Ribavirin

Although active against ortho- and paramyxoviruses, ribavirin (Virazole) is approved only for the treatment of respiratory syncytial virus (RSV) infection in infants. The drug is administered as a small-particle aerosol (particle diameter, 1 to 3 µm) so that it can reach the lower respiratory tract. Aerosolized ribavirin treatment results in more rapid cessation of viral shedding and resolution of clinical symptoms without signs of systemic toxicity.

Idoxuridine and Trifluridine

Because of their myelosuppressive, mutagenic and teratogenic effects following systemic administration, idoxuridine and trifluridine are only suitable for topical use. Trifluridine is superior to idoxuridine when used in eyedrops for the topical treatment of herpetic keratitis. Idoxuridine can be formulated for topical treatment of herpetic skin lesions.

Vidarabine

Vidarabine (Vira-A) is used for both topical and systemic treatment of herpes simplex virus (HSV) infections. A serious drawback is the poor solubility of this drug in aqueous media, which means that intravenous administration requires a large volume of fluid. When vidarabine and acyclovir were compared for efficacy in treating herpetic encephalitis and varicella-zoster virus (VZV) infection in immunocompromised hosts, acyclovir proved clearly superior to vidarabine. Vidarabine has various toxic side effects (i.e., tremor, ataxia, seizures, myalgia, nausea, vomiting, and diarrhea). Acyclovir is now generally preferred over vidarabine in the treatment of HSV and VZV infections.

Acyclovir, Valaciclovir and Famciclovir

Acyclovir (Zovirax) represents a major breakthrough in the treatment of herpesvirus infections. The main indications for its use are primary genital herpes, herpetic encephalitis and HSV and VZV infections in immunosuppressed patients. It can be used topically, intravenously, or perorally, although its oral absorption is only 20 percent. It offers limited benefit in the topical treatment of recurrent herpes labialis. It is also efficacious in preventing recurrent genital herpes, as well as in preventing HSV infections in renal allograft recipients. Based on an alteration of their thymidine kinase, HSV and VZV may develop resistance to acyclovir, particularly in immunocompromised patients. Valaciclovir (Valtrex) and Famciclovir (Famvir) represent two orally bioavailable compounds for the treatment of HSV and VZV infections. Their main indication is herpes zoster. Valaciclovir and famciclovir act as prodrugs of acyclovir and penciclovir, respectively. Penciclovir acts in a similar fashion as acyclovir, although it would generate higher intracellular levels of the triphosphate form, which is supposed to be the active metabolite for these compounds.

Ganciclovir, Foscarnet

Ganciclovir (Cytovene) is the preferred drug for treating cytomegalovirus (CMV) infections in patients with acquired immune deficiency syndrome (AIDS) or other immunodeficiencies. It has very poor oral bioavailability (3 %), and, therefore, mostly given intravenously. Of the various clinical manifestations of cytomegalovirus infection in immunosuppressed patients, cytomegalovirus retinitis responds best to ganciclovir therapy, but recurs after treatment is stopped. The most frequent adverse side effects are granulocytopenia (neutropenia) and thrombocytopenia. Foscarnet (Foscavir) is the second drug used in the treatment of CMV infections, particularly CMV retinitis, in immunocompromised patients. It must be given intravenously, and it has proved effective in delaying progression of CMV retinitis compared to untreated controls.