Valacyclovir (Valtrex)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

History

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 has been marketed under the trade name Valtex by GlaxoSmithKline since 1995. It was originally approved by the FDA in June 1995 for the treatment of herpes zoster (shingles). In December 1995 the FDA approved valacyclovir for the treatment of recurrent herpes genitalis and later for the treatment of initial infections of herpes genitalis in October 1996. Maintenance (suppressive) therapy 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)
• Chickenpox

Off-label & Investigational uses

• Bell's palsy 4
• Herpes simplex infection prophylaxis 5, 6
• Cytomegalovirus infection and disease after organ transplantation 7, 8
• 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, 10
• HSV encephalitis

Valacyclovir "pros" and "cons"

Advantages:

• 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, upto 60-70% 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

Disadvantages:

• Risk of renal failure and neurotoxicity 20, 21
• Does not eradicate latent virus
• Given the brief period of HSV replication and the rapid formation of lesions, the therapeutic window for treating acute 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.

Further reading

• Valacyclovir vs Famciclovir
• Acyclovir vs Valacyclovir

References

• 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 Patent 4,957,924
• 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 Jan;26(1):50-4. PubMed
• 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. PubMed
• 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. PubMed
• 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 Sep-Oct;7(5):372-81. PubMed
• 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 Jan-Feb;19(1-2):461-70. PubMed
• 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. PubMed
• 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.
• 21. Zhang Y, Cong Y, Teng Y. Acute renal injury induced by valacyclovir hydrochloride: A case report. Exp Ther Med. 2016 Dec;12(6):4025-4028.

Published: March 31, 2008
Last updated: January 21, 2017