valACYclovir 1 GM Oral Tablet
Generic Name: VALACYCLOVIR HYDROCHLORIDE
Brand Name: Valacyclovir Hydrochloride
- Substance Name(s):
- VALACYCLOVIR HYDROCHLORIDE
DRUG INTERACTIONS
7 No clinically significant drug-drug or drug-food interactions with valacyclovir are known [see Clinical Pharmacology (12.3) ].
OVERDOSAGE
10 Caution should be exercised to prevent inadvertent overdose [see Use in Specific Populations (8.5) , (8.6) ].
Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid.
In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored [see Dosage and Administration (2.4) ].
DESCRIPTION
11 Valacyclovir hydrochloride is the hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir.
Valacyclovir hydrochloride tablets are blue, film-coated tablets for oral administration.
Each tablet contains valacyclovir hydrochloride equivalent to 500 mg or 1 gram valacyclovir and the inactive ingredients croscarmellose sodium, FD&C Blue #2, hydrogenated castor oil, hypromellose, polyethylene glycol, polysorbate 80, starch (corn), and titanium dioxide.
The chemical name of valacyclovir hydrochloride is L-valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester, monohydrochloride.
It has the following structural formula: Valacyclovir hydrochloride is a white to off-white powder with the molecular formula C13H20N6O4•HCland a molecular weight of 360.80.
The maximum solubility in water at 25°C is 174 mg/mL.
The pkas for valacyclovir hydrochloride are 1.90, 7.47, and 9.43.
Structural Formula for valacyclovir hydrochloride
CLINICAL STUDIES
14 14.1 Cold Sores (Herpes Labialis) Two double-blind, placebo-controlled clinical trials were conducted in 1,856 healthy adults and adolescents (≥ 12 years old) with a history of recurrent cold sores.
Patients self-initiated therapy at the earliest symptoms and prior to any signs of a cold sore.
The majority of patients initiated treatment within 2 hours of onset of symptoms.
Patients were randomized to valacyclovir hydrochloride tablets 2 grams twice daily on Day 1 followed by placebo on Day 2, valacyclovir hydrochloride tablets 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 valacyclovir hydrochloride tablets or placebo in the prevention of progression of cold sore lesions beyond the papular stage.
14.2 Genital Herpes Infections Initial Episode: Six hundred and forty-three immunocompetent adults with first-episode genital herpes who presented within 72 hours of symptom onset were randomized in a double-blind trial to receive 10 days of valacyclovir hydrochloride tablets 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, 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.
Patients self-initiated therapy within 24 hours of the first sign or symptom of a recurrent genital herpes episode.
In 1 study, patients were randomized to receive 5 days of treatment with either valacyclovir hydrochloride tablets 500 mg twice daily (n = 360) or placebo (n = 259).
The median time to lesion healing was 4 days in the group receiving valacyclovir hydrochloride tablets 500 mg versus 6 days in the placebo group, and the median time to cessation of viral shedding in patients with at least 1 positive culture (42% of the overall study population) was 2 days in the group receiving valacyclovir hydrochloride tablets 500 mg versus 4 days in the placebo group.
The median time to cessation of pain was 3 days in the group receiving valacyclovir hydrochloride tablets 500 mg versus 4 days in the placebo group.
Results supporting efficacy were replicated in a second trial.
In a third study, patients were randomized to receive valacyclovir hydrochloride tablets 500 mg twice daily for 5 days (n = 398) or valacyclovir hydrochloride tablets 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.
Suppressive Therapy: Two clinical studies were conducted, one in immunocompetent adults and one in HIV-infected adults.
A double-blind, 12-month, placebo- and active-controlled study enrolled immunocompetent adults with a history of 6 or more recurrences per year.
Outcomes for the overall study population are shown in Table 5.
Table 5.
Recurrence Rates in Immunocompetent Adults at 6 and 12 Months 6 Months 12 Months Outcome Valacyclovir HC1 Tablets 1 gram once daily (n=269) Oral Acyclovir 400 mg twice daily (n=267) Placebo (n=134) Valacyclovir HC1 tablets 1gram once daily (n=269) Oral Acyclovir 400 mg twice daily (n=267) Placebo (n=134) Recurrence Free 55% 54% 7% 34% 34% 4% Recurrences 35% 36% 83% 46% 46% 85% Unknown 10% 10% 10% 19% 19% 10% Subjects with 9 or fewer recurrences per year showed comparable results with valacyclovir hydrochloride tablets 500 mg once daily.
