Valacyclovir: Clinical Uses and Indications
Valacyclovir is an oral antiviral medication used primarily to treat herpes simplex virus (HSV-1 and HSV-2) infections, including genital herpes and herpes labialis (cold sores), as well as varicella zoster virus (VZV) infections such as shingles (herpes zoster). 1
Primary Clinical Indications
Genital Herpes (HSV-2 and HSV-1)
First Episode Treatment
- Valacyclovir 1000 mg orally twice daily for 10 days is the standard regimen for initial genital herpes outbreaks 2, 3
- This dosing achieves equivalent efficacy to acyclovir 200 mg five times daily but with improved convenience 3
Recurrent Episodes (Episodic Treatment)
- Valacyclovir 500 mg orally twice daily for 5 days is the CDC-recommended first-line episodic regimen 4, 2, 5
- Treatment is most effective when initiated during prodrome or within 1 day of lesion onset 2
- Alternative dosing: 1000 mg once daily for 5 days is also effective 2
Suppressive Therapy for Frequent Recurrences
- For patients with ≥6 recurrences per year, valacyclovir 500 mg to 1 g once daily reduces recurrence frequency by ≥75% 4, 2, 6
- Valacyclovir 500 mg once daily is FDA-approved for once-daily suppressive dosing 5
- For very frequent recurrences (≥10 episodes/year), use valacyclovir 1 g once daily instead of 500 mg, as the lower dose is less effective in this population 4, 2
- Safety documented for up to 1 year of continuous suppressive therapy 4, 2
Herpes Labialis (Cold Sores)
- Valacyclovir is indicated for treatment of herpes labialis caused by HSV-1 4, 5, 7
- Treatment reduces duration and severity of cold sore outbreaks 7
Herpes Zoster (Shingles)
- Valacyclovir 1000 mg orally three times daily for 7 days is effective for herpes zoster in immunocompetent adults 8
- Valacyclovir is significantly more effective than acyclovir in reducing the duration of zoster-associated pain and postherpetic neuralgia 8, 7
Transmission Reduction
- Valacyclovir 500 mg once daily in HSV-2-infected persons reduces transmission to susceptible heterosexual partners by 50% 4
- This is the only antiviral FDA-approved for reduction of sexual transmission of genital herpes 7
Special Populations
HIV-Infected and Immunocompromised Patients
- HIV-infected patients often require higher doses and longer treatment durations 4
- For suppressive therapy in HIV-infected persons, use valacyclovir 500 mg twice daily (not once daily) 4
- Severe mucocutaneous HSV lesions may require IV acyclovir 5 mg/kg every 8 hours 4
- Critical warning: Avoid valacyclovir 8 g/day in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 4, 2, 9
Pregnancy
- The safety of valacyclovir in pregnancy has not been definitively established 4
- First-episode genital herpes during pregnancy may be treated with oral acyclovir; valacyclovir data are limited 4
- A pregnancy registry exists to monitor outcomes (maintained by manufacturer in cooperation with CDC) 4
Key Advantages Over Acyclovir
- Valacyclovir achieves 3-5 times higher acyclovir blood levels due to 54.5% bioavailability versus acyclovir's much lower oral bioavailability 1, 8, 3
- Less frequent dosing (twice daily or once daily) compared to acyclovir (5 times daily), improving adherence 4, 8, 7
- Equivalent clinical efficacy to acyclovir in all comparative trials 4, 3, 7
Important Clinical Pitfalls to Avoid
- Never use topical acyclovir—it is substantially less effective than oral therapy 2, 5
- Do not use valacyclovir 500 mg once daily for patients with ≥10 episodes/year; increase to 1 g once daily 4, 2
- Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, so transmission risk remains 4, 2, 5
- Suspect acyclovir resistance if lesions do not improve within 7-10 days; consider foscarnet 40 mg/kg IV every 8 hours for resistant cases 4, 2
- Dose adjustment required in renal impairment 1
Mechanism of Action
- Valacyclovir is rapidly converted to acyclovir and L-valine by first-pass intestinal/hepatic metabolism 1
- Acyclovir is phosphorylated by viral thymidine kinase, then inhibits viral DNA polymerase, causing DNA chain termination 1
- Active against HSV-1, HSV-2, and VZV 1