Renal Dosing (Adults)

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N.B. Estimates of GFR will not be accurate when the patient has an Acute Kidney Injury i.e. if the creatinine is rising or falling. The full clinical picture should always be taken into account.

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Acute Kidney Injury

  • For detailed information on antimicrobial dosing in Acute Kidney Injury, please see 'Critical Illness' reference on Medicines Complete, www.medicinescomplete.com .  This is available free of charge on all HSE desktops and is also available on your smartphone via www.hselibrary.ie , please contact the HSE Library directly for an account if you do not already have one.
  • A loading or initial dose of antimicrobial therapy should be administered as soon as possible in sepsis or septic shock (ideally within the first hour of presentation).
  • Even in renal dysfunction, the full dose of beta-lactams should be used for at least the first dose and potentially the first 24 to 48 hours unless patient is frail, elderly, or has very low body-weight (Critical Illness).  Contact Pharmacy for advice if needed.
  • Any dose reduction of beta-lactams in response to AKI needs to be undertaken with caution ; much AKI seen in critical care is related to sepsis. The apparent Vd of beta-lactams can increase in sepsis and septic shock. The therapeutic consequences of underdosing antimicrobials in these patients may be severe and there is generally considered to be a wide margin of error before toxicity.  Underdosing may lead to treatment failure and resistance. Due to these factors, it is common practice within critical care areas to administer standard doses for the first 24 to 48 hours.
  • For potential nephrotoxins , e.g. gentamicin , vancomycin , check LH Guidelines as well as Critical Illness Reference.  Also use clinical judgement with regard to dose.  Contact Pharmacy for advice if needed.
  • In patients presenting with an AKI, it is the acute changes in kidney function that must be considered and used to guide dose adjustments, rather than categories of function.
  • During AKI, serum creatinine levels lag behind the development of the injury and progress of recovery.  As creatinine rises, estimates of GFR will overestimate renal function and as creatinine falls and kidney function improves, estimates of GFR will underestimate renal function (BNF).

References:

  • Critical Illness, www.medicinescomplete.com, accessed 4/3/24
  • British National Formulary, www.medicinescomplete.com, accessed 4/3/24.

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Chronic Kidney Disease

Calculate Creatinine Clearance

These tables apply to adult patients with chronic kidney disease only. They do not apply to patients on dialysis or those with acute kidney injury.

Antimicrobial

Aciclovir IV

Adult Renal Dose Adjustment

GFR 25 – 50 ml/min : 5 – 10mg/kg every 12 hours

GFR 10 – 25 ml/min : 5 – 10mg/kg every 24 hours

GFR < 10 ml/min : 2.5 – 5mg/kg every 24 hours

References

Antimicrobial

Aciclovir ORAL

Adult Renal Dose Adjustment

GFR​ 25 – 50 ml/min : Simplex: Usual dose; Zoster: Usual dose

GFR 10 – 25 ml/min : Simplex: 200mg 4  times a day; Zoster: 800mg every 8 hours

GFR < 10 ml/min : Simplex: 200mg every 12 hours; Zoster: 800mg every 12 hours

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

Antimicrobial

Amikacin

Adult Renal Dose Adjustment

GFR 30 – 50 ml/min : 10mg/kg daily

GFR 10 – 30 ml/min : 5mg/kg daily

GFR < 10 ml/min : 3mg/kg STAT

NB. Check trough level 16 – 24 hours after first dose. Trough < 5mg/L.

If renal function stable, check trough level every 3 doses.

If renal function abnormal or unstable, check trough level daily and wait for result unless patient acutely septic – in this case, contact Dr for advice.

REVIEW DURATION OF AMIKACIN AS SOON AS POSSIBLE.

References

  • Beaumont Hospital Antimicrobial Guidelines, 2023. Obtained with permission from Consultant Microbiologist.

