Valacyclovir in Brief
- Active ingredient: valacyclovir hydrochloride
- Common brand names: Valtrex
- Drug class: Antiviral agent, Nucleoside analogue
- FDA Approved: June 1995
- Manufacturer: GlaxoSmithKline
- Patent expiration date: June 2009
- Pregnancy Category: B
- Originally discovered: 1988, USA
Burroughs Wellcome Co. (now GlaxoSmithKline) developed and investigated
several water-soluble esters of acyclovir. One of these valine
esters came to be known as "valaciclovir".
Burroughs Wellcome patented the invention of valine esters of acyclovir
in 1988 3.
Valacyclovir is marketed under the brand name Valtex by GlaxoSmithKline
since 1995. It was initially approved by the FDA in June 1995 for the
treatment of herpes zoster (shingles). In December 1995 the FDA approved
this drug for the treatment of recurrent herpes genitalis and then for
the treatment of initial infections of herpes genitalis in October 1996.
Maintenance (suppressive) use of valacyclovir for herpes genitalis was
approved in September 1997. Its use for herpes labialis was approved in September 2002.
FDA approved uses
- Herpes zoster (shingles)
- Initial episodes of genital herpes
- Recurrent episodes of genital herpes
- Suppressive therapy of recurrent genital herpes
- Reduction of transmission of genital herpes
- Cold sores (herpes labialis)
Off-label & Investigational uses
- Bell's palsy 4
- Herpes simplex infection prophylaxis 5,
- Cytomegalovirus infection and disease after organ transplantation
- Retinal necrosis syndrome 13
- Prophylaxis of recurrent genital herpes in late pregnancy 15
- Epstein-Barr virus 17
- Herpes zoster ophthalmicus 16
- Symptoms of schizophrenia 9,
- HSV encephalitis
Valacyclovir "pros" and "cons"
- high efficacy against HSV and VZV infections
- significantly reduces the risk of transmission of genital herpes 2
- decreases asymptomatic shedding of the virus
- more effective than acyclovir for herpes zoster 18, significantly decreases the likelihood and severity of post-herpes zoster pain
- provide better oral bioavailability, approximately 70% 19
- convenient dosing regimen
- favorable safety profile
- considered safe for the mother and baby during pregnancy (so far,
no adverse outcomes in the fetus or newborn have been reported)
- minor risk of drug interactions
- risk of renal failure and neurotoxicity 20
- does not eradicate latent virus
- given the brief period of HSV replication and the rapid formation of lesions, the therapeutic window for treating herpes outbreaks with valacyclovir is early and short
Mode of action
Valacyclovir is rapidly and nearly completely converted to acyclovir
by intestinal and hepatic metabolism. Acyclovir is converted to acyclovir
monophosphate by virus-specific thymidine kinase then further converted
to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate
inhibits DNA synthesis and viral replication by competing with deoxyguanosine
triphosphate for viral DNA polymerase and being incorporated into viral DNA.
Valacyclovir cannot prevent the death of a cell once it is infected, but it can reduce the quantity of
virions (virus particles) produced by an infected cell.
Time to clear out of the system
Valacyclovir has a short half-life about 2.5 to 3.3 hours.
- 1. Physicians’ Desk Reference, 54th ed. Valtrex
(valacyclovir) Prescribing Information. Medical Economics, Thomson
Healthcare: Montvale, NJ; 2000.
- 2. Corey L, Wald A , Patel R, Sacks SL, Tyring
SK, Warren T, Douglas JM, Paavonen J, Morrow RA , Beutner KR, Stratchounsky
LS, Mertz G, Keene ON, Watson HA, Tait D, Vargas-Cortes M. Once-daily
valacyclovir to reduce the risk of transmission of genital herpes.
N Engl J Med. 2004 Jan 1;350(1):11-20. PubMed
- 3. Therapeutic valine esters of acyclovir and
pharmaceutically acceptable salts thereof. US
- 4. Hato N, Yamada H, Kohno H, Matsumoto S, Honda
N, Gyo K, Fukuda S, Furuta Y, Ohtani F, Aizawa H, Aoyagi M, Inamura
H, Nakashima T, Nakata S, Murakami S, Kiguchi J, Yamano K, Takeda
T, Hamada M, Yamakawa K. Valacyclovir and prednisolone treatment for
Bell's palsy: a multicenter, randomized, placebo-controlled study.
