Renal Dosing

General Principles

Many medicines are excreted by the kidneys and require dose adjustment in renal impairment to avoid toxicity.
Antimicrobial dosage depends on the type and severity of the infection, sensitivity of the causative organism and the general condition of the patient. For severe infections the higher end of the dose range should be used.
For some drugs, although the size of the maintenance dose is reduced, it is important to still give a loading dose when recommended.
Caution if concomitant hepatic and renal impairment – a further reduction in dosing may be indicated.
There is inconsistency among published sources of information on drug dosing in renal impairment. Recommendations in these guidelines are largely derived from The Renal Drug Database (RDD), which in some cases may be higher than the manufacturer’s recommendations in the Summary of Product Characteristics (SPC) and the BNF.
Doses of Antimicrobials in Renal impairment are outlined in Table . Antimicrobials marked with an asterix have significant differences in dosing between reference sources. In some cases a dose range is given – the higher end of the range should be used for severe infections. See HPRA.ie for licensed dose recommendations.
“Usual” dose refers to the dose and interval recommended for adults with normal renal and hepatic function in GUH Antimicrobial Guidelines and GUH Intravenous Administration Guide.

Assessing Renal Function

1. Published information on the effects of renal impairment on drug elimination is usually stated in terms of creatinine clearance, calculated using Cockcroft & Gault equation, as a surrogate for GFR.

2. The Evolve system reports renal function as eGFR (estimated glomerular filtration rate) normalised to a body surface area of 1.73m ² , calculated using the CKD-EPI equation.

3. Although the two measures of renal function are NOT interchangeable, for most drugs and for most adult patients of average build and height, eGFR (rather than CrCl) can be used to determine dosage adjustments.

4. The BNF now uses eGFR for dose reduction for most (but not all) drugs, as does the Dosing Table for Antimicrobials in Renal impairment . Exceptions to the use of eGFR, where calculation of creatinine clearance (Cockcroft & Gault equation) is recommended, include:

Elderly patients aged 75 years and over
Patients at extremes of muscle mass (BMI less than 18 kg/m ² or greater than 40 kg/m ² )
Nephrotoxic drugs and drugs with a narrow therapeutic index that are mainly renally excreted. The BNF doesn’t specify which drugs but examples specified in the Dosing Table include:
- Aminoglycosides (e.g. Amikacin, Gentamicin, Tobramycin)
- Vancomycin
- Foscarnet
- Ganciclovir
- Valganciclovir

5. Using serum creatinine to derive eGFR has a number of limitations; serum creatinine levels are dependent on muscle mass and diet, therefore estimates should be interpreted with caution in certain individuals (such as the elderly, body builders, amputees, in muscle-wasting disorders and vegans)—estimates will be higher or lower than the true value.

6. Creatinine-derived measurements are also not useful in periods of rapidly changing renal function (e.g. critical care) or in patients with Acute Kidney Injury (AKI).

7. In principle, in the acutely critically ill patient with AKI, antimicrobials with wide therapeutic indices and minimal safety concerns e.g. beta lactams should/may be given at full dose for the first 24-48h. Regular monitoring of renal function is advised in acutely ill patients to ensure drug use and dosing is appropriate.

8. Dosing should be assessed on an individual patient basis, balancing risk versus benefit, and taking urine output and clinical picture into account.

9. The gentamicin calculator incorporates a creatinine clearance (CrCL) calculator, which calculates CrCl (ml/min) using Cockcroft and Gault . This may be used for dose adjustment for other antimicrobials.

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Cockcroft and Gault Equation

Cockcroft and Gault Equation

Creatinine Clearance (CrCl) (ml/min)

1.Calculate Ideal Body Weight (IBW) in kg (see below)

2. If actual body weight < IBW, use actual body weight in this equation

N = 1.23 males & 1.04 females

Ideal Body Weight (IBW) (kg) =

Male:

50kg + (2.3kg x inches over 5 feet) OR 50kg + (0.9kg x cm over 152cm)

Female:

45.5kg + (2.3kg x inches over 5 feet) OR 45.5kg + (0.9kg x cm over 152cm)

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Renal Replacement Therapy

Intermittent Haemodialysis (IHD) : Assume GFR <10ml/min . Many drugs are removed by haemodialysis. If dialysed, it is recommended to time administration to take place post dialysis and at the same time every day including dialysis days (to avoid the need to give a supplemental dose post dialysis). In GUH medium flux filters are most commonly used for intermittent haemodialysis, although high flux filters may be used for some patients.
A haemodialysis unit guideline summarises dosing of Vancomycin, CefAZOLin, Daptomycin & Gentamicin for patients with chronic renal impairment on IHD.
Continuous renal replacement therapy (CRRT): Recommendations for dosing of antimicrobials for patients on CRRT in critical care are not covered in these guidelines. In GUH, continuous venovenous haemodiafiltration (CVVHDF) is the type of continuous renal replacement used. ICU pharmacist is available for advice during working hours.

