Practical Guidelines for Drug Dosing in Patients with Impaired Kidney Function



Practical Guidelines for Drug Dosing in Patients with Impaired Kidney Function


Ali Olyaei

William M. Bennett



Decreased renal function, regardless of etiology, presents significant challenges to prescribing providers. Additional considerations when selecting and dosing medications for patients with renal dysfunction include comorbidities (hypertension, diabetes, heart disease, advanced age) and the multiple drugs used to manage those conditions. These factors highlight the critical importance of establishing baseline kidney function prior to initiating new medication regimens, as well as appropriately frequent monitoring of renal function throughout the course of medication management. Monitoring therapeutic plasma concentration, if possible, is an important consideration. However, for many pharmacotherapeutic agents, plasma concentration cannot be monitored in the clinical setting. Thus, it is important for health care providers to understand the relationship between reduced or impaired renal function, pharmacokinetics and appropriate drug selection and dosing protocol for specific disease state.

Properly functioning kidneys facilitate homeostasis required for optimal cellular and metabolic functioning through regulating solute and water transport, excreting metabolic waste products, conserving nutrients, and balancing acids and bases. These functional components play integral roles in the absorption, distribution, metabolism, and especially the excretion of medications and metabolites. Chronic kidney disease (CKD) and in particular uremic state influences every organ system and every aspect of drug disposition. The physiological changes associated with CKD are not limited only to drugs with high renal excretion; in fact, renal disease has pronounced effects on the pharmacology of many drugs. Any significant decrease in kidney function, as indicated by a glomerular filtration rate (GFR), presents therapeutic drug selection and dosing challenges. Decreased GFR is commonly seen in elderly patients and obviously in patients with acute kidney injury (AKI) and CKD.

While many prescribers realize that CKD-related decreases in renal function and end-stage renal disease (ESRD) significantly alter the pharmacokinetics and pharmacodynamics of many medications, there is an increased awareness that many more patients are affected by poor renal function than previously thought. Therefore, establishing baseline renal function, as well as systematic and ongoing assessment of renal function on all appropriate patients throughout the therapeutic regimen is necessary in order to avoid further damage to the kidneys, as well as to achieve the desired clinical outcome for the patient.

Decreases in age-related renal function are caused primarily by a decrease in patient size, blood flow, and subsequently GFR. With changes in renal vasculature
and profusion, the number of nephrons also decreases. The speed of this loss accelerates as the patient progresses to ESRD. The kidneys also undergo degenerative changes that decrease the ability of the kidneys to concentrate urine. In addition, the injured kidney loses its ability to adapt to various stresses; glucose, sodium, and bicarbonate are not reabsorbed as efficiently, and because of decreased rates of secretion, hyperkalemia can occur more commonly. Acid-base balance is more difficult to maintain, changes in pH and fluid load can lead to critical imbalances that can lead to and exacerbate toxicity in medications that are metabolized and eliminated via renal processes.


CHRONIC KIDNEY DISEASE AND DRUG PHARMACOKINETIC


Absorption

Drug absorption in CKD is affected by possible increases in gastric pH, gastroparesis, bowel wall edema, vomiting and diarrhea, and decreasing intestinal CYP450 activity. In general, it is difficult to assess the effect of CKD on drug absorption as many of these patients take multiple medications, many of which cannot be discontinued or withheld to study the alterations in absorption of other drugs. Medications taken by CKD patients to manage these conditions, such as antacids, proton pump inhibitors, and H2 receptor antagonists, also impact other drug’s absorption. Increased gastric pH decreases the absorption, and therefore the bioavailability of drugs that are more readily absorbed in an acidic environment. Taking antacids can also decrease drug absorption, especially of tetracyclines and fluoroquinolones, through chelation of those components into insoluble compounds. Gastroparesis, or delayed gastric emptying, is common in CKD patients, and can increase the amount of time needed to achieve maximum drug concentrations, although this appears to only impact very short-acting medications. Also, bowel wall edema, vomiting, and diarrhea can decrease overall drug absorption in CKD patients. Lastly, renal insufficiency is linked with decreased gastrointestinal (GI) CYP450 activity. This can drastically increase the amount of drug absorbed by significantly reducing the amount of drug metabolized via CYP450 in the GI tract.


