VALACYCLOVIR HYDROCHLORIDE- valacyclovir tablet, film coated

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

VALACYCLOVIR HYDROCHLORIDE (UNII: G447S0T1VC) (ACYCLOVIR - UNII:X4HES1O11F)

Tilgjengelig fra:

Mylan Pharmaceuticals Inc.

INN (International Name):

VALACYCLOVIR HYDROCHLORIDE

Sammensetning:

VALACYCLOVIR 500 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Valacyclovir tablets are indicated for treatment of cold sores (herpes labialis). The efficacy of valacyclovir tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. Valacyclovir tablets are indicated for treatment of the initial episode of genital herpes in immunocompetent adults. The efficacy of treatment with valacyclovir tablets when initiated more than 72 hours after the onset of signs and symptoms has not been established. Valacyclovir tablets are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults. The efficacy of treatment with valacyclovir tablets when initiated more than 24 hours after the onset of signs and symptoms has not been established. Valacyclovir tablets are indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-1–infected adults. The efficacy and safety of valacyclovir tablets for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-1–infected patients have not been established. Valacyclovir tablets are indicated for the reduction of transmission of genital herpes in immunocompetent adults. The efficacy of valacyclovir tablets for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established. The efficacy of valacyclovir 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 ). Valacyclovir tablets are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults. The efficacy of valacyclovir tablets when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets for treatment of disseminated herpes zoster have not been established. Valacyclovir tablets are indicated for the treatment of cold sores (herpes labialis) in pediatric patients aged greater than or equal to 12 years. The efficacy of valacyclovir tablets initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. Valacyclovir is indicated for the treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years. Based on efficacy data from clinical trials with oral acyclovir, treatment with valacyclovir should be initiated within 24 hours after the onset of rash [see Clinical Studies (14.4)]. The efficacy and safety of valacyclovir have not been established in: Valacyclovir tablets are contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valacyclovir, acyclovir, or any component of the formulation [see Adverse Reactions (6.3)] . Clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, have not identified a drug associated risk of major birth defects. There are insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes (see Data) . There are risks to the fetus associated with untreated herpes simplex during pregnancy (see Clinical Considerations). In animal reproduction studies, no evidence of adverse developmental outcomes was observed with valacyclovir when administered to pregnant rats and rabbits at system exposures (AUC) 4 (rats) and 7 (rabbits) times the human exposure at the maximum recommended human dose (MRHD) (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The risk of neonatal HSV infection varies from 30% to 50% for genital HSV acquired in late pregnancy (third trimester), whereas with HSV acquisition in early pregnancy, the risk of neonatal infection is about 1%. A primary herpes occurrence during the first trimester of pregnancy has been associated with neonatal chorioretinitis, microcephaly, and, in rare cases, skin lesions. In very rare cases, transplacental transmission can occur resulting in congenital infection, including microcephaly, hepatosplenomegaly, intrauterine growth restriction, and stillbirth. Co-infection with HSV increases the risk of perinatal HIV transmission in women who had a clinical diagnosis of genital herpes during pregnancy. Clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, based on published literature, have not identified a drug-associated risk of major birth defects. There are insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes. The Acyclovir and the Valacyclovir Pregnancy Registries, both population-based international prospective studies, collected pregnancy data through April 1999. The Acyclovir Registry documented outcomes of 1,246 infants and fetuses exposed to acyclovir during pregnancy (756 with earliest exposure during the first trimester, 197 during the second trimester, 291 during the third trimester, and 2 unknown). The occurrence of major birth defects during first-trimester exposure to acyclovir was 3.2% (95% CI: 2.0% to 5.0%) and during any trimester of exposure was 2.6% (95% CI: 1.8% to 3.8%). The Valacyclovir Pregnancy Registry documented outcomes of 111 infants and fetuses exposed to valacyclovir during pregnancy (28 with earliest exposure in the first trimester, 31 during the second trimester, and 52 during the third trimester).The occurrence of major birth defects during first-trimester exposure to valacyclovir was 4.5% (95% CI: 0.24% to 24.9%) and during any trimester of exposure was 3.9% (95% CI: 1.3% to 10.7%). Available studies have methodological limitations including insufficient sample size to support conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Valacyclovir was administered orally to pregnant rats and rabbits (up to 400 mg/kg/day) during organogenesis (Gestation Days 6 through 15, and 6 through 18, respectively). No adverse embryo-fetal effects were observed in rats and rabbits at acyclovir exposures (AUC) of up to approximately 4 (rats) and 7 (rabbits) times the exposure in humans at the