CHHS18/169

Canberra Hospital and Health ServicesClinical Guideline Gentamicin - Clinical Guidelines for Dosing and Monitoring of Once Daily Gentamicin in Paediatric PatientsContents

Contents....................................................................................................................................1

Guideline Statement.................................................................................................................2

Scope........................................................................................................................................ 2

Section 1 – Indications, Contraindications and Precautions.....................................................3

Section 2 – Restrictions.............................................................................................................3

Section 3 – Prescribing the initial dose.....................................................................................3

Section 4 – Preparation.............................................................................................................4

Section 5 – Administration........................................................................................................5

Section 6 – Therapeutic Drug Monitoring (TDM)......................................................................5

Section 7 – Incompatibilities and Interactions..........................................................................6

Section 9 – Adverse Effects.......................................................................................................6

Section 10 – Monitoring of clinical outcomes for toxicity.........................................................7

Implementation........................................................................................................................ 8

Related Policies, Procedures, Guidelines and Legislation.........................................................8

References................................................................................................................................ 8

Definition of Terms...................................................................................................................9

Search Terms............................................................................................................................ 9

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Guideline Statement

BackgroundGentamicin use is indicated in the management of suspected or proven gram negative bacterial infections. Due to concerns about nephrotoxicity and ototoxicity, its use should be limited to 3 doses (within 48 hours duration) wherever possible.

The pharmacodynamic properties of gentamicin make once daily administration preferable to the traditional divided doses approach of giving aminoglycosides (e.g. three times daily dosing) in most children.

Key ObjectiveTo ensure the safe prescribing, administration and therapeutic drug monitoring of the aminoglycoside antimicrobial gentamicin, in 0-16 year old patients for the treatment of infection at the Canberra Hospital and Health Services (CHHS).

Alerts Despite monitoring and maintaining gentamicin levels within an accepted range (when drug monitoring is indicated), it is possible, although uncommon, for toxicity to occur. The most reliable way to prevent gentamicin toxicity is to minimise its use. Patients with risk factors for toxicity should have therapeutic drug monitoring (TDM).

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Scope

The document applies to ACT Health staff working within their scope of practice that prescribe, administer, monitor or advise on the use of once daily gentamicin in paediatric patients at CHHS.

This procedure does not apply to: Adults: (see Intravenous Dosing and Monitoring of Aminoglycosides in Adults Procedure) Patients admitted to the Neonatal Intensive Care Unit or Special Care Nursery Greater frequency than once daily dosing, e.g. treatment of bacterial endocarditis Routes of administration other than intravenous (I.V.) or intramuscular (I.M.) e.g. intra-

peritoneal or inhaled gentamicin

If therapy is required in the above situations, please refer to the relevant Procedure, or seek expert advice from a Pharmacist, Infectious Diseases Physician, Paediatrician or Renal Physician, regarding dosage and monitoring.

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Section 1 – Indications, Contraindications and Precautions

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Indications Empiric treatment of severe Gram negative infections (maximum 48 hours, 3 doses) Other serious infections due to sensitive organisms that are resistant to other

antimicrobials Surgical prophylaxis per Therapeutic Guidelines: Antibiotic

Contraindications Hypersensitivity to aminoglycosides Previous aminoglycoside-induced ototoxicity or nephrotoxicity

Precautions A paediatric nephrologist or renal service should be consulted in the following situations

as the gentamicin dose may need to be decreased o A child ≤ 2yo with an elevated creatinine o A child > 2yo with an estimated Glomerular Filtration Rate (eGFR) less than

70mL/min/1.73m2

Note: eGFR (mL/min/1.73m2 ) = 36.5 x height (cm) / serum creatinine (micromol/L)

Pre-existing hearing impairment Neuromuscular disease

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Section 2 – Restrictions

Gentamicin is an “ORANGE” restricted antimicrobial (as per the Antimicrobial Stewardship procedure).

If Gentamicin is required beyond 48 hours (i.e. 3 doses) an application for AMS approval must be requested. For instructions on seeking AMS approval, refer to the Antimicrobial Stewardship procedure.

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Section 3 – Prescribing the initial dose

Gentamicin can be given via the intramuscular route in the absence of intravenous access.

Dose is based on lean body weight (LBW) whenever the patient’s actual weight is ≥20% above their LBW.

Dose varies with the age of the patient.

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Paediatric Dose of I.V. or I.M. Once Daily GentamicinBirth (at term) – 1 month 4 - 5mg/kg/dose> 1 month - 10 years old 7.5 mg/kg/dose (max 320mg)>10 years old 6-7 mg/kg/dose (max 560mg)Base dose on lean body weight (LBW) whenever actual weight is ≥ 20% above LBW

How to calculate lean body weight (LBW)o Plot the patient’s height on the appropriate height for age percentile chart and

determine their height percentile. Then, using the appropriate weight for age percentile chart, determine the weight that corresponds to the patient’s height percentile. This weight is the patient’s Lean Body Weight (LBW).

o If the patient’s actual weight is 20% more than their LBW, use the LBW for aminoglycoside dose calculation.

