Acyclovir Intravenous Dosing in Adults

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Acyclovir induced renal failure occurs in greater than 10% of cases, range 10-48%, with crystal obstruction being the most common cause. Crystal nephropathy is characterized by a decrease in renal function with a rapid rise in serum creatinine. Dialysis may be needed in severe cases. Acyclovir is filtered by glomeruli and secreted in renal tubules producing high tubular concentrations. It is relatively insoluble in urine. Intra-tubular crystals obstruct the nephron leading to acute renal failure. Crystalluria usually develops within 24-72 hours of initiation of therapy. Severe intra-parenchymal crystals may cause interstitial congestion and hemorrhage. Higher concentrations are produced in the tubules when there is decreased urine flow, dehydration, IV administration rather than oral, and rapid IV administration. Laboratory findings include increasing serum creatinine, hematuria, pyuria, and urine crystals which may be seen under polarizing light microscopy. Acyclovir is a small drug MW 225 Da with a low plasma protein binding, volume of distribution of 0.6 L/kg, and a partition coefficient (log P) of -1.56 denoting a hydrophilic nature. Maximum solubility at physiological pH is 2.5 mg/ml. Acyclovir is distributed into the lean body compartment. Acyclovir is 60-90% renally eliminated unchanged by glomerular filtration and tubular secretion. Renal clearance is approximately 3 fold higher than creatinine clearance. Urinary concentrations of acyclovir are highest during IV administration and several hours post administration due to renal clearance. Urine flow rates less than 100 ml/hour are more likely to produce acyclovir urine concentrations above the solubility point producing precipitants. Optimal dosing and administration are needed to minimize the risk of nephropathy. Risks may be reduced by maintaining euvolemia (institution of a hydration protocol), urine flow rates of 100-150 ml/hour, administering IV doses over 2 hours in 250 ml of fluid, adjusting the dose for renal function, avoiding other nephrotoxins, and early discontinuation based on viral PCR tests. AKI is more frequent in patients with DM, obesity, renal dysfunction, and concomitant NSAIDs or vancomycin. Treatment of acyclovir nephrotoxicity includes IV fluids to maintain high urine flow rate greater than 150 ml/hour, loop diuretics, and discontinuation of acyclovir or dosage reduction. Dialysis may be needed.

Conversion unit,1 uM = 0.225 mcg of acyclovir. Most studies measure serum levels in uM/L or nM/ml.

The results of 7 acyclovir single and multiple dose intermittent infusion pharmacokinetic studies in adults, were pooled by Blum in 1982 who worked at Burroughs Wellcome Laboratories. Seventy patients, age 16-68 years old, with varying degrees of renal function were studied. Total body clearance (L/hour/1.73 m2) = 0.2022 Clcr per 1.73 m2 + 1.722, R²=0.34, Vd steady state of approximately 48 L/1.73m2, and central volume of distribution 21 L/1.73m2. This is the basis of the package insert dosing recommendations for renal dysfunction which were designed to maintain similar AUC ranges over a 24 hour period of 45-101 mg*hour/liter per 24 hours for 5 mg/kg doses. Pharmacodynamics parameters include Time > EC50% (time concentration remains above the 50% inhibitory concentration) and AUC. In encephalitis a trough above 2-4 mg/L is recommended.

Spector studied continuous infusion acyclovir in 16 immunocompromised patients with Varicella Zoster infections, age 17-66 years, using 6 different infusion rates of 7.2, 14.4, 21.6, 28.8, 36, 43.2 mg/kg/day (15-126 mg/hr) with average steady state serum levels were 0.9, 2.3, 4.6, 3.2, 5.6 and 8.2 mcg/ml respectively. Average urinary concentrations were 0.09, 0.33, 0.67, 0.68, 0.97, and 0.84 mg/ml with a solubility limit of acyclovir in the urine of 1.3 mg/ml. Seven of thirteen patients had no new vesicle formation after three days and all patients stopped new vesicle formation after five days of therapy. No clinical or laboratory signs of systemic toxicity or infusion site reactions were noted during the study or follow up period. Total body clearance (L/hour/1.73m2) = 0.091*Clcr per 1.73m2 + 7.52, R² =0.45. Note: continuous infusion of the same total daily dose given as intermittent infusions produces much lower peak urinary levels with a reduction of risk of crystalluria.