In a second study, 293 HIV-infected adults on stable antiretroviral therapy with a history of 4 or more recurrences of ano-genital herpes per year were randomized to receive either valacyclovir hydrochloride tablets 500 mg twice daily (n = 194) or matching placebo (n = 99) for 6 months.
The median duration of recurrent genital herpes in enrolled subjects was 8 years, and the median number of recurrences in the year prior to enrollment was 5.
Overall, the median prestudy HIV-1 RNA was 2.6 log10 copies/mL.
Among patients who received valacyclovir hydrochloride tablets, the prestudy median CD4+ cell count was 336 cells/mm3; 11% had <100 cells/mm3, 16% had 100 to 199 cells/mm3, 42% had 200 to 499 cells/mm3, and 31% had ≥500 cells/mm3.
Outcomes for the overall study population are shown in Table 6.
Table 6.
Recurrence Rates in HIV-Infected Adults at 6 Months Outcome Valacyclovir HCl Tablets 500 mg twice daily (n = 194) Placebo (n = 99) Recurrence free 65% 26% Recurrences 17% 57% Unknown 18% 17% Reduction of Transmission of Genital Herpes: A double-blind, placebo-controlled study 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 study period.
Source partners were randomized to treatment with either valacyclovir hydrochloride 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 7.
Table 7.
Percentage of Susceptible Partners Who Acquired HSV-2 Defined by the Primary and Selected Secondary Endpoints Valacyclovir HCl Tablets Placebo Endpoint (n = 743) (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 hydrochloride tablets were compared with placebo in patients less than 50 years of age, and with oral acyclovir in patients greater than 50 years of age.
All patients were treated within 72 hours of appearance of zoster rash.
In patients less than 50 years of age, the median time to cessation of new lesion formation was 2 days for those treated with valacyclovir hydrochloride tablets compared with 3 days for those treated with placebo.
In patients greater than 50 years of age, the median time to cessation of new lesions was 3 days in patients treated with either valacyclovir hydrochloride tablets or oral acyclovir.
In patients less than 50 years of age, no difference was found with respect to the duration of pain after healing (post-herpetic neuralgia) between the recipients of valacyclovir hydrochloride tablets and placebo.
In patients greater than 50 years of age, among the 83% who reported pain after healing (post-herpetic neuralgia), the median duration of pain after healing [95% confidence interval] in days was: 40 [31, 51], 43 [36, 55], and 59 [41, 77] for 7-day valacyclovir hydrochloride tablets, 14-day valacyclovir hydrochloride tablets, and 7-day oral acyclovir, respectively.
Labeling describing clinical studies of valacyclovir HCL in pediatric patients with chickenpox (ages 2 to ≤ 18 years) for the treatment of chickenpox is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of those clinical studies is not approved for this valacyclovir HCL tablet product.
HOW SUPPLIED
16 /STORAGE AND HANDLING Valacyclovir hydrochloride tablets (blue, film-coated, capsule-shaped tablets), with a partial scorebar on both sides) containing valacyclovir hydrochloride equivalent to 1 gram valacyclovir and debossed with “WPI” on one side and “3249” on the other side.
Bottles of 4 NDC 21695-965-04 Bottles of 7 NDC 21695-965-07 Bottles of 21 NDC 21695-965-21 Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature}.
Dispense in a well-closed container as defined in the USP.
RECENT MAJOR CHANGES
Warnings and Precautions, Central Nervous System Effects (5.3) 3/2010
GERIATRIC USE
8.5 Geriatric Use Of the total number of subjects in clinical studies of valacyclovir hydrochloride tablets, 906 were 65 and over, and 352 were 75 and over.
In a clinical study of herpes zoster, the duration of pain after healing (post-herpetic neuralgia) was longer in patients 65 and older compared with younger adults.
Elderly patients are more likely to have reduced renal function and require dose reduction.
Elderly patients are also more likely to have renal or CNS adverse events [see Dosage and Administration (2.4) , Warnings and Precautions ( 5.2 , 5.3 ), Clinical Pharmacology (12.3) ].
DOSAGE FORMS AND STRENGTHS
3 Tablets: 500 mg: blue, film-coated, capsule-shaped tablets debossed with “W PI” on one side and “3248” on the other side.
1 gram: blue, film-coated, capsule-shaped tablets, with a partial scorebar on both sides, debossed with “WPI” on one side and “324 9” on the other side.
Tablets: 500 mg (unscored), 1 gram (partially scored) (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Valacyclovir is an antiviral drug [see Clinical Pharmacology (12.4) ].