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Dosing Table for Antimicrobials in Renal Impairment

This dosage adjustment table is intended for use in the treatment of infection of hospitalised patients only.
It recommends dose adjustment using the patient’s eGFR value (or Creatinine Clearance using Cockcroft and Gault (CrCL) if specified).
Please refer to General principles and Assessing Renal function . Clinical judgement should be used alongside any estimates derived from equations or suggested dose adjustments.
For some medicines, the renal dose information is presented as a dose range –use the higher end of the dose range for severe infections. Antimicrobials marked with an *asterix have significant differences in dosing between reference sources.
In situations where a range of dosing is recommended, patient, indication and severity of infection need to be considered. Specific factors include age, immune function, degree of renal impairment, risk of adverse effects etc.
More detailed information on some antimicrobials is available in GUH IV guides . See links in individual monographs.
“Usual” dose refers to the dose and interval recommended for adults with normal renal and hepatic function in GUH Antimicrobial Guidelines and GUH Intravenous Administration Guide.

Doses of Antimicrobials in Renal Impairment (Adults)
Aciclovir IV If obese, use ideal or adjusted body weight to calculate dose - See IV guideline for details.	eGFR 25 to 50 Usual dose every 12h	eGFR 10 to 25 Usual dose every 24h	eGFR <10 50% of usual dose every 24h	Maintain adequate hydration. Risk of crystalluria / neurological reactions increased.
Amikacin Reserve antimicrobial	CrCl < 80 : Reduce dose. See Amikacin Dosing Table	Monitor levels. Must use CrCl (not eGFR).
* Amoxicillin IV/PO	eGFR 10 to 50 No dose adjustment required	eGFR <10 250mg to 1g q8h High dose regimens e.g. endocarditis & listeria meningitis: max 2g q8h
Amphotericin Liposomal AmBisome ^® Reserve antimicrobial	No dose adjustment required	Highly nephrotoxic – monitor renal function, potassium and magnesium
Anidulafungin Reserve antimicrobial	No dose adjustment required
Artesunate	No dose adjustment required
Atovaquone	eGFR 10 to 50 No dose adjustment required	eGFR <10 Usual dose with caution	Monitor more closely in renal impairment.
Azithromycin	Usual but use with caution if eGFR <10	33% increase in systemic exposure to azithromycin in patients when GFR<10
Aztreonam Reserve antimicrobial	eGFR 30 to 50 No dose adjustment required	eGFR 10 to 30 Usual first dose, then 50% of usual dose	eGFR <10 Usual first dose, then 25% of usual dose	Nebulised: Dose as in normal renal function
Benzylpenicillin	eGFR 20 to 50 No dose adjustment required	eGFR 10 to 20 600mg to 2.4g q6h	eGFR <10 600mg to 1.2g q6h	Increased risk of neurotoxicity (seizures) in renal impairment
Use higher doses for severe infection only e.g. endocarditis
Caspofungin Reserve antimicrobial	No dose adjustment required
* CefALEXin	eGFR 40 to 50 No dose adjustment required	eGFR 10 to 40 500mg q8h	eGFR <10 500mg q12-24h
* CefAZOLin	eGFR 35-54 Usual dose q8h	eGFR 11-34 1 – 2g q12h	eGFR <10 1 – 2g q24h Haemodialysis See Haemodialysis Dosing Guidelines	High doses in severe infection as per ID/Micro only Caution - Increased risk of convulsions in renal impairment
CefoTAXime Reserve antimicrobial	eGFR 5 to 50 No dose adjustment required	eGFR <5 50% of usual dose For severe/life-threatening infection contact Micro/ID	Reduce dose further if concurrent hepatic and renal failure.
CefTAROLine Reserve ‘red-light‘ antimicrobial Standard dose: 600mg q12h High dose: 600mg q8h	eGFR 31 to 50 400mg q12h 400mg q8h	eGFR 15 to 30 300mg q12h 300mg q8h	eGFR <15 200mg q12h 200mg q8h
CefTAZidime Reserve antimicrobial	eGFR 31 to 50 1g to 2g q12h	eGFR 16 to 30 1g to 2g q24h	eGFR 6 to 15 500mg to 1g q24h eGFR <5 500mg to 1g q48h
CefTAZidime/ Avibactam (Zavicefta) Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	eGFR 31 to 50 1.25g q8h	eGFR 16 to 30 0.94g q12h	eGFR 6 to 15 0.94g q24h eGFR <6 0.94g q48h
CefTOLOzane/ Tazobactam (Zerbaxa) Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	eGFR <50 Reduce dose. Renal dose depends on indication. See IV Guide .
CefTRIAXone Reserve antimicrobial	eGFR 10 to 50 No dose adjustment required	eGFR <10 Usual max 2g q24h Meningitis only: 2g BD (see comment)	High dose (in meningitis in eGFR <10 to be discussed with Micro/ID. Max 2 g q24h if severe renal impairment in combination with hepatic impairment
CefUROXime IV	eGFR 20 to 50 No dose adjustment required	eGFR 10 to 20 750mg to 1.5g q12h	eGFR <10 750mg to 1.5g q24h
* CefUROXime PO	No dose adjustment required
Chloramphenicol Reserve antimicrobial	eGFR 10 to 50 No dose adjustment required	eGFR <10 No dose adjustment required - but use only if no alternative. Discuss with Micro/ID	Monitor levels in renal impairment (but not routinely available). See IV guide for additional information
