Literature search and review of mechanism of renal toxicity for acyclovir.

Fråga: Literature search and review of mechanism of renal toxicity for acyclovir.

Sammanfattning: Increase in serum creatinine levels, and neurological deterioration have been observed in 5 to 25 per cent of patients treated with acyclovir. Although dialysis is sometimes necessary, total functional recovery is generally achieved within a few days of discontinuing therapy. Attention should be paid to concomitant nephrotoxic drugs and hydration state of the patient.

Svar: Acyclovir is an antiviral agent, specifically active against herpes simplex virus type I and type II. It is well tolerated but side effets sometimes occur when given intravenously. Neurotoxicity and nephrotoxicity are well-known side effects and may be present in 5 to 25 per cent of the patients (1,2).

Signs of nephrotoxicity typically begin within the first 24 hours after administration of a single dose or after a few doses, with a rise in serum creatinine level. Despite stopping drug administration serum creatinine may continue to increase. At the same time, neurological function deteriorates until a lethargic status or coma develops. Dialysis may be necessary to reduce creatinine level and improve neurological function (3-6). The renal function recovers without lasting symptoms, and readministration of acyclovir in a lower dose or at a slower infusion rate can be tried (3-6).

The mechanism of this toxicity is unclear, but intratubular obstruction has been proposed. Animal studies suggest that crystals may be formed when the concentration of acyclovir in the collecting duct of the nephron exceeds its limit for solubility. This probably occurs for short periods when the acyclovir plasma concentrations are very high immediately after a bolus injection (7). Concomitant administration of other nephrotoxic drugs, or dehydration and hypovolemia can exacerbate the condition (3, 5-7). 1 Goodman and Gilman, The pharmacological basis of therapeutics. 1985; 7th ed: 1231

2 Meyler´s, Side effects of drugs. Ed by MNG Dukes. Elsevier, Amsterdam. 1984; 10th ed: 561-562
3 Spiegal DM, Lau K: Acute renal failure and coma secondary to acyclovir therapy. JAMA 1986; 255: 1882-1883
4 Jones PG, Beier-Hanratty SA: Acyclovir: neurologic and renal toxicity. Ann Intern Med 1986; 104: 892

5 Johnson R, Douglas J, Corey L, Krasney H: Adverse effects with acyclovir and meperidine. Ann Intern Med 1985; 103: 962-963 6 Peterslund NA, Black PT, Tauris P: Impaired renal function after bolus injections of acyclovir. Lancet 1983; I: 243 7 Brigden D, Rosling AE, Woods NC: Renal function after acyclovir intravenous injection. Am J Med 1982; 73(1A): 182-185