INDICATIONS AND USAGE
1 Valacyclovir hydrochloride tablets are a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients ( 1.1 ) Cold Sores (Herpes Labialis) Genital Herpes Treatment in immunocompetent patients (initial or recurrent episode) Suppression in immunocompetent or HIV-infected patients Reduction of transmission Herpes Zoster Pediatric Patients ( 1.2 ) Cold Sores (Herpes Labialis) Limitations of Use ( 1.3 ) The efficacy and safety of valacyclovir hydrochloride tablets have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.
1.1 Adult Patients Cold Sores (Herpes Labialis): Valacyclovir hydrochloride tablets are indicated for treatment of cold sores (herpes labialis).
The efficacy of valacyclovir hydrochloride tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Genital Herpes: Initial Episode: Valacyclovir hydrochloride tablets are indicated for treatment of the initial episode of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir hydrochloride tablets when initiated more than 72 hours after the onset of signs and symptoms has not been established.
Recurrent Episodes: Valacyclovir hydrochloride tablets are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults.
The efficacy of treatment with valacyclovir hydrochloride tablets when initiated more than 24 hours after the onset of signs and symptoms has not been established.
Suppressive Therapy: Valacyclovir hydrochloride tablets are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-infected adults.
The efficacy and safety of valacyclovir hydrochloride tablets for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-infected patients have not been established.
Reduction of Transmission: Valacyclovir hydrochloride tablets are indicated for the reduction of transmission of genital herpes in immunocompetent adults.
The efficacy of valacyclovir hydrochloride tablets for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established.
The efficacy of valacyclovir hydrochloride tablets for the reduction of transmission of genital herpes in individuals with multiple partners and non-heterosexual couples has not been established.
Safer sex practices should be used with suppressive therapy (see current Centers for Disease Control and Prevention [CDC] Sexually Transmitted Diseases Treatment Guidelines).
Herpes Zoster: Valacyclovir hydrochloride tablets are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults.
The efficacy of valacyclovir hydrochloride tablets when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir hydrochloride tablets for treatment of disseminated herpes zoster have not been established.
1.2 Pediatric Patients Cold Sores (Herpes Labialis): Valacyclovir hydrochloride tablets are indicated for the treatment of cold sores (herpes labialis) in pediatric patients ≥12 years of age.
The efficacy of valacyclovir hydrochloride tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages 2 to ≤ 18 years) is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.
1.3 Limitations of Use The efficacy and safety of valacyclovir hydrochloride tablets have not been established in: Immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients with a CD4+ cell count ≥100 cells/mm3.
Patients <12 years of age with cold sores (herpes labialis).
Patients <18 years of age with genital herpes.
Patients <18 years of age with herpes zoster.
Neonates and infants as suppressive therapy following neonatal herpes simplex virus (HSV) infection.
Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages of 2 to ≤ 18 years) is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.
PEDIATRIC USE
8.4 Pediatric Use Valacyclovir hydrochloride tablets are indicated for treatment of cold sores in pediatric patients ≥12 years of age [see Indications and Usage (1.2) , Dosage and Administration (2.2) ].
The use of valacyclovir hydrochloride tablets for treatment of cold sores is based on 2 double-blind, placebo-controlled clinical trials in healthy adults and adolescents (≥12 years of age) with a history of recurrent cold sores [see Clinical Studies (14.1) ].
The efficacy and safety of valacyclovir have not been established in pediatric patients: <12 years of age with cold sores <18 years of age with genital herpes <18 years of age with herpes zoster for suppressive therapy following neonatal HSV infection.
In infants 1 month to <3 months of age, mean acyclovir exposures resulting from a 25 mg/kg dose were higher (Cmax: ↑30%, AUC: ↑60%) than acyclovir exposures following a 1 gram dose of valacyclovir in adults.
Labeling describing pediatric use information in pediatric patients with chickenpox (ages 2 to ≤ 18 years) and additional pharmacokinetic studies in pediatric patients (ages 3 months to < 12 years) treated with valacyclovir HCL is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, that additional pediatric information is not approved for this valacylcovir HCL tablet product.
PREGNANCY
8.1 Pregnancy Pregnancy Category B.
There are no adequate and well-controlled studies of valacyclovir or acyclovir in pregnant women.
Based on prospective pregnancy registry data on 749 pregnancies, the overall rate of birth defects in infants exposed to acyclovir in utero appears similar to the rate for infants in the general population.
Valacyclovir hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999.
There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes.
The occurrence rate of birth defects approximates that found in the general population.
However, the small size of the registry is insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses.
