ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT
ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT | |
Version |
3.0 |
Date ratified |
March 2009 updated January 2010 |
Review date |
January 2012 |
Ratified by |
|
Authors |
Annette Clarkson Microbiology pharmacist Judith Gregory Renal pharmacist |
Consultation |
Nottingham University hospitals Antibiotic Guidelines Committee members Nottingham University Hospitals NHS Trust Drugs and Therapeutics Committee Renal consultants |
Evidence base |
|
Changes from previous Guideline |
|
Inclusion criteria |
Adult patients with renal impairment |
Distribution |
- Pharmacists/Medicines Information - Clinical Effectiveness Database - Renal Unit doctors handbook distributed to all SHOs and SpRs - Junior doctors handbook available via the intranet - NUH Antibiotic Guidelines intranet site http://nuhnet/diagnostics_clinical_support/antibiotics |
Local contacts |
Dr V Weston Consultant Microbiologist Annette Clarkson Microbiology pharmacist Judith Gregory Renal pharmacist |
This guideline has been registered with the Trust. Clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague. Caution is advised when using guidelines after a review date. |
ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT
Assessing Renal Function Renal function in adults is now commonly reported via NOTIS on the basis of estimated glomerular filtration rate (eGFR) normalised to a body surface area of 1.73m2 and derived from the Modification of Diet in Renal Disease (MDRD) formula. Published information on the effects of renal impairment on drug elimination has historically been stated in terms of creatinine clearance (not normalised for body surface area). The Cockgroft-Gault formula has been used to estimate this and in recent years the advice has been to continue to use Cockcroft-Gault estimates for drug dosing in renal impairment. The Cockcroft Gault equation is shown below and there is a calculator on the antibiotic website. CrCl (ml/min) = F x (140-age) x weight (kg) serum creatinine (micromol/L) The latest edition of the British National Formulary gives dosage adjustments for many drugs expressed in terms of eGFR rather than creatinine clearance. Although the two equations are not interchangeable, there is relatively good correlation between the two for calculating renal function in patients of average build and height, and either could be used for the majority of drugs. However, eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI of less than 18.5 kg/m2 or greater than 30 kg/m2), nor for potentially toxic drugs of a narrow therapeutic index. In these cases, the correlation between the two measures can be significant and potential drug over/under doses could arise. BMI = Weight (kg) Height (m2) · eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI of less than 18.5 kg/m2 or greater than 30 kg/m2)therefore for those who are obese (>20% above IBW) ideal body weight should be calculated and then used to create a creatinine clearance using Cockcroft-Gault.
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IBW for males = 50 + (2.3 x (height in inches - 60))
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IBW for female = 45 + (2.3 x (height in inches - 60))
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Equally for those patients who have a BMI<18.5kg/m2 creatinine clearance using Cockcroft-Gault should be calculated.
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eGFR should not be used for calculating drug doses for potentially toxic drugs of a narrow therapeutic index. For the purposes of this guideline creatinine clearance using Cockcroft-Gault should always be used for vancomycin, gentamicin, foscarnet, ganciclovir, valganciclovir.
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Neither equation is a perfect marker of renal function. When using the equation, creatinine levels should be stable and the clinical picture should always be taken into account.
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Patients that are oligoanuric (dialysis dependency/acute kidney injury) should be assumed to have a GFR <10 ml/min and neither equation is valid.
Renal dosing monographs
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The doses recommended are derived from the references stated and represent those commonly used in Nottingham (these may vary from the SPC)
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If 50% quoted, give half the dose but retain the normal frequency
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For dosing advice in haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients: refer to Renal Pharmacist (bleep 80-7078)
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For dosing advice in continuous veno-venous haemofiltration (CVVH): refer to Critical Care Pharmacist
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Drugs marked * = Contact microbiologist for advice on assays where appropriate.
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The sodium content of some IV antibiotic preparations may be significant
(refer to ward pharmacist or Medicines Information)
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Give post HD (haemodialysis): If patient is on daily or alternate day therapy this advice refers only to administration on dialysis days: ie on non-dialysis days the drug is given at the normal time.
