Valacyclovir
Tablet, Film Coated · Oral
Uses
Valacyclovir tablets are a deoxynucleoside 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-1-infected patients Reduction of transmission Herpes Zoster Pediatric Patients ( 1.2 ) Cold Sores (Herpes Labialis) Chickenpox 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. 1.1 Adult Patients 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, USP 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, USP when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets, USP for treatment of disseminated herpes zoster have not been established. 1.2 Pediatric Patients 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) ] . 1.3 Limitations of Use 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 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.
Dosage and administration
Valacyclovir tablets may be given without regard to meals. Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500 mg valacyclovir tablets for use in pediatric patients for whom a solid dosage form is not appropriate [see Dosage and Administration (2.3) ] . 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 ) 2.1 Adult Dosing Recommendations Cold Sores (Herpes Labialis) The recommended dosage of valacyclovir 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 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 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 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‑1-infected patients with a CD4 + cell count greater than or equal to 100 cells/mm 3 , the recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily. Reduction of Transmission: The recommended dosage of valacyclovir 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 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 tablets for the treatment of cold sores in pediatric patients aged greater than or equal to 12 years is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). Chickenpox The recommended dosage of valacyclovir tablets for treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptom [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) , Clinical Studies (14.4) ] . 2.3 Extemporaneous Preparation of Oral Suspension Ingredients and Preparation per USP-NF Valacyclovir tablets 500 mg, cherry flavor, and Suspension Structured Vehicle USP-NF (SSV). Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) should be prepared in lots of 100 mL. Instructions for Preparing Suspension at Time of Dispensing Prepare SSV according to the USP-NF. Using a pestle and mortar, grind the required number of valacyclovir tablets 500 mg until a fine powder is produced (5 valacyclovir tablets for 25 mg/mL suspension; 10 valacyclovir tablets for 50 mg/mL suspension). Gradually add approximately 5 mL aliquots of SSV to the mortar and triturate the powder until a paste has been produced. Ensure that the powder has been adequately wetted. Continue to add approximately 5 mL aliquots of SSV to the mortar, mixing thoroughly between additions, until a concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL SSV for both the 25 mg/mL and 50 mg/mL suspensions. Transfer the mixture to a suitable 100 mL measuring flask. Transfer the cherry flavor* to the mortar and dissolve in approximately 5 mL of SSV. Once dissolved, add to the measuring flask. Rinse the mortar at least 3 times with approximately 5 mL aliquots of SSV, transferring the rinsing to the measuring flask between additions. Make the suspension to volume (100 mL) with SSV and shake thoroughly to mix. Transfer the suspension to an amber glass medicine bottle with a child-resistant closure. The prepared suspension should be labeled with the following information “Shake well before using. Store suspension between 2°C to 8° C (36°F to 46° F) in a refrigerator. Discard after 28 days.” *The amount of cherry flavor added is as instructed by the suppliers of the cherry flavor. 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 tablets in pediatric patients with a creatinine clearance less than 50 mL/min/1.73 m 2 . Table 1.
Dosage forms and strengths
Tablets: 500 mg: blue colored, capsule-shaped, film-coated tablets, debossed with "RX 904" on one side and plain on the other side. 1 gram: blue colored, capsule-shaped, film-coated tablets, debossed with "RX 905" on one side and partial score bar on both sides. Tablets: 500 mg (unscored), 1 gram (partially scored) (3)
Contraindications
Valacyclovir hydrochloride is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction [e.g., anaphylaxis, severe cutaneous adverse reactions (SCARs)] to valacyclovir, acyclovir, or any component of the formulation [see Warnings and Precautions (5.4) , Adverse Reactions (6.3) ] . Hypersensitivity to valacyclovir (e.g., anaphylaxis), acyclovir, or any component of the formulation. ( 4 )
Warnings and precautions
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): Has occurred in patients with advanced HIV-1 disease and in allogenic bone marrow transplant and renal transplant patients receiving 8 grams per day of valacyclovir hydrochloride 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 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 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 ) Severe cutaneous adverse reactions (SCARs): Including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS) have been reported during the postmarketing experience with valacyclovir. Discontinue valacyclovir hydrochloride immediately if a painful rash with mucosal involvement or a progressive severe rash develops, and closely monitor clinical status. ( 5.4 ) 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-1 disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of valacyclovir hydrochloride at doses of 8 grams per day. Treatment with valacyclovir hydrochloride 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 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 for their level of renal function. Dosage reduction is recommended when administering valacyclovir hydrochloride 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 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 for their level of renal function. Elderly patients are more likely to have central nervous system adverse reactions. Valacyclovir hydrochloride should be discontinued if central nervous system adverse reactions occur [see Adverse Reactions (6.3) , Use in Specific Populations (8.5 , 8.6) ]. 5.4 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported during postmarketing experience with valacyclovir [see Contraindications (4) and Adverse Reactions (6.3) ] . Discontinue valacyclovir hydrochloride immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Closely monitor clinical status and initiate appropriate therapy. Valacyclovir hydrochloride is contraindicated in patients who have developed SCARs with the use of valacyclovir or acyclovir, or any component of the formulation [see Contraindications (4) , Adverse Reactions (6.3) ] .
