Valaciclovir

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Valaciclovir
Valaciclovir structure.svg
Clinical data
Trade namesValtrex, Zelitrex, others
AHFS/Drugs.comMonograph
MedlinePlusa695010
License data
Pregnancy
category
  • AU: B3
  • US: B (No risk in non-human studies)
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • 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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.114.479 Edit this at Wikidata
Chemical and physical data
FormulaC13H20N6O4
Molar mass324.336 g/mol g·mol−1
3D model (JSmol)
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Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles).[1] It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases.[1] It is taken by mouth.[1]

Common side effects include headache and vomiting.[1] Severe side effects may include kidney problems.[1] Use in pregnancy appears to be safe.[1] It is a prodrug, which works after being converted to aciclovir in a person's body.[1]

Valaciclovir was patented in 1987 and came into medical use in 1995.[2][3] It is available as a generic medication.[4] A month supply in the United Kingdom costs the NHS about £3 as of 2019.[4] In the United States the wholesale cost of this amount is about US$2.80.[5] In 2016 it was the 168th most prescribed medication in the United States with more than 3 million prescriptions.[6]

Medical uses[edit]

Valtrex brand valaciclovir 500mg tablets

Valaciclovir is used for the treatment of HSV and VZV infections, including:[7]

  • Oral and genital herpes simplex (treatment and prevention)
  • Reduction of HSV 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.[8]
  • Prevention of cytomegalovirus following organ transplantation
  • Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy)[9]

It has shown promise as a treatment for infectious mononucleosis,[10][11][12] and is preventively administered in suspected cases of herpes B virus exposure.[citation needed]

Adverse effects[edit]

Common adverse drug reactions (≥1% of people) associated with valaciclovir are the same as for aciclovir, its active metabolite, and include: nausea, vomiting, diarrhea and headache. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, edema, arthralgia, sore throat, constipation, abdominal pain, rash, weakness and/or 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.[7]

Mechanism of action[edit]

Valaciclovir belongs to a family of molecules. Valaciclovir is a prodrug, an esterified version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir (10–20%). It is converted by esterases to the active drug aciclovir, as well as the amino acid valine, via hepatic first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase.[citation needed] Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.[13]

Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity:[14]

The drug is predominantly active against HSV, and to a lesser extent VZV. It is only of limited efficacy against EBV and CMV; however, valacyclovir has recently 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.[10][11][12] Although it can prevent the establishment of viral latency, acyclovir therapy has not proven effective at eradicating latent viruses in nerve ganglia.[14]

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, altering substrate sensitivity.[15]

It also is used for herpes B virus postexposure prophylaxis.[16]

Formulations[edit]

It is marketed by GlaxoSmithKline under the trade names Valtrex and Zelitrex. Valaciclovir has been available as a generic drug in the U.S. since November 25, 2009.[17]

Valtrex is offered in 250 mg, 500 mg, and 1 gram tablets, the active ingredient being valacyclovir hydrochloride, with the inactive ingredients carnauba wax, colloidal silicon dioxide, crospovidone, FD&C Blue No. 2 Lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.[18]

References[edit]

  1. ^ a b c d e f g "Valacyclovir Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 17 March 2019.
  2. ^ Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 1437727026.
  3. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 504. ISBN 9783527607495.
  4. ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 625–626. ISBN 9780857113382.
  5. ^ "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
  6. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
  7. ^ a b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3[page needed]
  8. ^ Lille, H. Martina; Wassilew, Sawko W. (2006). "Antiviral therapies of shingles in dermatology". In Gross, Gerd; Doerr, H.W. (eds.). Herpes zoroster: recent aspects of diagnosis and control. Monographs in virology. 26. Basel (Switzerland): Karger Publishers. p. 124. ISBN 978-3-8055-7982-7. Retrieved January 1, 2012.
  9. ^ Elad S, Zadik Y, Hewson I, et al. (August 2010). "A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea". Support Care Cancer. 18 (8): 993–1006. doi:10.1007/s00520-010-0900-3. PMID 20544224.
  10. ^ a b Balfour et al. (December 2005) A controlled trial of valacyclovir in infectious mononucleosis. Presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC., December 18, 2005. Abstract V1392
  11. ^ a b Simon, Michael W.; Robert G. Deeter; Britt Shahan (March 2003). "The Effect of Valacyclovir and Prednisolone in Reducing Symptoms of EBV Illness In Children: A Double-Blind, Placebo-Controlled Study" (PDF). International Pediatrics. 18 (3): 164–169.[dead link]
  12. ^ a b Balfour HH, Hokanson KM, Schacherer RM, et al. (May 2007). "A virologic pilot study of valacyclovir in infectious mononucleosis". Journal of Clinical Virology. 39 (1): 16–21. doi:10.1016/j.jcv.2007.02.002. PMID 17369082.
  13. ^ http://www.uscnk.us/protein-antibody-elisa/Valaciclovir-%28VCV%29-V511.htm[permanent dead link]
  14. ^ a b O'Brien JJ, Campoli-Richards DM (March 1989). "Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy". Drugs. 37 (3): 233–309. doi:10.2165/00003495-198937030-00002. PMID 2653790.
  15. ^ Sweetman, Sean C., ed. (2005). Martindale: the complete drug reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4. OCLC 56903116.[page needed]
  16. ^ "B Virus—First Aid and Treatment—Herpes B—CDC". Retrieved June 6, 2015.
  17. ^ Ahmed, Rumman (November 27, 2009). "Ranbaxy Launches Generic Valtrex in U.S." The Wall Street Journal. Retrieved January 16, 2010.
  18. ^ "Valtrex Prescribing Information" (PDF). GlaxoSmithKline. September 2008. Retrieved May 7, 2009.

External links[edit]