MRHD. Early embryo death, fetal growth retardation (weight and length), and variations in fetal skeletal development (primarily extra ribs and delayed ossification of sternebrae) were observed in rats and associated with maternal toxicity (200 mg/kg/day; approximately 6 times higher than human exposure at the MRHD). In a pre/postnatal development study, valacyclovir was administered orally to pregnant rats (up to 200 mg/kg/day from Gestation Day 15 to Post-Partum Day 20) from late gestation through lactation. No significant adverse effects were observed in offspring exposed daily from before birth through lactation at maternal exposures (AUC) of approximately 6 times higher than human exposures at the MRHD. Although there is no information on the presence of valacyclovir in human milk, its metabolite, acyclovir, is present in human milk following oral administration of valacyclovir. Based on published data, a 500-mg maternal dose of valacyclovir tablets twice daily would provide a breastfed child with an oral acyclovir dosage of approximately 0.6 mg/kg/day (see Data) . There is no data on the effects of valacyclovir or acyclovir on the breastfed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for valacyclovir tablets and any potential adverse effects on the breastfed child from valacyclovir or from the underlying maternal condition. Following oral administration of a 500-mg dose of valacyclovir tablets to 5 lactating women, 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 dose of valacyclovir tablets twice daily would provide a breastfed child with an oral acyclovir dosage of approximately 0.6 mg/kg/day. Unchanged valacyclovir was not detected in maternal serum, breast milk or infant urine. Valacyclovir is indicated for treatment of cold sores in pediatric patients aged greater than or equal to 12 years and for treatment of chickenpox in pediatric patients aged 2 to less than 18 years [see Indications and Usage (1.2), Dosage and Administration (2.2)] . The use of valacyclovir tablets for treatment of cold sores is based on 2 double-blind, placebo-controlled clinical trials in healthy adults and adolescents (aged greater than or equal to 12 years) with a history of recurrent cold sores [see Clinical Studies (14.1)] . The use of valacyclovir for treatment of chickenpox in pediatric patients 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 efficacy and safety data from 3 randomized, double-blind, placebo-controlled trials evaluating oral acyclovir in pediatric subjects with chickenpox [see Dosage and Administration (2.2), Adverse Reactions (6.2), Clinical Pharmacology (12.3), Clinical Studies (14.4)] . The efficacy and safety of valacyclovir have not been established in pediatric patients: The pharmacokinetic profile and safety of valacyclovir oral suspension in children aged less than 12 years were studied in 3 open-label trials. No efficacy evaluations were conducted in any of the 3 trials. Trial 1 was a single-dose pharmacokinetic, multiple-dose safety trial in 27 pediatric subjects aged 1 to less than 12 years with clinically suspected varicella-zoster virus (VZV) infection [see Dosage and Administration (2.2), Adverse Reactions (6.2), Clinical Pharmacology (12.3), Clinical Studies (14.4)] . Trial 2 was a single-dose pharmacokinetic and safety trial in pediatric subjects aged 1 month to less than 6 years who had an active herpes virus infection or who were at risk for herpes virus infection. Fifty-seven subjects were enrolled and received a single dose of 25 mg/kg valacyclovir oral suspension. In infants and children aged 3 months to less than 6 years, this dose provided comparable systemic acyclovir exposures to that from a 1-gram dose of valacyclovir in adults (historical data). In infants aged 1 month to less than 3 months, 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. Acyclovir is not approved for suppressive therapy in infants and children following neonatal HSV infections; therefore, valacyclovir is not recommended for this indication because efficacy cannot be extrapolated from acyclovir. Trial 3 was a single-dose pharmacokinetic, multiple-dose safety trial in 28 pediatric subjects aged 1 to less than 12 years with clinically suspected HSV infection. None of the subjects enrolled in this trial had genital herpes. Each subject was dosed with valacyclovir oral suspension 10 mg/kg twice daily for 3 to 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 recurrent genital herpes. The mean projected daily acyclovir systemic exposures in pediatric subjects across all age-groups (1 to less than 12 years) were lower (Cmax : ↓ 20%, AUC: ↓ 33%) compared with the acyclovir systemic exposures in adults receiving valacyclovir 500 mg twice daily but were higher (daily AUC: ↑ 16%) than systemic exposures in adults receiving acyclovir 200 mg 5 times daily. Insufficient data are available to support valacyclovir for the treatment of recurrent genital herpes in this age-group because clinical information on recurrent genital herpes in young children is limited; therefore, extrapolating efficacy data from adults to this population is not possible. Moreover, valacyclovir has not been studied in children aged 1 to less than 12 years with recurrent genital herpes. Of the total number of subjects in clinical trials of valacyclovir tablets, 906 were 65 and over, and 352 were 75 and over. In a clinical trial of herpes zoster, the duration of pain after healing (post-herpetic neuralgia) was longer in subjects 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 reduction is recommended when administering valacyclovir tablets to patients with renal impairment [see Dosage and Administration (2.4), Warnings and Precautions (5.2, 5.3)].