Distribution

Drug distribution in CKD patients is affected by alterations in fluid states and changes in the extent of protein binding in plasma, which impacts therapeutic drug concentrations, and tissue binding, which affects volume of distribution. Patients with advanced renal insufficiency are commonly uremic and have low plasma albumin levels. Acidic drugs are most significantly affected by hypoalbuminemia because of increased competition for available binding sites. This can lead to both accumulation of other medications and metabolites while also increasing levels of free drug in the plasma, which can also lead to toxicity or conversely to more drug undergoing biotransformation, resulting in decreased drug action. Fluid status and overall body composition are also significantly impacted by CKD and are important considerations when choosing and dosing drugs. Prescribers must be aware that volume of distribution will change in patients with ascites, edema, and overall hydration status, especially with hydrophilic drugs. Increased adipose tissue and decreased lean muscle mass, or patients with muscle wasting, is also common for elderly patients and CKD patients. These changes in body composition can reduce the volume of distribution, thereby increasing serum levels of hydrophilic drugs.



Metabolism

Metabolism of both renal and nonrenal metabolized drugs and metabolites is significantly slowed in patients with renal impairment. This can lead to accumulation of drugs, pharmacologically active agents, as well as toxic metabolites and can lead to significant adverse events. When a drug undergoes biotransformation, an active drug metabolite is a frequent by-product. These metabolites have an effect and action, and while the initial drug may be effectively excreted via urine, the still-active metabolite can easily accumulate to potentially dangerous levels, causing adverse clinical outcomes. CKD also impacts drug metabolism through impaired CYP450 activities in both Phase I and Phase II reactions, which are necessary for drugs to undergo predictable biotransformation and subsequent therapeutic outcomes.


Elimination

Drug elimination of drug and active metabolites is dependent on several aspects of renal functioning; GFR, tubular secretion, and reabsorption. Drug elimination via glomerular filtration in CKD patients occurs in relation to the patient’s level of GFR, the amount of free drug compared with the amount of drug bound to protein. CKD patients also experience decreased tubular secretion, as well as reduced medication reabsorption, which is indicated by higher levels of urine concentrations of renally eliminated drugs. Finally, it is important to review that renal insufficiency slows the elimination of active drug metabolites, which are still biologically active, and when they reach a certain level of accumulation can cause adverse clinical outcomes. For many drugs, the kidneys are the primary route for drug elimination within the body. CKD reduces glomerular filtration and can be assessed by creatinine clearance. To calculate renal function or adjust for drug elimination, the following calculations are recommended when determining creatinine clearance for those adults with stable renal function.


Cockcroft-Gault (CG) equation

CrCl (mL/min) = [(140 − age) × Weight in kg]/(serum creatinine × 72) × (0.85 if female)

Ideal body weight (IBW) was used unless actual body weight (ABW) < IBW. If ABW was >30% of IBW, adjusted body weight was used where:

adjusted body weight = [(ABW − IBW) × 0.4] + IBW.

IBWmale = 50 + 2.3 × (Height in inches − 60);

IBWfemale = 45.5 + 2.3 × (Height in inches − 60)

For obese men and women the equation should be modified:


wgt = patient’s weight in kg

hgt = patient’s height in cm


Modification of Diet in Renal Disease re-expressed equation (MDRD)

eGFR MDRD = 175 × SCr − 1.154 × Age − 0.203 × (0.742 if female) × (1.21 if AA)

AA refers to African American



Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)

eGFR CKD-EPI= 141 × min(SCr/κ, 1)α × max(SCr/κ, 1) − 1.209 × 0.993 Age × 1.018 [if female] × 1.159 [if African American], where κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of SCr/κ or 1, and max indicates the maximum of SCr/κ or 1.

