What information is available for dosing acyclovir IV in obese adults and pediatrics?

What information is available for dosing acyclovir IV in obese adults and pediatrics? e.g. use adjusted body weight based on BMI, weight 120-140% x IBW, or other suggestions.

Comment by InpharmD Researcher

Limited data exists on the optimal dosing weight for intravenous (IV) acyclovir in patients with a body mass index (BMI) greater than 40 kg/m^2. One retrospective study suggested that adjusted body weight (AdjBW) dosing resulted in reduced drug exposure compared to ideal body weight (IBW) dosing, while another study indicated lower acyclovir exposure in obese patients dosed on IBW compared to normal-weight patients dosed on total body weight (TBW), suggesting potential similarity in exposure with AdjBW dosing in obese patients. For pediatric patients, published guidance similarly suggests the use of IBW for dosing acyclovir in children with obesity, although there is a lack of data to corroborate this claim. Overall, more data is needed to establish the appropriate dosing strategy for these specific patient populations.

Pubmed: acyclovir IV obese (5 results; 3 relevant) Google Scholar: IV acyclovir obese (11,700 results; 4 relevant)

Background

A poster abstract describing a 2020 retrospective observational chart review assessed the impact of different dosing strategies of intravenous (IV) acyclovir in obese patients. The study included 51 adult patients with a body mass index (BMI) greater than or equal to 30 kg/m^2 who received at least 48 hours of high-dose IV acyclovir therapy. Efficacy analysis was conducted by stratifying patients into ideal body weight (IBW), adjusted body weight (AdjBW), and total body weight (TBW) groups. Treatment failure was observed in 3 out of 51 patients (1 patient in IBW group, 2 patients in AdjBW group, p= 0.445). Median length of stay (p= 0.977) and median duration of IV therapy (p= 0.78) did not show significant differences. Nephrotoxicity occurred in 22.2%, 19.2%, and 22.7% of patients in the IBW, AdjBW, and TBW groups, respectively (p= 1). The study suggested that, while comparing different dosing modalities, there were no significant differences in the outcome of infection, duration of therapy, or length of stay. However, dosing patients according to AdjBW resulted in smaller doses of acyclovir, reducing drug exposure. It is important to interpret the results with caution due to the small sample size and the limited available information based on a poster abstract. [1]

An abstract published on the Eshelman School of Pharmacy website describes a retrospective study that assessed the nephrotoxicity of IV acyclovir between traditional dosing and BMI-based dosing at a single institution center. Patients with BMI ≥ 40 kg/m^2 were dosed using AdjBW while patients with BMI less than 40 kg/m^2 were dosed using actual body weight (ABW). Nephrotoxicity was defined as an increase of 2x or greater in serum creatinine (SCr) from baseline. When patients were divided by BMI groups, those between 30 to 39 kg/m^2 experienced the highest rate of nephrotoxicity compared to traditional protocol dosing (9.5% vs 0%), although there were only a total of 4 of 70 events in the BMI-based protocol group. The rate for those with BMI ≥ 40 kg/m^2 were not published. The dosing protocol for IV acyclovir was also not specified within the abstract. [2]

In children with obesity, drug dosing methods are recommended to be determined based on patient characteristics, possible increased toxicity, and the effect of obesity on dosing parameters. Guidance from the Pediatric Pharmacy Advocacy Group suggests that empiric determination of medication dosage may be guided by the following points: weight-based dosing in patients aged <18 years who are <40 kg; weight-based dosing used for children ≥40 kg, unless the patient’s dose or dose per day exceeds the recommended adult dose for the specific indication; avoidance of exceeding the recommended maximum adult dose; and occurrence of modifications of pharmacokinetic parameters for adjusting drug dosage when possible. One narrative review suggests that in medications such as acyclovir, digoxin, and morphine, ideal body weight should be utilized for proper dosing of medications. No further data is provided on acyclovir in obese pediatric patients to support the authors’ recommendations. [3], [4]

Relevant Prescribing Information

Dosage and Administration
Therapy should be initiated as early as possible following onset of signs and symptoms of herpes infections. A maximum dose equivalent to 20 mg/kg every 8 hours should not be exceeded for any patient.

Dosage
HERPES SIMPLEX INFECTIONS
MUCOSAL AND CUTANEOUS HERPES SIMPLEX (HSV-1 and HSV-2) INFECTIONS IN IMMUNOCOMPROMISED PATIENTS:
Adults and Adolescents (Aged 12 years and older): 5 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Pediatrics (Aged 3 months to 12 years): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.

