Foscarnet, AIDS

Neurotoxicity and seizures Foscarnet was associated with seizures in AIDS patients. 

Renal function Impairment The major toxicity of foscarnet is renal impairment, which occurs to some degree in most patients. Approximately 33% of 189 patients with AIDS and CMV retinitis who received IV foscarnet in clinical studies developed significant impairment of renal function, manifested by a rise in serum creatinine concentration to 2 mg/dL or more. 

The topical ophthalmic antiviral preparations appear to interfere with viral reproduction by altering DNA synthesis. Trifluridine is effective treatment for herpes simplex infections of the conjunctiva and cornea. Ganciclovir is indicated for use in immunocompromised patients with cytomegalovirus (CMV) retinitis and for prevention of CMV retinitis in transplant patients. Foscarnet is indicated for use only in AIDS patients with CMV retinitis. 

Foscarnet sodium is an pyrophosphate analogue. It inhibits viral DNA polymerase and reverse transcriptase. Its main indication is cytomegalovirus retinitis in AIDS patients which have contraindications for ganciclovir. 

Foscarnet is an inorganic pyrophosphate analogue which causes selective inhibition of viral DNA polymerase and reverse transcriptase. Topical foscarnet cream has appeared to be a safe and effective treatment for aciclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients. 

Foscarnet is indicated for the treatment of CMV retinitis in AIDS patients. Its effectiveness is comparable to that of ganciclovir these drugs are synergistic when given to counteract refractory retinitis. A decreased incidence of Kaposi s sarcoma has been observed in AIDS patients who have undergone foscarnet therapy. 

Foscarnet has been administered intravitreally for the treatment of CMV retinitis in patients with AIDS, but data regarding efficacy and safety are incomplete. 

Foscarnet and ganciclovir are two antiviral drugs, which are investigated as candidates for iontophoretic administration for local treatment of cytomegalovirus (CMV) retinitis, which is most common in AIDS patient. These two drugs were successfully delivered into the vitreous, where high therapeutic levels were maintained for up to 24 h in the case of ganciclovir [76] and for 60 h after foscarnet delivery [78]. 

Antiviral Efficacy and Clinical Use. Foscarnet (Fos-cavir) is primarily given to treat CMV retinitis in patients with AIDS.6,24 This agent may also help control other infections in patients with a compromised immune system, including serious cytomegaloviral infections (pneumonia, gastrointestinal infections) and some herpesvirus infections (herpes simplex, varicella-zoster). 

Ausayakhun S, Watananikorn S, Ngamtiphakorn S, Prasitsilp J. Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS. J Med Assoc Thai. 2005 88 103-107. 

Foscarnet represents a diphosphate analogue. Incorporation of nucleotide into a DNA strand entails cleavage of a diphosphate residue. Foscarnet inhibits DNA polymerase by interacting with its binding site for the diphosphate group. Indications systemic therapy in severe cytomegaly infections in AIDS patients local therapy of herpes simplex infections. 

Blanshard C, Benhamou Y, Dohin E, Lernestedt JO, Gazzard BG, Katlama C. Treatment of AIDS-associated gastrointestinal cytomegalovirus infection with foscarnet and ganciclovir a randomized comparison. J Infect Dis 1995 172(3) 622-8. 

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. 

Huycke MM, Naguib MT, Stroemmel MM, Blick K, Monti K, Martin-Munley S, Kaufman C. A double-blind placebo-con-troUed crossover trial of intravenous magnesium sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients with AIDS and cytomegalovirus infection. Antimicrob Agents Chemother 2000 44(8) 2143-8. 

Roos TC, Albrecht H. Foscarnet-associated eosinophilic folhcuhtis in a patient with AIDS. J Am Acad Dermatol 2001 44(3) 546-7. 

Another previous report [187] described severe hypocalcemia with tetany in patients with AIDS concomitantly receiving pentamidine and foscarnet. The hypocalcemia, however, was attributed to the administration of foscarnet. Despite magnesium replacement, magnesium wasting may persist up to two months after the discontinuation of pentamidine, suggesting that anatomic renal tubular injury may be responsible [183,185]. Both abnormalities developed within 6 to 10 days of pentamidine administration. Because life-threatening arrhythmias can develop, especially at serum magnesium levels less than 1.6 mg/dl, early replacement therapy is clinically warranted. 

Youle MS, Clarbour J, Gazzard B, Chanas A. Severe hypocalcaemia in AiDS patients treated with foscarnet and pentamidine. Lancet. 1988 Jun 25 1 (8600) 455-6. 

Trolliet P, Dijoud F,Cotte L,Cahen R, FrancoisB,TrepoC,Patricot EM. Crescentic glomerulonephritisand crystals within glomerular capillaries in an AIDS patient treated with foscarnet. Am J Nephrol 1995 15 256-259. 

Maurice-Estapa L, Daudon M, Katlama C, Jouanneau C, Sazdovitch V, Lacour B, Beaufils El. Identification of crystals in kidneys of AIDS patients treated with foscarnet. Am J Kid Dis 1998 32 392-400. 

Youle MS,Clarbour J,Gazzard B,Chanas A. Severe hypocalcemia in AIDS patientstreated with foscarnet and pentamadine. Lancet 1988 1 1455-1456. 

Immunocompromised patients are at greatest risk for severe and recurrent HSV infections. Acyclovir, valacyclovir, and famciclovir have been used to prevent reactivation of infection in patients seropositive for HSV who undergo transplantation procedures or induction chemotherapy for acute leukemia. Immunocompromised individuals, such as patients with AIDS, who fail treatment or prophylaxis with recommended antiviral doses frequently demonstrate improved response with higher doses. If resistance is suspected or confirmed with recommended first-line antivirals, foscarnet is usually effective. However, its use is associated with a greater risk of serious... 

Acyclovir-resistant HSV has been isolated from patients with AIDS. The primary mechanism of resistance appears to be a deficiency in viral thymidine kinase. Strategies that have been employed for management of severe acyclovir-resistant HSV infections include increasing the dose of acyclovir, discontinuing acyclovir, and use of an alternative antiviral agent. Vidarabine and foscarnet, because they do not require phosphorylation by thymidine kinase, are examples of potential alternative agents. A randomized comparison of foscarnet and vidarabine indicated that foscarnet is more effective and associated with fewer adverse reactions than vidarabine. ... 

Palestine A, Polis M, de Smet M, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991 115 665-673. 

Studies of the Ocular Conrphcations of AIDS Research Group. Mortahty in patients with the acqtrired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992 326 213-220. 

Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trial Group. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. Arch Ophthamol 1996 114 23-33. 

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