Fletcher studied continuous infusion acyclovir in 13 patients with life threatening HSV, EBV, or CMV infections age 4-57 years old, with infusion rate of 0.45-9.7 mg/kg/hour (25-280 mg/hour). Target goal levels were: HSV 4.5-9 mg/L, EBV 6.8-13.5 mg/L, CMV 9-18 mg/L. Two of five patients with CMV, three of three with HSV, and two of four with EBV had clinical improvement and resolution. Three patients developed neutropenia. Nephrotoxic was not observed. Total body clearance (L/hour/1.73m2) = 0.178*Clcr per 1.73 m2 + 2.92, R²=0.88

Few pharmacokinetic studies are available in obese adult patients. A study by Davis in 1991 of 7 morbidity obese patients and 5 normal weight patients found similar pharmacokinetic profiles between the groups, Vd of 43 liters. Dosing using actual body weight resulted in serum levels twice as high in obese patients and the authors recommended dosing by IBW. A prospective study by Turner in 2016 of 14 patient given a prophylactic dose of 5 mg/kg based on IBW. Patient average age was 54 years, BMI > 40 in 7 patients, and BMI 22.5 in 7 patients. Clearance, AUC, and peak levels were statistically different for obese versus non obese, but time above HSV inhibitory therapeutic break points were not. The author concluded: while not directly studied dosing by adjusted body in morbid obesity more closely approximate the exposure seen in normal weight patients and that further research is needed to validate their results and clarify the proper dosing in obese patients.

A few studies of factors related to toxicity have been published. A retrospective study by Ryan of 269 patients in 2018 found an AKI rate of 13%. All doses were given over at least 60 minutes. Factors associated with AKI were CKD, DM and higher daily doses (2173 vrs 1819 mg/day). The author recommended dosing based on IBW. A retrospective study by Lee of 287 patients in 2018 found DM, NSAID, and vancomycin to be independent risk factors for AKI during acyclovir therapy. A retrospective study by Barber of 115 patients in 2019 found obesity, BMI greater than 30, and concomitant vancomycin use were independently associated with nephrotoxicity. The nephrotoxicity rate was 21%. Median acyclovir IV dose was 10.1 mg/kg based on ideal body weight with a range of 9.8-11.4 mg/kg. Twenty-one percent of patient developed toxicity as defined by Rifle criteria. A retrospective study by Kim 2015 of 216 patients compared the effect of IV hydration on renal function parameters in patient with normal renal function treated for CNS HSV infection with 10 mg/kg infused over one hour Q8H. Baseline renal function parameters and 3 days after the start of treatment were compared (Scr, BUN, eGRF). Outcomes for those with hydration > 2 liter per day were significantly better P< 0.05 than those with less than 2 liters of hydration per day or no IV hydration. Average serum creatinine (mg/dL) pre and 3 days after start of treatment were: no hydration 0.73 to 2.22, < 2 liters hydration 0.84 to 1.7, > 2 liters of hydration 0.79 to 0.87. Average eGFR (ml/min) pre and 3 days into treatment were: no hydration 104 to 53, < 2 liters per day hydration 87 to 60, > 2 liters per day hydration 107 to 89.

There are no clinical trials of herpes viral infections treated with IV acyclovir comparing efficacy by dosing weight (lean, adjusted, total) in obese adults patients.

Acyclovir intravenous intermittent infusion is indicated in adults for Herpes Simplex infections in immunocompromised (5 mg/kg Q8H for 7 days), initial episodes of Herpes Genitalis (5 mg/kg Q8H for 5 days), Herpes Simplex Encephalitis (10 mg/kg Q8H for 10 days), and Varicella-Zoster infections in immunocompromised (10 mg/kg Q8H for 7 days).