Side effects
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome [see Warnings and Precautions (5.1) ]. Acute Renal Failure [see Warnings and Precautions (5.2) ] . Central Nervous System Effects [see Warnings and Precautions (5.3) ] . Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.4) ] . The most common adverse reactions reported in at least 1 indication by greater than 10% of adult subjects treated with valacyclovir hydrochloride and observed more frequently with valacyclovir hydrochloride compared with placebo are headache, nausea, and abdominal pain. The only adverse reaction reported in greater than 10% of pediatric subjects aged less than 18 years was headache. The most common adverse reactions reported in at least one indication by greater than 10% of adult subjects treated with valacyclovir hydrochloride and more commonly than in subjects treated with placebo are headache, nausea, and abdominal pain. ( 6.1 ) The only adverse reaction occurring in greater than 10% of pediatric subjects aged less than 18 years was headache. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience in Adult Subjects Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cold Sores (Herpes Labialis) In clinical trials for the treatment of cold sores, the adverse reactions reported by subjects receiving valacyclovir hydrochloride 2 grams twice daily (n = 609) or placebo (n = 609) for 1 day, respectively, included headache (14%, 10%) and dizziness (2%, 1%). The frequencies of abnormal ALT (greater than 2 times ULN) were 1.8% for subjects receiving valacyclovir hydrochloride compared with 0.8% for placebo. Other laboratory abnormalities (hemoglobin, white blood cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies in the 2 groups. Genital Herpes Initial Episode: In a clinical trial for the treatment of initial episodes of genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving valacyclovir hydrochloride 1 gram twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%). For the incidence of laboratory abnormalities see Table 2. Recurrent Episodes: In 3 clinical trials for the episodic treatment of recurrent genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving valacyclovir hydrochloride 500 mg twice daily for 3 days (n = 402), valacyclovir hydrochloride 500 mg twice daily for 5 days (n = 1,136), or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%). For the incidence of laboratory abnormalities see Table 2. Suppressive Therapy: Suppression of Recurrent Genital Herpes in Immunocompetent Adults: In a clinical trial for the suppression of recurrent genital herpes infections, the adverse reactions reported by subjects receiving valacyclovir hydrochloride 1 gram once daily (n = 269), valacyclovir hydrochloride 500 mg once daily (n = 266), or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%, 8%), abdominal pain (11%, 9%, 6%), dysmenorrhea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%). For the incidence of laboratory abnormalities see Table 2. Suppression of Recurrent Genital Herpes in HIV-1 ‑ Infected Subjects: In HIV-1‑infected subjects, frequently reported adverse reactions for valacyclovir hydrochloride (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13%, 8%), fatigue (8%, 5%), and rash (8%, 1%). Post‑randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4%, 2%), elevated ALT (14%, 10%), elevated AST (16%, 11%), decreased neutrophil counts (18%, 10%), and decreased platelet counts (3%, 0%), respectively. Reduction of Transmission: In a clinical trial for the reduction of transmission of genital herpes, the adverse reactions reported by subjects receiving valacyclovir hydrochloride 500 mg once daily (n = 743) or placebo once daily (n = 741), respectively, included headache (29%, 26%), nasopharyngitis (16%, 15%), and upper respiratory tract infection (9%, 10%). Herpes Zoster In 2 clinical trials for the treatment of herpes zoster, the adverse reactions reported by subjects receiving valacyclovir hydrochloride 1 gram 3 times daily for 7 to 14 days (n = 967) or placebo (n = 195), respectively, included nausea (15%, 8%), headache (14%, 12%), vomiting (6%, 3%), dizziness (3%, 2%), and abdominal pain (3%, 2%). For the incidence of laboratory abnormalities see Table 2. Table 2.
Drug interactions
No clinically significant drug-drug or drug-food interactions with valacyclovir hydrochloride are known [see Clinical Pharmacology (12.3) ].
Use in specific populations
8.1 Pregnancy 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. 8.2 Lactation 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 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 clincial need for valacyclovir and any potential adverse effects on the breastfed child from valacyclovir or from the underlying maternal condition. Data Following oral administration of a 500-mg dose of valacyclovir 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 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.
