Valacyclovir Hydrochloride
Generic: VALACYCLOVIR HYDROCHLORIDE
Basic Information
Manufacturer
ST. MARY'S MEDICAL PARK PHARMACY
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
275c0198-10a5-139e-e063-6394a90a72be
Indications & Usage
1 INDICATIONS AND USAGE Valacyclovir hydrochloride is 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 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.
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.
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 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.
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.
Adverse Reactions
6 ADVERSE REACTIONS 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) ] .
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 Rising Health, LLC at 1-833-395-6928 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 x 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.
Incidence (%) of Laboratory Abnormalities in Herpes Zoster and Genital Herpes Trial Populations a Data were not collected prospectively.
LLN = Lower limit of normal.
ULN = Upper limit of normal.
Herpes Zoster Genital Herpes Treatment Genital Herpes Suppression Laboratory Abnormality Valacyclovir Hydro- chloride 1 gram 3 Times Daily (n = 967) Placebo (n = 195) Valacyclovir Hydro- chloride 1 gram Twice Daily (n = 1,194) Valacyclovir Hydro-chloride 500 mg Twice Daily (n = 1,159) Placebo (n = 439) Valacyclovir Hydro-chloride 1 gram Once Daily (n = 269) Valacyclovir Hydro-chloride 500 mg Once Daily (n = 266) Placebo (n = 134) Hemoglobin (<0.8 x LLN) 0.8% 0% 0.3% 0.2% 0% 0% 0.8% 0.8% White blood cells (<0.75 x LLN) 1.3% 0.6% 0.7% 0.6% 0.2% 0.7% 0.8% 1.5% Platelet count (<100,000/mm 3 ) 1% 1.2% 0.3% 0.1% 0.7% 0.4% 1.1% 1.5% AST (SGOT) (>2 x ULN) 1% 0% 1% a 0.5% 4.1% 3.8% 3% Serum creatinine (>1.5 x ULN) 0.2% 0% 0.7% 0% 0% 0% 0% 0% 6.2 Clinical Trials Experience in Pediatric Subjects The safety profile of valacyclovir hydrochloride has been studied in 177 pediatric subjects aged 1 month to less than 18 years.
Sixty-five of these pediatric subjects, aged 12 to less than 18 years, received oral tablets for 1 to 2 days for treatment of cold sores.
The remaining 112 pediatric subjects, aged 1 month to less than 12 years, participated in 3 pharmacokinetic and safety trials and received valacyclovir oral suspension.
Fifty-one of these 112 pediatric subjects received oral suspension for 3 to 6 days.
The frequency, intensity, and nature of clinical adverse reactions and laboratory abnormalities were similar to those seen in adults.
Pediatric Subjects Aged 12 to Less than 18 Years (Cold Sores) In clinical trials for the treatment of cold sores, the adverse reactions reported by adolescent subjects receiving valacyclovir hydrochloride 2 grams twice daily for 1 day, or valacyclovir hydrochloride 2 grams twice daily for 1 day followed by 1 gram twice daily for 1 day (n = 65, across both dosing groups), or placebo (n = 30), respectively, included headache (17%, 3%) and nausea (8%, 0%).
Pediatric Subjects Aged 1 Month to Less than 12 Years Adverse events reported in more than 1 subject across the 3 pharmacokinetic and safety trials in children aged 1 month to less than 12 years were diarrhea (5%), pyrexia (4%), dehydration (2%), herpes simplex (2%), and rhinorrhea (2%).
No clinically meaningful changes in laboratory values were observed.
6.3 Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of valacyclovir hydrochloride.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to valacyclovir hydrochloride.
General Facial edema, hypertension, tachycardia.
Allergic Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria [see Contraindications (4) ] .
Central Nervous System (CNS) Symptoms Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5 , 8.6) ] .
Eye Visual abnormalities.
Gastrointestinal Diarrhea.
Hepatobiliary Tract and Pancreas Liver enzyme abnormalities, hepatitis.
Renal Renal failure, renal pain (may be associated with renal failure) [see Warnings and Precautions (5.2) , Use in Specific Populations (8.5 , 8.6) ] .
