Cytomegalovirus foscarnet

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. 

Another anti-herpes compound is the remarkably simple foscarnet (9.15, phospho-noformate). This is an inorganic pyrophosphate compound that inhibits viral DNA polymerase and RNA polymerase without requiring activation by phosphorylation. Fomivirsen is an oligonucleotide that inhibits human cytomegalovirus (CMV) via an... 

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]. 

Organism Viral infections Cytomegalovirus Type of Infection Pneumonia hepatitis chorioretinitis involvement of many other organs Drug Treatment Foscarnet or ganciclovir... 

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 Inhibition of viral DNA polymerase and reverse transcriptase at the pyrophosphate-binding site Cytomegalovirus, acyclovir-resistant herpes simplex, acyciovir-resistant variceila-zoster 6... 

Foscarnet is used for the treatment of cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant herpes simplex virus (HSV) infections. It may also be beneficial in other types of CMV or HSV infections (Wagstaff and Bryson, 1994). 

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. 

Patients who have undergone renal transplantation and then require treatment for cytomegalovirus infection are at special risk of renal damage due to foscarnet. 

One renal transplant recipient developed the nephrotic syndrome, with microscopic hematuria and non-ohguric acute renal insufficiency within 15 days after starting foscarnet therapy for cytomegalovirus infection (13). A kidney biopsy showed crystals in aU glomeruh and in the proximal tubules. The crystals consisted of several forms of foscarnet salts. Renal function and proteinuria nevertheless improved progressively, and a second transplant biopsy 8 months after the first one showed... 

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. 

Velez G, Roy CE, Whitcup SM, Chan CC, Robinson MR. High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis. Am J Ophthalmol 2001 131(3) 396-7. 

Ringden O, Lonnqvist B, Paulin T, Ahimen J, Klintmalm G, Wahren B, Lernestedt J-0. Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients. J Antimicrob Chemother 1986 17 373-387. 

Jacobson MA, O Donnell JJ, Mills J. Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Antimicrob Agents Chemother 1989 33 736-741. 

Justrabo E, Zanetta G, Martin L, Assem M, Mousson C, Maurice-Estepa L, Rifle G,Tanter Y. Irreversible glomerular lesions induced by crystal precipitation in a renal transplant after foscarnet therapy for cytomegalovirus infection. Eiistopathology 1999 34 365-369. 

Farese RV Jr, Schambelan M, Flollander FI, Stringari S, Jacobson MA. Nephrogenic diabetes insipidus associated with foscarnet treatment of cytomegalovirus retinitis. Ann Intern Med 1990 112 955-956. 

Cytomegalovirus Pulmonary, blood, urinary tract, Gl tract Ganciclovir 5 mg/kg every 12 h foscarnet 60 mg/ kg every 8 h hyperimmune globulins 100-500 mg/kg every 1-2 wk... 

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. 

Diaz-llopis M, Chipont E, Sanchez S, et al. Intravitreal foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome. Am J Ophthalmol 1992 14 742-747. 

Studies of the Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials group. Foscarnet-ganciclovir cytomegalovirus retinitis trial. 4. Visual outcomes. Ophthalmology 1994 101 (7) 1250 1261. 

Foscarnet (trisodium phosphonoformate) is an inorganic pyrophosphate analog, which inhibits many DNA polymerases, retroviral reverse transcriptase, and some RNA polymerases, and has antiviral activity against all of the herpes viruses and HIV. Foscarnet has been used primarily for the treatment of serious cytomegalovirus infection. 

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). 

Foscarnet (Foscavin) Analog of pyrophosphate. Competes for pyrophosphate site in viral, but not human, DNA polymerase and reverse transcriptase. Cytomegalovirus retinitis in immunocompromised patients. 

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