Animal reproduction studies performed at oral doses that provided up to 10 and 7 times the human plasma levels during the period of major organogenesis in rats and rabbits, respectively, revealed no evidence of teratogenicity.
NUSRING MOTHERS
8.3 Nursing Mothers Following oral administration of a 500 mg dose of valacyclovir hydrochloride tablets to 5 nursing mothers, peak acyclovir concentrations (Cmax)in breast milk ranged from 0.5 to 2.3 times (median 1.4) the corresponding maternal acyclovir serum concentrations.
The acyclovir breast milk AUC ranged from 1.4 to 2.6 times (median 2.2) maternal serum AUC.
A 500 mg maternal dosage of valacyclovir hydrochloride tablets twice daily would provide a nursing infant with an oral acyclovir dosage of approximately 0.6 mg/kg/day.
This would result in less than 2% of the exposure obtained after administration of a standard neonatal dose of 30 mg/kg/day of intravenous acyclovir to the nursing infant.
Unchanged valacyclovir was not detected in maternal serum, breast milk, or infant urine.
Caution should be exercised when valacyclovir hydrochloride tablets are administered to a nursing woman.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): Has occurred in patients with advanced HIV disease and in allogenic bone marrow transplant and renal transplant patients receiving 8 grams per day of valacyclovir hydrochloride tablets in clinical trials.
Discontinue treatment if clinical symptoms and laboratory findings consistent with TTP/HUS occur.
(5.1) Acute renal failure: May occur in elderly patients (with or without reduced renal function), patients with underlying renal disease who receive higher than recommended doses of valacyclovir hydrochloride tablets for their level of renal function, patients who receive concomitant nephrotoxic drugs, or inadequately hydrated patients.
Use with caution in elderly patients and reduce dosage in patients with renal impairment.
(2.4, 5.2) Central nervous system adverse reactions (e.g., agitation, hallucinations, confusion, and encephalopathy): May occur in both adult and pediatric patients (with or without reduced renal function) and in patients with underlying renal disease who receive higher than recommended doses of valacyclovir hydrochloride tablets for their level of renal function.
Elderly patients are more likely to have central nervous system adverse reactions.
Use with caution in elderly patients and reduce dosage in patients with renal impairment.
(2.4, 5.3) 5.1 Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS) TTP/HUS, in some cases resulting in death, has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of valacyclovir hydrochloride tablets at doses of 8 grams per day.
Treatment with valacyclovir hydrochloride tablets should be stopped immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS occur.
5.2 Acute Renal Failure Cases of acute renal failure have been reported in: Elderly patients with or without reduced renal function.
Caution should be exercised when administering valacyclovir hydrochloride tablets to geriatric patients, and dosage reduction is recommended for those with impaired renal function [see Dosage and Administration (2.4) , Use in Specific Populations (8.5) ].
Patients with underlying renal disease who received higher than recommended doses of valacyclovir hydrochloride tablets for their level of renal function.
Dosage reduction is recommended when administering valacyclovir hydrochloride tablets to patients with renal impairment [see Dosage and Administration (2.4) , Use in Specific Populations (8.6) ].
Patients receiving other nephrotoxic drugs.
Caution should be exercised when administering valacyclovir hydrochloride tablets to patients receiving potentially nephrotoxic drugs.
Patients without adequate hydration.
Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid.
Adequate hydration should be maintained for all patients.
In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored [see Dosage and Administration (2.4) , Adverse Reactions (6.3) ].
5.3 Central Nervous System Effects Central nervous system adverse reactions, including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and pediatric patients with or without reduced renal function and in patients with underlying renal disease who received higher than recommended doses of valacyclovir hydrochloride tablets for their level of renal function.
Elderly patients are more likely to have central nervous system adverse reactions.
Valacyclovir hydrochloride tablets should be discontinued if central nervous system adverse reactions occur [see Adverse Reactions (6.3) , Use in Specific Populations ( 8.5 , 8.6 )].
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.6).
17.1 Importance of Adequate Hydration Patients should be advised to maintain adequate hydration.
17.2 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 hydrochloride tablets are not a cure for cold sores.
17.3 Genital Herpes Patients should be informed that valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride 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-infected patients.
17.4 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.
Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages of 2 to ≤ 18 years) for the treatment of chickenpox is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that use is not approved for this valacyclovir HCL tablet product.
17.6 FDA-Approved Patient Labeling Patient labeling is provided as a tear-off leaflet at the end of this full prescribing information.
This product’s prescribing information may have been updated.
Please contact Watson Laboratories, Inc.
at 1-800-272-5525 for the most current version.