Hematologic Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS [see Warnings and Precautions (5.1) ] .
Skin Erythema multiforme, rashes including photosensitivity, alopecia.
Acute Renal Failure [see Warnings and Precautions (5.2) ] .
Central Nervous System Effects [see Warnings and Precautions (5.3) ] .
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 Rising Health, LLC at 1-833-395-6928 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 x 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.
Incidence (%) of Laboratory Abnormalities in Herpes Zoster and Genital Herpes Trial Populations a Data were not collected prospectively.
LLN = Lower limit of normal.
ULN = Upper limit of normal.
Herpes Zoster Genital Herpes Treatment Genital Herpes Suppression Laboratory Abnormality Valacyclovir Hydro- chloride 1 gram 3 Times Daily (n = 967) Placebo (n = 195) Valacyclovir Hydro- chloride 1 gram Twice Daily (n = 1,194) Valacyclovir Hydro-chloride 500 mg Twice Daily (n = 1,159) Placebo (n = 439) Valacyclovir Hydro-chloride 1 gram Once Daily (n = 269) Valacyclovir Hydro-chloride 500 mg Once Daily (n = 266) Placebo (n = 134) Hemoglobin (<0.8 x LLN) 0.8% 0% 0.3% 0.2% 0% 0% 0.8% 0.8% White blood cells (<0.75 x LLN) 1.3% 0.6% 0.7% 0.6% 0.2% 0.7% 0.8% 1.5% Platelet count (<100,000/mm 3 ) 1% 1.2% 0.3% 0.1% 0.7% 0.4% 1.1% 1.5% AST (SGOT) (>2 x ULN) 1% 0% 1% a 0.5% 4.1% 3.8% 3% Serum creatinine (>1.5 x ULN) 0.2% 0% 0.7% 0% 0% 0% 0% 0% 6.2 Clinical Trials Experience in Pediatric Subjects The safety profile of valacyclovir hydrochloride has been studied in 177 pediatric subjects aged 1 month to less than 18 years.
Sixty-five of these pediatric subjects, aged 12 to less than 18 years, received oral tablets for 1 to 2 days for treatment of cold sores.
The remaining 112 pediatric subjects, aged 1 month to less than 12 years, participated in 3 pharmacokinetic and safety trials and received valacyclovir oral suspension.
Fifty-one of these 112 pediatric subjects received oral suspension for 3 to 6 days.
The frequency, intensity, and nature of clinical adverse reactions and laboratory abnormalities were similar to those seen in adults.
Pediatric Subjects Aged 12 to Less than 18 Years (Cold Sores) In clinical trials for the treatment of cold sores, the adverse reactions reported by adolescent subjects receiving valacyclovir hydrochloride 2 grams twice daily for 1 day, or valacyclovir hydrochloride 2 grams twice daily for 1 day followed by 1 gram twice daily for 1 day (n = 65, across both dosing groups), or placebo (n = 30), respectively, included headache (17%, 3%) and nausea (8%, 0%).
Pediatric Subjects Aged 1 Month to Less than 12 Years Adverse events reported in more than 1 subject across the 3 pharmacokinetic and safety trials in children aged 1 month to less than 12 years were diarrhea (5%), pyrexia (4%), dehydration (2%), herpes simplex (2%), and rhinorrhea (2%).
No clinically meaningful changes in laboratory values were observed.
6.3 Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of valacyclovir hydrochloride.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to valacyclovir hydrochloride.
General Facial edema, hypertension, tachycardia.
Allergic Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria [see Contraindications (4) ] .
Central Nervous System (CNS) Symptoms Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5 , 8.6) ] .
Eye Visual abnormalities.
Gastrointestinal Diarrhea.
Hepatobiliary Tract and Pancreas Liver enzyme abnormalities, hepatitis.
Renal Renal failure, renal pain (may be associated with renal failure) [see Warnings and Precautions (5.2) , Use in Specific Populations (8.5 , 8.6) ] .
Hematologic Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS [see Warnings and Precautions (5.1) ] .
Skin Erythema multiforme, rashes including photosensitivity, alopecia.