Contact microbiology or pharmacy for advice on dosing in renal impairment for any antimicrobial agents that are not included in the table below.
|
Creatinine clearance (ml/min) |
Comments |
||
50-20 |
20-10 |
<10 |
||
*Aciclovir IV |
Normal dose every 12h |
Normal dose every 24h |
50% of normal dose every 24h |
Give post HD |
Aciclovir po |
Normal |
Simplex: 200mg qds Zoster: 800mg tds |
Simplex: 200mg bd Zoster: 800mg bd |
Give post HD |
*Amikacin |
5-6 mg/kg 12h |
3-4 mg/kg 24h |
2mg/kg 24-48h HD: 5mg/kg post HD and monitor levels |
Give post HD Monitor blood levels & adjust dose as req’d |
Amoxicillin |
Normal |
Normal |
250mg-1g 8h Endocarditis (refer to microbiology):max 6g per day |
Give post HD |
Lipid associated Amphotericin IV (Abelcet© and Ambisome©) |
Normal- see note below |
Normal- see note below |
Normal- see note below |
For further advice on dosing and administration see antibiotic website, local guidelines and Trust IV guide |
Amphotericin is highly NEPHROTOXIC. Daily monitoring of renal function is essential |
||||
Azithromycin |
Normal |
Normal |
Normal |
|
Benzylpenicillin |
Normal |
600mg-2.4g every 6 hours |
600mg-1.2g every 6 hours Endocarditis (refer to microbiology): max 4.8g per day |
Give post HD |
Caspofungin |
Normal |
Normal |
Normal |
|
Cefalexin |
Normal |
Normal |
250-500mg tds |
Give post HD |
Cefradine |
Normal |
Normal |
250mg-500mg 6h |
Give post HD |
Ceftazidime |
CrCl 30-50 ml/min 1-2g 12h |
CrCl 20-30 ml/min 1-2g 24h |
CrCl 5-20 ml/min 500mg-1g 24h CrCl<5 ml/min 500mg-1g 48h |
Give post HD |
Ceftriaxone |
Normal |
Normal |
Normal Max 2g/day |
|
Cefuroxime IV |
Normal |
750mg – 1.5g 12h |
750mg 12h |
Give post HD |
Chloramphenicol |
Normal |
Normal |
Normal |
|
Ciprofloxacin IV+po |
Normal |
PO 250-500mg bd IV 200mg-400mg bd |
PO 250-500mg bd IV 200mg-400mg bd |
|
Clarithromycin IV + po |
Normal |
Normal |
250-500mg bd |
Give post HD |
Clindamycin IV +po |
Normal |
Normal |
Normal |
|
Co-Amoxiclav IV (Augmentin) |
CrCl 30-50 Normal |
CrCl 10-30 1.2g 12h |
1.2g stat then 600-1.2g 12h |
Give post HD |
Co-Amoxiclav po (Augmentin) |
Normal |
Normal |
Normal |
Give post HD |
Colistin IV |
Normal |
50% of normal dose |
30% of normal dose |
|
*Co-trimoxazole IV + po (Treatment doses only) |
CrCl 30–50 ml/min Normal |
CrCl 15-30 ml/min PCP: Normal for 3/7 then 50% Other infections: 50% |
CrCl <15ml/min All infections: 50% |
Give post HD Monitor sulfamethoxazole levels |
Daptomycin |
CrCl 30-50ml/min Normal |
CrCl<30ml/min 4mg/kg every 48 hours |
Not dialysed |
|
Antimicrobial |
Creatinine clearance (ml/min) |
Comments |
||
50-20 |
20-10 |
<10 |
||
Doxycycline |
Normal |
Normal |
Normal |
All other tetracyclines contraindicated in renal impairment |
Ertapenem |
CrCl 30-50 ml/min Normal |
CrCl 10-30 ml/min 50-100% of dose |
50% of dose or 1g three times a week |
Give post HD |
Erythromycin po |
Normal |
Normal |
250-500mg qds |
|
*Ethambutol |
Normal |
7.5-15mg/kg/day |
5-7.5mg/kg/day |
Give post HD |
Monitor levels if Crcl < 30ml/min (contact Micro) |
||||
Flucloxacillin IV+po |
Normal |
Normal |
Normal Max 4g/day |
|
Fluconazole |
Normal |
Normal |
50% Oral dose min 50mg |
Give post HD No adjustments for single doses required |
*Flucytosine |
50mg/kg 12h |
50mg/kg 24h |
50mg/kg stat then dose according to levels. |