Antimicrobial

Amoxicillin IV / ORAL

Adult Renal Dose Adjustment

GFR​ 10 – 50ml/min : Usual dose

GFR < 10 ml/min : 250mg – 1g every 8 hours (max 6g per day in endocarditis)

References

Antimicrobial

Anidulafungin

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Aztreonam

Adult Renal Dose Adjustment

GFR 30 – 50 ml/min : Usual dose

GFR 10 – 30 ml/min : 1 – 2g loading dose, then 50% of usual dose [note – maximum daily dose 8g if normal renal function]

LH: Usual practice 1g TDS IV

GFR < 10 ml/min : 1 – 2g loading dose, then 25% of usual dose [note – maximum daily dose 8g if normal renal function]

LH: Usual practice 500mg TDS IV

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

Antimicrobial

Benzylpenicillin

Adult Renal Dose Adjustment

GFR 20 – 50 ml/min : Usual dose

GFR 10 – 20 ml/min : 600mg to 2.4g every 6 hours

GFR < 10 ml/min : 600mg to 1.2g every 6 hours

References

Antimicrobial

Cef-AL-exin

Adult Renal Dose Adjustment

GFR 30 – 50 ml/min : Usual dose

GFR​ 10 – 30 ml/min : 250mg – 500mg every 8 to 12 hours

GFR < 10 ml/min : 250mg – 500mg every 12 to 24 hours

References

Antimicrobial

Cef-AZ-olin

Adult Renal Dose Adjustment

GFR > 35 ml/min: Usual dose

GFR 11 – 34 ml/min: 500mg to 1g every 12 hours

GFR < 10 ml/min: 500mg to 1g every 24 hours

References

Antimicrobial

Cef-O-taxime

Adult Renal Dose Adjustment

GFR 5 – 50ml/min : Usual dose

GFR < 5 ml/min : 50% of dose at usual frequency

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Cef-TAZ-idime

Adult Renal Dose Adjustment

GFR 31 – 50 ml/min :1g – 2g every 12 hours

GFR 16 – 30 ml/min :1g – 2g every 24 hours

GFR​ 6 – 15 ml/min : 500mg – 1g every 24 hours

GFR < 5 ml/min : 500mg – 1g every 48 hours

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Cef-TRI-axone

Adult Renal Dose Adjustment

GFR 10 – 50ml/min : Usual dose

GFR​ < 10 ml/min : Maximum dose 2g every 24 hours

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Cef-UR-oxime IV

Adult Renal Dose Adjustment

GFR 20 – 50ml/min : Usual dose

GFR​ 10 – 20ml/min: 750mg – 1.5g every 12 hours

GFR < 10ml/min: 750mg – 1.5g every 24 hours

References

Antimicrobial

Ciprofloxacin IV / ORAL

Adult Renal Dose Adjustment

GFR​ 30 – 50 ml/min : Usual dose

GFR 10 – 30 ml/min : 50 – 100% of usual dose

GFR < 10 ml/min : 50% of usual dose

References

Antimicrobial

Clarithromycin IV / ORAL

Adult Renal Dose Adjustment

GFR 30 – 50 ml/min : Usual dose

GFR < 30ml/min : 250mg – 500mg every 12 hours

References

Antimicrobial

Clindamycin IV / ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Co-amoxiclav IV

Adult Renal Dose Adjustment

GFR 30 – 50 ml/min : Usual dose

GFR < 30 ml/min : 1.2g every 12 hours

References

Antimicrobial

Co-amoxiclav ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

Antimicrobial

Co-trimoxazole IV / ORAL

Treatment doses only

Note Trimethoprim causes a functional increase in creatinine

Adult Renal Dose Adjustment

GFR​ 30 – 50 ml/min : Usual dose

GFR 15 – 30 ml/min : 50% of dose; PCP: 60mg/kg every 12 hours for 3 days then 30mg/kg every 12 hours

GFR​ < 15 ml/min : 50% of dose; PCP: 30mg/kg every 12 hours

**Only to be given if haemodialysis facilities available**

References

Antimicrobial

Daptomycin

Adult Renal Dose Adjustment

GFR​ 30 – 50 mL/min: Usual dose

GFR < 30 mL/min : Usual dose 48 hourly

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

Antimicrobial

Doxycycline

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Erythromycin IV / ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

