Valaciclovir

Source: Wikipedia, the free encyclopedia.
(Redirected from
Valtrex
)

Valaciclovir
Clinical data
Trade namesValtrex, Zelitrex, others
Other namesvalacyclovir, valacyclovir hydrochloride (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa695010
License data
Pregnancy
category
  • AU: B3
Antiviral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability55%
Protein binding13–18%
MetabolismLiver (to aciclovir)
Elimination half-life<30 minutes (valaciclovir);
2.5–3.6 hours (aciclovir)
ExcretionKidney 40–50% (aciclovir),
faecal 47% (aciclovir)
Identifiers
  • 2-[(2-Amino-6-oxo-1H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate
JSmol)
  • O=C(OCCOCn1c2N\C(=N/C(=O)c2nc1)N)[C@@H](N)C(C)C
  • InChI=1S/C13H20N6O4/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20)/t8-/m0/s1 checkY
  • Key:HDOVUKNUBWVHOX-QMMMGPOBSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Valaciclovir, also spelled valacyclovir, is an

by mouth.[2]

Common side effects include

kidney problems.[2] Use in pregnancy appears to be safe.[2] It is a prodrug, which works after being converted to aciclovir in a person's body.[2]

Valaciclovir was patented in 1987 and came into medical use in 1995.

generic medication.[6] In 2021, it was the 114th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[7][8]

Medical uses

Valtrex brand valaciclovir 500mg tablets

Valaciclovir is used for the treatment of HSV and VZV infections, including:[9]

  • Oral and genital
    prevention
    )
  • Reduction of HSV and VZV transmission from people with recurrent infection to uninfected individuals
  • Herpes zoster (shingles): the typical dosage for treatment of herpes is 1,000 mg orally three times a day for seven consecutive days.[10]
  • Prevention of cytomegalovirus following organ transplantation
  • Prevention of herpesviruses in immunocompromised people (such as those undergoing cancer chemotherapy)[11]
  • Chickenpox in children (ages 2–18)[1]

It has shown promise as a treatment for infectious mononucleosis[12][13][14] and is preventively administered in suspected cases of herpes B virus exposure.[15]

Bell's palsy does not seem to benefit from using valaciclovir as its only treatment.[16][17]

Adverse effects

Common

renal impairment. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic symptoms, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis.[9]

Pharmacology

Valaciclovir is a prodrug, an

first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is more effective (3000 times) in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into a disphosphate by cellular guanylate kinase and then into the active triphosphate form, aciclo-GTP, by cellular kinases.[1]

Mechanism of action

Aciclo-GTP, the active triphosphate metabolite of aciclovir, is a very potent inhibitor of

GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolized within the cell, possibly by cellular phosphatases.[18]

Aciclovir is active against most species in the

herpesvirus family. In descending order of activity:[19]

The drug is predominantly active against HSV and, to a lesser extent, VZV. It is only of limited efficacy against EBV and CMV. However, valaciclovir has been shown to lower or eliminate the presence of the Epstein–Barr virus in subjects afflicted with acute mononucleosis, leading to a significant decrease in the severity of symptoms.[12][13][14] Valaciclovir and acyclovir act by inhibiting viral DNA replication, but as of 2016 there was little evidence that they are effective against Epstein–Barr virus.[20] Acyclovir therapy does prevent viral latency, but has not proven effective at eradicating latent viruses in nerve ganglia.[19]

As of 2005, resistance to valaciclovir has not been significant. Mechanisms of resistance in HSV include deficient viral thymidine kinase and mutations to viral thymidine kinase and/or DNA polymerase that alter substrate sensitivity.[21]

It also is used for

herpes B virus postexposure prophylaxis.[15][22]

Chemistry

Details of the synthesis of valaciclovir were first published by scientists from the

Wellcome Foundation
.

Aciclovir was esterified with a

dicyclohexylcarbodiimide as the dehydrating agent. In the final step, the protecting group was removed by hydrogenation using a palladium on alumina catalyst.[23][24]

History

Valaciclovir was patented in 1987 and came into medical use in 1995.

generic medication.[6] In 2021, it was the 114th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[7][8]

Society and culture

Brand names

It is marketed by

GlaxoSmithKline under the brand names Valtrex[1] and Zelitrex. Valaciclovir has been available as a generic drug in the U.S. since November 2009.[25]

References

  1. ^ a b c d e f "Valtrex- valacyclovir hydrochloride tablet, film coated". DailyMed. 14 June 2021. Retrieved 22 May 2022.
  2. ^ a b c d e f g "Valacyclovir Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 17 March 2019.
  3. ^
    ISBN 978-1437727029
    .
  4. ^
    ISBN 9783527607495
    .
  5. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  6. ^
    ISBN 9780857113382
    .
  7. ^ a b "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  8. ^ a b "Valacyclovir - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  9. ^
    ISBN 0-9757919-2-3[page needed
    ]
  10. ISBN 978-3-8055-7982-7
    . Retrieved 1 January 2012.
  11. S2CID 2969472
    .
  12. ^ a b Balfour HH, Hokanson KM, Schacherer RM (December 2005). A controlled trial of valacyclovir in infectious mononucleosis. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC. pp. 16–19. Abstract V1392.
  13. ^ a b Simon MW, Deeter RG, Shahan B (March 2003). "The Effect of Valacyclovir and Prednisolone in Reducing Symptoms of EBV Illness In Children: A Double-Blind, Placebo-Controlled Study". International Pediatrics. 18 (3): 164–169 – via ResearchGate.
  14. ^
    PMID 17369082
    .
  15. ^ a b "Herpes B Virus: Information For Healthcare Providers". U.S. Centers for Disease Control and Prevention (CDC). 31 January 2019. Retrieved 22 May 2022.
  16. S2CID 36915347
    .
  17. PMID 31486071
    .
  18. ^ "Valaciclovir (VCV) - USCN LIFE SCIENCE INC". www.uscnk.us. Archived from the original on 3 December 2014.
  19. ^
    S2CID 240858022
    .
  20. PMID 27933614
    .
  21. OCLC 56903116.[page needed
    ]
  22. S2CID 4652818
    .
  23. ^ EP patent 308065, Krenitsky, Thomas Anthony & Beauchamp, Lilia Marie, "Therapeutic nucleosides", published 1989-03-22, assigned to Wellcome Foundation 
  24. S2CID 75449475
    .
  25. ^ Ahmed R (27 November 2009). "Ranbaxy Launches Generic Valtrex in U.S." The Wall Street Journal. Retrieved 16 January 2010.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Valaciclovir&oldid=1211451025"