Give post HD. Monitor pre-dialysis levels |
Foscarnet |
Dose reduction required seek further advice from pharmacy/renal drug handbook |
|||
Fusidic acid |
Normal |
Normal |
Normal |
|
Ganciclovir |
Dose reduction required seek further advice from pharmacy/renal drug handbook |
|||
1) Gentamicin ONCE DAILY |
CrCl 10–40ml/min 3mg/kg (max 300mg) Check levels 18-24 hours after first dose. Re-dose only when level < 1mg/L. |
CrCl<10ml/min 2 mg/kg (max 200mg) re-dose according to levels |
BOTH METHODS: Give post HD Monitor blood levels & U&Es. see antibiotic website. In the obese use a dose determining weight- see antibiotic website. |
|
2) Gentamicin Multiple daily dosing regimen |
80mg 12h (60mg if <60kg) |
80mg 24h (60mg if <60kg) |
80mg 48h (60mg if <60kg) HD:1-2 mg/kg post HD redose according to levels |
|
Isoniazid |
Normal |
Normal |
200mg-300mg 24h |
Give post HD |
Itraconazole |
Normal |
Normal |
Normal |
|
Levofloxacin |
500mg stat then 250mg bd** |
500mg stat then 125mg bd** |
500mg stat then 125mg od |
** Applies if full dose is 500mg bd. If full dose 500mg od give the reduced dose daily |
Linezolid |
Normal |
Normal |
Normal |
Give post HD |
Meropenem Higher doses needed in CNS infection d/w micro |
500mg-2g bd |
500mg-1g bd |
500mg-1g od |
Give post HD |
Metronidazole |
Normal |
Normal |
Normal |
Give post HD |
Nitrofurantoin |
Use at normal dose with caution |
Contraindicated |
Contraindicated |
Monitor for toxicity e.g blood dyscrasias, neuropathy |
Oseltamivir (treatment dose) |
CrCl >30ml/min 75mg bd |
CrCl 10-30ml/min 75mg od |
30mg stat |
HD: 75mg stat then 75mg after each dialysis session |
Penicillin V |
Normal |
Normal |
Normal |
Give post HD |
Piperacillin/ Tazobactam (Tazocin) |
Normal |
4.5g 8-12h |
4.5g 12h |
Give post HD |
Posaconazole |
Normal |
Normal |
Normal |
|
Pyrazinamide |
Normal |
Normal |
Normal |
|
Rifampicin |
Normal |
Normal |
50-100% |
|
Antimicrobial |
Creatinine Clearance (ml/min) |
Comments |
||
50-20 |
20-10 |
<10 |
||
Teicoplanin* |
Normal |
Normal loading dose then 200-400mg every 24-48h |
Normal loading dose then 200-400mg every 48-72h |
Normal Loading dose 400mg every 12 hours for 3 doses Monitor levels |
Tetracycline |
Use Doxycycline see above |
|||
Tigecycline |
Normal |
Normal |
Normal |
|
Trimethoprim |
Normal |
Use alternative agent if possible Normal |
Ineffective for UTI, other indications: Normal but use alternative agent if possible |
Give post HD Consider short term folic acid supplementation. NB May cause temporary rise in creatinine due to reduced creatinine secretion rather than a fall in CrCl |
Valaciclovir |
CrCl 30-50ml/min Normal |
Dose reduction required for Crcl<30ml/min seek further advice from pharmacy/renal drug handbook |
||
Valganciclovir |
Dose reduction required seek further advice from pharmacy/renal drug handbook |
|||
Vancomycin |
1g od Check pre dose level before 3rd dose. |
1g 48 h Check pre dose level before 2nd dose |
1g stat (or 15mg/kg max 2g). Check level after 4-5 days. ONLY re-dose when level <12mg/L. If deep seated when <15mg/L |
Monitor blood levels & adjust dose as required |
Voriconazole |
Normal |
Normal |
Normal |
Give post HD Caution in the use of IV in renal impairment due to accumulation of vehicle-discuss with pharmacy |
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