Pregnancy
8.1 Pregnancy 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.
Pediatric use
8.4 Pediatric Use 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.
Geriatric use
8.5 Geriatric Use 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) ] .
Overdosage
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
Valacyclovir hydrochloride, USP is the hydrochloride salt of the L ‑valyl ester of the antiviral drug acyclovir. Valacyclovir tablets, USP are for oral administration. Each film-coated tablet contains 556.2 mg or 1.112 grams of valacyclovir hydrochloride, USP (hydrous) equivalent to 500 mg or 1 gram valacyclovir, respectively, and the inactive ingredients crospovidone, FD&C blue #2/indigo carmine aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, polyethylene glycol 6000, polysorbate 80, povidone, and titanium dioxide. The chemical name of valacyclovir hydrochloride is L -valine, 2-[(2-amino-1,6-dihydro-6-oxo-9 H -purin-9-yl)methoxy]ethyl ester, monohydrochloride. It has the following structural formula: Valacyclovir hydrochloride, USP (hydrous) is a white to off‑white powder with the molecular formula C 13 H 20 N 6 O 4
• HCl and a molecular weight of 360.80. Valacyclovir hydrochloride, USP (hydrous) is soluble in water and insoluble in dichloromethane, the maximum solubility in water at 25° C is 174 mg/mL. The pk a s for valacyclovir hydrochloride are 1.90, 7.47, and 9.43. Meets USP Dissolution Test 2. Valacyclovir Structural formula
Mechanism of action
12.1 Mechanism of Action Valacyclovir is an antiviral drug active against α-herpes viruses [see Microbiology (12.4) ].
How supplied
Valacyclovir tablets, USP (blue colored, capsule-shaped, film-coated tablets) containing 556.2 mg of valacyclovir hydrochloride, USP (hydrous) equivalent to 500 mg valacyclovir and debossed with "RX 904" on one side and plain on the other side. NDC 63304-904-03 Bottles of 10 NDC 63304-904-30 Bottles of 30 NDC 63304-904-90 Bottles of 90 NDC 63304-904-05 Bottles of 500 NDC 63304-904-77 Blister pack of 100 Valacyclovir tablets, USP (blue colored, capsule-shaped, film-coated tablets) containing 1.112 grams of valacyclovir hydrochloride, USP (hydrous) equivalent to 1 gram valacyclovir and debossed with "RX 905" on one side and partial score bar on both sides. NDC 63304-905-03 Bottles of 10 NDC 63304-905-30 Bottles of 30 NDC 63304-905-90 Bottles of 90 NDC 63304-905-05 Bottles of 500 NDC 63304-905-77 Blister pack of 100 Storage: Store at 20° C to 25° C (68° F to 77° F) [See USP Controlled Room Temperature]. Dispense in a well-closed container as defined in the USP.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Severe Cutaneous Adverse Reactions Inform patients that severe skin reactions including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and erythema multiforme (EM) have been reported with valacyclovir. Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking valacyclovir tablets and seek medical attention if a painful rash with mucosal involvement develops [see Contraindications (4), Warnings and Precautions (5.4), Adverse Reactions (6.3)] . Importance of Adequate Hydration Patients should be advised to maintain adequate hydration. Missed Dose Instruct patients that if they miss a dose of valacyclovir tablets, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose. Cold Sores (Herpes Labialis) Patients should be advised to initiate treatment at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). There are no data on the effectiveness of treatment initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer). Patients should be instructed that treatment for cold sores should not exceed 1 day (2 doses) and that their doses should be taken about 12 hours apart. Patients should be informed that valacyclovir tablets are not a cure for cold sores. Genital Herpes Patients should be informed that valacyclovir tablets are not a cure for genital herpes. Because genital herpes is a sexually transmitted disease, patients should avoid contact with lesions or intercourse when lesions and/or symptoms are present to avoid infecting partners. Genital herpes is frequently transmitted in the absence of symptoms through asymptomatic viral shedding. Therefore, patients should be counseled to use safer sex practices in combination with suppressive therapy with valacyclovir tablets. Sex partners of infected persons should be advised that they might be infected even if they have no symptoms. Type‑specific serologic testing of asymptomatic partners of persons with genital herpes can determine whether risk for HSV‑2 acquisition exists. Valacyclovir tablets have not been shown to reduce transmission of sexually transmitted infections other than HSV‑2. If medical management of a genital herpes recurrence is indicated, patients should be advised to initiate therapy at the first sign or symptom of an episode. There are no data on the effectiveness of treatment initiated more than 72 hours after the onset of signs and symptoms of a first episode of genital herpes or more than 24 hours after the onset of signs and symptoms of a recurrent episode. There are no data on the safety or effectiveness of chronic suppressive therapy of more than 1 year’s duration in otherwise healthy patients. There are no data on the safety or effectiveness of chronic suppressive therapy of more than 6 months’ duration in HIV‑1-infected patients. Herpes Zoster There are no data on treatment initiated more than 72 hours after onset of the zoster rash. Patients should be advised to initiate treatment as soon as possible after a diagnosis of herpes zoster. Chickenpox Patients should be advised to initiate treatment at the earliest sign or symptom of chickenpox. Manufactured by:Ohm Laboratories Inc.New Brunswick, NJ 08901 Distributed by: Sun Pharmaceutical Industries, Inc.Cranbury, NJ 08512 November 2025 FDA-18
