Intravenous Amoxicillin-Clavulanic acid

Document ID CHQ-PMG-01240 Version no. 2.0 Approval date 24/09/2019

Executive sponsor Executive Director Medical Services Effective date 24/09/2019
Author/custodian Pharmacist Advanced – Safety and Quality Review date 24/09/2021
Pharmacist Advanced – Antimicrobial Stewardship
Supersedes 1.0
Applicable to All Children’s Health Queensland (CHQ) clinical staff
Authorisation Executive Director Clinical Services

Purpose
The purpose of this guideline is to provide clinical advice around the use of Intravenous Amoxicillin-
Clavulanic acid in paediatric patients at the Queensland Children’s Hospital (QCH).

Scope
This guideline is intended to assist all clinical staff to prescribe and administer Intravenous Amoxicillin-
Clavulanic acid appropriately to patients at QCH. It is not intended to be a substitute for specific professional
or clinical advice, or to replace consultation with senior staff, which should always be sought if clinically
relevant.
This material is published by Children’s Health Queensland with the intention of providing a guideline for use
at QCH. Anyone wishing to use this guideline outside QCH should refer to their local Medicines Committee
before using.

Related documents
Procedures, Guidelines, Protocols
• CHQ-PROC-01035 Antimicrobial Restriction
• CHQ Antimicrobial Restriction list
• CHQ-PROC-01039 Medication - Administration
• CHQ-PROC-01000 Medication
Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

Description and Indications for Use

Intravenous Amoxicillin-clavulanic acid is a broad spectrum antibiotic that covers gram-positive, gram-
negative and anaerobic organisms excluding Pseudomonas. This agent does not currently feature in the
Therapeutic Guidelines: Antibiotic, however there is extensive clinical experience overseas. For directed
therapy against a cultured organism, consult your CHQ Infectious Diseases (ID) and Antimicrobial
Stewardship team for further advice.
Table 1: IV Amoxicillin-clavulanic acid may be used empirically for the following situations for
paediatric patients:

Indication Approved duration/ ID review required

Retropharyngeal abscess Up to 24 hours then seek ID review/ advice

Severe Animal bites/ wounds Up to 24 hours then seek ID review/ advice

Complicated Appendicitis (e.g. perforation, Up to 4 days then seek ID review/ advice

appendiceal collection / abscess) and Peritonitis

Prescribing Instructions
Table 2: Dosing recommendations in paediatric patients with normal renal function1
* Dose based on actual body weight. # All doses are expressed as Amoxicillin component

Age group * Dosing regimen #

Neonates and infants If less than 4kg: 25 mg/kg/dose (amoxicillin component) IV every 12 hours
(Birth to 3 months of
If more than 4kg: 25 mg/kg/dose (amoxicillin component) IV every 8 hours
age)

Infant and children Mild to moderate infection: 25 mg/kg/dose (amoxicillin component) IV

every 8 hourly (maximum 1000 mg amoxicillin component per dose)
(3 months to 12 years of
age)
Severe infection: 25 mg/kg/dose (amoxicillin component) IV
every 6 hourly (maximum 1000 mg amoxicillin component per dose)
Note: Maximum 800 mg clavulanic acid per 24 hour period.

Children and Mild to moderate infection: 1000 mg (amoxicillin component) IV every 8 hourly
adolescents
Severe infection: 1000 mg (amoxicillin component) IV every 6 hourly
(weighing more than
Note: Maximum 800 mg clavulanic acid per 24 hour period.
40 kg)
Critically ill patient with life-threatening infection: 25 mg/kg/dose (amoxicillin
component) IV every 6 hourly (maximum 2000 mg amoxicillin component per
dose. Note: Maximum 800 mg clavulanic acid per 24 hour period)

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Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

Table 3: Dosing recommendations in paediatric patients with renal impairment1

Creatinine Clearance (calculated using modified Schwartz formula $)

Creatinine Clearance $ Dose recommendation

Serious infection and Dose as for normal renal function

CrCl more than 30 mL/min

Moderate renal impairment 25 mg/kg/dose (amoxicillin component) IV every 8 hourly