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Section 4 – Preparation

Gentamicin is available in the following forms: Gentamicin sulphate 80mg/2mL solution for injection. Gentamicin sulphate 10mg/1mL solution for injection. For all paediatric patients, double check all dose calculations/manipulations with a

second Registered Nurse/Medical Officer/Medication Endorsed Enrolled Nurse. Draw up required dose of gentamicin. Dilute the dose with a patient appropriate volume of sodium chloride 0.9% solution (as

per Royal Children’s Hospital Melbourne Paediatric Injectable Guidelines publication 5th Edition).

Invert the diluted dose to ensure adequate mixing of the solution. Inspect the product to ensure it is free from particulate matter or discolouration. Label the syringe/minibag and IV line with a user applied label in accordance with the

National Recommendations for User-applied Labelling of Injectable Medicines, Fluids and Lines, available on the Policy Register.

To reduce the risk of microbiological contamination, infuse as soon as possible after dilution.

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Section 5 – Administration

The initial aminoglycoside dose should be administered as soon as clinically required.

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Perform correct patient identification procedures prior to medication administration. Refer to Patient Identification and Procedure Matching Procedure.

Infuse intravenously over 30 minutes. It is imperative for therapeutic drug monitoring (if required) that the starting

administration time is accurately recorded on the medication chart.

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Section 6 – Therapeutic Drug Monitoring (TDM)

No TDM is necessary for: Term neonates, infants and children, if treatment course is planned for up to 3 doses

(48hrs) only; and Renal function is normal at baseline and during treatment if checked; and No concurrent nephrotoxic or ototoxic drugs are used.

Note:Oncology patients with febrile neutropaenia do not require routine TDM unless in high risk categories as listed below.

High risk patients/TDM Indications Treatment required beyond 48 hours Preterm neonate- refer to NICU Risk of Nephrotoxicity:

o Critically unwell / ICU patient; or o Cystic fibrosis patients; or o Obese patient (>95th centile BMI); or o Renal impairment (i.e. creatinine above normal range for age) o Concurrent (or recent) administration of potentially nephro- or ototoxic medications

1. Nephrotoxic agents include frusemide, vancomycin, amphotericin, cisplatin, other aminoglycosides, aciclovir, regular use of NSAIDs

2. Ototoxic agents: eg. cisplatin and other aminoglycosides o Frequent courses of aminoglycosides (e.g. in preceding 6 months) o Previous aminoglycoside-induced toxicity

TDM Methods: For term neonates and older, with normal renal function, if further dosing beyond 48

hours is required: o take a trough level before the fourth dose (at 72 hours)

1. if trough level is high (> 1 mg/L), discuss extending the dosing interval with the patient’s paediatrician and consider discussing with infectious diseases team.

2. further levels are usually indicated every 48 hours but more frequently if renal function is changing rapidly or substantially.

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Patients with renal impairment or at risk of nephrotoxicity (see list above):o take a trough level before the second dose (at 24 hours) and adjust dose in

consultation with paediatrician or paediatric nephrologist. The usual target trough is <1mg/L. In renal impairment, TDM should be done prior to each dose whilst renal function is impaired.

Patients receiving multiple daily dosing regimen (e.g. treatment of endocarditis): o trough levels (e.g. before the fourth dose) and liaise with paediatrician and

cardiologist. This protocol does not cover oral gentamicin which may be used for conditions such as

small bowel bacterial overgrowth. Please consult with the patient’s paediatric gastroenterologist for guidance, but levels are not required as it is not enterally absorbed.

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Section 7 – Incompatibilities and Interactions

Aminoglycosides have many incompatibilities, so should not be mixed with other drugs. For more information on specific drug incompatibilities refer to the Australian Injectable Drugs Handbook (6th edition).

Aminoglycosides are inactivated by penicillins, cephalosporins and teicoplanin so these drugs should not be administered simultaneously. If both medications are scheduled at the same time, administer the gentamicin first, flush the line well with sodium chloride 0.9%, and then give the other antibiotic.

Avoid concurrent administration with other nephrotoxic drugs. Potent diuretics such as frusemide may contribute to ototoxicity and nephrotoxicity and

may also cause alterations in serum and tissue concentrations. The neuromuscular blocking activity of some drugs, such as anaesthetic agents or opioid

analgesics may be enhanced. For more information on specific drug interactions contact Medicines Information

extension 43333.

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Section 9 – Adverse Effects

Nephrotoxicity (usually reversible)o Gradual worsening of renal function, increasing serum creatinine and proteinuria.o May present as acute tubular necrosis.o More common in patients with pre-existing renal impairment.o In vitro, once daily dosing results in lower renal cortical concentrations compared to

continuous infusions or traditional dosing and it is therefore hypothesised that once daily dosing may lessen nephrotoxicity.

o More likely to be associated with duration of treatment longer than 7 days.

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Ototoxicity (irreversible in approximately half of cases)o Aminoglycosides affect both cochlear and vestibular function, with high frequency

being affected before low frequency hearing. o May present as nausea, vertigo or tinnitus.

