Adult

Amikacin

General Information

Restricted formulary antimicrobial: For details see OUH netFormulary

AWaRe antibiotic classification: 'Watch'. Use as per guidelines. All other indications to be discussed with Micro/ID.

  • Amikacin is given intravenously or if this route is unavailable, by intramuscular injection.
  • It is not suitable for oral use.

Use of more than 2 doses is for exceptional circumstances and should be discussed with Micro/ID unless for Non-Tuberculosis Mycobacterium (NTM) infection in cystic fibrosis patients or MDR TB.

Cautions

  • Do not give amikacin to patients with myasthenia gravis or a familial susceptibility to aminoglycoside toxicity.
  • Patients at higher risk of renal toxicity:
    • Haemodynamic compromise, e.g. dehydration* or shock (cardiogenic, septic), especially in combination with nephrotoxic drugs e.g. ACE-inhibitor, diuretics (especially IV), NSAIDs, ciclosporin, colistimethate sodium, radio-contrast media, high-dose methotrexate or amphotericin B liposomal (Tillomed/Gilead/AmBisome).
    • Chronic renal impairment (CKD 3-5) i.e. creatinine clearance less than 60ml/min.

          In these scenarios use amikacin with caution. Monitor serum creatinine and amikacin concentrations.

*Correct dehydration where possible before commencing amikacin.

  •  Risk of renal toxicity increases when duration of the treatment course exceeds 5 days. Longer courses of amikacin should only be prescribed when clinical benefit outweighs the risk.

 

Mitochondrial mutations MHRA drug safety update (January 2021)

Evidence suggests an increased risk of aminoglycoside-associated ototoxicity in patients with certain mitochondrial mutations (particularly the m.1555A>G mutation), including cases in which the patient’s aminoglycoside serum levels were within the recommended range. These mitochondrial mutations are rare and frequency of complication is uncertain. 

Genetic testing should not delay urgently needed aminoglycoside treatment but consider the need for genetic testing, particularly in those requiring recurrent or long-term treatment with aminoglycosides.

Where the patient has a susceptible mutation consider the need for aminoglycoside treatment versus alternative options. 

Reference:  MHRA. Drug Safety update (January 2021) Aminoglycosides (gentamicin, amikacin, tobramycin, and neomycin): increased risk of deafness in patients with mitochondrial mutations. Accessed at https://www.gov.uk/drug-safety-update/aminoglycosides-gentamicin-amikacin-tobramycin-and-neomycin-increased-risk-of-deafness-in-patients-with-mitochondrial-mutations

Adverse effects

Most adverse effects due to amikacin are dose related. Amikacin has a narrow therapeutic index.

Irreversible vestibular and auditory damage, and nephrotoxicity are the most common adverse effects. They occur most frequently in elderly patients and in those with higher risk of renal toxicity as described above.

To minimise the risks of adverse events, including ototoxicity, monitor in all patients:

  • Renal function (serum creatinine, creatinine clearance) before, during and after treatment.
  • Hepatic function before, during and after treatment.
  • If treatment is longer than 2 weeks or if 15g per treatment course reached (whichever is sooner), auditory testing is needed at beginning and end of treatment. Test sooner if patient develops symptoms of deafness or vestibular dysfunction develops.
  • Patients should be advised to report immediately the onset of any sign of deafness or vestibular dysfunction.

NB: For information for Audiometry assessment see  Audiometry and intravenous aminoglycosides

Amikacin IV Treatment – calculating initial dose

STEP 1. Calculate the dosing weight (DW)

Calculate the dosing weight (DW) ie weight that is used to calculate the amikacin dose – this may differ from actual body weight as below.

a)    Obtain actual body weight in kg (ABW)

b)    Estimate ideal body weight (IBW). IBW (kg) = [males 50kg, females 45kg] + 2.3kg per inch over 5ft.

c)    Establish DW

If ABW within 20% of IBW then DW = ABW

If overweight by more than 20% above IBW then calculate DW using the formula:

                                                           DW = IBW + 0.4 x (ABW – IBW)

If underweight by more than 20% below IBW then calculate DW using the formula:

                                                           DW = IBW - 0.4 x (IBW –ABW)

 STEP 2. Determine Creatinine Clearance (CrCl)

Determine Creatinine Clearance using the Cockcroft-Gault equation (below).