Antimicrobial

Flucloxacillin IV / ORAL

Adult Renal Dose Adjustment

GFR 10 – 50ml/min : Usual dose

GFR < 10 ml/min : Maximum 4g per day

References

Antimicrobial

Fluconazole IV / ORAL

Adult Renal Dose Adjustment

No dose adjustment required for single dose therapy

GFR 10 – 50 ml/min : 50 – 100% of usual dose

GFR < 10 ml/min : 50% of usual dose

References

Antimicrobial

Gentamicin IV ONCE DAILY

Adult Renal Dose Adjustment

GFR 10 – 50 ml/min : 3mg/kg once daily

GFR < 10 ml/min : 1.5mg/kg stat, redose when level < 1mg/L

NB. Check trough level 16 – 24 hours after first dose. Trough < 1mg/L.

If renal function stable, check trough level every 3 doses.

If renal function abnormal or unstable, check trough level daily and wait for result unless patient acutely septic – in this case, contact Dr for advice.

REVIEW DURATION OF GENTAMICIN AS SOON AS POSSIBLE.

References

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

  • Beaumont Hospital Antimicrobial Guidelines, 2023. Obtained with permission from Consultant Microbiologist.

Antimicrobial

Levofloxacin IV / ORAL

Adult Renal Dose Adjustment

GFR 20 – 50 ml/min : 500mg stat, then 250mg every 12 hours

GFR 10 – 20 ml/min : 500mg stat, then 125mg every 12 hours

GFR < 10 ml/min : 500mg stat, then 125mg every 24 hours

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

  • BMJ Group and Pharmaceutical Press. British National Formulary. Available from www.medicinescomplete.com , accessed 30/04/18.

Antimicrobial

Linezolid IV / ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment. Use with caution when CrCl < 10 mL/min and monitor FBC closely.  Metabolites with MAOI activity may accumulate in renal failure, monitor patients closely .

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

Antimicrobial

Meropenem

Adult Renal Dose Adjustment

GFR 26 – 50 ml/min : 500mg – 2g every 12 hours. For severe or CNS infections, can use 1g every 8 hours.

GFR 10 – 25ml/min : 500mg – 1g every 12 hours or 500mg every 8 hours

GFR < 10 ml/min : 500mg – 1g every 24 hours

References

Antimicrobial

Metronidazole IV / ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Nitrofurantoin

Adult Renal Dose Adjustment

GFR 45 – 60 ml/min : Usual dose, use with caution

GFR 30 -  45 ml/min : Contra-indicated.  An expert group from the MHRA has advised nitrofurantoin may be used with caution as short-course therapy for lower UTI in patients with eGFR 30–44 mL/min/1.73m 2 to treat resistant pathogens , when the benefits may outweigh the risks.

GFR < 30 ml/min : Avoid

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

  • BMJ Group and Pharmaceutical Press. British National Formulary. Available from www.medicinescomplete.com , accessed Jan 2023.

Antimicrobial

Oseltamivir

Adult Renal Dose Adjustment

GFR 30 – 60 ml/min: Usual dose

GFR 10 - 30 ml/min:

Treatment: 75 mg once daily or 30 mg twice daily.

Prophylaxis: 75 mg every 48 hours or 30 mg once daily.

GFR < 10 ml/min:

Treatment: 75 mg as a single dose.

Prophylaxis: 30 mg once a week (2 doses).

References

Antimicrobial

Phenoxymethylpenicillin

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

Antimicrobial

Piperacillin with Tazobactam

Adult Renal Dose Adjustment

GFR 40 to 50 ml/min: Usual dose

GFR 20 to 40 ml/min : 4.5g every 8 hours

GFR < 20 ml/min : 4.5g every 12 hours

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed Jan 2023.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed Jan 2023.

  • BMJ Group and Pharmaceutical Press. British National Formulary. Available from www.medicinescomplete.com , accessed Jan 2023.

