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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H20N6O4.ClH.2H2O
Molecular Weight 396.827
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALACYCLOVIR HYDROCHLORIDE DIHYDRATE

SMILES

O.O.Cl.CC(C)[C@H](N)C(=O)OCCOCN1C=NC2=C1N=C(N)NC2=O

InChI

InChIKey=QMVFKSCLPIIINF-CZDIJEQGSA-N
InChI=1S/C13H20N6O4.ClH.2H2O/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20;;;/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20);1H;2*1H2/t8-;;;/m0.../s1

HIDE SMILES / InChI

Molecular Formula C13H20N6O4
Molecular Weight 324.3357
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01682109 | https://www.ncbi.nlm.nih.gov/pubmed/19957998 | https://www.ncbi.nlm.nih.gov/pubmed/7625798 | https://www.ncbi.nlm.nih.gov/pubmed/11454935

Valacyclovir is the hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir. Valacyclovir is a nucleoside analog DNA polymerase inhibitor. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against HSV types 1 (HSV-1) and 2 (HSV-2) and VZV both in cell culture and in vivo. The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analog. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In biochemical assays, acyclovir triphosphate inhibits replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK. The resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of VZV with reduced susceptibility to acyclovir have been recovered from patients with AIDS. Valaciclovir is indicated for the treatment of HSV and VZV infections, including Oral and genital herpes simplex (treatment and prophylaxis), Reduction of HSV transmission from people with recurrent infection to uninfected individuals, Prevention of cytomegalovirus following organ transplantation, Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy). Common adverse drug reactions (≥1% of patients) associated with valaciclovir therapy are the same as for aciclovir, its active metabolite, and include nausea, vomiting, diarrhea, and headache. Infrequent adverse effects (0.1–1% of patients) include agitation, vertigo, confusion, dizziness, edema, arthralgia, sore throat, constipation, abdominal pain, rash, weakness and/or renal impairment. Rare adverse effects (<0.1% of patients) include coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic symptoms, crystalluria, anorexia, fatigue, hepatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis.

CNS Activity

Curator's Comment: Valacyclovir hydrochloride is rapidly converted to acyclovir which was detected in CSF after oral administration of valacyclovir.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZOVIRAX

Approved Use

Oral ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Zoster Infections: ZOVIRAX is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: ZOVIRAX is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: ZOVIRAX is indicated for the treatment of chickenpox (varicella). Injectable ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Simplex Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients. Initial Episodes of Herpes Genitalis: ZOVIRAX for Injection is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immunocompetent patients. Herpes Simplex Encephalitis: ZOVIRAX for Injection is indicated for the treatment of herpessimplex encephalitis. Neonatal Herpes Simplex Virus Infection: ZOVIRAX for Injection is indicated for the treatmentof neonatal herpes infections. Varicella-Zoster Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.

Launch Date

3.86208006E11
Primary
ZOVIRAX

Approved Use

Oral ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Zoster Infections: ZOVIRAX is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: ZOVIRAX is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: ZOVIRAX is indicated for the treatment of chickenpox (varicella). Injectable ZOVIRAX® (acyclovir) is indicated for the treatment: Herpes Simplex Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients. Initial Episodes of Herpes Genitalis: ZOVIRAX for Injection is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immunocompetent patients. Herpes Simplex Encephalitis: ZOVIRAX for Injection is indicated for the treatment of herpessimplex encephalitis. Neonatal Herpes Simplex Virus Infection: ZOVIRAX for Injection is indicated for the treatmentof neonatal herpes infections. Varicella-Zoster Infections in Immunocompromised Patients: ZOVIRAX for Injection is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.

Launch Date

3.86208006E11
Primary
VALTREX

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07896321E12
Primary
VALTREX

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07887683E12
Primary
VALTRE

Approved Use

INDICATIONS AND USAGE. VALTREX is a nucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients Cold Sores (Herpes Labialis), Genital Herpes, Treatment in immunocompetent patients (initial or recurrent episode), Suppression in immunocompetent or HIV-infected patients, Reduction of transmission, Herpes Zoster. Pediatric Patients Cold Sores (Herpes Labialis), Chickenpox Limitations of Use. The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Launch Date