It is very important to mention that these equations can only be applied in patients with stable renal function. Thus, during AKI, the serum creatinine or creatinine clearance will no longer reflect the true renal or drug clearance rate. In these cases, other methods should be applied (a timed urine collection) to estimate renal function. Finally, in oliguric patients, the creatinine clearance should be considered as less than 5 mL/minute.

One of the main limitations of the newer available GFR estimation equations (CKD-EPI and MDRD) is the lack of information about drug dosing in CKD. For obese and older patients, growing evidence suggests that the Cockcroft-Gault equation is superior to the other GFR estimates obtained by use of the MDRD and CKDEPI. For all these equations, the recognition of the limitations of these estimation equations is essential when considering for drug dosing in kidney impairment.


DRUG DOSING IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Selecting and dosing drugs for patients with CKD is a significant clinical challenge and requires close coordination between the patient, the prescriber, and the pharmacist. A comprehensive initial assessment of the patient, including liver function tests, serum albumin levels, allergies, degree of renal functioning, fluid status, in addition to all medications, over the counter and prescribed, allergies and comorbidities, is paramount. The review of the patient’s medication list at this time is to ensure a clinical valid reason for maintaining that therapy and to ensure that medications are not a causal agent in the patient’s decreased renal functioning. If additional drugs are needed, it is critical to choose the least nephrotoxic drug available and to work closely with the pharmacist to select the appropriate loading and maintenance doses. Finally, frequent monitoring of drug levels when available and of renal function is critical to ensure protection of remaining kidney function (Table 16-1). There are two methods for dosage adjustment in patients with reduced renal function: prolonged interval or reduced dose. Prolonging the dose interval is often a convenient and cost-effective method for altering the drug dose in patients with renal impairment. This method is particularly useful for drugs with wide therapeutic ranges and long plasma half-lives. Extended parenteral therapy can be completed without prolonged hospitalization when the dose interval can safely be lengthened to allow for home therapy. If the range between the therapeutic and toxic levels is too narrow, either potentially toxic or subtherapeutic plasma concentrations may result.

To maintain the same dose interval as for patients with normal renal function, one may decrease the amount of each individual dose given to renal impaired patients. This method is effective for drugs with narrow therapeutic ranges and short plasma half-lives in patients with renal insufficiency. In practice, a combination of the methods is often effective and convenient. The combination method uses modification of both the dose and dose interval. For drugs with particularly long half-lives in patients with impaired renal function, give the total daily dose as a single dose each day. Similarly, divide the total daily dose in half and give twice daily. The decision to extend the dosing interval beyond a 24-hour period should be based on the necessity


to maintain therapeutic peak or trough drug levels. When the peak level is most important, prolong the dose interval. However, when the minimum trough level must be maintained, modification of the individual dose or a combination of the dose and interval methods may be preferred. The following tables provide information about drug dosing in several categories in patients with CKD.








Table 16-1. Therapeutic Drug Monitoring in Patients with Chronic Kidney Disease
























































































Drug Name

Therapeutic Range

When to Draw Sample

How Often to Draw Levels


Aminoglycosides (conventional dosing)


Gentamicin, Tobramycin, Amikacin

Gentamicin and Tobramycin:


Trough: 0.5-2 mg/L


Peak: 5-8 mg/L


Amikacin:


Peak: 20-30 mg/L


Trough: <10 mg/L

Trough: Immediately prior to dose


Peak: 30 min after a 30-45 min infusion

Check peak and trough with third dose


For therapy less than 72 h, levels not necessary. Repeat drug levels weekly or if renal function changes


Aminoglycosides (24-h dosing) Gentamicin, Tobramycin, Amikacin

0.5-3 mg/L

Obtain random drug level 12 h after dose

After initial dose, repeat drug level in 1 week or if renal function changes


Carbamazepine

4-12 µg/mL

Trough: Immediately prior to dosing

Check 2-4 days after first dose or change in dose


Cyclosporin

150-400 ng/mL

Trough: Immediately prior to dosing

Daily for first week, then weekly


Digoxin

0.8-2.0 ng/mL

12 h after maintenance dose

5-7 days after first dose for patients with normal renal and hepatic function; 15-20 days in anephric patients


