Description

Simple

A medication used to treat cold sores and genital herpes.

Clinical

An guanine nucleoside antiviral used to treat herpes exacerbations.

Overview

Valaciclovir (valacyclovir), also known as _Valtrex_, is an antiviral drug that has been used to manage and treat various herpes infections for more than 2 decades. It was initially approved by the FDA in 1995 [FDA label] and marketed by GlaxoSmithKline [8]. Valacyclovir is the L-valine ester of aciclovir. It is a member of the purine (guanine) nucleoside analog drug class [9]. This class of drugs forms an important part of hepatitis, HIV, and cytomegalovirus drug regimens [4].

One major use of valacyclovir is the treatment of genital herpes episodes or outbreaks. Genital herpes is a frequently diagnosed sexually transmitted disease which currently affects more than 400 million individuals worldwide. It is caused by infection with the herpes simplex virus (HSV). Infection with this virus is lifelong with periodic episodes of reactivation [5].

Pharmacology

Indication

Valacyclovir is a nucleoside analog DNA polymerase inhibitor indicated for [FDA label]:

**Adults**

• Cold Sores (Herpes Labialis)

• Genital Herpes

• Treatment of genital herpes lesions in immunocompetent patients (initial or recurrent episode)

• Suppression of genital herpes lesions... Read more

Pharmacodynamic

**Antiviral effects**

Valacyclovir shows varying levels of inhibition towards herpes simplex virus types 1 (HSV-1), 2 (HSV-2), Varicella Zoster Virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The quantitative relationship between the cell culture susceptibility of herpesviruses... Read more

Mechanism of action

Valacyclovir is the L-valine ester of aciclovir. It is classified as a nucleoside analog DNA polymerase enzyme inhibitor. Aciclovir is a purine (guanine) nucleoside analog is a metabolite that heavily contributes to the pharmacological actions of valacyclovir. In fact, most of valacyclovir's activit... Read more

Absorption

After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal (GI) tract and converted to acyclovir and L-valine. The absolute bioavailability of acyclovir after administration of valacyclovir was measured at 54.5% ± 9.1% after the administration of a 1 gram ora... Read more

Protein binding

The binding of valacyclovir to human plasma proteins is low and ranges from 13.5% to 17.9% [FDA label].

Volume of distribution

Cerebrospinal fluid (CSF) penetration, determined by CSF/plasma AUC ratio, is approximately 25% for aciclovir and the metabolite _8-hydroxy-aciclovir_ (8-OH-ACV), and approximately 2.5% for the metabolite _9-(carboxymethoxy)methylguanine_ [ Read more

Clearance

Renal clearance of acyclovir following the administration of a single 1 gram dose of valacylcovir to 12 healthy437 volunteers was approximately 255 ± 86 mL/min, which represents 42% of total acyclovir apparent plasma clearance [FDA label].

Half life

The plasma elimination half-life of acyclovir typically averaged 2.5 to 3.3 hours in several studies of valacyclovir in volunteers with normal renal function [FDA label].

Route of elimination

After oral administration of a single 1 gram dose of radiolabeled valacyclovir to 4 healthy subjects, 46% and 47% of administered radioactivity was measured in urine and feces, respectively, over 96 hours. Acyclovir accounted for 89% of the radioactivity excreted in the urine [FDA label].

Toxicity

**LD50 Oral**

Rat – 903.5 mg/kg [10]

