or severe, and potentially permanent, neurovascular damage. CNS effects
include anxiety, agitation, fear of death and hallucinations. (1, 5, 10)
Common: pain and inflammation at the injection site, rash, urticaria, skin eruptions (most
commonly maculopapular), nausea, diarrhoea, fever, fatigue, Jarisch-Herxheimer reaction (fever,
chills, headache, hypotension and flare-up of lesions due to the release of pyrogens from the
organism at the time of first administration e.g. syphilis).(1, 3, 12)

Rare: Clostridium difficile-associated disease, anaphylaxis or other immediate hypersensitivity

reactions, black tongue, electrolyte disturbances, neurotoxicity with high doses (including
drowsiness, hallucinations, coma and seizures), blood dyscrasias, bleeding. (1, 3)
STORAGE

 Store between 2-8°C. Refrigerate, do not freeze. (3)

 Benzathine benzylpencillin may be stored below 30°C for a single period of up to 2 months
prior to expiry.(3) The date the product is placed outside of refrigerated storage and stored
below 30°C should be written in the space provided on the carton.

INTERACTIONS
This medication may interact with other medications; consult PCH approved references (e.g.
Clinical Pharmacology), a clinical pharmacist or PCH Medicines Information Service on extension
63546 for more information.
**Please note: The information contained in this guideline is to assist with the preparation and administration
of Benzathine Benzylpenicillin. Any variations to the doses recommended should be clarified with the
prescriber prior to administration**

REFERENCES
1. Rossi S, editor. Australian Medicines Handbook. Adelaide, S. Aust.: Australian Medicines
Handbook; 2021.
2. Antibiotic Writing Group. eTG complete. West Melbourne: Therapeutic Guidelines Ltd; 2020.
Available from: https://tgldcdp-tg-org-au.pklibresources.health.wa.gov.au/etgAccess.
3. MIMS Australia. MIMS online [full product information]. St Leonards, N.S.W: CMP Medica
Australia.; 2021. p. 1v. (various pagings).
4. Symons K. Ermer J. (editors). Australian injectable drugs handbook. Collingwood: The Society of
Hospital Pharmacists of Australia; 2020.
5. Taketomo CK, Hodding JH, Kraus DM. Pediatric and Neonatal dosage handbook with international
trade names index. 26th edition ed. Ohio: Lexi-comp; 2019-2020.
6. Congenital syphilis guidelines for the Northern Territory: Assessment and management of syphilis
in pregnancy and the neonatal period. Darwin: Department of Health - Northern Territory; 2015. Available
from:
https://digitallibrary.health.nt.gov.au/prodjspui/bitstream/10137/707/1/Congenital%20syphilis%20guidelines
%20for%20the%20Northern%20Territory%20Nov%202015.pdf.
7. Sexual Health and Blood-borne virus program. Silver book - A guide for managing sexually
transmitted infections. Department of Health - Western Australia; 2020.
8. Asha Bowen et al. The Australian guideline for prevention, diagnosis and management of acute
rheumatic fever and rheumatic heart disease (2nd edition). Currie B RA, editor: National Heart Foundation
of Australia and the Cardiac Society of Australia and New Zealand; 2020.

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 Benzathine Benzylpenicillin Monograph - Paediatric
9. Centres for Disease Control and Prevention. 2015 Sexually Transmitted Diseasea Treatment
Guidelines. Centres for Disease Control and Prevention,; 2015. p. 1-137.
10. Clinical Pharmacology [Internet]. Elsvier BV. 2021 [cited 14/01/2021]. Available from:
http://www.clinicalpharmacology-ip.com.pklibresources.health.wa.gov.au/default.aspx.
11. Paediatric Formulary Committee. BNF for Children: 2020. London: BMJ Group Pharmaceutical
Press; 2021.
12. IBM Micromedex [Internet]. Truven Health Analytics. 2021 [cited 11/05/2021]. Available from:
http://www-micromedexsolutions-com.pklibresources.health.wa.gov.au/micromedex2/librarian.

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File Path: W:\Paediatrics\PMH\ChAMP\Monographs\FINALISED\00 Current version 00

Document Owner: Head of Department – Infectious Diseases
Reviewer / Team: Children’s Antimicrobial Management Program Pharmacist
Date First Issued: January 2015 Last Reviewed: April 2021
Amendment Dates: April 2020, June 2020, March 2021 Next Review Date: April 2024
Approved by: Medication Safety Committee Date: April 2021
Endorsed by: Drugs and Therapeutics Committee Date: April 2021
Standards
Applicable: NSQHS Standards:
NSMHS: N/A
Child Safe Standards: N/A
Printed or personally saved electronic copies of this document are considered uncontrolled

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