(maximum 1000 mg amoxicillin component per dose)
(CrCl 10 to 30 mL/min)

Severe renal impairment 25 mg/kg/dose (amoxicillin component) IV every 12 hourly

(maximum 1000 mg amoxicillin component per dose)
(CrCl less than 10 mL/min)
Seek specialist/clinical pharmacist advice on dosing in renal
replacement therapy

$ Modified Schwartz formula is used to calculate Paediatric Creatinine Clearance (CrCl):

CrCl (mL/min/1.73m2) = [36.5 x Height (cm)] / Creatinine (micromol/L) = .............................................. mL/min/1.73 m2

**Not validated to be used in children <1 year of age. Cap CrCl at maximum of 150 mL/min/1.73m2.

Formulations1, 2
IV Amoxicillin-clavulanic acid is available in 500mg/100mg; 1000mg/200mg and 2000mg/200mg vials.
• Each 500/100 mg vial contains 0.5 mmoL (19.6 mg) of potassium and 1.4 mmoL (31.4 mg) of sodium
(approx.).
• Each 1000/200 mg vial contains 1 mmoL (39.3 mg) of potassium and 2.7 mmoL (62.9 mg) of sodium
(approx.).
• Each 2000/200 mg vial contains 1 mmoL (39.3 mg) of potassium and 5.5 mmoL (125.9 mg) of sodium
(approx.).

Powder volume:
• 500 mg/ 100 mg vial (0.5mL)
• 1000 mg/ 200 mg vial (0.9mL)
• 2000 mg/ 200 mg vial (0.9mL)

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Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

Reconstitution/Dilution1, 2
IV Amoxicillin-clavulanic acid 500/100mg vial:
Reconstitute contents of 500 mg/100 mg Amoxicillin/Clavulanic acid vial with 9.5 mL Water for Injection B.P.
(final volume 10 mL; final concentration 50 mg/mL amoxicillin component).
Dilute dose further with a compatible fluid to a final concentration of 10 mg/mL amoxicillin component, before
administering.

Note: Reconstituted solution is only stable for 20 minutes at room temperature (25 °C).

IV Amoxicillin-clavulanic acid 1000/200 mg vial:

Reconstitute contents of 1000 mg/200 mg Amoxicillin/Clavulanic acid vial with 19.1 mL Water for Injection
B.P. (final volume 20 mL; final concentration 50 mg/mL amoxicillin component).
Dilute dose further with a compatible fluid to a final concentration of 10 mg/mL amoxicillin component, before
administering.

Note: Reconstituted solution is only stable for 20 minutes at room temperature (25 °C).

IV Amoxicillin-clavulanic acid 2000/200 mg vial:

Reconstitute contents of 2000 mg/200 mg Amoxicillin/Clavulanic acid vial with 19.1 mL Water for Injection
B.P. (final volume 20 mL; final concentration 100 mg/mL amoxicillin component).
Dilute dose further with a compatible fluid to a final concentration of 10 mg/mL amoxicillin component, before
administering.

Note: Reconstituted solution is only stable for 20 minutes at room temperature (25 °C).

Stability1, 2
Vial: store below 25 °C. Protect from light.

Reconstituted solution: stable for 20 minutes at room temperature (25 °C).

Diluted solution:
Stable in sodium chloride 0.9% for 4 hours and in Hartmann's and Ringer's for 3 hours at room temperature
(25 °C).
Stable in sodium chloride 0.9% for 8 hours at 2 to 8 °C when added to a pre-refrigerated bag.

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Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

Compatibility1-3
Table 4: IV Amoxicillin/Clavulanic acid compatibility/incompatibility
Compatible Incompatible
Fluids Hartmann's (3 hours only) Glucose 5%
Ringer's lactate (3 hours only) Total parenteral nutrition (TPN)
Sodium chloride 0.9% (4 hours only) Lipids (SMOF, Clinoleic, Intralipid etc)
Blood products
Medications No information available Amiodarone
Amikacin
Ciprofloxacin
Gentamicin
Hydrocortisone
Methylprednisolone
Metronidazole
Midazolam
Sodium bicarbonate
Tobramycin

Route and Method of Administration1

Intravenous slow Injection
• NOT suitable for children aged less than 3 months
• In infants and children older than 3 months: Infuse the reconstituted solution over 3 to 5 minutes
• Caution: May cause thrombophlebitis if administered via peripheral intravenous cannula.

