Valacyclovir microbiology

Valacyclovir
VALTREX® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Clinical Studies
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Microbiology

Antiviral Activities: The quantitative relationship between the cell culture susceptibility of herpesviruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (EC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the EC50 values against herpes simplex virus isolates range from 0.09 to 60 μM (0.02 to 13.5 mcg/mL) for HSV─1 and from 0.04 to 44 µM (0.01 to 9.9 mcg/mL) for HSV─2. The EC50 values for acyclovir against most laboratory strains and clinical isolates of VZV range from 0.53 to 48 µM (0.12 to 10.8 mcg/mL). Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean EC50 of 6 µM (1.35 mcg/mL).

Resistance: Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of VZV with reduced susceptibility to acyclovir have been recovered from patients with AIDS. In these cases, TK-deficient mutants of VZV have been recovered.

Resistance of HSV and VZV to acyclovir occurs by the same mechanisms. While most of the acyclovir─resistant mutants isolated thus far from immunocompromised patients have been found to be TK─deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have also been isolated. TK─negative mutants may cause severe disease in immunocompromised patients. The possibility of viral resistance to valacyclovir (and therefore, to acyclovir) should be considered in patients who show poor clinical response during therapy.

References

Adapted from the FDA Package Insert.