* Ciprofloxacin IV/PO Reserve antimicrobial	eGFR 30 to 50 No dose adjustment required	eGFR 10 to 30 50 to 100% of usual dose	eGFR <10 50% of usual dose but if severe infection discuss with Micro or ID (may consider higher dose for short period)	Higher end of dose range for severe infection should be discussed with Micro/ ID. Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section
* Clarithromycin IV/PO	eGFR 30 to 50 No dose adjustment required	eGFR<30 250 to 500mg q12h. Use higher end of dose range for severe infection.	Avoid if severe hepatic failure also present. May cause vomiting if eGFR <10
Clindamycin IV/PO	No dose adjustment required- but see comment if eGFR <10	Dosage reduction or monitoring may be necessary in severe renal impairment
Co-amoxiclav IV	eGFR 30 to 50 No dose adjustment required	eGFR<30 1.2g q12h
* Co-amoxiclav PO	No dose adjustment required
Colistin IV Reserve ‘red-light‘ antimicrobial Conventional dosing (Cystic Fibrosis) (1-2 Million International Units q8h)	CrCl <20 Reduce dose. Renal dose depends on indication. See IV Guide.	Must use CrCl (not eGFR).
Colistin IV Reserve ‘red-light‘ antimicrobial High dose regimen (non-Cystic Fibrosis) (9 Million International Units, then 4.5 Million International Units q12h) On Micro or ID approval only	CrCl <50 Reduce dose. Renal dose depends on indication. See IV Guide.	Must use CrCl (not eGFR).
* Co-trimoxazole IV/PO doses are expressed based on the combination of trimethoprim/sulfamethoxazole Treatment doses only	eGFR 30 to 50 No dose adjustment required	eGFR 15 to 30 PJP : Usual dose for 3 days, then 30mg/kg q12h Other indications: 50% of dose	eGFR <15 (Use only if haemodialysis facilities available) PJP : 30mg/kg q12h Other indications: Avoid if possible if levels cannot be monitored (or use 50% of dose if ID/Micro approved)	Monitor levels in renal impairment (but not routinely available)
Dapsone	eGFR 20 to 50 No dose adjustment required	eGFR 10-20 No dose adjustment required. Use with caution	eGFR <10 50-100mg daily. Use with caution. No dose reduction is required for malaria prophylaxis.	Regular blood counts in renal impairment
Daptomycin Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	eGFR 30 to 50 No dose adjustment required	eGFR <30 Usual dose q48h	Caution in renal impairment- monitor renal function & CPK closely if eGFR <80
Doxycycline	No dose adjustment required
Erythromycin IV/PO	No dose adjustment required	Increased risk of ototoxicity in renal impairment especially at high doses. Max 1.5g daily in severe renal impairment
Ethambutol	eGFR >30 No dose adjustment required	eGFR <30 15 - 25mg/kg (Max 2.5g) 3 times/week	Preferably avoid in renal impairment. Monitor levels if eGFR <30 (but not routinely available)
Fidaxomicin Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	No dose adjustment required	Use with caution in severe impairment
Flucloxacillin IV/PO	eGFR 10 to 50 No dose adjustment required	eGFR <10 Usually max 1g q6h but may require 2g q6h if recommended by Micro or ID e.g. for endocarditis	Use with caution if concomitant liver impairment/ consider lower doses. Accumulation of electrolytes can occur
Fluconazole IV/PO	eGFR 10 to 50 1st dose: No dose adjustment required Subsequent doses: 50-100% of usual dose	eGFR <10 50% of usual dose
Flucytosine IV	eGFR 20 to 40 50mg/kg q12h	eGFR 10 to 20 50mg/kg q24h	eGFR <10 50mg/kg stat, then dose according to levels. Dose of 0.5 to 1 g daily is usually adequate.	Must use CrCl (not eGFR). Monitor levels (but not routinely available)
Foscarnet	Reduce dose. See IV Guide.	Must use CrCl (not eGFR). Maintain adequate hydration.
Fosfomycin PO Reserve antimicrobial On Micro or ID approval only	eGFR 10 to 50 Uncomplicated UTI: 3g as a single dose	eGFR <10 Avoid
Fosfomycin IV Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	eGFR<40 Reduce dose according to indication. See IV Guide.	SPC advises use with caution in renal impairment
Fusidic Acid	No dose adjustment required
Ganciclovir	CrCl <70 Reduce dose. See IV Guide.	Must use CrCl (not eGFR). Maintain adequate hydration.
Gentamicin	CrCl < 80 : Reduce dose as per GAPP app calculator CrCl <10 on haemodialysis : See Haemodialysis Dosing Guidelines	Monitor levels. Must use CrCl (not eGFR).
Isavuconazole Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	No dose adjustment required	Therapeutic Drug Monitoring may be required. Discuss with ID/Micro
Isoniazid	eGFR 10 to 50 No dose adjustment required	eGFR <10 200 to 300mg q24h
Itraconazole PO	No dose adjustment required	Therapeutic Drug Monitoring may be required. Discuss with ID/Micro
Itraconazole IV	eGFR 30 to 80 Use with caution	eGFR<30 Avoid	IV vehicle may accumulate in renal impairment.
