Medical Pharmacology Chapter 36:  Antiviral Drugs

• Antiviral Drugs

  •  Acyclovir and Related Drugs continued:

    • Acyclovir (Cyclovir, Zovirax etc.) is available in several formulations including intravenous (IV), oral and topical.² 

      • Acyclovir (Zovirax)⁵

    • By contrast, valacyclovir (Valtrex, Zelitrex) is an oral formulation.

      • Valacyclovir (Valtrex)⁵

    • IV acyclovir has a number of uses including treatment of mucocutaneous herpes simplex virus (HSV) infections in immunocompromised patients.² 

      • Efficacy assessment of oral acyclovir treatment for mucocutaneous HSV infections in immunocompromised marrow transplant recipients is based in part on results from a randomized, double-blinded, placebo-controlled clinical trial.

        • In that trial oral acyclovir was administered (400 mg five times a day for 10 days) with results compared to that of placebo.

        • The individuals were marrow transplant patients with tissue culture-establish recurrent mucocutaneous herpes simplex infection.

          • 12 patients were assigned to receive acyclovir while 9 patients received placebo.

          • Acyclovir administration decreased mean duration of viral shedding, decreased new lesion formation as well as time to first decrease in pain.

            • Resolution of pain, 50% healing and total healing were also improved by acyclovir.

              • The study results were considered comparable to those earlier obtained both with IV acyclovir or topical acyclovir⁸.

              • Some of these results are described in the figures below.

               

            • Time-to-event curves for immunosuppressed marrow transplant recipients with mucocutaneous herpes simplex given either acyclovir (solid circles) or placebo (open circles)⁷

              "Time-to-event curves for immunosuppressed marrow transplant recipients given acyclovir (solid circles) or placebo (open circles) for mucocutaneous herpes simplex." "Probability of continued pain. The curves are significantly different at p = 0.05." This figure corresponds to figure 1B in reference 7.	"Time-to-event curves for immunosuppressed marrow transplant recipients given acyclovir (solid circles) or placebo (open circles) for mucocutaneous herpes simplex." "Probability of incomplete healing. The curves are significantly different at p = 0.01." This figure corresponds to figure 1C in reference 7.

      •  

        Chronic mucocutaneous Herpes Lesion in HIV-Positive Patient⁶

        "This HIV-positive patient was exhibiting a chronic mucocutaneous herpes lesion for one month in duration. Herpes simplex virus type1 usually is the cause for oral lesions sometimes referred to as “cold sores”, “fever blisters” or more technically known as “recurrent herpes labialis”."6

         

      • The benefit of using IV acyclovir in these patients include reduced pain duration, reduced time to healing and diminished viral shedding.² 

      • If IV acyclovir is administered prior to drug-induced immunosuppression in the context of chemotherapy or transplantation and if it is administered before lesion development, the drug decreases the likelihood of HSV-associated disease.

        • However, following discontinuation of this prophylactic IV acyclovir administration, HSV lesions can recur.²  

      • Varicella-zoster-zoster virus (VZV) disease may afflict about 30% of allogenic hematopoietic cell transplant recipients if they had a history of VZV infection.⁹ 

        • Acyclovir administration reduced VZV infection likelihood at one year following transplantation.

        • This result was obtained in a double-blind controlled trial. In the study 77 hemopoietic cell transplant recipients known to be at risk for VZV reactivation were randomized either to acyclovir (800 mg twice daily) or placebo administered for one year following transplantation.

        • The principal endpoint was VZV disease at one year.⁹  

        • Acyclovir administration was found to reduce the likelihood of VZV infections at one year following transplantation (P = 0.006).

          • After one year i.e. following acyclovir discontinuation, VZV-related disease was observed.⁹  

          • This result is described in the figure below.⁹ 

            • "Time to first VZV disease in the modified intent-to-treat population"⁹

              "Acyclovir prophylaxis significantly reduced VZV disease at the end of the active treatment period (1 year). "The vertical dotted line indicates 1 year after transplantation (note:  patients were randomized approximately 2 months after transplantation)." Attribution:  The figure above corresponds to Fig. 2 in reference 9.

      • IV acyclovir is also central in the treatment of HSV encephalitis, which if untreated is associated with high mortality rates and even with treatment, HSV encephalititis may be associated with significant post-infection morbidity.²

      • Acyclovir is also used in treating varicella-zoster (VZV) infection and the drug must be administered at higher doses since VZV appears less sensitive to acyclovir compared to herpes simplex virus.² 

        • In immunocompromised patients with herpes zoster, IV acyclovir reduces the likelihood of cutaneous dissemination and visceral complications.

          • Oral acyclovir may provide some benefit on localized herpes zoster lesions in both immunocompromised and immunocompetent patients.

            • Furthermore, combining acyclovir with prednisone (tapering regimen) is likely more effective than acyclovir alone, using quality-of-life outcome measures as the metric, in immunocompetent patients over age 50 with herpes zoster.

            • Using the endpoint of resolution of zoster-associated pain, valacyclovir (Valtrex, Zelitrex) may be more effective compared to acyclovir (Cyclovir, Zovirax) in immunocompetent individuals.

            • Oral acyclovir was also found to decrease complications in herpes zoster ophthalmicus.² 

               

              • Herpes Zoster Ophthalmicus (left)¹⁰; Trigeminal Nerve Distribution (right)¹¹ 

                "Herpes Zoster Ophthalmicus (HZO), commonly known as shingles, is a viral disease characterized by a painful skin rash in one or more dermatome distributions of the fifth cranial nerve, shared by the eye and orbit."10	Distribution Scheme of the Trigeminal Nerve11

      • In chickenpox (varicella-zoster) some clinical benefit has been noted with oral acyclovir when treatment is initiated within a day of rash onset in children (otherwise healthy) or adults.²   

        • In children who are immunocompromised and suffering chickenpox, IV acyclovir may be an effective therapy.²