Lidocaine

1-5 µg/mL

8 h after i.v. infusion started or changed


Lithium

Acute: 0.8-1.2 mmol/L Chronic: 0.6-0.8 mmol/L

Trough: Before a.m. dose at least 12 h since last dose


Phenobarbital

15-40 µg/mL

Trough: Immediately prior to dosing

Check 2 weeks after first dose or change in dose. Follow-up level in 1-2 months


Phenytoin Free Phenytoin

10-20 µg/mL


1-2 µg/mL

Trough: Immediately prior to dosing

5-7 day after first dose or after change in dose


Procainamide


NAPA (n-acetyl procainamide), a procainamide metabolite

4-10 µg/mL


Trough: 4 µg/mL


Peak: 8 µg/mL


10-30 µg/mL

Trough: Immediately prior to next dose or 12-18 h after starting or changing an infusion


Draw with procainamide sample


Quinidine

1-5 µg/mL

Trough: Immediately prior to next dose


Sirolimus

10-20 ng/dL

Trough: Immediately prior to next dose


Tacrolimus (FK-506)

10-15 ng/mL

Trough: Immediately prior to next dose

Daily for first week, then weekly


Theophylline p.o. or Aminophylline i.v.

15-20 µg/mL

Trough: Immediately prior to next dose


Valproic acid (divalproex sodium)

40-100 µg/mL

Trough: Immediately prior to next dose

Check 2-4 d after first dose or change in dose


Vancomycin

Trough: 5-15 mg/L Peak: 25-40 mg/L

Trough: Immediately prior to dose


Peak: 60 min after a 60 min infusion

With third dose (when initially starting therapy, or after each dosage adjustment). For therapy less than 72 h, levels not necessary. Repeat drug levels if renal function changes




Suggested Readings

Abdelhafiz AH, Tan E, El Nahas M. The epidemic challenge of chronic kidney disease in older patients. Postgrad Med 2008;120(4):87-94.

Aronow WS. Treatment of hypertension in the elderly. Compr Ther 2008;34(3-4): 171-176.

Beers MH, Ouslander JG, Fingold SF, et al. Inappropriate medication prescribing in skilled-nursing facilities. Ann Intern Med 1992;117(8):684-689.

Culberson JW, Ziska M. Prescription drug misuse/abuse in the elderly. Geriatrics 2008;63(9):22-31.

Ferrario CG. Geropharmacology: a primer for advanced practice. Acute care and critical care nurses, part I. AACN Adv Crit Care 2008;19(1):23-35.

Ferrario CG. Geropharmacology: a primer for advanced practice. Acute care and critical care nurses, part II. AACN Adv Crit Care 2008;19(2):134-149.

Garinis GA, van der Horst GT, Vijg J, Hoeijmakers JH. DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol 2008;10(11):1241-1247.

Giavarina D, Cruz DN, Soffiati G, Ronco C. Comparison of estimated glomerular filtration rate (eGFR) using the MDRD and CKD-EPI equations for CKD screening in a large population. Clin Nephrol 2010;74(5):358-363.

Le Couteur DG, Kendig H. Pharmaco-epistemology for the prescribing geriatrician. Australas J Ageing 2008;27(1):3-7.

Lipcsey M, Furebring M, Rubertsson S, Larsson A. Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients. Ups J Med Sci 2011;116(1):39-46.

McDonald M, Hertz RP, Unger AN, Lustik MB. Prevalence, awareness, and management of hypertension, dyslipidemia, and diabetes among United States adults aged 65 and older. J Gerontol A Biol Sci Med Sci 2009;64A(2):256-263.

Papaioannou A, Clarke JA, Campbell G, Bedard M. Assessment of adherence to renal dosing guidelines in long-term care facilities. J Am Geriatr Soc 2000;48(11):1470-1473.

