Amikacin is a partially restricted (amber) antibiotic for the treatment of infections due to gentamicin resistant Gram negative bacilli or as advised by microbiology. As with other aminoglycosides, therapeutic drug monitoring is required for amikacin due to adverse effects such as nephotoxicity and ototoxicity. The patient s renal function should be assessed prior to and daily during therapy. Amikacin has a high urine concentration, hence patients should be well hydrated prior to and during therapy to minimise chemical irritation to the renal tubules. Amikacin affects auditory function to a lesser extent than gentamicin. Dose recommendations: Amikacin does not distribute well in fatty tissues therefore should be dosed according to patient s ideal body weight (IBW) or adjusted body weight (ABW) for obese patients. Do not use patient s actual body weight unless the weight is < IBW. (a) Non-obese patients: Use ideal body weight (IBW) unless actual body weight is less. Use the following equation to calculate IBW: IBW for males (kg) = 50 + (2.3 x height in inches over 5 ft) IBW for females (kg) = 45.5 + (2.3 x height in inches over 5 ft) (b) Obese patients To avoid excessive dosage in obese patients (>20% of ideal body weight), the adjusted body weight (ABW)* should be used to calculate the required dose for obese patients: ABW (kg) = IBW + 0.4 (Actual body weight IBW) Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 1
The following chart tabulates height against ideal body weight, and indicates the weight above which the patient is defined as being obese: MEN WOMEN Height (ft) IBW (kg) Obese if >kg IBW (kg) Obese if > kg 5.0 50 61 45.5 55 5.1 52.3 63 47.5 58 5.2 54.6 66 50.1 61 5.3 56.9 69 52.4 63 5.4 59.2 72 54.7 66 5.5 61.5 74 57 69 5.6 63.8 77 59.3 72 5.7 66.1 80 61.6 74 5.8 68.4 83 63.9 77 5.9 70.7 85 66.2 80 5.10 73 88 68.5 83 5.11 75.3 91 70.8 85 6.0 77.6 94 73.1 88 6.1 79.9 96 75.4 91 6.2 82.2 99 77.7 94 6.3 84.5 102 80.0 96 6.4 86.8 105 82.3 99 Patient Category Obese (> 20% of IBW) Amikacin Dosage weight adjusted body weight (ABW)*: IBW + 0.4 (actual body weight IBW) Between IBW and not obese <IBW Use IBW Use actual body weight Renal Impairment The egfr can be used as a quick estimate for calculating the initial dose. Do not use egfr in patients at both extremes of weight (BMI <18.5kg/m 2 or greater than 30kg/m 2 ). The absolute glomerular filtration rate or creatinine clearance (calculated from the Cockcroft and Gault formular) should be used in these cases (see below). In patients >80years, reduce creatinine clearance by 20%. Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 2
Creatinine clearance can be estimated using the Cockcroft and Gault equation as below: Male Female CrCl = 1.23 (140 age) x weight* (kg) Serum Creatinine (μmol/l) CrCl = 1.04 (140 age) x weight* (kg) Serum Creatinine (μmol/l) * Obese patients those whose actual weight is 20% over their IBW, should have their dose calculated based on their adjusted body weight (see above) This equation will not work for Muscle wasting (patient s CrCl will be overestimated) Oedematous patients (use IBW) Ascites (use IBW and consider dilutional effect on serum creatinine) Acute renal failure. This may represent non-steady state serum creatinine levels and may underestimate the level of renal impairment CrCl can overestimate renal function in the elderly, consider 20% reduction of calculated CrCl for patients >80 years of age Dosage regimes Amikacin may be administered in several ways: 1. Single STAT dose/ Once daily dosing regimen: 15mg/kg once daily Amikacin exhibits a concentration-dependent bactericidal activity and a postantibiotic effect. Hence the administration of a large, once daily dose is intended for maximising the rate of killing bacteria, whilst the post-antibiotic effect prevents regrowth of bacteria. The lower trough concentrations may potentially result in a lower incidence of toxicity. Dose: 15mg/kg OD (Maximum daily dose: 1.5g for a maximum of 10 days) Administration: in 100ml sodium chloride 0.9% or glucose 5% infused over 30mins Exclusion of once daily dose regimen: High dose once daily regimen should be avoided in patients with: Endocarditis Burns of >20% of total body surface area Febrile Calculated creatinine clearance of < 20ml/min neutropenia Meningitis Pregnancy Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 3