Label text from the FDA structured product label by SUN PHARMACEUTICAL INDUSTRIES, INC. (revised Jun 4, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Valacyclovir Hydrochloride in 52 products
Valacyclovir NDC products (52)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-2510 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-2575 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-6581 | Valacyclovir Hydrochloride 500 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-7270 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-7484 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-7702 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 53401-031 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71335-2534 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-2566 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-0630 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 31722-705 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-704 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 62135-613 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Chartwell RX, LLC | ANDA |
| 62135-614 | Valacyclovir Hydrochloride 1 g/1 Tablet | Chartwell RX, LLC | ANDA |
| 67046-1071 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Coupler LLC | ANDA |
| 67046-1347 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Coupler LLC | ANDA |
| 72189-594 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Direct _Rx | ANDA |
| 61919-066 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Direct Rx | ANDA |
| 72189-630 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Direct_Rx | ANDA |
| 51407-108 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Golden State Medical Supply, Inc. | ANDA |
| 51407-107 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Golden State Medical Supply, Inc. | ANDA |
| 68071-3749 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals, Inc. | ANDA |
| 68071-3747 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals, Inc. | ANDA |
| 68071-4805 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-3624 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 72789-452 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 43063-771 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 72789-586 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 68788-4105 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-8705 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-7587 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Preferred Pharmaceuticals, Inc. | ANDA |
| 82804-212 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 82804-009 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Proficient Rx LP | ANDA |
| 82804-006 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Proficient Rx LP | ANDA |
| 63187-950 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 82009-040 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | Quallent Pharmaceuticals Health LLC | ANDA |
| 82009-041 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | Quallent Pharmaceuticals Health LLC | ANDA |
| 67296-2146 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Redpharm Drug | ANDA |
| 70518-4661 | Valacyclovir Hydrochloride 500 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 70518-4417 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 70518-4100 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 70518-2402 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 85766-270 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Sportpharm LLC | ANDA |
| 85766-271 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Sportpharm LLC | ANDA |
| 60760-469 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | St Mary's Medical Park Pharmacy | ANDA |
| 60760-856 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | St. Mary's Medical Park Pharmacy | ANDA |
| 63304-904 | Valacyclovir Hydrochloride 500 mg/1 Tablet, Film Coated | SUN PHARMACEUTICAL INDUSTRIES, INC. | ANDA |
| 63304-905 | Valacyclovir Hydrochloride 1 g/1 Tablet, Film Coated | SUN PHARMACEUTICAL INDUSTRIES, INC. | ANDA |
| 69367-263 | Valacyclovir Hydrochloride 1000 mg/1 Tablet | Westminster Pharmaceuticals, LLC | ANDA |
| 69367-262 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Westminster Pharmaceuticals, LLC | ANDA |
| 69117-0011 | Valacyclovir Hydrochloride 1 g/1 Tablet | Yiling Pharmaceutical, Inc. | ANDA |
| 69117-0010 | Valacyclovir Hydrochloride 500 mg/1 Tablet | Yiling Pharmaceutical, Inc. | ANDA |
Valacyclovir recalls
- D-0602-2018 Mar 21, 2018 · Class II · Terminated
Temperature Abuse: Valganciclovir Tablets USP 450 mg and Valacyclovir Tablets USP 1 gram were exposed to higher temperature at airport or cargo and in the same consignment of Famciclovir complaint batch (D-0415-2018).
Frequently asked questions
What is Valacyclovir used for?
Valacyclovir tablets are a deoxynucleoside 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-1-infected patients Reduction of transmission Herpes Zoster Pediatric Patients ( 1.2 ) Cold Sores (Herpes Labialis) Chickenpox…
What are the side effects of Valacyclovir?
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome [see Warnings and Precautions (5.1) ]. Acute Renal Failure [see Warnings and Precautions (5.2) ] . Central Nervous System Effects [see Warnings and Precautions (5.3) ] . Severe Cutaneous Adverse Reactions [see Warnings and… See the full label for the complete list.
Who makes Valacyclovir?
Valacyclovir is listed by 25 labelers in the FDA NDC directory, including A-S Medication Solutions, Aphena Pharma Solutions - Tennessee, LLC, Bryant Ranch Prepack, Camber Pharmaceuticals, Inc..
Has Valacyclovir been recalled?
The FDA enforcement database lists 1 recall for Valacyclovir, most recently D-0602-2018 (class ii): Temperature Abuse: Valganciclovir Tablets USP 450 mg and Valacyclovir Tablets USP 1 gram were exposed to higher temperature at airport or cargo and in the…