Rule AD, Amer H, Cornell LD, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med 2010;152(9):561-567.

Tam-McDevitt J. Polypharmacy, aging, and cancer. Oncology (Williston Park) 2008;22(9):1052-1055, discussion.


















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Jun 11, 2016 | Posted by in NEPHROLOGY | Comments Off on Practical Guidelines for Drug Dosing in Patients with Impaired Kidney Function

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Antimicrobial Dosing in Renal Failure


Drugs

Normal Dosage

% of Renal Excretion

Dosage Adjustment in Renal Failure

Comments


GFR >50

GFR 10-50

GFR <10


Aminoglycoside antibiotics






Nephrotoxic. Ototoxic. Toxicity worse when hyperbilirubinemic. Measure serum levels for efficacy and toxicity. Peritoneal absorption increases with presence of inflammation. Volume of distribution (Vd) increases with edema, obesity, and ascites


Streptomycin

7.5 mg/kg q12h (1.0 g q24h for tuberculosis)

60%

q24h

q24-72h

q72-96h

For the treatment of tuberculosis. May be less nephrotoxic than other members of class


Kanamycin

7.5 mg/kg q8h

50-90%

60-90%


q12h or 100%


q12-24h

30-70% q12-18h


or 100% q24-48h

20-30%


q24-48h


or 100%


q48-72h

Nephrotoxic. Ototoxic. Toxicity worse when hyperbilirubinemic. Vd increases with edema, obesity, and ascites. Do not use once-daily dosing in patients with creatinine clearance less than 30-40 mL/min or in patients with acute renal failure or uncertain level of kidney function


Gentamicin

1.7 mg/kg q8h

95%

60-90%


q8-12h or 100%


q12-24h

30-70% q12h or 100% q24-48h

20-30% q24-48h or 100% q48-72h

Concurrent penicillins may result in subtherapeutic aminoglycoside levels. Peak 6-8, trough <2


Tobramicin

1.7 mg/kg q8h

95%

60-90%


q8-12h or 100%


q12-24h

30-70% q12h or 100% q24-48h

20-30%


q24-48h or 100%


q48-72h

Concurrent penicillins may result in subtherapeutic aminoglycoside levels. Peak 6-8, trough <2


Netilmicin

2 mg/kg q8h

95%

50-90%


q8-12h or 100%


q12-24h

20-60% q12h or 100% q24-48h

10-20%


q24-48h or 100%


q48-72h

May be less ototoxic than other members of class. Peak 6-8, trough <2


Amikacin

7.5 mg/kg q12h

95%

60-90%


q12h or 100%


q12-24h

30-70% q12-18h or 100% q24-48h

20-30%


q24-48h or 100%


q48-72h

Monitor levels.


Peak 20-30, trough <5


Cephalosporin






Coagulation abnormalities, transitory elevation of blood urea nitrogen, rash and serum sickness-like syndrome


Oral Cephalosporin







Cefaclor

250-500 mg tid

70%

100%

100%

50%


Cefadroxil

500 mg-1 g bid

80%

100%

100%

50%


Cefixime

200-400 mg q12h

85%

100%

100%

50%


Cefpodoxime

200 mg q12h

30%

100%

100%

100%


Ceftibuten

400 mg q24h

70%

100%

100%

50%


Cefuroxime axetil

250-500 mg tid

90%

100%

100%

100%

Malabsorbed in presence of H2 blockers. Absorbed better with food


Cephalexin

250-500 mg tid

95%

100%

100%

100%

Rare allergic interstitial nephritis. Absorbed well when given intraperitoneally. May cause bleeding from impaired prothrombin biosynthesis


Cephradine

250-500 mg tid

100%

100%

100%

50%

Rare allergic interstitial nephritis. Absorbed well when given intraperitoneally. May cause bleeding from impaired prothrombin biosynthesis.