Levofloxacin IV/PO Reserve ‘red-light‘ antimicrobial On Micro or ID approval only	eGFR 20 to 50 500mg stat, then 250mg q12h	eGFR 10 to 20 500mg stat, then 125mg q12h	eGFR <10 500mg stat, then 125mg q24h	Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section
Linezolid IV/PO On Micro or ID approval only	No dose adjustment required Monitor FBC closely if eGFR <10	Caution in CrCl <30. Monitor platelets and for serotonin syndrome in renal impairment
Meropenem On Micro or ID approval only	eGFR 26 to 50 500mg to 2g q12h	eGFR 10 to 25 500mg to 1g q12h	eGFR <10 500mg to 1g q24h	Higher end of dose range for CNS / MDRO infection should be discussed with Micro/ ID.
Metronidazole IV/PO	No dose adjustment required
Moxifloxacin IV/PO On Micro or ID approval only	No dose adjustment required	Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section
Nitrofurantoin	eGFR <45 Contraindicated. However, a short 3 to 7 day course may be used with caution in certain patients with an eGFR of 30 to 44 - to treat lower UTI with suspected/proven multidrug resistant pathogens when the benefits of nitrofurantoin are considered to outweigh the risks of side effects.	May be ineffective in eGFR <60ml/min (RDD) due to inadequate urinary concentration; risk of peripheral neuropathy and blood dyscrasias. Monitor for pulmonary adverse events
* Ofloxacin	eGFR 10 to 50 200 to 400mg q24h	eGFR <10 100 to 200mg q24h	Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section
Oseltamivir Treatment dose	CrCl 31 to 60 30mg q12h	CrCl 11 to 30 30mg q24h	CrCl ≤10 30mg one dose	(Dose in CrCl <10) Use CrCl if available; otherwise use eGFR
Oseltamivir Prophylaxis dose	CrCl 31 to 60 30mg q24h	CrCl 11 to 30 30mg q48h	CrCl ≤10 30mg one dose, repeat after 7 days	(Dose in CrCl <10) Use CrCl if available; otherwise use eGFR
Oxytetracycline	e GFR 10 to 50 No dose adjustment required (but see comment)	eGFR <10 250mg q6h	Avoid if possible in renal impairment May exacerbate renal failure. Use only if essential
Pentamidine	eGFR 10 to 50 No dose adjustment required	eGFR <10 PJP Severe infection : 4mg/kg once daily IV for 7-10 days, then 4mg/kg on alternate days to complete the course of at least 14 doses PJP Non-severe infection : 4mg/kg IV on alternate days to complete the course of at least 14 doses
Phenoxymethyl-penicillin	No dose adjustment required
Piperacillin/ tazobactam	eGFR 20 to 40 4.5g q8h	eGFR <20 4.5g q12h
Posaconazole IV/PO Reserve antimicrobial	Oral: Usual IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.	IV vehicle may accumulate in renal impairment Therapeutic Drug Monitoring may be required. Discuss with ID/Micro
Pyrazinamide	eGFR 30 to 50 No dose adjustment required	eGFR <30 25 - 30 mg/kg 3 times/week
Quinine	Oral: No dose adjustment required IV for treatment of malaria: see IV guide
Rifampicin	eGFR 10 to 50 No dose adjustment required	eGFR <10 50 to 100% of usual dose TB : Give usual dose	Use with caution in renal impairment if dose above 600mg daily, elderly or co-existing liver impairment
Teicoplanin Reserve antimicrobial	eGFR 30 to 80 Give usual dose on days 1 to 4, then give usual dose q48h	eGFR <30 Give usual dose on days 1 to 4, then give usual dose q72h	Levels are not routinely available
Tigecycline Reserve ‘red-light‘ antimicrobial	No dose adjustment required
Tobramycin	CrCl < 80 : Reduce dose. See GAPP app calculator	Monitor levels. Must use CrCl (not eGFR).
* Trimethoprim	eGFR 15-30 Use normal dose for treatment – See Comment.	eGFR <15 50-100% of normal dose	May cause temporary rise in creatinine due to competition for renal secretion rather than a fall in CrCl, therefore avoid in those where acute rises in creatinine would complicate the clinical picture. Can cause hyperkalaemia, do not use in patients with CrCl<30ml/min where hyperkalaemia is a problem or if they are on other medications which can cause hyperkalaemia (e.g. ACE inhibitor, spironolactone)
ValACIclovir	Reduce dose according to indication and renal function HSV: eGFR <30: Reduce dose Herpes zoster: eGFR <50: Reduce dose CMV prophylaxis: eGFR <75: Reduce dose See Renal Drug Database or contact pharmacy	Maintain adequate hydration
ValGANCIclovir	CrCl <60 Reduce dose. See Renal Drug Database and/or specialist centre advice. www.renaldrugdatabase.com	Must use CrCl (not eGFR). Maintain adequate hydration
Vancomycin IV Reserve antimicrobial	CrCl <50 : Reduce dose as per GAPP app calculator CrCl <10 on haemodialysis : See Haemodialysis Dosing Guidelines	Monitor levels. Must use CrCl (not eGFR)
Voriconazole IV/PO Reserve antimicrobial	Oral: No dose adjustment required IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.	IV vehicle may accumulate in renal impairment Therapeutic Drug Monitoring may be required. Discuss with ID/Micro
*Antimicrobials marked with an asterix have significant differences in dosing between reference sources**