Otol Neurotol. 2007 Apr;28(3):408-13.PubMed
- 5. Gilbert S, McBurney E. Use of valacyclovir
for herpes simplex virus-1 (HSV-1) prophylaxis after facial resurfacing:
a randomized clinical trial. Dermatol Surg. 2000
- 6. Eisen D, Essell J, Broun ER, Sigmund D, DeVoe
M. Clinical utility of oral valacyclovir compared with oral acyclovir
for the prevention of herpes simplex virus mucositis following autologous
bone marrow transplantation or stem cell rescue therapy. Bone Marrow
Transplant. 2003 Jan;31(1):51-5. PubMed
- 7. Egan JJ, Carroll KB, Yonan N, Woodcock A,
Crisp A. Valacyclovir prevention of cytomegalovirus reactivation after
heart transplantation: a randomized trial. J Heart Lung Transplant.
2002 Apr;21(4):460-6. PubMed
- 8. Lowance D, Neumayer HH, Legendre CM, Squifflet
JP, Kovarik J, Brennan PJ, Norman D, Mendez R, Keating MR, Coggon
GL, Crisp A, Lee IC. Valacyclovir for the prevention of cytomegalovirus
disease after renal transplantation. International Valacyclovir Cytomegalovirus
Prophylaxis Transplantation Study Group. N Engl J Med. 1999 May 13;340(19):1462-70.
- 9. Bechter K. The mild encephalitis-hypothesis--new
findings and studies. Psychiatr Prax. 2004 Nov;31 Suppl 1:S41-3. PubMed
- 10. 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.
- 12. Wu JJ, Brentjens MH, Torres G, Yeung-Yue
K, Lee P, Tyring SK. Valacyclovir in the treatment of herpes simplex,
herpes zoster, and other viral infections. J Cutan Med Surg. 2003
- 13. Aizman A, Johnson MW, Elner SG. Treatment
of acute retinal necrosis syndrome.
Ophthalmology. 2007 Feb;114(2):307-12. PubMed
- 14. Field HJ, Thackray AM. Early therapy with
valaciclovir or famciclovir reduces but does not abrogate herpes simplex
virus neuronal latency. Nucleosides Nucleotides Nucleic Acids. 2000
- 15. Sheffield JS, Hill JB, Hollier LM, Laibl
VR, Roberts SW, Sanchez PJ, Wendel GD Jr. Valacyclovir prophylaxis
to prevent recurrent herpes at delivery: a randomized clinical trial.
Obstet Gynecol. 2006 Jul;108(1):141-7. PubMed
- 16. Colin J, Prisant O, Cochener B, Lescale
O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety
of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus.
Ophthalmology. 2000 Aug;107(8):1507-11. PubMed
- 17. Lerner AM, Beqaj SH, Deeter RG, Dworkin
HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O'Neill W. A six-month
trial of valacyclovir in the Epstein-Barr virus subset of chronic
fatigue syndrome: improvement in left ventricular function. Drugs
Today (Barc). 2002 Aug;38(8):549-61. PubMed
- 18. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir therapy for herpes zoster
in immunocompetent adults. Antimicrob Agents Chemother. 1995 Jul;39(7):1546-53.
- 19. Bras AP, Sitar DS, Aoki FY. Comparative
bioavailability of acyclovir from oral valacyclovir and acyclovir
in patients treated for recurrent genital herpes simplex virus infection.
Can J Clin Pharmacol. 2001 Winter;8(4):207-11. PubMed
- 20. Carlon R, Possamai C, Corbanese U. Acute
renal failure and severe neurotoxicity following valacyclovir. Intensive
Care Med. 2005 Nov;31(11):1593.
Published: March 31, 2008
Last updated: June 15, 2013
- Valacyclovir is the best prophylaxis for reducing the frequency and severity of herpes outbreaks.
- In herpes zoster, valacyclovir is more effective than acyclovir
and equally effective as famciclovir (Famvir) at hastening the healing
of zoster-associated pain and PHN 12.
- Early therapy with valacyclovir reduces but does not abrogate
herpes simplex virus neuronal latency 14.