1.07887683E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
599.2 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3015.7 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.9 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACYCLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
79%
ACYCLOVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Atypical Herpes simplex keratitis (HSK) presenting as a perforated corneal ulcer with a large infiltrate in a contact lens wearer: multinucleated giant cells in the Giemsa smear offered a clue to the diagnosis.
2001
A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.
2001
Interventions for herpes simplex virus epithelial keratitis.
2001
Prophylaxis against herpesvirus infections in transplant recipients.
2001
Management of neonatal herpes simplex virus infection.
2001
Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer.
2001
Cough syncope with herpetic tracheobronchitis.
2001 Apr
Rotavirus encephalopathy: pathogenesis reviewed.
2001 Apr
Heart transplantation and the Batista operation for children with refractory heart failure.
2001 Apr
Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year follow up.
2001 Apr
[Peptide transporter family].
2001 Apr
Acyclovir treatment in 2 patients with benign trigeminal sensory neuropathy.
2001 Apr
Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.
2001 Apr
Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killing.
2001 Apr 1
Practice parameter: Steroids, acyclovir, and surgery for Bell's palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
2001 Apr 10
Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.
2001 Apr 13
Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with aciclovir.
2001 Apr 7
Postherpetic neuralgia. Pathogenesis of postherpetic neuralgia should be determined.
2001 Apr 7
[Photoallergy to Zovirax cream].
2001 Feb
Painful skin erosions and fever in an infant. Eczema herpeticum.
2001 Feb
Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella.
2001 Feb
Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.
2001 Feb
Anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)-cycloprop-1'-yl]methyl] x guanine (A-5021) in vitro and in vivo.
2001 Feb
Genetic risks of antiviral nucleoside analogues--a survey.
2001 Feb
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir?
2001 Feb-Mar
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients.
2001 Feb-Mar
Antiviral drugs can inhibit lymphocyte apoptosis induced by cytomegalovirus antigens.
2001 Feb-Mar
Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.
2001 Jan
[Valaciclovir in the treatment of initial infection by genital herpes virus: comparative study].
2001 Jan
Epstein-Barr virus-related lymphoproliferative disease complicating childhood acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow transplantation.
2001 Jan
8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.
2001 Jan
Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder.
2001 Jan 15
Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazol.
2001 Jan-Feb
[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].
2001 Mar
[Benign acute ataxia in an adult with VZV infection].
2001 Mar
A pilot study of treatment of herpes labialis with 1072 nm narrow waveband light.
2001 Mar
[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?].
2001 Mar
A 35-year-old man with recurrent aseptic meningitis.
2001 Mar
Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group.
2001 Mar
Investigation of aciclovir-resistant herpes simplex virus I infection in a bone marrow transplantation unit: genotyping shows that different strains are involved.
2001 Mar
Long-term high-dose acyclovir and AIDS-related non-Hodgkins lymphoma.
2001 Mar 15
The management of varicella-zoster virus exposure and infection in pregnancy and the newborn period. Australasian Subgroup in Paediatric Infectious Diseases of the Australasian Society for Infectious Diseases.
2001 Mar 19
Neurotoxicity of valacyclovir in peritoneal dialysis: a pharmacokinetic study.
2001 Mar-Apr
[Intrauterine herpes simplex virus infection].
2001 Mar-Apr
Coexpression of guanylate kinase with thymidine kinase enhances prodrug cell killing in vitro and suppresses vascular smooth muscle cell proliferation in vivo.
2001 May
Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study.
2001 May
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.
2001 May
Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir.
2001 May
Enhancement of the anti-herpetic effect of trichosanthin by acyclovir and interferon.
2001 May 11
Synthesis and biological evaluation of purine-containing butenolides.
2001 May 24
Patents

Sample Use Guides

Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days. Genital Herpes: Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.
Route of Administration: Other
In Vitro Use Guide
Penciclovir (PCV) and acyclovir are acyclic guanine analogs which inhibit herpes simplex virus (HSV) DNA polymerase. Their 50% infective doses were 0.5 to 0.8 microgram/ml for clinical isolates of HSV-1 and 1.3 to 2.2 micrograms/ml for HSV-2.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:16:14 UTC 2023
Edited
by admin
on Wed Jul 05 23:16:14 UTC 2023
Record UNII
A7JO128919
Record Status Validated (UNII)
Record Version
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Name Type Language
VALACYCLOVIR HYDROCHLORIDE DIHYDRATE
Common Name English
L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, MONOHYDROCHLORIDE, DIHYDRATE
Common Name English
L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, MONOHYDROCHLORIDE DIHYDRATE
Common Name English
L-VALINE, 2-((2-AMINO-1,6-DIHYDRO-6-OXO-9H-PURIN-9-YL)METHOXY)ETHYL ESTER, HYDROCHLORIDE, HYDRATE (1:1:2)
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID90198248
Created by admin on Wed Jul 05 23:16:14 UTC 2023 , Edited by admin on Wed Jul 05 23:16:14 UTC 2023
PRIMARY
CAS
502421-45-6
Created by admin on Wed Jul 05 23:16:14 UTC 2023 , Edited by admin on Wed Jul 05 23:16:14 UTC 2023
PRIMARY
PUBCHEM
135565067
Created by admin on Wed Jul 05 23:16:14 UTC 2023 , Edited by admin on Wed Jul 05 23:16:14 UTC 2023
PRIMARY
SMS_ID
100000183986
Created by admin on Wed Jul 05 23:16:14 UTC 2023 , Edited by admin on Wed Jul 05 23:16:14 UTC 2023
PRIMARY
FDA UNII
A7JO128919
Created by admin on Wed Jul 05 23:16:14 UTC 2023 , Edited by admin on Wed Jul 05 23:16:14 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE