United States - English - NLM (National Library of Medicine)

wockhardt limited - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - 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 c

United States - English - NLM (National Library of Medicine)

aidarex pharmaceuticals llc - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - 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 c

United States - English - NLM (National Library of Medicine)

mckesson corporation dba sky packaginng - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - cold sores (herpes labialis): 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. genital herpes: initial episode: 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. recurrent episodes:  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. suppressive therapy: 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. reduction of transmission:  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 ). herpes zoster: 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. cold sores (herpes labialis): 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. chickenpox: valacyclovir tablets are indicated for the treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years. based on efficacy data from clinical studies with oral acyclovir, treatment with valacyclovir tablets should be initiated within 24 hours after the onset of rash [see clinical studies (14.4)] . 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 with a cd4+ cell count greater than or equal to 100 cells/mm 3 . - patients aged less than 12 years with cold sores (herpes labialis). - patients aged less than 2 years with chickenpox. - patients aged less than 18 years with genital herpes. - patients aged less than 18 years with herpes zoster. - neonates and infants as suppressive therapy following neonatal herpes simplex virus (hsv) infection. 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)] . risk summary 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. clinical considerations disease-associated maternal and/or embryo/fetal risk: 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. data human data: 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. animal data: 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. risk summary 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 hydrochloride 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 hydrochloride and any potential adverse effects on the breastfed child from valacyclovir hydrochloride or from the underlying maternal condition. data following oral administration of a 500 mg dose of valacyclovir hydrochloride to 5 lactating women, peak acyclovir concentrations (c max ) 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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: • aged less than 12 years with cold sores • aged less than 18 years with genital herpes • aged less than 18 years with herpes zoster • aged less than 2 years with chickenpox • for suppressive therapy following neonatal hsv infection. 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 (c max : ↑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 (c max : ↓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 hydrochloride, 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 hydrochloride to patients with renal impairment [see dosage and administration (2.4), warnings and precautions (5.2, 5.3)] .

United States - English - NLM (National Library of Medicine)

blenheim pharmacal, inc. - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 1 g - cold sores (herpes labialis): valacyclovir tablets, usp are indicated for treatment of cold sores (herpes labialis). the efficacy of valacyclovir hydrochloride 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 tablets, usp are indicated for treatment of the initial episode of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir hydrochloride when initiated more than 72 hours after the onset of signs and symptoms has not been established. recurrent episodes: valacyclovir tablets, usp are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir hydrochloride when initiated more than 24 hours after the onset of signs and symptoms has not been established. suppressive therapy: valacyclovir t

United States - English - NLM (National Library of Medicine)

northstar rx llc - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - cold sores (herpes labialis) 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. genital herpes initial episode: 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. recurrent episodes:  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. suppressive therapy: 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. reduction of transmission:  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 ). herpes zoster 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. cold sores (herpes labialis) 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. chickenpox valacyclovir tablets are 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 tablets should be initiated within 24 hours after the onset of rash [see clinical studies (14.4)] . 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 with a cd4+ cell count greater than or equal to 100 cells/mm3 . - patients aged less than 12 years with cold sores (herpes labialis). - patients aged less than 2 years or greater than or equal to 18 years with chickenpox. - patients aged less than 18 years with genital herpes. - patients aged less than 18 years with herpes zoster. - neonates and infants as suppressive therapy following neonatal herpes simplex virus (hsv) infection. 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)] . risk summary 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. clinical considerations disease-associated maternal and/or embryo/fetal risk: 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. data human data: 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. animal data: 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. risk summary 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 hydrochloride 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 hydrochloride and any potential adverse effects on the breastfed child from valacyclovir hydrochloride or from the underlying maternal condition. data following oral administration of a 500 mg dose of valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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: - aged less than 12 years with cold sores - aged less than 18 years with genital herpes - aged less than 18 years with herpes zoster - aged less than 2 years with chickenpox - for suppressive therapy following neonatal hsv infection. 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 hydrochloride, 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 hydrochloride to patients with renal impairment [see dosage and administration (2.4), warnings and precautions (5.2, 5.3)] .