Doses of Antimicrobials in Renal Impairment (Adults)

Antimicrobial

eGFR (ml/min/1.73m ² )

Comment

Aciclovir IV

If obese, use ideal or adjusted body weight to calculate dose - See IV guideline for details.

eGFR 25 to 50

Usual dose

every 12h

eGFR 10 to 25

Usual dose

every 24h

eGFR <10

50% of usual dose every 24h

Maintain adequate hydration. Risk of crystalluria / neurological reactions increased.

Amikacin

Reserve antimicrobial

CrCl < 80 : Reduce dose. See Amikacin Dosing Table

Monitor levels. Must use CrCl (not eGFR).

* Amoxicillin IV/PO

eGFR 10 to 50

No dose adjustment required

eGFR <10

250mg to 1g q8h

High dose regimens e.g. endocarditis & listeria meningitis: max 2g q8h

Amphotericin Liposomal

AmBisome ^®

Reserve antimicrobial

No dose adjustment required

Highly nephrotoxic – monitor renal function, potassium and magnesium

Anidulafungin

Reserve antimicrobial

No dose adjustment required

Artesunate

No dose adjustment required

Atovaquone

eGFR 10 to 50

No dose adjustment required

eGFR <10

Usual dose with caution

Monitor more closely in renal impairment.

Azithromycin

Usual but use with caution if eGFR <10

33% increase in systemic exposure to azithromycin in patients when GFR<10

Aztreonam

Reserve antimicrobial

eGFR 30 to 50

No dose adjustment required

eGFR 10 to 30

Usual first dose, then 50% of usual dose

eGFR <10

Usual first dose, then 25% of usual dose

Nebulised: Dose as in normal renal function

Benzylpenicillin

eGFR 20 to 50

No dose adjustment required

eGFR 10 to 20

600mg to 2.4g q6h

eGFR <10

600mg to 1.2g q6h

Increased risk of neurotoxicity (seizures) in renal impairment

Use higher doses for severe infection only e.g. endocarditis

Caspofungin

Reserve antimicrobial

No dose adjustment required

* CefALEXin

eGFR 40 to 50

No dose adjustment required

eGFR 10 to 40

500mg q8h

eGFR <10

500mg q12-24h

* CefAZOLin

eGFR 35-54

Usual dose q8h

eGFR 11-34

1 – 2g q12h

eGFR <10

1 – 2g q24h

Haemodialysis

See Haemodialysis Dosing Guidelines

High doses in severe infection as per ID/Micro only

Caution - Increased risk of convulsions in renal impairment

CefoTAXime

Reserve antimicrobial

eGFR 5 to 50

No dose adjustment required

eGFR <5

50% of usual dose

For severe/life-threatening infection contact Micro/ID

Reduce dose further if concurrent hepatic and renal failure.

CefTAROLine

Reserve ‘red-light‘ antimicrobial

Standard dose: 600mg q12h

High dose: 600mg q8h

eGFR 31 to 50

400mg q12h

400mg q8h

eGFR 15 to 30

300mg q12h

300mg q8h

eGFR <15

200mg q12h

200mg q8h

CefTAZidime

Reserve antimicrobial

eGFR 31 to 50

1g to 2g q12h

eGFR 16 to 30

1g to 2g q24h

eGFR 6 to 15

500mg to 1g q24h

eGFR <5

500mg to 1g q48h

CefTAZidime/

Avibactam (Zavicefta)

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

eGFR 31 to 50

1.25g q8h

eGFR 16 to 30

0.94g q12h

eGFR 6 to 15

0.94g q24h

eGFR <6

0.94g q48h

CefTOLOzane/

Tazobactam (Zerbaxa)

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

eGFR <50

Reduce dose. Renal dose depends on indication. See IV Guide .