Dosing of acyclovir per manufacture guidelines is by total body weight but there is a warning against using total body weight in obesity where ideal body weight is recommended. The product was released in 1982 long before obesity was common. Using adjusted body weight for patients BMI >30 and total body weight for all others causes patients with a BMI of < 30 to get larger doses than patients with a BMI > 30, with a dosing error of 15-20%. The higher the BMI break point the greater the resulting dosing error. For a male patient 70 inches tall the total body weight needs to increase by 32 kg for the obese patient dosed by adjusted body weight to receive the same dose as the patient who has a BMI of 30 dosed by total body weight. Visual inspection of the graphic shows a 82 kg patient dosed by total body weight gets the same dose as a 95 kg patient dosed by adjusted body weight and a 94 kg patient dosed by total body weight gets the same dose as a 125 kg patient dosed by adjusted body weight. This type of dosing is mathematical illogical as smaller patients are given larger doses than heavier patients. If adjusted body weight is used it should be used on all patients weighing more than their ideal weight. If not than a lower BMI break point, such as a BMI of 25 should be used, as it causes less dosing discrepancies. See graphic below

Acyclovir Intravenous Dosing Based On Ideal Body Weight, Adjusted Body Weight, Or Adjusted Body Weight If BMI Greater than 30

Acyclovir Intravenous Dosing Based On Ideal Body Weight, Adjusted Body Weight, Or Adjusted Body Weight If BMI Greater Than 40

The following equation may be used to calculated the increase in total body weight required for an obese patient dosed by adjusted body weight to be given the same dose as patient who is dosed by total body weight who is just before the break point for BMI. Weight (kg) = 1.5*BMI Breakpoint*(Inches in height*2.54/100)^2 - 1.5((Inches in height-60)*2.3 + 50)

The attached Excel tool demonstrates the results discussed above graphically and may be downloaded. The tool allows for input of dose, height, sex, and BMI break point. Acyclovir Excel Dosing Weight Comparisons
There is a tab in the Excel file that can be used to see the impact of dose, infusion time, and urine flow on serum levels and urinary levels. There is also a comparison to a continuous infusion of acyclovir.

A review of online institutional renal dosing protocols, accessed 6/88/22, reveal a lack of standardization with a wide array of dosing recommendations.
Ideal body weight: Centegra HealthSystem, CCKM@uwhealth.org
Dosing weight not mentioned: UNMC.edu
Adjusted body weight: Nebraska Medicine
Adjusted body weight for BMI > 30 and ideal for non obese: Wake Forrest -WakeHealth.edu,
Adjusted body weight for BMI > 30 and total body weight for non obese: University of Michigan, Stanford Health Care
Adjusted body weight for BMI > 35, actual body weight others: Asp.nm.org
Adjusted body weight if weight > 120% of ideal, total body weight if weight <= 120% of ideal: University of California San Francisco
Adjusted body weight is > 190% of IBW, IBW if overweight (> 130-190% of IBW): University of Toledo:
Adjusted body weight for BMI > 40 and life threatening and ideal body weight for BMI > 30 : Washington.edu (HMC/UWMC)

Recommendations to minimize IV Acyclovir induced nephrotoxicity in adults:
As there are few pharmacokinetic studies in obese adults, published studies have conflicting results, and there are no outcomes studies comparing the use of different dosing weights on efficacy in obese adult patients with HSV infections, a conservative approach is warranted. Nephrotoxicity is dose related and occurs at higher rates in obese patients even when dosed by IBW. Unnecessarily increasing the dose may place patients at higher risk of nephrotoxicity.
Dosing by adjusted body weight, if used, should be uniform applied to all patients who weight more than their ideal body weight. If a BMI break point is used a value of 25 is suggested to minimize dosing discrepancies.
Obese patients, BMI > 30, should not be dosed by total body weight.
Patients should receive IV hydration of > 2 liters per day while receiving IV acyclovir and maintain urine flow rates of 100-150 ml/hour or approximately 1.5 ml/kg/hour urine flow based on acyclovir dosing weight.
Doses should be administer over 2 hours, rather than 1 hour, if possible. Continuous infusion of the total daily dose may be used to improve efficacy and decrease risk of nephrotoxicity.
Dilute doses of 10 mg/kg in 250 ml rather than 100 ml for intermittent infusions.
Early discontinuation of acyclovir is recommended if viral tests are negative.
Monitor renal function and CBC daily.