Manufactured for: Watson Laboratories, Inc.
Corona, CA 92880 USA Manufactured by: Cipla Ltd.
Verna, Goa, INDIA Issued: April 2010 Repackaged by: Rebel Distributors Corp Thousand Oaks, CA 91320
DOSAGE AND ADMINISTRATION
2 Valacyclovir hydrochloride tablets may be given without regard to meals.
Labeling describing use of valacyclovir HCL in pediatric patients for whom a solid dosage form is not appropriate is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that information is not approved for this valacyclovir HCL tablet product.
Adult Dosage ( 2.1 ) Cold Sores 2 grams every 12 hours for 1day Genital Herpes Initial Episode 1 gram twice daily for 10 days Recurrent Episodes 500 mg twice daily for 3 days Suppressive therapy Immunocopetent patients 1 gram once daily Alternate dose in patients 500 mg once daily with ≤ 9 recurrences/yr HIV-infected patients 500 mg twice daily Reduction of transmission 500 mg once daily Herpes Zoster 1 gram 3 times daily for 7 days Pediatric Dosage ( 2.2 ) Cold Sores (≥ 12 years of age) 2 grams every 12 hours for 1 day Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages 2 to ≤ 18 years) is approved for GlaxoSmith Kline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.
2.1 Adult Dosing Recommendations Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir hydrochloride tablets 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 valacyclovir hydrochloride tablets 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 valacyclovir hydrochloride tablets for treatment of recurrent genital herpes is 500 mg twice daily for 3 days.
Initiate treatment at the first sign or symptom of an episode.
Suppressive Therapy: The recommended dosage of valacyclovir hydrochloride tablets 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-infected patients with a CD4+ cell count ≥100 cells/mm3, the recommended dosage of valacyclovir hydrochloride tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.
Reduction of Transmission: The recommended dosage of valacyclovir hydrochloride tablets 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 valacyclovir hydrochloride tablets 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.
2.2 Pediatric Dosing Recommendations Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir hydrochloride tablets for the treatment of cold sores in pediatric patients ≥12 years of age 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).
Labeling describing additional dosing of valacyclovir HCL for pediatric patients with chickenpox is approved for GlaxoSmithKline’s Valtrex®* Caplets.
However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that additional dosing information is not approved for this valacyclovir HCL tablet product.
2.4 Patients With Renal Impairment Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Use in Specific Populations ( 8.5 , 8.6 ), Clinical Pharmacology (12.3) ].
Data are not available for the use of valacyclovir hydrochloride tablets in pediatric patients with a creatinine clearance <50 mL/min/1.73 m2.
Table 1.
Valacyclovir Hydrochloride Tablets Dosage Recommendations for Adults With Renal Impairment Normal Dosage Regimen Creatinine Clearance (mL/min) Indications (Creatinine Clearance ≥ 50 mL/min) 30 to 49 10 to 29 <10 Cold sores (Herpes labialis) Do not exceed 1 day of treatment.
Two 2 gram doses taken 12 hours apart Two 1 gram doses taken 12 hours apart Two 500 mg doses taken 12 hours apart 500 mg single dose Genital herpes: Initial E pisode 1 gram every 12 hours no reduction 1 gram every 24 hours 500 mg every 24 hours Genital herpes: Recurrent episode 500 mg every 12 hours no reduction 500 mg every 24 hours 500 mg every 24 hours Genital herpes: Suppressive therapy Immunocompetent 1 gram every no reduction 500 mg every 500 mg every patients 24 hours 24 hours 24 hours Alternate dose for 500 mg every no reduction 500 mg every 500 mg every immunocompetent 24 hours 48 hours 48 hours patients with ≤ 9 recurrences/year HIV-Infected patients 500 mg every no reduction 500 mg every 500 mg every 12 hours 24 hours 24 hours Herpes zoster 1 gram every 8 hours 1 gram every 12 hours 1 gram every 24 hours 500 mg every 24 hours Hemodialysis: Patients requiring hemodialysis should receive the recommended dose of valacyclovir hydrochloride tablets after hemodialysis.
During hemodialysis, the half-life of acyclovir after administration of valacyclovir hydrochloride tablets is approximately 4 hours.
About one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session.
Peritoneal Dialysis: There is no information specific to administration of valacyclovir hydrochloride tablets in patients receiving peritoneal dialysis.
The effect of chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied.
The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with end-stage renal disease (ESRD) not receiving hemodialysis.
Therefore, supplemental doses of valacyclovir hydrochloride tablets should not be required following CAPD or CAVHD.