**Carcinogenesis, Mutagenesis, Impairment of Fertility**

Valacyclovir was noncarcinogenic in lifetime carcinogenicity assays at single daily gavage dose... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Headache US
  • adult
  • Kind: experimental
    • Percent: 35-38%
  • Kind: placebo
    • Percent: 34%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 29%
  • Kind: placebo
    • Percent: 26%
  • Clinical Trial
    Decreased neutrophil counts US
    • adult
  • Kind: experimental
    • Percent: 18%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Headache US
    • adolescent
  • Kind: experimental
    • Percent: 17%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 11-16%
  • Kind: placebo
    • Percent: 14%
  • Clinical Trial
    Nasopharyngitis US
    • adult
  • Kind: experimental
    • Percent: 16%
  • Kind: placebo
    • Percent: 15%
  • Clinical Trial
    Elevated AST US
    • adult
  • Kind: experimental
    • Percent: 16%
  • Kind: placebo
    • Percent: 11%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 12%
  • Clinical Trial
    Elevated ALT US
    • adult
  • Kind: experimental
    • Percent: 14%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 13%
  • Kind: comparator
    • Percent: 10%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 13%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 11%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Abdominal Pain US
    • adult
  • Kind: experimental
    • Percent: 9-11%
  • Kind: placebo
    • Percent: 6%
  • Clinical Trial
    Upper Respiratory Tract Infection US
    • adult
  • Kind: experimental
    • Percent: 9%
  • Kind: placebo
    • Percent: 10%
  • Clinical Trial
    Dysmenorrhea US
    • adult
  • Kind: experimental
    • Percent: 5-8%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Nausea US
    • adolescent
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Fatigue US
    • adult
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Rash US
    • adult
  • Kind: experimental
    • Percent: 8%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Depression US
    • adult
  • Kind: experimental
    • Percent: 5-7%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Arthralgia US
    • adult
  • Kind: experimental
    • Percent: 5-6%
  • Kind: placebo
    • Percent: 4%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 6%
  • Kind: comparator
    • Percent: 6%
  • Clinical Trial
    Vomiting US
    • adult
  • Kind: experimental
    • Percent: 6%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 4-5%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Diarrhea US
    • pediatric
  • Kind: experimental
    • Percent: 5%
  • Clinical Trial
    Dizziness US
    • adult
  • Kind: experimental
    • Percent: 2-4%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Pyrexia US
    • pediatric
  • Kind: experimental
    • Percent: 4%
  • Clinical Trial
    Elevated AST/SGOT levels US
    • adult
  • Kind: experimental
    • Percent: 4%
  • Kind: placebo
    • Percent: 3%
  • Clinical Trial
    Vomiting US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Dizziness US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Abdominal Pain US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Decreased platelet counts US
    • adult
  • Kind: experimental
    • Percent: 3%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Decrease in white blood cells count US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Abnormal ALT US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Dizziness US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Rhinorrhea US
    • pediatric
  • Kind: experimental
    • Percent: 2%
  • Clinical Trial
    Dehydration US
    • pediatric
  • Kind: experimental
    • Percent: 2%
  • Clinical Trial
    Herpes Simplex US
    • pediatric
  • Kind: experimental
    • Percent: 2%
  • Clinical Trial
    Decrease in platelet count US
    • adult
  • Kind: experimental
    • Percent: ≤1%
  • Kind: placebo
    • Percent: 2%
  • Clinical Trial
    Decreased hemoglobin levels US
    • adult
  • Kind: experimental
    • Percent: ≤1%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Decrease in white blood cells count US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: <1%
  • Clinical Trial
    Elevated serum creatinine US
    • adult
  • Kind: experimental
    • Percent: <1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Decreased hemoglobin levels US
    • adult
  • Kind: experimental
    • Percent: <1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Elevated AST/SGOT levels US
    • adult
  • Kind: experimental
    • Percent: ≤1%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Decrease in platelet count US
    • adult
  • Kind: experimental
    • Percent: <1%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Elevated AST/SGOT levels US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Elevated serum creatinine US
    • adult
  • Kind: experimental
    • Percent: <1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Decreased hemoglobin levels US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: 0%
  • Clinical Trial
    Decrease in white blood cells count US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial

    Contraindications

    • Route:
      • Oral
    • Hypersensitivity:
      • true
      • Acyclovir
    • Regions: US
    • Route:
      • Oral
    • Hypersensitivity:
      • true
    • Regions: US

    Food Interactions

    Take with or without food.