Adverse outcomes should be recorded in the patient notes, as well as documented in Riskman as per the ACT Health Incident Management policy. Unexpected or serious adverse events should be reported to the Therapeutic Goods Administration.

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Section 10 – Monitoring of clinical outcomes for toxicity

Renal Function o Serum creatinine or estimated GFR should be determined:

a. at baselineb. with serum gentamicin levels after 3 doses if planning to continue and then

every 3 days during therapy (or more frequently if renal impairment is detected at any time).

o Worsening renal function may be an early indicator of impending clinical toxicity. o If nephrotoxicity occurs at any time, consider alternative antimicrobial therapy.

Hearing and vestibular function o Absence of hearing impairment should be assessed by history at the start of

therapy.o Absence of clinically significant vestibular dysfunction should be assessed by history

at the start of therapy. Symptoms include dizziness and unsteady gait. o Testing for hearing and vestibular function should be done for patients receiving

gentamicin for longer than 5 days and repeated periodically if therapy is continued for more than 14 days. Signs of vestibular dysfunction include nystagmus, ataxia and a positive Romberg’s sign.

Alert: Ototoxicity and vestibular toxicity is often irreversible. If developing, treatment with gentamicin should usually be stopped and alternatives considered.

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Implementation

Procedure will be available on the CHHS policy register. Education sessions will be held with nursing and medical staff involved the in the provision of antimicrobial agents to paediatric patients at CHHS.

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Related Policies, Procedures, Guidelines and Legislation

Policies Patient Identification and Procedure Matching Policy Nursing and Midwifery Continuing Competence Policy Medication Handling Policy

Procedures Procedure Intravenous Dosing and Monitoring of Aminoglycosides in Adults Patient Identification and Procedure Matching Procedure Antimicrobial Stewardship Procedure Healthcare Associated Infections Procedure

Guidelines Intravenous Dosing and Monitoring of Aminoglycosides in Adults

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References

1. Clinical Excellence Commission (2017) Safe Gentamicin Prescribing in Paediatrics available at http://www.cec.health.nsw.gov.au/patient-safety-programs/paediatric-patient-safety/pqp-medication-safety accessed on 17/05/2018.

2. Sydney Children’s Hospital (2015) Once Daily Gentamicin Practice Guideline available at http://www.schn.health.nsw.gov.au/_policies/pdf/2012-7008.pdf accessed on 17/05/2018.

3. The Children’s Hospital at Westmead (2015) Aminoglycoside dosing and monitoring- CHW Practice Guideline available at http://www.schn.health.nsw.gov.au/_policies/pdf/2011-8018.pdf accessed on 17/05/2018.

4. Australian Medicines Handbook; Children’s Dosing Companion (2018) Gentamicin available at https://childrens.amh.net.au/monographs/gentamicin accessed on 17/05/2018.

5. Kids Cancer Centre, Sydney Children’s Hospital Randwick (2017) Supportive Management Information for Medical and Nursing Staff. Accessed January 2018.

6. MIMS Online (2017) Gentamicin Injection BP available at https://www.mimsonline.com.au/Search/Search.aspx accessed 17/05/2018.

7. eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; March 2018.8. The Royal Children’s Hospital Melbourne (2011) Paediatric Injectable Guidelines. 4th

Edition. Parkville, Victoria. 9. The Society of Hospital Pharmacists of Australia (2016) Australian Injectable Drugs

Handbook. 7th ed. Collingwood.

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10. Hermsen, E. (2012) Nebraska Medicine Pharmacokinetic Training Packet for Pharmacists (revised June 2012). Available at from nebraskamed.com/app_files/pdf/careers/education-programs/asp/pk_trainingpacket_2012.pdf accessed 04/06/2018.

11. Australian Commission on Safety and Quality in Health Care (2012) National Recommendations for User-applied Labelling of Injectable Medicines, Fluids and Lines available at https://www.safetyandquality.gov.au/wp-content/uploads/2015/09/National-Standard-for-User-Applied-Labelling-Aug-2015.pdf accessed on 17/05/2018.

12. Wolters Kluwer Health (2018) Stedman’s Medical Dictionary available at: http://www.medilexicon.com/dictionary accessed on 14/05/2018.

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Definition of Terms

Romberg’s sign: Romberg's sign is a test used in an exam of neurological function for balance.

Nephrotoxicity: The quality or state of being toxic to kidney cells.

Ototoxicity: The property of being injurious to the functions of the ear.

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Search Terms

Gentamicin, Paediatric gentamicin, Gentamicin dosing, Gentamicin monitoring

Disclaimer: This document has been developed by Health Directorate, Canberra Hospital and Health Services specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and Health Directorate assumes no responsibility whatsoever.

Policy Team ONLY to complete the following:Date Amended Section Amended Divisional Approval Final Approval 18 Apr 18 Complete Review Karen Faichney, A/g ED

WY&CCHHS Policy Committee

This document supersedes the following: Document Number Document NameCHHS14-009 Paediatrics - Clinical Guidelines for Dosing and Monitoring of Once Daily

Gentamicin and Tobramycin in Paediatric Patients

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