IV Cephalo-Sporin







Cefamandole

1-2 g IV q6-8h

100%

q6h

q8h

q12h


Cefazolin

1-2 g IV q8h

80%

q8h

q12h

q12-24h


Cefepime

1-2 g IV q8h

85%

q8-12h

q12h

q24h


Cefmetazole

1-2 g IV q8h

85%

q8h

q12h

q24h


Cefoperazone

1-2 g IV q12h

20%

No renal adjustment is required

Displaced from protein by bilirubin. Reduce dose by 50% for jaundice. May prolong prothrombin time


Cefotaxime

1-2 g IV q6-8h

60%

q8h

q12h

q12-24h

Active metabolite in ESRD. Reduce does further for combined hepatic and renal failure


Cefotetan

1-2 g IV q12h

75%

q12h

q12-24h

q24h


Cefoxitin

1-2 g IV q6h

80%

q6h

q8-12h

q12h

May produce false increase in serum creatinine by interference with assay


Ceftazidime

1-2 g IV q8h

70%

q8h

q12h

q24h


Ceftriaxone

1-2 g IV q24h

50%

No renal adjustment is required


Cefuroxime sodium

0.75-1.5 g IV q8h

90%

q8h

q8-12h

q12-24h

Rare allergic interstitial nephritis. Absorbed well when given intraperitoneally. May cause bleeding from impaired prothrombin biosynthesis


Penicillin






Bleeding abnormalities, hypersensitivity, seizures


Oral Penicillin







Amoxicillin

500 mg p.o. tid

60%

100%

100%

50-75%


Ampicillin

500 mg p.o. q6h

60%

100%

100%

50-75%


Dicloxacillin

250-500 mg p.o. q6h

50%

100%

100%

50-75%


Penicillin V

250-500 mg p.o. q6h

70%

100%

100%

50-75%


IV Penicillin







Ampicillin

1-2 g IV q6h

60%

q6h

q8h

q12h


Nafcillin

1-2 g IV q4h

35%

No renal adjustment is required


Penicillin G

2-3 million units IV q4h

70%

q4-6h

q6h

q8h

Seizures. False-positive urine protein reactions. Six million units/d upper limit dose in ESRD


Piperacillin

3-4 g IV q4-6h


No renal adjustment is required

Specific toxicity: Sodium, 1.9 mEq/g


Ticarcillin/clavulanate

3.1 g IV q4-6h

85%

1-2 g q4h

1-2 g q8h

1-2 g q12h

Specific toxicity: Sodium, 5.2 mEq/g


Piperacillin/tazobactam

3.375 g IV q6-8h

75-90%

q4-6h

q6-8h

q8h

Specific toxicity: Sodium, 1.9 mEq/g


Quinolones






Photosensitivity, food, dairy products, tube feeding, and Al(OH)3 may decrease the absorption of quinolones


Cinoxacin

500 mg q12h

55%

100%

50%

Avoid


Fleroxacin

400 mg q12h

70%

100%

50-75%

50%


Ciprofloxacin

200-400 mg IV q24h

60%

q12h

q12-24h

q24h

Poorly absorbed with antacids, sucralfate, and phosphate binders. Intravenous dose 1/3 of oral dose. Decreases phenytoin levels


Lomefloxacin

400 mg q24h

76%

100%

200-400 mg q48h

50%

Agents in this group are malabsorbed in the presence of magnesium, calcium, aluminum, and iron. Theophylline metabolism is impaired. Higher oral doses may be needed to treat CAPD peritonitis


Levofloxacin

500 mg p.o. qd

70%

q12h

250 q12h

250 q12h

L-isomer of ofloxacin: appears to have similar pharmacokinetics and toxicities


Moxifloxacin

400 mg qd

20%

No renal adjustment is required


Nalidixic acid

1.0 g q6h

High

100%

Avoid

Avoid

Agents in this group are malabsorbed in the presence of magnesium, calcium, aluminum, and iron. Theophylline metabolism is impaired. Higher oral doses may be needed to treat CAPD peritonitis