Antimicrobial

Rifampicin

Adult Renal Dose Adjustment

GFR 10 – 50ml/min : Usual dose

GFR < 10 ml/min : 50 – 100% of usual dose

References

Antimicrobial

Sodium Fusidate

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

Antimicrobial

Vancomycin IV

Adult Renal Dose Adjustment

GFR 20 – 50 ml/min : 25mg/kg STAT dose, then 15mg/kg every 24 hours starting approx. 24 hours after STAT dose (No loading dose if pregnant)

GFR < 20 ml/min : 25mg/kg STAT dose. Check trough level daily and wait for result. Re-dose with 15mg/kg when trough < 20mg/L and adjust further doses based on trough level results. (No loading dose if pregnant)

N.B. Check trough level within one hour before dose on day 3 (pre-4 th or 5 th dose for twice or three times daily dosing). Trough level 15 – 20 mg/L.

References

  • LH Vancomycin Dosing and Monitoring Guideline, 2018.

Antimicrobial

Voriconazole IV

Adult Renal Dose Adjustment

When GFR < 50 ml/min, accumulation of the intravenous vehicle, sulphobutylether beta cyclodextrin sodium occurs. Use oral voriconazole unless a risk benefit assessment justifies use of IV. Voriconazole has 96% oral bioavailability.

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

Antimicrobial

Voriconazole ORAL

Adult Renal Dose Adjustment

No dose adjustment required in renal impairment

References

  • Health Products Regulatory Authority.  Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  • CRC Press. The Renal Drug Database. Available from www.renaldrugdatabase.com , accessed 30/7/18.

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Assessing Renal Function

  • Published information on the effects of renal impairment on drug elimination is usually stated in terms of creatinine clearance (CrCl), calculated using the Cockcroft and Gault Equation.

  • In some cases, renal function may be reported on the basis of estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula.

  • The two equations are NOT interchangeable, however there is relatively good correlation between them for adult patients of average build and height, and either could be used for the majority of drugs.

  • Creatinine clearance using the Cockcroft and Gault Equation should be calculated for drugs with a narrow therapeutic index , such as gentamicin and vancomycin, and for dose reduction of all drugs in patients at extremes of body weight (BMI < 18kg/m 2 or > 40kg/m 2 ).
  • N.B. Estimates of GFR will not be accurate when the patient has an acute kidney injury (AKI), i.e. if the creatinine is rising or falling. The full clinical picture should always be taken into account.
  • During AKI, serum creatinine levels lag behind the development of the injury and progress of recovery.  As creatinine rises, estimates of GFR will overestimate renal function and as creatinine falls and kidney function improves, estimates of GFR will underestimate renal function.

Cockcroft and Gault Equation:

K = 1.23 for males and 1.04 for females

Which weight to use for CrCl calculation?

If Body Mass Index (BMI) < 30kg/m 2 , use actual weight to calculate CrCl

If BMI > 30kg/m 2 , use Obese Dosing Weight (ODW) to calculate CrCl

BMI = Weight(kg)/Height(m) 2

Ideal Body Weight (IBW) (kg) = R + 2.3kg for every inch over 5ft

R = 50 for males and 45.5 for females

ODW (kg) = IBW + 0.4(Actual weight – IBW)

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References

  1. Health Products Regulatory Authority. Summary of Product Characteristics for each product available from www.hpra.ie , accessed 01/05/18.

  2. Ashley C and Dunleavy A [Editors]. The Renal Drug Database. UK: Radcliffe Publishing Limited; 2014. Available from www.renaldrugdatabase.com , accessed 9/1/2023.

  3. John Hopkins ABX Guide, www.hopkinsguides.com , accessed 25/01/23.

  4. BMJ Group and Pharmaceutical Press. British National Formulary. Available from www.medicinescomplete.com , accessed 30/04/18.

  5. Beaumont Hospital Antimicrobial Guidelines, 2023. On file in OLOL Pharmacy.

  6. McKenna C. Medicines Information Enquiry on which weight to use for creatinine clearance, 2014. On file in OLOL Pharmacy.