General Information

Valtrex (valacyclovir) is a deoxynucleoside analogue DNA polymerase inhibitor

Valtrex is indicated for:

Adult Patients

• Cold Sores (Herpes Labialis)
• Genital Herpes
  • Treatment in immunocompetent patients (initial or recurrent episode)
  • Suppression in immunocompetent or HIV-1−infected patients
  • Reduction of transmission
• Herpes Zoster

Pediatric Patients

• Cold Sores (Herpes Labialis)
• Chickenpox

Valtrex may be given without regard to meals. 

Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500-mg VALTREX tablets for use in pediatric patients for whom a solid dosage form is not appropriate.

The dosing recommendations are as follows:

Adult Dosing Recommendations

• Cold Sores (Herpes Labialis): The recommended dosage of Valtrex for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).
• Genital Herpes
  • Initial Episode: The recommended dosage of Valtrex for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.
  • Recurrent Episodes: The recommended dosage of Valtrex for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an 4 episode.
  • Suppressive Therapy: The recommended dosage of Valtrex for chronic suppressive therapy of recurrent genital herpes is 1 gram once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg once daily.
  • In HIV-1−infected patients with a CD4+ cell count greater than or equal to 100 cells/mm3 , the recommended dosage of Valtrex for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.
  • Reduction of Transmission: The recommended dosage of Valtrex for reduction of transmission of genital herpes in patients with a history of 9 or fewer recurrences per year is 500 mg once daily for the source partner.
• Herpes Zoster: The recommended dosage of Valtrex for treatment of herpes zoster is 1 gram 3 times daily for 7 days. Therapy should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the onset of rash.

Pediatric Dosing Recommendations

• Cold Sores (Herpes Labialis): The recommended dosage of Valtrex for the treatment of cold sores in pediatric patients aged greater than or equal to 12 years is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).
• Chickenpox: The recommended dosage of Valtrex for treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptom.

Mechanism of Action

Valacyclovir is an antiviral drug active against α-herpes viruses. Valacyclovir is a deoxynucleoside analogue DNA polymerase inhibitor. Valacyclovir 20 hydrochloride is rapidly converted to acyclovir, which has demonstrated antiviral activity against HSV types 1 (HSV-1) and 2 (HSV-2) and VZV both in cell culture and in vivo. Acyclovir is a synthetic purine deoxynucleoside that is phosphorylated intracellularly by the viral encoded thymidine kinase (TK; pUL23) of HSV or VZV into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In biochemical assays, acyclovir triphosphate inhibits replication of α-herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.

Side Effects

Adverse effects associated with the use of Valtrex may include the following:

• headache
• nausea
• diarrhea
• dizziness

Clinical Trial Results

Cold Sores (Herpes Labialis)

Two double-blind, placebo-controlled clinical trials were conducted in 1,856 healthy adults and adolescents (aged greater than or equal to 12 years) with a history of recurrent cold sores. Subjects self-initiated therapy at the earliest symptoms and prior to any signs of a cold sore. The majority of subjects initiated treatment within 2 hours of onset of symptoms. Subjects were randomized to VALTREX 2 grams twice daily on Day 1 followed by placebo on Day 2, VALTREX 2 grams twice daily on Day 1 followed by 1 gram twice daily on Day 2, or placebo on Days 1 and 2. The mean duration of cold sore episodes was about 1 day shorter in treated subjects as compared with placebo. The 2-day regimen did not offer additional benefit over the 1-day regimen. No significant difference was observed between subjects receiving VALTREX or placebo in the prevention of progression of cold sore lesions beyond the papular stage.

Genital Herpes Infections

Initial Episode

Six hundred forty-three immunocompetent adults with first-episode genital herpes who presented 24 within 72 hours of symptom onset were randomized in a double-blind trial to receive 10 days of VALTREX 1 gram twice daily (n = 323) or oral acyclovir 200 mg 5 times a day (n = 320). For both treatment groups the median time to lesion healing was 9 days, the median time to cessation of pain was 5 days, and the median time to cessation of viral shedding was 3 days.

Recurrent Episodes

Three double-blind trials (2 of them placebo-controlled) in immunocompetent adults with recurrent genital herpes were conducted. Subjects self-initiated therapy within 24 hours of the first sign or symptom of a recurrent genital herpes episode. In 1 trial, subjects were randomized to receive 5 days of treatment with either VALTREX 500 mg twice daily (n = 360) or placebo (n = 259). The median time to lesion healing was 4 days in the group receiving VALTREX 500 mg versus 6 days in the placebo group, and the median time to cessation of viral shedding in subjects with at least 1 positive culture (42% of the overall trial population) was 2 days in the group receiving VALTREX 500 mg versus 4 days in the placebo group. The median time to cessation of pain was 3 days in the group receiving VALTREX 500 mg versus 4 days in the placebo group. Results supporting efficacy were replicated in a second trial. In a third trial, subjects were randomized to receive VALTREX 500 mg twice daily for 5 days (n = 398) or VALTREX 500 mg twice daily for 3 days (and matching placebo twice daily for 2 additional days) (n = 402). The median time to lesion healing was about 4½ days in both treatment groups. The median time to cessation of pain was about 3 days in both treatment groups.

Herpes Zoster

Two randomized, double-blind clinical trials in immunocompetent adults with localized herpes zoster were conducted. VALTREX was compared with placebo in subjects aged less than 50 years and with oral acyclovir in subjects aged greater than 50 years. All subjects were treated within 72 hours of appearance of zoster rash. In subjects aged less than 50 years, the median time to cessation of new lesion formation was 2 days for those treated with VALTREX compared with 3 days for those treated with placebo. In subjects aged greater than 50 years, the median time to cessation of new lesions was 3 days in subjects treated with either VALTREX or oral acyclovir. In subjects aged less than 50 years, no difference was found with respect to the duration of pain after healing (post-herpetic neuralgia) between the recipients of VALTREX and placebo. In subjects aged greater than 50 years, among the 83% who reported pain after healing (post-herpetic neuralgia), the median duration of pain after healing (95% CI) in days was: 40 (31, 51), 43 (36, 55), and 59 (41, 77) for 7-day VALTREX, 14-day VALTREX, and 7-day oral acyclovir, respectively.

Chickenpox

The use of VALTREX for treatment of chickenpox in pediatric subjects aged 2 to less than 18 years is based on single-dose pharmacokinetic and multiple-dose safety data from an open-label trial with valacyclovir and supported by safety and extrapolated efficacy data from 3 randomized, double-blind, placebo-controlled trials evaluating oral acyclovir in pediatric subjects.