Valacyclovir Hydrochloride (Page 11 of 13)

Reduction of Transmission of Genital Herpes

A double-blind, placebo-controlled trial to assess transmission of genital herpes was conducted in 1,484 monogamous, heterosexual, immunocompetent adult couples. The couples were discordant for HSV-2 infection. The source partner had a history of 9 or fewer genital herpes episodes per year. Both partners were counseled on safer sex practices and were advised to use condoms throughout the trial period. Source partners were randomized to treatment with either valacyclovir tablets 500 mg once daily or placebo once daily for 8 months. The primary efficacy endpoint was symptomatic acquisition of HSV-2 in susceptible partners. Overall HSV-2 acquisition was defined as symptomatic HSV-2 acquisition and/or HSV-2 seroconversion in susceptible partners. The efficacy results are summarized in Table 10.

Table 10. Percentage of Susceptible Partners Who Acquired HSV-2 Defined by the Primary and Selected Secondary Endpoints
*
Results show reductions in risk of 75% (symptomatic HSV-2 acquisition), 50% (HSV-2 seroconversion), and 48% (overall HSV-2 acquisition) with valacyclovir tablets versus placebo. Individual results may vary based on consistency of safer sex practices.

Endpoint

Valacyclovir Tablets *

(n = 743)

Placebo

(n = 741)

Symptomatic HSV-2 acquisition

4 (0.5%)

16 (2.2%)

HSV-2 seroconversion

12 (1.6%)

24 (3.2%)

Overall HSV-2 acquisition

14 (1.9%)

27 (3.6%)

14.3 Herpes Zoster

Two randomized, double-blind clinical trials in immunocompetent adults with localized herpes zoster were conducted. Valacyclovir tablets were 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 valacyclovir tablets 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 valacyclovir tablets 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 valacyclovir tablets 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 valacyclovir tablets, 14-day valacyclovir tablets, and 7-day oral acyclovir, respectively.

14.4 Chickenpox

The use of valacyclovir 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.

The single-dose pharmacokinetic and multiple-dose safety trial enrolled 27 pediatric subjects aged 1 to less than 12 years with clinically suspected VZV infection. Each subject was dosed with valacyclovir oral suspension, 20 mg/kg 3 times daily for 5 days. Acyclovir systemic exposures in pediatric subjects following valacyclovir oral suspension were compared with historical acyclovir systemic exposures in immunocompetent adults receiving the solid oral dosage form of valacyclovir or acyclovir for the treatment of herpes zoster. The mean projected daily acyclovir exposures in pediatric subjects across all age-groups (1 to less than 12 years) were lower (Cmax : ↓ 13%, AUC: ↓ 30%) than the mean daily historical exposures in adults receiving valacyclovir 1 gram 3 times daily, but were higher (daily AUC: ↑ 50%) than the mean daily historical exposures in adults receiving acyclovir 800 mg 5 times daily. The projected daily exposures in pediatric subjects were greater (daily AUC approximately 100% greater) than the exposures seen in immunocompetent pediatric subjects receiving acyclovir 20 mg/kg 4 times daily for the treatment of chickenpox. Based on the pharmacokinetic and safety data from this trial and the safety and extrapolated efficacy data from the acyclovir trials, oral valacyclovir 20 mg/kg 3 times a day for 5 days (not to exceed 1 gram 3 times daily) is recommended for the treatment of chickenpox in pediatric patients aged 2 to less than 18 years. Because the efficacy and safety of acyclovir for the treatment of chickenpox in children aged less than 2 years have not been established, efficacy data cannot be extrapolated to support valacyclovir treatment in children aged less than 2 years with chickenpox. Valacyclovir is also not recommended for the treatment of herpes zoster in children because safety data up to 7 days’ duration are not available [see Use in Specific Populations (8.4)].

16 HOW SUPPLIED/STORAGE AND HANDLING

Valacyclovir Tablets, USP are available containing 556.2 mg or 1.112 grams of valacyclovir hydrochloride, USP (hydrous) equivalent to 500 mg or 1 gram of valacyclovir, respectively.

The 500 mg tablets are white, film-coated, oval, unscored tablets with M122 imprinted with black ink on one side of the tablet and plain on the other side of the tablet. They are available as follows:

NDC 0378-4275-93
bottles of 30 tablets

NDC 0378-4275-77
bottles of 90 tablets

The 1 gram tablets are white, film-coated, oval tablets with a partial break line on both sides of the tablet and M123 imprinted with black ink on one side of the tablet. They are available as follows:

NDC 0378-4276-93
bottles of 30 tablets

NDC 0378-4276-77bottles of 90 tablets

Storage: Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Importance of Adequate Hydration: Patients should be advised to maintain adequate hydration.

Missed Dose: Instruct patients that if they miss a dose of valacyclovir tablets, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose.

Cold Sores (Herpes Labialis): Patients should be advised to initiate treatment at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). There are no data on the effectiveness of treatment initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer). Patients should be instructed that treatment for cold sores should not exceed 1 day (2 doses) and that their doses should be taken about 12 hours apart. Patients should be informed that valacyclovir tablets are not a cure for cold sores.

Genital Herpes: Patients should be informed that valacyclovir tablets are not a cure for genital herpes. Because genital herpes is a sexually transmitted disease, patients should avoid contact with lesions or intercourse when lesions and/or symptoms are present to avoid infecting partners. Genital herpes is frequently transmitted in the absence of symptoms through asymptomatic viral shedding. Therefore, patients should be counseled to use safer sex practices in combination with suppressive therapy with valacyclovir tablets. Sex partners of infected persons should be advised that they might be infected even if they have no symptoms. Type-specific serologic testing of asymptomatic partners of persons with genital herpes can determine whether risk for HSV-2 acquisition exists.

Valacyclovir tablets have not been shown to reduce transmission of sexually transmitted infections other than HSV-2.

If medical management of a genital herpes recurrence is indicated, patients should be advised to initiate therapy at the first sign or symptom of an episode.

There are no data on the effectiveness of treatment initiated more than 72 hours after the onset of signs and symptoms of a first episode of genital herpes or more than 24 hours after the onset of signs and symptoms of a recurrent episode.

There are no data on the safety or effectiveness of chronic suppressive therapy of more than 1 year’s duration in otherwise healthy patients. There are no data on the safety or effectiveness of chronic suppressive therapy of more than 6 months’ duration in HIV-1–infected patients.

Herpes Zoster: There are no data on treatment initiated more than 72 hours after onset of the zoster rash. Patients should be advised to initiate treatment as soon as possible after a diagnosis of herpes zoster.

Chickenpox: Patients should be advised to initiate treatment at the earliest sign or symptom of chickenpox.

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