Produkt oppsummering:

Valacyclovir Tablets, USP are available containing 556.2 mg or 1.112 grams of valacyclovir hydrochloride, USP (hydrous), which are equivalent to 500 mg or 1 gram of valacyclovir, on the anhydrous basis, 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 0378-4276-77 bottles 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.

Autorisasjon status:

Abbreviated New Drug Application

Preparatomtale

VALACYCLOVIR HYDROCHLORIDE- VALACYCLOVIR TABLET, FILM COATED
MYLAN PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
VALACYCLOVIR TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
VALACYCLOVIR TABLETS.
VALACYCLOVIR TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1995
INDICATIONS AND USAGE
Valacyclovir tablets are a deoxynucleoside analogue DNA polymerase
inhibitor indicated for:
Adult Patients (1.1)
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•
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Pediatric Patients (1.2)
•
•
Limitations of Use (1.3)
The efficacy and safety of valacyclovir tablets have not been
established in immunocompromised patients
other than for the suppression of genital herpes in HIV-1–infected
patients.
DOSAGE AND ADMINISTRATION
ADULT DOSAGE (2.1)
Cold Sores
2 grams every 12 hours for 1 day
Genital Herpes
Initial episode
1 gram twice daily for 10 days
Recurrent episodes
500 mg twice daily for 3 days
Suppressive therapy
Immunocompetent patients
1 gram once daily
Alternate dose in patients with less than or
equal to 9 recurrences/year
500 mg once daily
HIV-1–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 (aged greater than or equal to 12
years)
2 grams every 12 hours for 1 day
Chickenpox (aged 2 to less than 18 years)
20 mg/kg 3 times daily for 5 days; not to exceed 1
gram 3 times daily
Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) can be prepared
from the 500 mg valacyclovir
tablets. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 500 mg (unscored), 1 gram (partial break line) (3)
CONTRAINDICATIONS
Hypersensitivity to valacyclovir (e.g., anaphylaxis), acyclovir, or
any component of the formulation. (4)
WARNINGS AND PRECAUTIONS
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ADVERSE REACTIONS
Cold Sores (Herpes Labialis)
Genital Herpes
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Treatment in immunocompetent patients (initial or recurrent episode)
Suppression in immunocompetent or HIV-1–infected patients
Reduction of trans