SEVERE INITIAL CLINICAL EPISODES OF HERPES GENITALIS:
Adults and Adolescents (Aged 12 years and older): 5 mg/kg infused at a constant rate over 1 hour, every 8 hours for 5 days.

HERPES SIMPLEX ENCEPHALITIS:
Adults and Adolescents (Aged 12 years and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days.
Pediatrics (Aged 3 months to 12 years): 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days.
NEONATAL HERPES SIMPLEX VIRUS INFECTIONS:
PMA of at Least 34 Weeks: 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 21 days.
PMA of Less than 34 Weeks: 20 mg/kg infused at a constant rate over 1 hour, every 12 hours for 21 days.

In neonates with ongoing medical conditions affecting their renal function beyond the effect of prematurity, the doses recommended should be used with caution.

VARICELLA-ZOSTER INFECTIONS
ZOSTER IN IMMUNOCOMPROMISED PATIENTS
Adults and Adolescents (Aged 12 years and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Pediatrics (Younger than 12 years): 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Obese Patients: Obese patients should be dosed at the recommended adult dose using Ideal Body Weight.

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

What information is available for dosing acyclovir IV in obese adults and pediatrics? e.g. use adjusted body weight based on BMI, weight 120-140% x IBW, or other suggestions.

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-3 for your response.

Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients
Design	Prospective, open-label, matched-pair, pharmacokinetic study N= 14
Objective	To evaluate the pharmacokinetics of intravenous (IV) acyclovir in morbidly obese patients utilizing dosing recommendations from the manufacturer's prescribing information
Study Groups	Morbidly obese (n= 7) Normal weight (n= 7)
Inclusion Criteria	Age ≥18 years; requiring IV acyclovir as part of routine clinical care
Exclusion Criteria	Serum creatinine >1.4 mg/dL; exhibited clinical instability (intensive care unit [ICU] admission or use of vasopressor support); receiving medications known to interact with acyclovir; received acyclovir or valacyclovir within the previous 24 hours
Methods	Consistent with manufacturer recommendations, patients received intravenous acyclovir 5 mg/kg using ideal body weight if morbidly obese and total body weight if normal weight. Acyclovir was prepared in 100 mL of normal saline and infused over 60 min via an infusion pump. Blood samples were collected serially immediately prior to the first dose of acyclovir and at 30, 60, 75, 90, 120, 180, 300, 420, 540, and 720 min following initiation of the infusion for analysis. Samples were analyzed by high-performance liquid chromatography separation using positive-ion electrospray tandem mass spectrometry (LC-MS/MS) for detection and quantitation.
Duration	Up to 12 hours after the first acyclovir dose
Outcome Measures	Pharmacokinetic parameters
Baseline Characteristics		Morbidly obese (n= 7)	Normal weight (n= 7)	p-value
	Age, years	54.3 ± 9.6	53.0 ± 16.3	0.87
	Female	85.7%	85.7%	1.0
	White	100%	100%	1.0
	Body weight, kg Body mass index, kg/m²	120.5 ± 15.7 45.0 ± 3.4	61.2 ± 5.1 22.5 ± 2.2	0.016 0.016
	Glomerular filtration rate, mL/min/1.73 m²	93.4 ± 24.9	93.7 ± 25.7	0.94
	All patients in the morbidly obese group were classified as class III obesity (body mass index [BMI] ≥40 kg/m²).
Results		Morbidly obese (n= 7)	Normal weight (n= 7)	p-value
	Acyclovir dose, mg	285 ± 44	303 ± 26	0.55
	C_max, mg/L	5.8 ± 0.9	8.2 ± 1.3	0.031
	AUC_0-∞, mg*h/L	15.2 ± 2.9	24.0 ± 9.4	0.011
	Systemic clearance, L/h	19.4 ± 5.3	14.3 ± 5.4	0.047
	Volume of distribution	31.8 ± 9.9	25.9 ± 10.4	0.29
	Time above 0.5625 mg/L Time above 1.125 mg/L	402.6 ± 204.2 264.9 ± 54.5	524.3 ± 253.0 373.1 ± 181.6	0.22 0.08
	C_max: maximum concentration; AUC: area under the curve from time 0 to infinity
Adverse Events	None reported
Study Author Conclusions	These data suggest that morbidly obese patients treated with IV acyclovir dosed by ideal body weight experience substantially decreased overall exposure compared to normal weight patients dosed by total body weight.
InpharmD Researcher Critique	This study is limited by the small sample size, use of a low acyclovir dose (5 mg/kg), and single-dose observation; however, the authors state the kinetics observed are likely to be similar if dosed over several days. Included patients were receiving acyclovir for prophylaxis and were not actively infected or critically ill; altered pharmacokinetics are often present in critically ill patients. Patients with BMI ranges from 25.0 to 39.9 kg/m² were not evaluated, so these results should not be generalized to them.

