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 do... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Patient Conditions:
      • Name: Hypersensitivity to acyclovir
      • Drugbank Id: DBCOND0118176
  • Regions: US
  • Patient Conditions:
      • Name: Hypersensitivity to valacyclovir or any component of the formulation
      • Drugbank Id: DBCOND0118175

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Valaciclovir
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
Abacavir
Valaciclovir may decrease the excretion rate of Abacavir which could result in a higher serum level.
Acarbose
Valaciclovir may decrease the excretion rate of Acarbose which could result in a higher serum level.
Aceclofenac
Valaciclovir may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Valaciclovir which could result in a higher serum level.
Acetaminophen
Valaciclovir may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetazolamide
Acetazolamide may increase the excretion rate of Valaciclovir which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid
Valaciclovir may decrease the excretion rate of Acetylsalicylic acid which could result in a higher serum level.
Aclidinium
Valaciclovir may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Acrivastine
Valaciclovir may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Acyclovir
Valaciclovir may decrease the excretion rate of Acyclovir which could result in a higher serum level.
Adefovir
Adefovir may decrease the excretion rate of Valaciclovir which could result in a higher serum level.
Adefovir dipivoxil
Adefovir dipivoxil may decrease the excretion rate of Valaciclovir which could result in a higher serum level.
Adenovirus type 7 vaccine live
The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Valaciclovir.
Albutrepenonacog alfa
Valaciclovir may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
Alclofenac
Valaciclovir may decrease the excretion rate of Alclofenac which could result in a higher serum level.
Aldesleukin
Valaciclovir may decrease the excretion rate of Aldesleukin which could result in a higher serum level.
Alendronic acid
The risk or severity of nephrotoxicity and hypocalcemia can be increased when Valaciclovir is combined with Alendronic acid.
Allopurinol
Valaciclovir may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Allylestrenol
Valaciclovir may decrease the excretion rate of Allylestrenol which could result in a higher serum level.
Almasilate
Valaciclovir may decrease the excretion rate of Almasilate which could result in a higher serum level.
10 References
  1. 1 . Beutner KR: Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antiviral Res. 1995 Dec;28(4):281-90.PubMed: 8669888
  2. 2 . Asahi T, Tsutsui M, Wakasugi M, Tange D, Takahashi C, Tokui K, Okazawa S, Okudera H: Valacyclovir neurotoxicity: clinical experience and review of the literature. Eur J Neurol. 2009 Apr;16(4):457-60. doi: 10.1111/j.1468-1331.2008.02527.x.PubMed: 19187258
  3. 3 . Perry CM, Faulds D: Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections. Drugs. 1996 Nov;52(5):754-72. doi: 10.2165/00003495-199652050-00009.PubMed: 9118821
  4. 4 . De Clercq E, Li G: Approved Antiviral Drugs over the Past 50 Years. Clin Microbiol Rev. 2016 Jul;29(3):695-747. doi: 10.1128/CMR.00102-15.PubMed: 27281742
  5. 5 . Groves MJ: Genital Herpes: A Review. Am Fam Physician. 2016 Jun 1;93(11):928-34.PubMed: 27281837
  6. 6 . Bomgaars L, Thompson P, Berg S, Serabe B, Aleksic A, Blaney S: Valacyclovir and acyclovir pharmacokinetics in immunocompromised children. Pediatr Blood Cancer. 2008 Oct;51(4):504-8. doi: 10.1002/pbc.21638.PubMed: 18561175
  7. 7 . Valacyclovir: AAFP Link
  8. 8 . Valacyclovir approval package Link
  9. 9 . Valtrex tablets, MedSafe NZ File
  10. 10 . Valacyclovir hydrochloride hydrate MSDS File