Norfloxacin

400 mg p.o. q12h

30%

q12h

q12-24h

q24h

See above


Ofloxacin

200-400 mg p.o. q12h

70%

q12h

q12-24h

q24h

See above


Pefloxacin

400 mg q24h

11%

100%

100%

100%

Excellent bidirectional transperitoneal movement


Sparfloxacin

400 mg q24h

10%

100%

50-75%

50% q48h


Trovafloxacin

200-300 mg p.o. q12h

10%

No renal adjustment is required


Miscellaneous Agents







Azithromycin

250-500 mg p.o. qd

6%

No renal adjustment is required

No drug-drug interaction with Cyclosporine/Tacrolimus (CSA/FK)


Clarithromycin

500 mg p.o. bid





20%


Clindamycin

150-450 mg p.o. tid

10%

No renal adjustment is required

Increase CSA/FK level


Dirithromycin

500 mg p.o. qd


No renal adjustment is required

Nonenzymatically hydrolyzed to active compound erythromycylamine


Erythromycin

250-500 mg p.o. qid

15%

No renal adjustment is required

Increase CSA/FK level, avoid in transplant patients


Imipenem/Cilastatin

250-500 mg IV q6h

50%

500 mg q8h

250-500 q8-12h

250 mg q12h

Seizures in ESRD. Nonrenal clearance in acute renal failure is less than in chronic renal failure. Administered with cilastatin to prevent nephrotoxicity of renal metabolite


Meropenem

1 g IV q8h

65%

1 g q8h

0.5-1 g q12h

0.5-1 g q24h


Metronidazole

500 mg IV q6h

20%

No renal adjustment is required

Peripheral neuropathy, increase LFTs, disulfiram reaction with alcoholic beverages


Pentamidine

4 mg/kg/day

5%

q24h

q24h

q48h

Inhalation may cause bronchospasm, IV administration may cause hypotension, hypoglycemia, and nephrotoxicity


Trimethoprim/sulfamethoxazole

800/160 mg p.o. bid

70%

q12h

q18h

q24h

Increase serum creatinine. Can cause hyperkalemia


Vancomycin

1 g IV q12h

90%

q12h

q24-36h

q48-72h

Nephrotoxic, ototoxic, may prolong the neuromuscular blockade effect of muscle relaxants. Peak 30, trough 5-10


Vancomycin

125-250 mg p.o. qid

0%

100%

100%

100%

Oral vancomycin is indicated only for the treatment of C. difficile


Antituberculosis Antibiotics







Rifampin

300-600 mg p.o. qd

20%

No renal adjustment is required

Decrease CSA/FK level. Many drug interactions


Antifungal Agents







Amphotericin B

0.5-1.5 mg/kg/day

<1%

No renal adjustment is required

Nephrotoxic, infusion-related reactions, give 250 cc NS before each dose


Amphotec

4-6 mg/kg/day

<1%

No renal adjustment is required


Abelcet

5 mg/kg/day

<1%

No renal adjustment is required


AmBisome

3-5 mg/kg/day

<1%

No renal adjustment is required


Azoles and Other Antifungals






Increase CSA/FK level


Fluconazole

200-800 mg IV qd/bid

70%

100%

100%

50%


Flucytosine

37.5 mg/kg

90%

q12h

q16h

q24h

Hepatic dysfunction. Marrow suppression more common in azotemic patients


Griseofulvin

125-250 mg q6h

1%

100%

100%

100%


Itraconazole

200 mg q12h

35%

100%

100%

50%

Poor oral absorption


Ketoconazole

200-400 mg p.o. qd

15%

100%

100%

100%

Hepatotoxic


Miconazole

1,200-3,600 mg/day

1%

100%

100%

100%


Terbinafine

250 mg p.o. qd

>1%

100%

100%

100%


Voriconazole

4 mg/kg q12h

>1%

100%

100%

100%

IV use should be limited for only few doses in patients with CrCl <30 mL/min


Antiviral Agents







Acyclovir

200-800 mg p.o. 5×/day

50%

100%

100%

50%