A large prospective pharmacokinetic study in obese patients treated for severe HSV infections is needed to validate pharmacokinetic parameters, efficacy and toxicity rates using different dosing weights. Use of nephrotoxicity reducing measures should be included to evaluate their impact on toxicity.

References:
PMID- 25504951
OWN - NLM
STAT- MEDLINE
DCOM- 20150806
LR - 20141216
IS - 1552-4175 (Electronic)
IS - 1099-8004 (Linking)
VI - 17
IP - 1
DP - 2015 Jan
TI - Comparison of renal function indicators according to hydration volume in patients
receiving intravenous acyclovir with CNS infection.
PG - 55-61
LID - 10.1177/1099800414531483 [doi]
AB - PURPOSE: We aimed to compare the changes in renal function indicators as a
function of hydration volume in patients treated with acyclovir for suspected
herpes simplex virus (HSV) infection. METHOD: We obtained data from 216
acyclovir-treated patients hospitalized between 2007 and 2012 for suspected HSV
infection. Intravenous hydration volume and renal function indicators (serum
creatinine [sCr], blood urea nitrogen [BUN], glutamate oxaloacetate transferase,
glutamate pyruvate transferase, and uric acid levels; estimated glomerular
filtration rate [eGFR]; and urine pH) were compared among the patients. The
indicators were assessed before acyclovir infusion and after 3 days of acyclovir
infusion. RESULTS: Before acyclovir infusion, all the indicators were within
normal ranges in all groups (hydration volume lower than 2 L/day, higher than 2
L/day, and without hydration). After acyclovir infusion for 3 days, the groups
without hydration and with a volume lower than 2 L/day showed increased sCr (2.22
± 0.51 and 1.70 ± 0.35 mg/dl, respectively), BUN levels (28.33 ± 0.57 and 22.14 ±
7.95 mg/dl, respectively), and glutamate oxaloacetate transferase (48.00 ± 2.65
IU/L, without hydration) and eGFRs lower than the normal range (53.03 ± 3.05 and
59.66 ± 10.25 ml/min, respectively; p < .001 for all parameters). The renal
function indicators were within normal limits in the group with a hydration
volume higher than 2 L/day. CONCLUSIONS: Renal function indicators in
acyclovir-treated patients varied according to hydration volume. Health care
providers should consider whether the hydration volume in each patient receiving
intravenous acyclovir is sufficient for preventing nephropathy.
CI - © The Author(s) 2014.
FAU - Kim, Sanghee
AU - Kim S
AD - Neuroscience Center, Seoul National University Bundang Hospital, Seongnam-si,
Gyeonggi-do, Republic of Korea even07@ewhain.net.

PMID- 27006000
OWN - NLM
STAT- MEDLINE
DCOM- 20161222
LR - 20161230
IS - 1872-7913 (Electronic)
IS - 0924-8579 (Linking)
VI - 47
IP - 4
DP - 2016 Apr
TI - Pharmacokinetics of acyclovir in a morbidly obese patient with renal impairment.
PG - 340-1
LID - S0924-8579(16)00040-6 [pii]
LID - 10.1016/j.ijantimicag.2016.01.006 [doi]
FAU - Smith, Tonya C
AU - Smith TC
AD - Department of Pharmacy, University of Utah Health Sciences Center, 50 N. Medical
Drive, Pharmacy Administration, Room A-050, Salt Lake City, UT 84132, USA.

Bastiaan TGM Sallevelt, Erin H Smeijsters, Toine CG Egberts, Kim CM van der Elst, Tania Mudrikova,
Acute renal and neurotoxicity due to weight-based dosing of intravenous acyclovir: How to dose in obese patients?,
Clinical Infection in Practice,
Volumes 7–8,
2020,
100046,
ISSN 2590-1702,
https://doi.org/10.1016/j.clinpr.2020.100046.
(https://www.sciencedirect.com/science/article/pii/S2590170220300339)