Monitoring level for once daily regimen: Amikacin assays are sent to the Brompton for testing, results is usually available on the same day. Aim for a pre-dose (trough) level of < 5mg/L Routine peak level monitoring is unnecessary Take a pre-dose level (18-24 hours) before giving the next dose. Clearly mark on the request form how many hours after the dose the sample has been taken. Unless patients are at risk of nephrotoxicity due to pre-existing renal impairment or are receiving multiple nephrotoxic agents (e.g some chemotherapy agents). Do not wait for the result to come back before giving the next dose, adjust the regimen around the next and subsequent dose if applicable. Post dose (peak) levels are not required. Daily serum creatinine and urea is recommended for patients on IV amikacin If a patient s renal function is poor or deteriorates, await assay result and give dose when level < 5mg/L. Always monitor renal function carefully by checking urine output daily and serum creatinine levels 2 3 times per week, especially for courses longer than 5 days duration. Risk of toxicity increases when duration of the treatment course exceeds 5 days. Prolonged courses of amikacin must only be given only when there is a clear clinical need. Serum levels Trough level < 5mg/L Trough level > 5mg/L Continue current regimen Provided the renal function is stable and continued administration is required, monitor level every 3 5 days Check when the level was taken level taken < 18hrs are not true trough level Omit next dose, re-assay in 24hours. Re-dose if clinically indicated when levels fall 5mg/L but extend the dosing interval accordingly for subsequent doses depending on the creatinine clearance (see table below for dosing in renal impairment) Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 4
Renal impairment: The following table may be used as a guide for 15mg/kg regimen: Renal function (CrCl) Approx Creatinine value Dosing interval 60-120 ml/min (normal) 60-110 micromol/l 24 hours 40 59 ml/min 111-160 micromol/l 36 hours 21-39 ml/min 161 299 micromol/l 48-72 hours <20 ml/min > 300 micromol/l Avoid speak to microbiology or use conventional multiple dosing regimen (b) Conventional multiple daily dose therapeutic regimen: 7.5mg/kg BD Amikacin assays are sent to the Brompton for testing, results is usually available on the same day. Once daily amikacin regimen has largely superseded multiple daily dose regimens however may be used in certain circumstances (see exclusion for OD regimen) Dose: 7.5 mg/kg BD Maximum dose: 1.5g/day for maximum 10 days Monitoring level for multiple dose therapeutic regimen Both pre and post dose levels are required. Take pre-dose (trough level) sample before giving the 3 rd or 4 th dose after commencement. This should also be the case after any dose adjustment. Pre-dose (trough level) should be taken 8 or 12 hours after the previous dose for tds and bd regimens respectively Post-dose (peak level) should be taken ONE HOUR after the end of the infusion. Aim for pre-dose level (trough) level <10mg/L and 1 hr post dose (peak) levels not exceeding 30mg/L. Contact clinical ward pharmacist if in doubt. Renal impairment: In patients with renal impairment, determine the dose and dosing interval using the following table: Creatinine Clearance Dose Dosing Interval 20-50 ml/min 5-6 mg/kg every 12 hours 10-20 ml/min 3-4 mg/kg every 24 hours <10 ml/min 2 mg/kg every 24-48 hours Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 5
Pre-dose level <10mg/L > 10 mg/l Continue current regimen. Ensure the patient is responding clinically. Further pre-dose level to be monitored twice weekly so long renal function is stable Establish if level is a true pre-dose level which should be taken after 8hrs and 12 hrs for tds and bd regimen respectively Check where sample is taken from falsely high levels can be taken at the same line where the drug was given through. If pre-dose level appears genuine, further doses should be withheld until level <10mg/L. If further doses are required, re-start with increased interval/decreased dose. Post-dose level Within normal range (< 30mg/L) Level is high (>30mg/L) Pre and Post dose levels Pre-dose level < 10 mg/l (normal) Post dose level is above target range (>30mg/L) Check patient s renal function as high pre-dose level may coincide with decreased creatinine clearance. Continue with current regimen. Ensure patient is responding clinically Ensure level is not taken via an intravenous catheter that is used for the administration of the antibiotic as this will give false high level. Check if level is not taken too soon after the dose (must be one hour post dose level) If high post dose level appears genuine, consider reducing the dose (and the dose frequency). Final action dependent on trough level also. Check patient s renal function as a high post-dose level may coincide with decreased creatinine clearance. Reduce the dose Both pre-dose (>10mg/L) and post-dose levels (>30mg/L) are above target range Omit next dose Review need for further amikacin Consider increasing the interval between doses Restart when pre-dose level < 10mg/L Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 6
References: 1. BNF 64. Accessed via www.bnf.org 2. Gloucestershire Hospitals NHS Foundation Trust. Once daily amikacin administration and monitoring protocol, issue date 2008. Accessed via http://www.gloshospitals.nhs.uk/sharepoint110/antibiotics%20web%20documen ts/amikacin%20protocol.pdf 3. Ashford and St Peter s Hospital NHS Foundation Trust. Protocol for once daily 15mg/kg amikacin prescribing 4. Summary of product characteristics for amikacin. Accessed via www.medicines.org.uk Amikacin prescribing guidelines, Approved by Antimicrobial Stewardship Group, August 2013. Review date Aug 2015 7