The mechanism of action, pharmacokinetics and toxicity of acyclovir — A review

Brigden, D.; Whiteman, Paul

doi:10.1016/s0163-4453(83)94041-0

Cited by 41 publications

(30 citation statements)

References 20 publications

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“…Therefore, the administration of an additional nephrotoxic agent (i.e., ceftriaxone) may have accounted for this significant increase in the proportion of patients experiencing nephrotoxicity. The additive nephrotoxicity that results from combining acyclovir with other substances is well noted [5,14]. Our data clearly point to that possibility, and suggest that careful attention must be paid to renal function when adding ceftriaxone to acyclovir treatment.…”

Section: Discussionsupporting

confidence: 72%

“…Sixteen percent (58/354) of adult patients treated with acyclovir were reported to experience a rise of serum creatinine [5]. In this series, some degree of impairment of renal function could be documented in all cases where baseline creatinine was measured.…”

Section: Discussionmentioning

confidence: 73%

“…The nephrotoxic potential of acyclovir is well documented [5]. In 1988, four cases of acute renal failure associated with high-dose intravenous acyclovir (1,500 mg/m 2 ) were reported in elderly people [6].…”

Section: Introductionmentioning

confidence: 99%

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Combination of ceftriaxone and acyclovir – an underestimated nephrotoxic potential?

et al. 2002

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Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 73%

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Combination of ceftriaxone and acyclovir – an underestimated nephrotoxic potential?

et al. 2002

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“…Serum acyclovir levels were not measured in our patient. Therapeutic dosage of acyclovir is dependent on diagnosis and ranges from 250 to 500 mg/m 2 per 8 h. In children with normal kidneys, the steady-state peak plasma acyclovir concentrations with these dosages are 45.78+17.78 and 92.0 ~tmol/1 (10.3+4.0 and 20.7 gg/ml), respectively [8]. Acyclovir levels in kidney tissue can reach 10 times those in serum and may account for the propensity of this drug to cause nephrotoxicity [8].…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic dosage of acyclovir is dependent on diagnosis and ranges from 250 to 500 mg/m 2 per 8 h. In children with normal kidneys, the steady-state peak plasma acyclovir concentrations with these dosages are 45.78+17.78 and 92.0 ~tmol/1 (10.3+4.0 and 20.7 gg/ml), respectively [8]. Acyclovir levels in kidney tissue can reach 10 times those in serum and may account for the propensity of this drug to cause nephrotoxicity [8]. The urinary sediment examined by polarizing microscopy showed birefringent needleshaped crystals within leukocytes in patients with high urine concentrations of acyclovir [5,7].…”

Section: Discussionmentioning

confidence: 99%

Acute renal failure in a child associated with acyclovir

et al. 1995

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A 9-year-old boy developed acute renal failure following intravenous acyclovir (30 mg/kg per day) administered for 6 days to treat herpetic encephalitis. Physical findings and urine output were normal, except for increasing blood urea nitrogen (BUN), serum creatinine and mild proteinuria. Acyclovir was discontinued. However BUN and serum creatinine continued to increase and peaked on the following day at 8.6 mmol/l of urea (24 mg/dl) and 194 mumol/l (2.2 mg/ml), respectively. Conservative treatment and hydration were carried out. The kidney function returned to normal within 1 week. The use of acyclovir when necessary in renal failure patients is discussed.

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Acyclovir in Lymphomatoid Papulosis and Mycosis Fungoides-Reply

Resnick¹

1986

JAMA

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The mechanism of action, pharmacokinetics and toxicity of acyclovir — A review

Cited by 41 publications

References 20 publications

Combination of ceftriaxone and acyclovir – an underestimated nephrotoxic potential?

Combination of ceftriaxone and acyclovir – an underestimated nephrotoxic potential?

Acute renal failure in a child associated with acyclovir

Acyclovir in Lymphomatoid Papulosis and Mycosis Fungoides-Reply

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