Herpes simplex virus infection vidarabine

Vidarabine, an antiviral agent (10 to 15 mg/kg/day for 5 to 10 days), is indicated in the treatment of herpes simplex virus encephalitis, neonatal herpes simplex virus infections, and herpes zoster in immunosuppressed patients. In addition, vidarabine (ophthalmic ointment 3% vidarabine monohydrate [equivalent to 2.8% vidarabine]) is indicated in the treatment of acute keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus types 1 and 2, or superficial keratitis caused by herpes simplex virus that has not responded to topical idoxuridine or when toxic or hypersensitivity reactions to idoxuridine have occurred. 

Vidarabine (adenine arabinoside, ara-A) is phos-phorylated in the cell to the triphosphate derivative which blocks DNA synthesis by inhibiting DNA polymerase. It is indicated for infections with herpes simplex virus and varicella-zoster however its use has to a large extend been surpassed by aciclovir. It is administered topically or intravenously. It is inactivated rapidly by adenosine deaminase which for systemic use necessitates constant infusion of the drug. Vidarabine is the least toxic of the purine analogues. Nausea and vomiting are the most frequent adverse effects and neurotoxicity may occur. 

Viral DNA polymerase is an important catalyst for the synthesis of viral nucleic acids. DNA polymerase inhibitors have already been encountered as antitumor agents. Ara-A (9.5, vidarabine) is a DNA polymerase inhibitor that has demonstrated activity against herpes simplex virus type I (HSV-1) infections, responsible for cold sores on... 

Antiviral Efficacy and Clinical Use. Vidarabine (Vira-A) was the first systemic agent used to treat herpesvirus infections, including CMV, herpes simplex virus, and varicella-zoster virus.42 In the past, this drug was administered by continuous intravenous infusion to treat severe systemic infections caused by these viruses, but systemic use of vidarabine has been replaced by safer and less toxic agents. Vidarabine is currently used primarily to treat local viral infections of the eye (e.g., herpes simplex keratoconjunctivitis) it is applied topically by ophthalmic ointment to treat these infections. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Vidarabine is used mainly in human HSV-1 and HSV-2 encephalitis, decreasing the mortality rate from 70 to 30%. Whitley et al. (57) reported that early vidarabine therapy is helpful in controlling complications of localized or disseminated herpes zoster in immunocompromised patients. Vidarabine also is useful in neonatal herpes labialis or genitalis, vaccinia virus, adenovirus, RNA viruses, papovavirus, CMV, and smallpox virus infections. Given the efficacy of vidarabine in certain viral infections, the U.S. FDA approved a 3% ointment for the treatment of herpes simplex keratoconjunctivitis and recurrent epithelial keratitis, and a 2% IV injection for the treatment of herpes simplex encephalitis and herpes zoster infections (Table 43.3). A topical ophthalmic preparation of vidarabine is useful in herpes simplex keratitis but shows little promise in herpes simplex labialis or genitalis. The monophosphate esters of vidarabine are more water-soluble and can be used in smaller volumes and even intramuscularly. These esters are under clinical investigation for the treatment of hepatitis B, systemic and cutaneous herpes simplex, and herpes zoster virus infections in immunocompromised patients. 

Vidarabine is a purine nucleoside analogue active against herpes viruses, influenza viruses, and some RNA viruses. Use of vidarabine for treatment of herpes simplex and varicella-zoster infections has largely been supplanted by acyclovir because of the superior efficacy, fewer adverse effects, and easier administration of the latter agent. Vidarabine has been associated with significant gastrointestinal, neurologic, and hematopoietic toxicities. Patients with renal insuffi-... 

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