CefTRIAXone

Reserve antimicrobial

eGFR 10 to 50

No dose adjustment required

eGFR <10

Usual max 2g q24h

Meningitis only:

2g BD (see comment)

High dose (in meningitis in eGFR <10 to be discussed with Micro/ID.

Max 2 g q24h if severe renal impairment in combination with hepatic impairment

CefUROXime IV

eGFR 20 to 50

No dose adjustment required

eGFR 10 to 20

750mg to 1.5g

q12h

eGFR <10

750mg to 1.5g

q24h

* CefUROXime PO

No dose adjustment required

Chloramphenicol

Reserve antimicrobial

eGFR 10 to 50

No dose adjustment required

eGFR <10

No dose adjustment required - but use only if no alternative. Discuss with Micro/ID

Monitor levels in renal impairment (but not routinely available). See IV guide for additional information

* Ciprofloxacin IV/PO

Reserve antimicrobial

eGFR 30 to 50

No dose adjustment required

eGFR 10 to 30

50 to 100% of usual dose

eGFR <10

50% of usual dose but if severe infection discuss with Micro or ID (may consider higher dose for short period)

Higher end of dose range for severe infection should be discussed with Micro/ ID.

Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section

* Clarithromycin IV/PO

eGFR 30 to 50

No dose adjustment required

eGFR<30

250 to 500mg q12h. Use higher end of dose range for severe infection.

Avoid if severe hepatic failure also present. May cause vomiting if eGFR <10

Clindamycin IV/PO

No dose adjustment required- but see comment if eGFR <10

Dosage reduction or monitoring may be necessary in severe renal impairment

Co-amoxiclav IV

eGFR 30 to 50

No dose adjustment required

eGFR<30

1.2g q12h

* Co-amoxiclav PO

No dose adjustment required

Colistin IV

Reserve ‘red-light‘ antimicrobial

Conventional dosing (Cystic Fibrosis) (1-2 Million International Units q8h)

CrCl <20

Reduce dose. Renal dose depends on indication. See IV Guide.

Must use CrCl (not eGFR).

Colistin IV

Reserve ‘red-light‘ antimicrobial

High dose regimen (non-Cystic Fibrosis) (9 Million International Units, then 4.5 Million International Units q12h)

On Micro or ID approval only

CrCl <50

Reduce dose. Renal dose depends on indication. See IV Guide.

Must use CrCl (not eGFR).

* Co-trimoxazole IV/PO

doses are expressed based on the combination of trimethoprim/sulfamethoxazole

Treatment doses only

eGFR

30 to 50

No dose adjustment required

eGFR 15 to 30

PJP : Usual dose for 3 days, then 30mg/kg q12h

Other indications:

50% of dose

eGFR <15 (Use only if haemodialysis facilities available)

PJP : 30mg/kg q12h

Other indications: Avoid if possible if levels cannot be monitored (or use 50% of dose if ID/Micro approved)

Monitor levels in renal impairment (but not routinely available)

Dapsone

eGFR 20 to 50

No dose adjustment required

eGFR 10-20

No dose adjustment required. Use with caution

eGFR <10

50-100mg daily. Use with caution. No dose reduction is required for malaria prophylaxis.

Regular blood counts in renal impairment

Daptomycin

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

eGFR 30 to 50

No dose adjustment required

eGFR <30

Usual dose q48h

Caution in renal impairment- monitor renal function & CPK closely if eGFR <80

Doxycycline

No dose adjustment required

Erythromycin IV/PO

No dose adjustment required

Increased risk of ototoxicity in renal impairment especially at high doses. Max 1.5g daily in severe renal impairment

Ethambutol

eGFR >30

No dose adjustment required

eGFR <30

15 - 25mg/kg (Max 2.5g)

3 times/week

Preferably avoid in renal impairment. Monitor levels if eGFR <30 (but not routinely available)

Fidaxomicin

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

No dose adjustment required

Use with caution in severe impairment

Flucloxacillin IV/PO

eGFR 10 to 50

No dose adjustment required

eGFR <10

Usually max 1g q6h but may require 2g q6h if recommended by Micro or ID e.g. for endocarditis

Use with caution if concomitant liver impairment/ consider lower doses. Accumulation of electrolytes can occur

Fluconazole IV/PO

eGFR 10 to 50

1st dose: No dose adjustment required

Subsequent doses: 50-100% of usual dose

eGFR <10

50% of usual dose

Flucytosine IV

eGFR 20 to 40

50mg/kg q12h

eGFR 10 to 20

50mg/kg q24h

eGFR <10

50mg/kg stat, then dose according to levels. Dose of 0.5 to 1 g daily is usually adequate.

Must use CrCl (not eGFR).

Monitor levels (but not routinely available)

Foscarnet

Reduce dose. See IV Guide.

Must use CrCl (not eGFR).

Maintain adequate hydration.

Fosfomycin PO

Reserve antimicrobial

On Micro or ID approval only

eGFR 10 to 50

Uncomplicated UTI: 3g as a single dose

eGFR <10

Avoid

Fosfomycin IV

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

eGFR<40

Reduce dose according to indication. See IV Guide.

