Acyclovir nephrotoxicity

The most important risk factors for acyclovir nephrotoxicity are intravascular volume contraction, preexisting kidney desease, and the use of a high-dose, rapid bolus intravenous infusion [7] Nephrotoxicity with oral acyclovir has been reported only rarely [23] The main non-renal toxicities of acyclovir are gastrointestinal and neurologic side effects, which primarily occur in patients on high-dose intravenous acyclovir. As acyclovir is primarily cleared by the kidney, lower intravenous doses and even oral administration can lead to neurotoxicity in patients with decreased kidney function from either CKD or AKI [15,17, 24, 25]. 

The most important risk factors for acyclovir nephrotoxicity are intravascular volume contraction, preexisting renal insufficiency, and high-dose, rapid bolus intravenous infusion [5-15]. Nephrotoxicity with oral acyclovir has been reported rarely [13]. 

Aksoy B, Altaykan-Hapa A, Cengiz A, Mete Aksoy H, Atakan N. Disseminated cutaneous herpes zoster complicated by acyclovir nephrotoxicity and successfully treated with brivudin. Eur J Dermatol 2010 20(2) 247-8. 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

Acyclovir 20 mg/kg IV every 8 hours (neonates) Alternative Therapy Foscarnet 120-200 mg/kg IV per day in divided doses every 8-12 hours neurotoxicity, phlebitis Nephrotoxicity, electrolyte imbalances, nausea/ vomiting, headache, penile ulceration, thrombophlebitis, seizures ... 

Renal function impairment Renal failure, sometimes fatal, has been observed with acyclovir therapy. Dosage adjustment is recommended in patients with renal impairment (see Administration and Dosage). Use caution when coadministering acyclovir with other potentially nephrotoxic agents. 

Occurrence of renal failure depends also on the patient s state of hydration, other treatments, and the rate of drug administration. Concomitant use of other nephrotoxic agents, pre-existing renal disease, and dehydration make further renal impairment with acyclovir more likely. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

The potential for drug interactions, particularly with other drugs that are actively secreted by the proximal tubules, should be considered. Probenecid has been shown to inhibit the renal clearance of acyclovir. Cyclosporine and other nephrotoxic agents may increase the risk of renal toxicity of acyclovir. 

Foscarnet should not be used in combination with drugs that cause renal toxicity (e.g., acyclovir, aminoglycosides, amphotericin B, NSAIDs). Abnormal renal function has been noted when foscarnet is used with ritonavir or ritonavir and saquinavir. Pentamidine may increase the risk of nephrotoxicity, hypocalcemia, and... 

Concurrent use of nephrotoxic agents may enhance the potential for nephrotoxicity. Probenecid and cimetidine decrease acyclovir clearance and increase exposure. Somnolence and lethargy may occur in patients receiving zidovudine and acyclovir. 

Chiang C-K, Fang C-C, Hsu W-D, Chu T-S, Tsai T-J. Hemodialysis reverses acyclovir-induced nephrotoxicity and neurotoxicity. Dial Transplant 2003 32 624. 

Increased nephrotoxicity with tenofovir, cidofovir, acyclovir, cyclosporine, gancyclovir... 

Increased risk of nephrotoxicity with acyclovir, aminoglycoside, cyclosporine, flucytosine, foscamet, gancyclovrr, mitomycin, penicillamine, sirolimus, vancomycin... 

Like acyclovir, valacyclovir is a well-tolerated drug. The most common adverse effects of valacyclovir are headache and nausea. Other adverse events associated with valacyclovir administration include vonuting, weakness, cUzziness, and abdoiifinal pain. Thrombotic thrombocytopenic purpura/ hemolytic ureiiuc syndrome has also been reported in a few patients after high doses of valacyclovir, as has confusion, hallucinations, and nephrotoxicity (Curran and Noble, 2001 Perry and Faulds, 1996). 

Valacyclovir is the L-valyl ester of acyclovir, with oral bioavailability three to five times that of oral acyclovir. Following ingestion, it is rapidly converted by intestinal and hepatic hydrolases to acyclovir. Valacyclovir has gastrointestinal and neurological side effects similar to those seen with acyclovir. To date, significant nephrotoxicity and crystalluria as seen with acyclovir has only rarely been reported with... 

Ganciclovir is an acyclic nucleoside analogue of guanine that is structurally similar to acyclovir, but is more effective in the treatment and prophylaxis of severe cytomegalovirus infection in immunocompromised hosts. Ganciclovir is myelotoxic, but has no significant nephrotoxicity [22]. It does, however, require dose adjustment for patients with reduced kidney function. 

DosSantos MDeFF, DosSantos OFP, Boim MA, Razvickas CV, DeMoura LAR, Ajzen H, Schor N. Nephrotoxicity of acyclovir and ganciclovir in rats evaluation of glomerular hemodynamics. J Am Soc Nephrol 1997 8 361-367. 

Oral acyclovir infrequently is associated with nausea, diarrhea, rash, or headache and very rarely with renal insufficiency or neurotoxicity. Valacyclovir also may cause headache, nausea, diarrhea, nephrotoxicity, and CNS symptoms. High doses of valacyclovir have been associated... 

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