Foscarnet nephrotoxicity

Acute kidney injury can be severe with foscarnet. Some degree of kidney injury has been reported to occur in as many as two-thirds of patients treated with foscarnet and has been a dose-limiting toxicity in 10-20% of cases [51-56]. Despite dose reduction or discontinuation of foscarnet, azotemia typically progresses for at least a few days before resolving. It may be possible to continue foscarnet at reduced doses in some patients with mild azotemia. Foscarnet-induced AKI is usually reversible, although temporary dialysis may be required [57]. Recovery may be slow, particularly in patients with preexisting kidney insufficiency. Elevated serum creatinine concentrations may persist for several months after discontinuation of foscarnet. Foscarnet nephrotoxicity may be also associated with mild proteinuria. Volume expansion with isotonic saline was effective in reducing the incidence of foscarnet nephrotoxicity to 13%, compared to 66% in non-hydrated historical controls, and allowed patients with prior kidney insufficiency to receive foscarnet without further reduction of kidney function [54, 58]. Intermittent, rather than continuous, infusion of foscarnet may also reduce the incidence of nephrotoxicity [52]. 

Deray G, Martinez F, Katlama C, Levaltier B, Beaufils El, Danis M, Rozenheim M, Baumelou A, Dohin E, Gentilini M, Jacobs C. Foscarnet nephrotoxicity mechanism, incidence, and prevention. Am J Nephrol 1989 9 316-321. 

Deray G, Katlama C, Dohin E. Prevention of foscarnet nephrotoxicity. Ann Intern Med 1990 113 332. 

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 ... 

Foscarnet Pentamidine IV Increased risk of severe nephrotoxicity/hypocalcemia Monitor renal functiorVserum calcium... 

Drugs that may interact with foscarnet include nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine), pentamidine, and zidovudine. Foscarnet decreases serum levels of ionized calcium. Exercise particular caution when other drugs known to influence serum calcium levels are used concurrently. 

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 most clinically significant adverse effect of foscarnet is renal impairment. Nephrotoxicity is most likely to occur during the second week of induction therapy but may occur at any time during induction or maintenance therapy. Serum creatinine levels may be elevated in up to 33 to 50% of patients this effect is usually reversible upon drug discontinuation. Dehydration, previous renal impairment, and concurrent administration of other nephrotoxic drugs increase the risk of renal toxicity. Infusion of fluids along with foscarnet decreases the likelihood of renal impairment to about 12%. Dosage adjustment is required for patients with renal insufficiency. 

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... 

The primary adverse effect of intravenous cidofovir is a dose-dependent nephrotoxicity. Concurrent administration of other potentially nephrotoxic agents (eg, amphotericin B, aminoglycosides, nonsteroidal anti-inflammatory drugs, pentamidine, foscarnet) should be avoided. Prior administration of foscarnet may increase the risk of nephrotoxicity. Other potential side effects include uveitis, decreased intraocular pressure, and probenecid-related hypersensitivity reactions. Neutropenia and metabolic acidosis are rare. The drug caused mammary adenocarcinomas in rats and is embryotoxic. 

CICLOSPORIN FOSCARNET, GANCICLOVIR t risk of nephrotoxicity Additive nephrotoxic effects Monitor renal function... 

AMINOGLYCOSIDES FOSCARNET SODIUM Possible T nephrotoxicity Additive side-effect Monitor renal function closely... 

Foscarnet Intravenous administration Intravitreal injection Primary toxicity = nephrotoxicity... 

Alterations in creatinine clearance or acute renal insufficiency occur in 10-20% of patients with AIDS receiving intravenous foscarnet (11), due to acute tubular damage. Severe renal insufficiency can be prevented in most cases by careful hydration before and during therapy (12). To minimize the residual incidence of nephrotoxicity, the dose of foscarnet should be frequently recalculated, based on the estimated creatinine clearance. 

Foscarnet 40-80 mgIVq. 8 hr 85% 40-20 mg q. 8-24 hr, according to Nephrotoxic, neurotoxic adverse effects are hypocaicemia, hypophosphatemia, hvoomaqnesemia.and hvookaiemia Dose after dialysis Dose for GFR<10 ml/min Dose for GFR 10-50 ml/min... 

Foscarnet 40-80 mg IV qShrs 85% 40-20 mg q8-24 hrs according to CICr Nephrotoxic, neurotoxic, hypocalcemia, hypophosphatemia, hypomagnesemia and hypokalemia... 

Clinical uses and toxicity The drug is used for prophylaxis and treatment of cytomegalovirus (CMV) infections (including CMV retinitis) and has activity against ganciclovir-resistant strains of this virus (Table 49-1). Foscarnet inhibits herpes DNA polymerase in acyclovir-resistant strains that are thymidine kinase-deficient and may suppress such resistant herpetic infections in patients with AIDS. Adverse effects include nephrotoxicity (30% incidence) with disturbances in electrolyte balance (especially hypocalcemia), genitourinary ulceration, and CNS effects (headache, hallucinations, seizures). 

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