SPC advises use with caution in renal impairment

Fusidic Acid

No dose adjustment required

Ganciclovir

CrCl <70

Reduce dose. See IV Guide.

Must use CrCl (not eGFR).

Maintain adequate hydration.

Gentamicin

CrCl < 80 : Reduce dose as per GAPP app calculator

CrCl <10 on haemodialysis : See Haemodialysis Dosing Guidelines

Monitor levels. Must use CrCl (not eGFR).

Isavuconazole

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

No dose adjustment required

Therapeutic Drug Monitoring may be required. Discuss with ID/Micro

Isoniazid

eGFR 10 to 50

No dose adjustment required

eGFR <10

200 to 300mg q24h

Itraconazole PO

No dose adjustment required

Therapeutic Drug Monitoring may be required. Discuss with ID/Micro

Itraconazole IV

eGFR 30 to 80

Use with caution

eGFR<30

Avoid

IV vehicle may accumulate in renal impairment.

Levofloxacin IV/PO

Reserve ‘red-light‘ antimicrobial

On Micro or ID approval only

eGFR 20 to 50

500mg stat, then 250mg q12h

eGFR 10 to 20

500mg stat, then 125mg q12h

eGFR <10

500mg stat, then 125mg q24h

Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section

Linezolid IV/PO

On Micro or ID approval only

No dose adjustment required Monitor FBC closely if eGFR <10

Caution in CrCl <30. Monitor platelets and for serotonin syndrome in renal impairment

Meropenem

On Micro or ID approval only

eGFR 26 to 50

500mg to 2g q12h

eGFR 10 to 25

500mg to 1g

q12h

eGFR <10

500mg to 1g

q24h

Higher end of dose range for CNS / MDRO infection should be discussed with Micro/ ID.

Metronidazole IV/PO

No dose adjustment required

Moxifloxacin IV/PO

On Micro or ID approval only

No dose adjustment required

Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section

Nitrofurantoin

eGFR <45

Contraindicated.

However, a short 3 to 7 day course may be used with caution in certain patients with an eGFR of 30 to 44 - to treat lower UTI with suspected/proven multidrug resistant pathogens when the benefits of nitrofurantoin are considered to outweigh the risks of side effects.

May be ineffective in eGFR <60ml/min (RDD) due to inadequate urinary concentration; risk of peripheral neuropathy and blood dyscrasias. Monitor for pulmonary adverse events

* Ofloxacin

eGFR 10 to 50

200 to 400mg q24h

eGFR <10

100 to 200mg q24h

Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning in the prescribing principles section

Oseltamivir

Treatment dose

CrCl 31 to 60

30mg q12h

CrCl 11 to 30

30mg q24h

CrCl ≤10

30mg one dose

(Dose in CrCl <10)

Use CrCl if available; otherwise use eGFR

Oseltamivir

Prophylaxis dose

CrCl 31 to 60

30mg q24h

CrCl 11 to 30

30mg q48h

CrCl ≤10

30mg one dose, repeat after 7 days

(Dose in CrCl <10)

Use CrCl if available; otherwise use eGFR

Oxytetracycline

e GFR 10 to 50

No dose adjustment required (but see comment)

eGFR <10

250mg q6h

Avoid if possible in renal impairment May exacerbate renal failure. Use only if essential

Pentamidine

eGFR 10 to 50

No dose adjustment required

eGFR <10

PJP Severe infection : 4mg/kg once daily IV for 7-10 days, then 4mg/kg on alternate days to complete the course of at least 14 doses

PJP Non-severe infection :

4mg/kg IV on alternate days to complete the course of at least 14 doses

Phenoxymethyl-penicillin

No dose adjustment required

Piperacillin/

tazobactam

eGFR 20 to 40

4.5g q8h

eGFR <20

4.5g q12h

Posaconazole IV/PO

Reserve antimicrobial

Oral: Usual

IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.

IV vehicle may accumulate in renal impairment

Therapeutic Drug Monitoring may be required. Discuss with ID/Micro

Pyrazinamide

eGFR 30 to 50

No dose adjustment required

eGFR <30

25 - 30 mg/kg

3 times/week

Quinine

Oral: No dose adjustment required

IV for treatment of malaria: see IV guide

Rifampicin

eGFR 10 to 50

No dose adjustment required

eGFR <10

50 to 100% of usual dose

TB : Give usual dose

Use with caution in renal impairment if dose above 600mg daily, elderly or co-existing liver impairment

Teicoplanin

Reserve antimicrobial

eGFR 30 to 80

Give usual dose on days 1 to 4, then give usual dose q48h

eGFR <30

Give usual dose on days 1 to 4, then give usual dose q72h

Levels are not routinely available

Tigecycline

Reserve ‘red-light‘ antimicrobial

No dose adjustment required

Tobramycin

CrCl < 80 : Reduce dose. See GAPP app calculator

Monitor levels. Must use CrCl (not eGFR).