Intravenous Infusion
• Dilute dose in Sodium Chloride 0.9% to a final concentration of 20 mg/mL (amoxicillin component) and
infuse over 30 to 40 minutes. Stable in sodium chloride for 4 hours at room temperature (25 °C)
• Caution: May cause thrombophlebitis if administered via peripheral intravenous cannula.
• Infusion is not stable for use as a continuous infusion. Seek pharmacy advice for more details.
• Protect medication/infusion from light.
• NOT suitable for Intramuscular (IM) injection
• NOT compatible with Glucose 5%

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Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

Contraindications/Precautions1
• Confirmed allergy to penicillin’s beta-lactam/beta-lactamase inhibitor combinations precluding their use
• History of cholestatic jaundice or hepatic dysfunction associated with beta-lactam/beta-lactamase inhibitor
combinations. (Note: Pre-existing hepatic impairment is not a contraindication)
• Please seek advice from local pharmacy department for further specific information regarding adverse
effects, other precautions and monitoring required for prolonged therapy.

Clinical Considerations
• For directed therapy against a cultured organism, consult your Infectious diseases/AMS team for further
advice.
• Consider if your patient may be suitable for Early IV to Oral switch (refer to CHQ-GDL-01057 Antimicrobial
treatment: Early intravenous to oral switch - Paediatric Guideline).
• Dosing: Amoxicillin-clavulanic 22.5 mg/kg/dose (Max 875mg amoxicillin component) orally, 12-hourly

Consultation
Key stakeholders who reviewed this version:
• Pharmacist Advanced - Antimicrobial Stewardship, CHQ
• Pharmacist Advanced – Medication Safety and Quality, CHQ
• Director, Infection Management and Prevention service, Immunology and Rheumatology, CHQ
• Director of Pharmacy, CHQ
• Senior Clinical Pharmacist (Critical care), CHQ
• Clinical Pharmacy team leader (Medical and Surgical), CHQ

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Paediatric Medication Guideline - Intravenous Amoxicillin-Clavulanic acid

References and suggested reading

1. Ashley C, Currie A. Renal drug handbook. 3rd edition. UK Renal Pharmacy Group. IV
Amoxicillin/Clavulanic acid monograph. New York. 2009
2. Intravenous Amoxicillin-clavulanic acid (Juno) Product information. Available from www.tga.gov.au.
Accessed 11/10/2017.
3. Amoxicillin with Potassium clavulanate. Australian Injectable Drugs Handbook 8th edition (2019). The
Society of Hospital Pharmacists of Australia. Accessed online via CKN:
https://aidh.hcn.com.au/browse/about_aidh . Accessed 02/07/2019
4. Stabilis- IV Amoxicillin-clavulanic acid monograph. Available online:
http://www.stabilis.org/Monographie.pdf.php?Molecule=Amoxicillin%20sodium%20/%20clavulanic%20
acid . Accessed 11/10/2017
5. Plover C, Porrello E. Paediatric Injectable Guidelines. 2019 Ed. Flemington, Vic: The Royal Children’s
Hospital; 2019. Accessed online via CKN: https://pig.rch.org.au/monographs/ . Accessed 02/07/2019

Guideline revision and approval history

Version No. Modified by Amendments authorised by Approved by
1.0 Antimicrobial Stewardship Director of Pharmacy Executive Director Medical
12/10/2017 Pharmacist Director of Infection services
Management and Prevention
Services
2.0 Pharmacist Advanced – CHQ Medicines Advisory Executive Director Clinical
24/09/2019 Antimicrobial Stewardship Committee services

Keywords Amoxicillin, clavulanic acid, clavulanate, c-amoxiclav, antimicrobial stewardship, intravenous,

01240
Accreditation NSQHS Standards (1-8):
references • Standard 3 – Preventing and Controlling Healthcare Associated Infections
(Antimicrobial Stewardship)
• Standard 4 – Medication Safety

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