PMID- 26824940
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR - 20220408
IS - 1098-6596 (Electronic)
IS - 0066-4804 (Print)
IS - 0066-4804 (Linking)
VI - 60
IP - 3
DP - 2016 Jan 11
TI - Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients.
PG - 1830-3
LID - 10.1128/AAC.02010-15 [doi]
AB - The current recommendations for intravenous (i.v.) acyclovir dosing in obese
patients suggest using ideal body weight (IBW) rather than total body weight
(TBW). To our knowledge, no pharmacokinetic analysis has validated this
recommendation. This single-dose pharmacokinetic study was conducted in an
inpatient oncology population. Enrollment was conducted by 1:1 matching of obese
patients (>190% of IBW) to normal-weight patients (80 to 120% of IBW). All
patients received a single dose of i.v. acyclovir, 5 mg/kg, infused over 60 min.
Consistent with current recommendations, IBW was used for obese patients and TBW
for normal-weight patients. Serial plasma concentrations were obtained and
compared. Seven obese and seven normal-weight patients were enrolled, with mean
body mass indexes of 45.0 and 22.5 kg/m(2), respectively. Systemic clearance was
substantially higher in the obese than normal-weight patients (mean, 19.4 ± 5.3
versus 14.3 ± 5.4 liters/h; P = 0.047). Area under the concentration-time curve
was lower in the obese patients (15.2 ± 2.9 versus 24.0 ± 9.4 mg · h/liter; P =
0.011), as was maximum concentration (5.8 ± 0.9 versus 8.2 ± 1.3 mg/liter; P =
0.031). Utilization of IBW for dose calculation of i.v. acyclovir in obese
patients leads to lower systemic exposure than dosing by TBW in normal-weight
patients. While not directly evaluated in this study, utilization of an adjusted
body weight for dose determination appears to more closely approximate the
exposure seen in normal-weight patients. (This study has been registered at
ClinicalTrials.gov under registration no. NCT01714180.).
CI - Copyright © 2016, American Society for Microbiology. All Rights Reserved.
FAU - Turner, R Brigg
AU - Turner RB
AD - West Virginia University Healthcare, Morgantown, West Virginia, USA.

PMID- 26985083
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160317
LR - 20190609
IS - 1920-2903 (Electronic)
IS - 0008-4123 (Print)
IS - 0008-4123 (Linking)
VI - 69
IP - 1
DP - 2016 Jan-Feb
TI - Interdisciplinary Systems-Based Intervention to Improve IV Hydration during
Parenteral Administration of Acyclovir.
PG - 7-13
AB - BACKGROUND: Intravenous (IV) hydration is considered a protective factor in
reducing the incidence of acyclovir-induced nephrotoxicity. A systems-based
review of cases of acyclovir-associated acute kidney injury can be used to
examine institution-, care provider-, and task-related factors involved in
administering the drug and can serve as a basis for developing a quality
improvement intervention to achieve safer administration of acyclovir.
OBJECTIVES: To explore the effectiveness of the study institution's
inter-disciplinary quality improvement intervention in increasing the dilution of
acyclovir before IV administration. METHODS: After conducting a systems-based
review for intervention development, a retrospective analysis was undertaken to
compare IV administration of acyclovir in the 6-month periods before and after
implementation of the intervention. The study population was a sequential sample
of all patients over 18 years of age who were seen in the emergency department or
admitted to a ward and who received at least one IV dose of acyclovir at the
study institution. The primary outcome was the volume in which each acyclovir
dose was delivered. The secondary outcomes were the hourly rate of fluid
administration, the frequency of an increase in hourly hydration rate, and the
incidence of acute kidney injury. RESULTS: Eighty-four patients (44 in the
pre-intervention period and 40 in the post-intervention period) received IV
acyclovir and had evaluable data for the primary outcome. The median volume in
which the acyclovir dose was administered was significantly higher in the
post-intervention group (250 mL versus 100 mL, p < 0.001). CONCLUSIONS: In this
study, an easily implemented intervention significantly increased the volume of
IV fluid administered to patients receiving acyclovir. Adequately powered
prospective studies are suggested to investigate the effectiveness of this
intervention on the clinically relevant incidence of acyclovir-induced
nephrotoxicity.
FAU - Dubrofsky, Lisa
AU - Dubrofsky L
AD - MDCM, is an Internal Medicine Resident with the Department of Medicine, McGill
University, Montréal, Quebec.

