Can disseminated varicella-zoster virus infection treatment be extended with oral valacyclovir after 7 days of intravenous acyclovir?

From the Guidelines

After 7 days of IV acyclovir, treatment for disseminated varicella-zoster virus (VZV) infection can be extended with oral valacyclovir, as this approach allows for continued antiviral therapy with a medication that has better bioavailability and can be administered outside the hospital setting. The decision to transition to oral valacyclovir should be based on clinical improvement, including the patient being afebrile for at least 48 hours, having no new lesions appear, and existing lesions crusting over 1.

Key Considerations

• The total treatment course should be 7-10 days, depending on clinical response and immune status, with longer courses (10-14 days total) often recommended for immunocompromised patients.
• Valacyclovir is preferred over acyclovir for oral therapy due to its better bioavailability (approximately 54% versus 15-30% for acyclovir), resulting in higher plasma concentrations and allowing for less frequent dosing 1.
• The conversion to oral therapy is appropriate because valacyclovir is a prodrug that converts to acyclovir in the body, providing similar antiviral activity.

Treatment Approach

• High-dose IV acyclovir remains the treatment of choice for VZV infections in compromised hosts, but oral therapy can be used to complete treatment once the patient has shown a clinical response to IV acyclovir 1.
• Oral acyclovir, famciclovir, and valacyclovir are beneficial for VZV infections in otherwise healthy hosts, but oral therapy should be reserved for mild cases of VZV disease in patients with transient immune suppression 1.

From the FDA Drug Label

The pharmacokinetics of valacyclovir and acyclovir after oral administration of VALTREX have been investigated in 14 volunteer trials involving 283 adults and in 3 trials involving 112 pediatric subjects aged 1 month to less than 12 years The absolute bioavailability of acyclovir after administration of VALTREX is 54.5% ± 9. 1% as determined following a 1-gram oral dose of VALTREX and a 350-mg intravenous acyclovir dose to 12 healthy volunteers. Acyclovir pharmacokinetic parameter estimates following administration of VALTREX to healthy adult volunteers are presented in Table 3 There is no accumulation of acyclovir after the administration of valacyclovir at the recommended dosage regimens in adults with normal renal function.

The answer to whether disseminated VZV treatment can be extended with oral valacyclovir after 7 days of IV acyclovir is not directly addressed in the provided drug labels. However, based on the information provided about the pharmacokinetics of valacyclovir and its conversion to acyclovir, it can be inferred that oral valacyclovir could potentially be used to extend treatment, as it is converted to acyclovir in the body. Key points to consider include:

• The bioavailability of acyclovir from valacyclovir
• The pharmacokinetic parameters of acyclovir after valacyclovir administration
• The lack of accumulation of acyclovir with recommended valacyclovir dosing However, without direct information on the use of valacyclovir for disseminated VZV treatment after IV acyclovir, caution is advised. The decision to extend treatment with oral valacyclovir should be made based on clinical judgment and consideration of the individual patient's condition, as the provided drug labels do not offer explicit guidance on this specific scenario 2.

From the Research

Disseminated VZV Treatment Extension with Oral Valacyclovir

• After 7 days of IV acyclovir, disseminated VZV treatment can be extended with oral valacyclovir, as supported by a case report where a patient was successfully treated with oral valacyclovir after only receiving two days of IV acyclovir 3.
• The efficacy of valacyclovir in the treatment of herpes zoster has been well documented in large clinical trials, and it is effective on zoster-associated pain 4.
• A study of 123 patients with VZV meningitis found that outcomes were favorable regardless of antiviral regimen, including those treated with a short course of IV acyclovir before switch to valacyclovir 5.

Treatment Considerations

• The development of resistance against aciclovir and other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals, but it can be a concern in immunocompromised patients 4.
• Foscarnet is a potentially effective and tolerable antiviral agent for patients with acyclovir-resistant varicella-zoster virus infection, but the optimal dosage and duration of therapy require further study 6.
• New antiherpes agents are needed to face clinical issues such as drug resistance, increased use of antiherpes prophylaxis in transplantation, and safety concerns in small children or pregnant women 7.