References:
[1] Turner RB, Cumpston A, Sweet M, et al. Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients. Antimicrob Agents Chemother. 2016;60(3):1830-1833. Published 2016 Jan 11. doi:10.1128/AAC.02010-15

Comparison of Dosing Strategies in Obese Patients Prescribed Intravenous Acyclovir and Evaluation of Rate of Acute Kidney Injury
Design	Retrospective cohort review N= 94
Objective	To compare adjusted body weight (AdjBW) to ideal body weight (IBW) dosing in obese patients prescribed IV acyclovir and determine if AdjBW dosing results in higher rates of acute kidney injury (AKI)
Study Groups	IBW (n= 61) AdjBW (n= 33)
Inclusion Criteria	Age ≥18 years with a BMI ≥30 kg/m² prescribed IV acyclovir from July 1, 2014 to August 31, 2021
Exclusion Criteria	Patients on renal replacement therapy, AKI prior to acyclovir, missing information in the electronic medical record (lack of dosing weight, or serum creatinine prior to or during therapy), patients who received both IBW and AdjBW dosing of acyclovir and those prescribed acyclovir for prophylaxis
Methods	Patients who met the inclusion criteria were divided into groups according to the dosage administered, either using IBW or AdjBW. Following the institution's protocol, AdjBW was calculated as IBW + 0.4 (TBW-IBW).
Duration	January 1, 2014 to August 31, 2021
Outcome Measures	AKI rates
Baseline Characteristics		IBW (n= 61)	AdjBW (n=33)
	Age, years	54.6	52.8
	Female	54.1%	57.6%
	Caucasian	68.9%	63.6%
	BMI, kg/m²	34.8 (31.5 to 40.6)	34.6 (32.7 to 39.6)
	Comorbidities Hypertension Diabetes mellitus Chronic kidney disease Renal transplant Heart failure Human immunodeficiency virus Cancer Cirrhosis Immunocompromised status	67.2% 32.8% 3.3% 1.6% 6.6% 11.5% 24.6% 1.6% 4.9%	63.6% 27.3% 3.0% 3.0% 3.0% 3.0% 24.2% 0 9.1%
	ICU admission when acyclovir initiated	34.4%	33.3%
	ICU length of stay, days	8.0	9.0
	Hospital length of stay, days	9.0	8.0
Results	Endpoint	IBW (n= 61)	AdjBW (n=33)	p-value
	Dose, mg/dose	600 (500-700)	800 (700-850)	<0.0001
	Doses per day	3.0 (3.0-3.0)	3.0 (3.0-3.0)	0.2024
	Dosing interval Every 12 hours Every 8 hours	3 (4.9%) 58 (95.1%)	0 33 (100.0%)	--
	Duration, days	5.0 (4.0-7.0)	5.0 (4.0-8.0)	>0.99
	Renal parameters AKI Baseline SCr, mg/dL Urine output, mL/kg/hr Dehydration status (BUN/Scr >20:1) Concomitant fluids Fluid bolus during acyclovir	8 (13.1%) 0.81 (0.71-0.97) 1.6 (1.1-2.2) 15 (24.6%) 34 (55.7%) 19 (31.1%)	0 0.84 (0.68-0.96) 1.3 (0.9-1.6) 9 (27.3%) 18 (54.5%) 4 (12.1%)	-- 0.704 0.100 0.776 0.916 0.041
	There was no difference in the use of concomitant nephrotoxic agents between groups. Overall, the most common nephrotoxins were vancomycin (64.9%), radiocontrast dye (48.9%), loop diuretics (33%), ACEi/ARBs (28.7%) and NSAIDS (17%).
Adverse Events	See results
Study Author Conclusions	In this study, 8.5% of all obese patients receiving acyclovir developed AKI. Further studies are needed to confirm dosing recommendations.
InpharmD Researcher Critique	Limitations include a smaller sample size compared to previous studies, difficulty accounting for all AKI-associated factors due to the retrospective design (e.g., lack of information on fluid mL/hour rate), and the impracticality of conducting a logistic regression due to a limited number of AKI cases. Only a few patients exceeded the 40 kg/m2 BMI in the IBW group, while none surpassed this limit in the AdjBW group.