United States - English - NLM (National Library of Medicine)

aurobindo pharma limited - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - cold sores (herpes labialis) 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. genital herpes initial episode: 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. recurrent episodes:  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. suppressive therapy:  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. reduction of transmission:  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 ). herpes zoster 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. cold sores (herpes labialis) 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. chickenpox valacyclovir tablets are 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 tablets should be initiated within 24 hours after the onset of rash [see clinical studies (14.4) ] . 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 with a cd4+ cell count greater than or equal to 100 cells/mm3 . - patients aged less than 12 years with cold sores (herpes labialis). - patients aged less than 2 years or greater than or equal to 18 years with chickenpox. - patients aged less than 18 years with genital herpes. - patients aged less than 18 years with herpes zoster. - neonates and infants as suppressive therapy following neonatal herpes simplex virus (hsv) infection. 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)] . risk summary 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. clinical considerations disease-associated maternal and/or embryo/fetal risk: 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. data human data: 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. animal data: 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. risk summary 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 hydrochloride 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 hydrochloride and any potential adverse effects on the breastfed child from valacyclovir hydrochloride or from the underlying maternal condition. data following oral administration of a 500 mg dose of valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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: - aged less than 12 years with cold sores - aged less than 18 years with genital herpes - aged less than 18 years with herpes zoster - aged less than 2 years with chickenpox - for suppressive therapy following neonatal hsv infection. 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 hydrochloride, 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 hydrochloride to patients with renal impairment [see dosage and administration (2.4), warnings and precautions (5.2, 5.3)] .

United States - English - NLM (National Library of Medicine)

rising pharma holdings, inc. - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - cold sores (herpes labialis) 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. genital herpes initial episode: 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. recurrent episodes:  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. suppressive therapy:   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. reduction of transmission:   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 ). herpes zoster 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. cold sores (herpes labialis) 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. chickenpox valacyclovir tablets are 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 tablets should be initiated within 24 hours after the onset of rash [see clinical studies (14.4)] . 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 with a cd4+ cell count greater than or equal to 100 cells/mm3 . - patients aged less than 12 years with cold sores (herpes labialis). - patients aged less than 2 years or greater than or equal to 18 years with chickenpox. - patients aged less than 18 years with genital herpes. - patients aged less than 18 years with herpes zoster. - neonates and infants as suppressive therapy following neonatal herpes simplex virus (hsv) infection. 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)] . risk summary 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. clinical considerations disease-associated maternal and/or embryo/fetal risk: 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. data human data: 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. animal data: 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. risk summary 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 hydrochloride 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 hydrochloride and any potential adverse effects on the breastfed child from valacyclovir hydrochloride or from the underlying maternal condition. data following oral administration of a 500 mg dose of valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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: - aged less than 12 years with cold sores - aged less than 18 years with genital herpes - aged less than 18 years with herpes zoster - aged less than 2 years with chickenpox - for suppressive therapy following neonatal hsv infection. 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 hydrochloride, 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 hydrochloride to patients with renal impairment [see dosage and administration (2.4), warnings and precautions (5.2, 5.3)] .

United States - English - NLM (National Library of Medicine)

state of florida doh central pharmacy - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - 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 ch

United States - English - NLM (National Library of Medicine)

mylan institutional inc. - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - valacyclovir 500 mg - 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 beyon

United States - English - NLM (National Library of Medicine)

nucare pharmaceuticals,inc. - valacyclovir hydrochloride (unii: g447s0t1vc) (acyclovir - unii:x4hes1o11f) - cold sores (herpes labialis): valacyclovir tablets, usp are indicated for treatment of cold sores (herpes labialis). the efficacy of valacyclovir tablets, usp 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 tablets, usp are indicated for treatment of the initial episode of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir tablets, usp when initiated more than 72 hours after the onset of signs and symptoms has not been established. recurrent episodes: valacyclovir tablets, usp are indicated for treatment of recurrent episodes of genital herpes in immunocompetent adults. the efficacy of treatment with valacyclovir tablets, usp when initiated more than 24 hours after the onset of signs and symptoms has not been established. suppressive therapy: valacyclovir tablets, usp are indicated for chronic suppressive therapy of recurrent episodes of genital her