CrCl (mL/min) = F x (140-age) x weight* (kg)              

                             Serum Cr (micromol/L)

where F=1.04 (females) or F=1.23 (males)

* use IBW if ABW is over 20% above IBW.

 

STEP 3. Calculate initial amikacin dose

  • Calculate initial amikacin dose using the dose by weight band table below
  • Use ABW or DW as calculated on step 1
  • Maximum daily dose is 1500mg
  • Recommended maximum dosage per treatment course: 15g (for example 1500mg for 10 days) due to risk of ototoxicity.
    • For NTM and MDRTB prolonged courses are often used but these have to be approved by Micro/ID/Respiratory
    • In difficult and complicated infections where treatment beyond 15g per treatment course is considered, the use of amikacin sulphate injection should be re-evaluated and, if continued, renal, auditory, vestibular function should be monitored, as well as serum amikacin levels.

Usual Treatment Dose (CrCl over 50ml/min): 15mg/kg IV 24 hourly (see weight banding below)

Usual Treatment Dose by Weight Band: 

Dosing weight (DW) - As calculated in STEP 1 above  Dose based on 15mg/kg DW
50 - 55kg 750mg 24 hourly 
56 - 63kg 875mg 24 hourly
64 - 73kg 1000mg 24 hourly 
74 - 81kg 1125mg 24 hourly
82 - 88kg 1250mg 24 hourly
89 - 99kg 1375mg 24 hourly 
100kg or greater  1500mg 24 hourly 

Indications where higher doses may be required:  When treating true infections due to DTR-PSAR/Multi-drug resistant infection, a higher dose may be appropriate and the target trough level might be different - follow Micro/ID advice. 

Difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PSAR) infection

Carbapenemase-producing Enterobacterales (CPE) treatment

Renal and hepatic impairment

Renal impairment

Amikacin is renally excreted and can accumulate in renal failure. The dose of amikacin must therefore be adjusted in renal impairment

Creatinine Clearance (ml/min)

 Dose

20-50

10mg/kg every 24 hours

10-19

3-4mg/kg every 24 hours

Less than 10

2mg/kg every 24-48 hours

HD/HDF/High Flux 

5mg/kg. Dialysed; to be given after dialysis

Note: dose ranges use creatinine clearance, rather than eGFR.

 

Hepatic impairment

  • Use with caution due to the risk of hepatorenal syndrome.
  • No dose adjustment required in hepatic impairment.

Monitoring (for patients receiving more than 2 doses of Amikacin)

  • Aim for a pre-dose (trough) level of less than 5mg/L
  • Routine peak level monitoring is unnecessary
  • Take a pre-dose (trough) level ONE HOUR before the dose is due.
    • For patient with CrCl greater than 50ml/min: level should be taken before the third dose after starting therapy
    • For patient with CrCl 50ml/min or less: level should be taken before the second dose after starting therapy.
  • Do not wait for the result to come back before giving the next dose, unless the patients are at risk of nephrotoxicity or the renal function is deteriorating.
  • If a patient is at risk of nephrotoxicity or renal function is impaired or deteriorating (AKI stage 2-3), await assay result and give dose when level less than 5mg/L.
  • Serum creatinine, urea and liver function tests are recommended daily around initation, after dose change or in patients with renal impairment.
  • For patients with stable renal and liver function monitor serum creatinine, urea and liver function every 3-5 days.

Actions required based on trough levels:

Serum Level

Action

 

Less than 5mg/L
  • Continue the same dose regime

Monitoring amikacin level:

  • If renal function is unstable or deteriorating (AKI stage 2-3): Monitor amikacin level daily
  • If renal function is stable: Monitor amikacin level every 3-5 days
  • For MDR TB, who required prolonged course: Monitor amikacin level weekly for 4 weeks then fortnightly when stable (discuss with Micro/ID)

 

5mg/L or more
  • Check when the amikacin level was taken to ensure it is a TRUE trough level
  • If level between 5 and 6.5mg/L: Re-check amikacin level in 12 hours
  • If greater than 6.5mg/L: Re-check amikacin level in 24 hours
  • Re-dose if clinically indicated when levels fall below 5mg/ml (as per renal impairment section)

Pregnancy and breastfeeding

Pregnancy

Use only if potential benefit outweighs risks. If given, serum-amikacin concentration monitoring is essential.                                                                   

Breastfeeding

Discuss with pharmacy.

References

Editorial Information

Next review date: 02 Mar 2026