Valacyclovir (Valtrex)

• Generic name: Valacyclovir hydrochloride
• Trade names: Valtrex
• Pharmacologic category: Guanosine nucleoside analogue, Antiviral agent
• FDA approved: December 15, 1995
• Pregnancy risk factor: B
• Patent Expiration Date: June 2009

Valacyclovir hydrochloride (Valtrex) is indicated for the treatment of herpes zoster (shingles); initial and recurrent episodes of genital herpes; suppression of recurrent genital herpes; cold sores. It is also DFA approved for the reduction of transmission of genital herpes to the uninfected partner.

Valacyclovir does not cure a herpes infection but may relieve the symptoms of viral infection and shorten the duration of an outbreak.

Herpes zoster (also called shingles) is a painful, blistering skin rash. Shingles results from reactivation of the varicella-zoster virus acquired during the primary varicella infection, or chickenpox. Whereas chickenpox happens generally during childhood, the incidence of shingles increases sharply with advancing age.

Valacyclovir may prevent the formation of new lesions, decrease viral shedding, decrease the severity and duration of pain, and promote healing and crusting of lesions. Also, it may shorten the duration of postherpetic neuralgia, particularly in people older than 50 years of age. Antiviral therapy for herpes zoster is most effective when initiated within 48-72 hours of rash onset.

Valacyclovir is very efficacious for shingles. The principal potential benefits of valacyclovir relative to acyclovir are improved oral bioavailability and consequent higher blood levels and more convenient dosing regimen. Also, Valacyclovir is more effective than its parent compound in speeding resolution of zoster-associated pain and postherpetic neuralgia 1.

Valtrex may be particularly beneficial for people with expansive lesions.

• Absorption and Bioavailability: After oral administration, valacyclovir is rapidly absorbed from the GI tract and nearly completely converted to acyclovir and L-valine. Bioavailability is about 50-60%. Administration with food does not alter bioavailability.
• Metabolism: Valacyclovir is converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism. Valacyclovir is not metabolized by cytochrome P450 enzymes.
• Elimination half-life: Elimination half-life is about 2.5-3.3 hours.
• Excretion: About 46% is recovered in urine. About 47% is recovered in feces.

• convenient dosing regimen
• suppresses asymptomatic viral shedding
• excellent safety profile
• high efficacy
• very low risk of drug interactions

• does not cure the viral infection
• risk of renal and nervous system problems

• Prophylaxis for herpes simplex virus2
• Posttransplantation cytomegalovirus (CMV) infection 3
• Reduction of schizophrenia symptoms in cytomegalovirus-seropositive individuals 4
• Suppressive therapy of recurrent genital herpes in pregnant women 5
• Herpes zoster ophthalmicus 6

Valacyclovir prevents the growth and multiplication of the herpes virus.

Valacyclovir is selectively phosphorylated only within virus-infected cells by viral thymidine kinase (TK). Further phosphorylation by cellular enzymes leads to the production of acyclovir triphosphate, which competes with the natural nucleotide, dGTP, resulting in the selective inhibition of viral DNA polymerase. Incorporation of the analogue triphosphate into the growing DNA chain prevents continued extension of the DNA chain.

• 1. Wu JJ, Brentjens MH, Torres G, Yeung-Yue K, Lee P, Tyring SK. Valacyclovir in the treatment of herpes simplex, shingles, and other viral infections. J Cutan Med Surg. 2003 Sep-Oct;7(5):372-81.
• 2. Beeson WH, Rachel JD. Valacyclovir prophylaxis for herpes simplex virus infection or infection recurrence following laser skin resurfacing. Dermatol Surg. 2002 Apr;28(4):331-6.
• 3. Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med. 1999 May 13;340(19):1462-70. PubMed
• 4. Dickerson FB, Boronow JJ, Stallings CR, Origoni AE, Yolken RH. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia. Am J Psychiatry. 2003 Dec;160(12):2234-6.
• 5. Andrews WW, Kimberlin DF, Whitley R, Cliver S, Ramsey PS, Deeter R. Valacyclovir therapy to reduce recurrent genital herpes in pregnant women. Am J Obstet Gynecol. 2006 Mar;194(3):774-81.
• 6. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety of valaciclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology. 2000 Aug;107(8):1507-11. PubMed

Last updated: February 14, 2011