PMID- 25203631
OWN - NLM
STAT- MEDLINE
DCOM- 20150626
LR - 20220330
IS - 1365-2710 (Electronic)
IS - 0269-4727 (Linking)
VI - 39
IP - 6
DP - 2014 Dec
TI - Impact of hospital guideline for weight-based antimicrobial dosing in morbidly
obese adults and comprehensive literature review.
PG - 584-608
LID - 10.1111/jcpt.12200 [doi]
AB - WHAT IS KNOWN AND OBJECTIVE: Obesity is a significant burden on the healthcare
system in the United States, and determining the appropriate antimicrobial dosing
regimen in morbidly obese patients is challenging. Morbidly obese patients have
documented differences in pharmacokinetic and pharmacodynamic properties compared
to normal-weight patients, which impact antibiotic efficacy and toxicity. The
Food and Drug Administration does not recognize obesity as a special population
and does not require pharmaceutical companies to perform studies specific to
obese patients. However, there are an increasing number of post-approval studies
in obese patients, and this manuscript reviews available clinical and
pharmacokinetic literature regarding weight-based antimicrobial agents.
Additionally, we describe a single-centre approach to optimize dosing in morbidly
obese patients. METHODS: A comprehensive literature search was performed on 15
weight-based antimicrobials in the setting of obesity: acyclovir,
aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin,
flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin,
trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based
antimicrobial dosing guideline for morbidly obese patients was developed. An
analysis of guideline compliance and cost analysis were performed following
guideline implementation. RESULTS AND DISCUSSION: This review describes the
pharmacokinetic changes that occur in obese patients, including increased volume
of distribution, altered hepatic metabolism, renal excretion and changes in
protein binding. The majority of weight-based antimicrobials result in increased
serum concentrations in morbidly obese patients compared to normal-weight
patients when the calculated dose is based on actual body weight. WHAT IS NEW AND
CONCLUSION: This review demonstrates different antibiotic pharmacokinetic
properties are altered in obese patients that could impact efficacy and toxicity.
A single-centre guideline for weight-based antimicrobial dosing in obesity was
developed and provides recommendations for using ideal body weight, adjusted body
weight or actual body weight when calculating antimicrobial doses. However, more
research is needed to better elucidate optimal dosing of weight-based
antimicrobials in obesity, with particular focus on efficacy and toxicity.
CI - © 2014 John Wiley & Sons Ltd.
FAU - Polso, A K
AU - Polso AK
AD - Department of Pharmacy, University of Michigan Hospitals and Health Centers, Ann
Arbor, MI, USA.

PMID- 22791803
OWN - NLM
STAT- MEDLINE
DCOM- 20130212
LR - 20220408
IS - 1757-790X (Electronic)
IS - 1757-790X (Linking)
VI - 2012
DP - 2012 Jul 12
TI - Acyclovir-induced acute renal failure and the importance of an expanding waist
line.
LID - 10.1136/bcr-2012-006264 [doi]
LID - bcr2012006264
AB - A 23-year-old gentleman with no significant medical history other than obesity
was admitted with a history of balance problems, double vision and strange
behaviour following a fall from bed. Systems examination was unremarkable. The
patient was given intravenous acyclovir and intravenous ceftriaxone given the
suspicion of encephalitis/meningitis. Investigations including routine bloods,
CT/MRI Head and lumbar puncture were unremarkable. Within 48&emsp14;h of
commencing intravenous acyclovir, there was a marked deterioration in renal
function. On stopping acyclovir therapy, renal function improved back to
baseline. No other cause for deterioration in renal function was identified. The
most likely cause for acute renal failure was secondary to acyclovir therapy.
This has been well documented and is due to intratubular crystal precipitation.
Moreover, in this case nephrotoxicity is likely secondary to the large boluses of
intravenous acyclovir that had been given as prescribed according to the total
body weight.
FAU - Seedat, Ahmed
AU - Seedat A
AD - Department of General Medicine, Basildon and Thurrock University Hospitals NHS,
Foundation Trust, Basildon, UK. aseedat@doctors.org.uk