* Trimethoprim

eGFR 15-30

Use normal dose for treatment – See Comment.

eGFR <15

50-100% of normal dose

May cause temporary rise in creatinine due to competition for renal secretion rather than a fall in CrCl, therefore avoid in those where acute rises in creatinine would complicate the clinical picture.

Can cause hyperkalaemia, do not use in patients with

CrCl<30ml/min where hyperkalaemia is a problem or if they are on other medications which can cause hyperkalaemia

(e.g. ACE inhibitor, spironolactone)

ValACIclovir

Reduce dose according to indication and renal function

HSV: eGFR <30: Reduce dose

Herpes zoster: eGFR <50: Reduce dose

CMV prophylaxis: eGFR <75: Reduce dose

See Renal Drug Database or contact pharmacy

Maintain adequate hydration

ValGANCIclovir

CrCl <60

Reduce dose. See Renal Drug Database and/or specialist centre advice. www.renaldrugdatabase.com

Must use CrCl (not eGFR).

Maintain adequate hydration

Vancomycin IV

Reserve antimicrobial

CrCl <50 : Reduce dose as per GAPP app calculator

CrCl <10 on haemodialysis : See Haemodialysis Dosing Guidelines

Monitor levels. Must use CrCl (not eGFR)

Voriconazole IV/PO

Reserve antimicrobial

Oral: No dose adjustment required

IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.

IV vehicle may accumulate in renal impairment

Therapeutic Drug Monitoring may be required. Discuss with ID/Micro

Antimicrobials marked with an *asterix have significant differences in dosing between reference sources

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Vancomycin, CefAZOLin, Daptomycin & Gentamicin Dosing in Haemodialysis

Vancomycin, CefAZOLin, Daptomycin & Gentamicin Dosing Guidelines for Patients on Intermittent Haemodialysis
Vancomycin A loading dose is essential to ensure adequate plasma levels Give 20mg/kg loading dose rounded to nearest 250mg	Weight	Loading dose	Maintenance dose 750mg with each dialysis During latter part of dialysis, by infusion	Administration For inpatients, administer in haemodialysis unit and record on inpatient drug chart See IV guide for more information on administration	Monitoring Not usually necessary to hold the dose pending levels unless previous level high or toxicity suspected
					Pre-dialysis trough level Check first trough level before the second dose, then once weekly Target trough 15 to 20mg/l The goal is to ensure effective plasma levels
	<50kg	750mg
	50-69kg	1g
	70-100kg	1.5g
	>100kg	2g
CefAZOLin	No loading dose required		Give 2g/2g/3g three times weekly with each dialysis: 2g when next dialysis 2 days later, and 3g when next dialysis 3 days later	Post dialysis	None required
Daptomycin	No loading dose required		Give 6/6/9 mg/kg three times weekly with each dialysis: 6mg/kg when next dialysis 2 days later, and 9mg/kg when next dialysis 3 days later	Post dialysis	None required
Gentamicin	2mg/kg to max 160mg Use ABW, unless ABW >20% above IBW, then use dosing wt = IBW + 0.4 (ABW-IBW)*		1mg/kg with each dialysis (max 80mg) Use ABW unless ABW >20% above IBW, then use dosing wt = IBW + 0.4 (ABW-IBW)*	Post dialysis	Trough level at end of dialysis but immediately prior to dose Target trough less than 2mg/l The goal is to minimise toxicity and to ensure effective plasma levels
IBW – ideal body weight; ABW – actual body weight. IBW (kg) = 50 (45.5 for women) + (2.3 x inches over 5 feet) Further Information: Vancomycin: 80-90% excreted unchanged by the kidneys. Not significantly removed by conventional HD, removal increased by high flux HD. Gentamicin: 100% excreted unchanged by the kidneys. 30% removed during 4 hour HD Developed by GUH Pharmacy & Nephrology Depts Ref: IDSA Guidelines for the diagnosis and management of intravascular catheter-related infection. Clin Infect Dis 2009;49:1-45*

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References

The Renal Drug Database www.renaldrugdatabase.com Accessed Feb 2021
BNF accessed online via Medicines Complete Feb 2021
Health Products Regulatory Authority. Summary of Product Characteristics (SPC): www.HPRA.ie
The Sanford Guide to Antimicrobial Therapy Digital Update Accessed Feb 2021
Johns Hopkins POC-IT ABX Guide. The Johns Hopkins University Accessed Feb 2021
GUH IV Administration Guide
Renal dosing of antibiotics: Are we jumping the gun? Clinical Infectious Diseases, 68 (9). 1596-1602 May 2019
Nottingham University Hospital Antimicrobial Doses for Adults in Renal Impairment September 2019 https://www.nuh.nhs.uk/download.cfm?doc=docm93jijm4n629.pdf&ver=19071

Acknowledgements

Written by Marie Tierney & Dr. Úna NíRiain May 2012, Updated March 2021.

Reviewed by pharmacists and nephrologists in GUH, PUH. Approved by Antimicrobial Stewardship Team.