References:
[1] Zelnicek TD, Siegrist EA, Miller JL, Neely SB, Higuita NIA, White BP. Comparison of Dosing Strategies in Obese Patients Prescribed Intravenous Acyclovir and Evaluation of Rate of Acute Kidney Injury [published online ahead of print, 2023 May 29]. Int J Antimicrob Agents. 2023;106871. doi:10.1016/j.ijantimicag.2023.106871

Safety of Different Weight-Based Dosing Strategies of Intravenous Acyclovir in Obese Patients: A Retrospective Cohort Study
Design	Retrospective cohort study N= 339
Objective	To compare the safety of the 3 dosing strategies in obese patients
Study Groups	TBW (n= 196) AdjBW (n= 86) IBW (n= 57)
Inclusion Criteria	All patients aged ≥18 years, with a BMI ≥30 kg/m2, who received IV acyclovir during their inpatient admission between January 1, 2015, and March 28, 2023
Exclusion Criteria	Patients with AKI, renal replacement therapy, creatinine clearance <10 mL/min/1.73m2 at baseline, those who did not have measured serum creatinine at baseline or during acyclovir therapy, and those who received less than 24 hours of IV acyclovir
Methods	Patients were categorized into TBW, AdjBW, or IBW groups based on the received doses. The primary outcome was the incidence of AKI. Other outcomes included the need for renal replacement therapy, neurotoxicity, length of stay, and in-hospital mortality. Data were extracted from electronic medical records
Duration	January 1, 2015, to March 28, 2023
Outcome Measures	Primary: Incidence of AKI Secondary: Need for renal replacement therapy, neurotoxicity, length of stay, in-hospital mortality
Baseline Characteristics		TBW (n = 196)	AdjBW (n = 86)	IBW (n = 57)
	Age (years), median (IQR)	44 (34-59)	40 (30-57)	42 (35-59)
	Male, n (%)	105 (53.6%)	54 (62.8%)	29 (50.9%)
	Weight (kg), median (IQR)	90 (80-100)	98 (90-112)	93 (85-106)
	IBW (kg), median (IQR)	56.9 (51-65.9)	63.2 (55.5-68.7)	58.7 (51.9-65.9)
	AdjBW (kg), median (IQR)	70.1 (63.7-79.1)	77.4 (72.5-82.5)	75.2 (66.4-80.9)
	BMI (kg/m2), median (IQR)	32.7 (31.2-35.5)	34.6 (31.7-39.8)	33.6 (31.2-37.6)
Results		TBW (n= 196)	AdjBW (n= 86)	IBW (n= 57)	p-value
	AKI incidence, n (%)	34 (17.3%)	10 (11.6%)	4 (7%)	<0.05
	Neurotoxicity, n (%)	5 (2.6%)	0 (0%)	2 (3.5%)	0.26
	LOS (days), median (IQR)	7 (3.8-12.5)	5.9 (3.9-11)	8.7 (4.7-14.7)	0.21
	Death, n (%)	5 (2.6%)	1 (1.2%)	1 (1.8%)	0.87
Adverse Events	Neurotoxicity occurred in 2.1% of patients. Manifestations included decreased Glasgow Coma Scale, worsened agitation and confusion, generalized-tonic clonic seizures, and delirium
Study Author Conclusions	In obese patients, either AdjBW or IBW dosing of IV acyclovir appears to be safer than TBW. The IBW dosing had the lowest odds of AKI among the 3 dosing strategies.
Critique	The study's strengths include a large sample size and adjustment for confounders. However, limitations include its retrospective nature, potential bias due to dose approximation, and lack of data on IV fluid infusion rates. The study may not be generalizable to patients with longer durations of therapy or pre-existing AKI.

References:
[1] Saad MO, Habib SO, Alhomosy AM, Salem IM, Hishari OM. Safety of Different Weight-Based Dosing Strategies of Intravenous Acyclovir in Obese Patients: A Retrospective Cohort Study. Ann Pharmacother. 2025;59(9):801-808. doi:10.1177/10600280251318017