PMID- 28509218
OWN - NLM
STAT- PubMed-not-MEDLINE
LR - 20220409
IS - 2192-4449 (Print)
IS - 2192-4449 (Electronic)
IS - 2192-4449 (Linking)
VI - 2
IP - 1
DP - 2013 May
TI - Acute kidney injury due to acyclovir.
PG - 38-40
LID - 10.1007/s13730-012-0035-0 [doi]
AB - Acyclovir is an antiviral agent widely used in herpetic infections in children.
Although acyclovir is generally well tolerated, severe nephrotoxicity has been
reported in some cases. In this report, we present a 16-year-old girl who
developed acute renal failure due to acyclovir treatment and who needed
repetitive hemodialysis. Renal biopsy was performed in order to confirm the
diagnosis. A diagnosis of drug-related acute tubulointerstitial nephritis with
focal tubular necrosis was made.
FAU - Yildiz, Cigdem
AU - Yildiz C
AD - Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty
of Medicine, Sıhhiye, Ankara, 06100, Turkey.

PMID- 20862348
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR - 20220409
IS - 1687-9635 (Electronic)
IS - 1687-9627 (Print)
VI - 2010
DP - 2010
TI - Acyclovir nephrotoxicity: a case report highlighting the importance of
prevention, detection, and treatment of acyclovir-induced nephropathy.
LID - 602783 [pii]
LID - 10.1155/2010/602783 [doi]
AB - Acute kidney injury is an unfortunate complication of acyclovir therapy secondary
to crystal-induced nephropathy. It is characterized by a decrease in renal
function that develops within 24-48 hours of acyclovir administration indicated
by a rapid rise in the serum creatinine. Failure to quickly realize this as an
etiology of acute kidney injury can lead to excessive morbidity to the patient.
The case described in this vignette is an example of the clinical manifestation
of acyclovir crystal obstructive nephrotoxicity. We will briefly discuss the
pathophysiology, diagnosis, prevention, and management of patients that present
with acyclovir nephrotoxicity.
FAU - Fleischer, Raymond
AU - Fleischer R
AD - Internal Medicine, University of Texas Health Science Center, San Antonio, TX
78229, USA.

PMID- 9243045
OWN - NLM
STAT- MEDLINE
DCOM- 19971010
LR - 20190512
IS - 1058-4838 (Print)
IS - 1058-4838 (Linking)
VI - 25
IP - 1
DP - 1997 Jul
TI - Antimicrobial dosing in obese patients.
PG - 112-8
AB - Although the dose of some drugs is commonly adjusted for weight, weight-related
dosage adjustments are rarely made for most antimicrobials. We reviewed the
English-language literature on antimicrobial pharmacokinetics and dosing in
obesity. Although there are many potential pharmacokinetic consequences of
obesity, the actual effect on the pharmacokinetics and clinical efficacy of most
antimicrobials is unknown. Since approximately 30% of adipose is water, an
empirical approach is use of the Devine formula to calculate ideal body weight
(IBW), to which is added a dosing weight correction factor (DWCF) of 0.3 times
the difference between actual body weight (ABW) and IBW (IBW + 0.3 x [ABW-IBW])
to arrive at a weight on which to base dosage of hydrophilic antibiotics. No
studies confirm this approach for beta-lactam drugs. Clinical studies suggest a
DWCF of approximately 0.40 for aminoglycosides and 0.45 for quinolones. Final
dosage adjustments for antimicrobials with a narrow toxic-therapeutic window
should be based on serum concentrations.
FAU - Wurtz, R
AU - Wurtz R
AD - Department of Medicine, Evanston Hospital, Illinois 60201, USA.

PMID- 31024972
OWN - NLM
STAT- PubMed-not-MEDLINE
LR - 20220408
IS - 2328-8957 (Print)
IS - 2328-8957 (Electronic)
IS - 2328-8957 (Linking)
VI - 6
IP - 4
DP - 2019 Apr
TI - Impact of Obesity on Acyclovir-Induced Nephrotoxicity.
PG - ofz121
LID - 10.1093/ofid/ofz121 [doi]
LID - ofz121
AB - BACKGROUND: Obesity is a major medical issue nationally, with rates continually
increasing. In obese patients, minimal data exist for appropriate dosing of
acyclovir to decrease the rates of nephrotoxicity. The purpose of this study was
to determine the prevalence of and risk factors associated with acyclovir-induced
nephrotoxicity. METHODS: A retrospective case-control of patients who received
intravenous acyclovir for >48 hours at the University of Mississippi Medical
Center over a 4-year period were evaluated to elucidate the prevalence of
acyclovir-induced nephrotoxicity. Additionally, risk factors for the development
of nephrotoxicity, including the effect of obesity and dosing strategy, were
assessed. RESULTS: One hundred fifteen patients were included in the study. A
total of 24 (21%) patients developed nephrotoxicity after acyclovir exposure and
were in the Risk (9.6%), Injury (4.3%), and Failure (7%) categories, defined by
the RIFLE criteria. Neither acyclovir dosage, fluid status, nor baseline
characteristics, other than obesity, varied between those who developed
nephrotoxicity vs those who did not. Independent predictors of nephrotoxicity
were obesity (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.19-8.67) and
receipt of vancomycin (OR, 4.73; 95% CI, 1.57-14.25). No differences in
vancomycin dosing or concentrations were observed between the patients who
developed nephrotoxicity and those who did not. CONCLUSIONS: In this study,
nephrotoxicity occurred in 21% of patients receiving acyclovir. Concomitant
vancomycin receipt and obesity led to higher rates of toxicity. Efforts should be
made to target obese patients on acyclovir plus vancomycin and discontinue
therapy in patients not warranting antiviral coverage to minimize chances of
toxicity.
FAU - Barber, Katie E
AU - Barber KE
AD - Department of Pharmacy Practice, University of Mississippi School of Pharmacy,
Jackson, Mississippi.

PMID- 30741619
OWN - NLM
STAT- MEDLINE
DCOM- 20190319
LR - 20200225
IS - 1525-6049 (Electronic)
IS - 0886-022X (Print)
IS - 0886-022X (Linking)
VI - 40
IP - 1
DP - 2018 Nov
TI - The incidence, risk factors, and clinical outcomes of acute kidney injury (staged
using the RIFLE classification) associated with intravenous acyclovir
administration.
PG - 687-692
LID - 10.1080/0886022X.2018.1487866 [doi]
AB - Intravenous (IV) acyclovir is commonly administered medication for viral
infection but is well known for its nephrotoxicity. However, there was no study
for incidence, risk factors, and clinical outcomes of acute kidney injury (AKI)
associated with IV acyclovir administration. We retrospectively reviewed the
medical records of 287 patients who were medicated IV acyclovir from January 2008
to May 2013 in Gyeongsang National University Hospital. All had documented
medical histories and underwent medical review. Demographic data, risk factors,
concomitant drugs, laboratory findings and outcome were gathered from the medical
records and analyzed. AKI occurred in 51 patients (17.8%). As per RIFLE
classification, renal injury was graded as either at risk of renal dysfunction
(62.7%), renal injury (15.6%), and renal failure (21.6%). There was no
significant difference in age, sex, total dose, drug duration, and presence of
hydration between AKI and non-AKI group. However, systolic pressure, underlying
diabetes, concomitant vancomycin and non-steroidal anti-inflammatory drugs
(NSAIDs) use was positively correlated with AKI occurrence (p = .04, p < .001,
0.01, and 0.04, respectively). Two patients underwent hemodialysis and these
patients died. Higher mortality was observed in AKI patients (p < .001).
Multivariate analysis also presented that presence of diabetes, concomitant
NSAIDs, and vancomycin use was independent risk factor of acyclovir associated
with AKI (p = .001, OR 3.611 (CI: 1.708-7.633), p = .050, OR 2.630 (CI:
1.000-6.917), and p = .009, OR 4.349 (CI: 1.452-13.022), respectively). AKI is
relatively common in patients administrating acyclovir injection. Physicians
should attempt to prevent, detect, and manage acyclovir associated AKI in
patients prescribing acyclovir due to possible association of poor prognosis.
FAU - Lee, Eun Ju
AU - Lee EJ
AD - a Department of Internal Medicine , Gyeongsang National University Hospital ,
Jinju , South Korea.

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