Valaciclovir

From Wikipedia, the free encyclopedia - View original article

Valaciclovir
Valaciclovir structure.svg
Systematic (IUPAC) name
(S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl-2-amino-3-methylbutanoate
Clinical data
Trade namesValtrex
AHFS/Drugs.commonograph
MedlinePlusa695010
Licence dataUS FDA:link
Pregnancy cat.B3 (AU) B (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability55%
Protein binding13–18%
MetabolismHepatic (to aciclovir)
Half-life<30 minutes (valaciclovir);
2.5–3.6 hours (aciclovir)
ExcretionRenal 40–50% (aciclovir),
faecal 47% (aciclovir)
Identifiers
CAS number124832-26-4 N
ATC codeJ05AB11
PubChemCID 60773
DrugBankDB00577
ChemSpider54770 YesY
UNIIMZ1IW7Q79D YesY
KEGGD00398 N
ChEBICHEBI:35854 YesY
ChEMBLCHEMBL1349 YesY
NIAID ChemDB070982
Chemical data
FormulaC13H20N6O4 
Mol. mass324.336 g/mol
 N (what is this?)  (verify)
 
Jump to: navigation, search
Valaciclovir
Valaciclovir structure.svg
Systematic (IUPAC) name
(S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl-2-amino-3-methylbutanoate
Clinical data
Trade namesValtrex
AHFS/Drugs.commonograph
MedlinePlusa695010
Licence dataUS FDA:link
Pregnancy cat.B3 (AU) B (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability55%
Protein binding13–18%
MetabolismHepatic (to aciclovir)
Half-life<30 minutes (valaciclovir);
2.5–3.6 hours (aciclovir)
ExcretionRenal 40–50% (aciclovir),
faecal 47% (aciclovir)
Identifiers
CAS number124832-26-4 N
ATC codeJ05AB11
PubChemCID 60773
DrugBankDB00577
ChemSpider54770 YesY
UNIIMZ1IW7Q79D YesY
KEGGD00398 N
ChEBICHEBI:35854 YesY
ChEMBLCHEMBL1349 YesY
NIAID ChemDB070982
Chemical data
FormulaC13H20N6O4 
Mol. mass324.336 g/mol
 N (what is this?)  (verify)

Valaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex, herpes zoster (shingles), and herpes B. It is a prodrug, being converted in vivo to aciclovir. 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.[1]

Chemistry[edit]

Valaciclovir is prepared starting from the natural proteinogenic amino acid L-valine.

Pharmacology[edit]

Mechanism of action[edit]

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. 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.

Microbiology[edit]

Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity:[2]

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.[3][4][5] It is inactive against latent viruses in nerve ganglia[citation needed].

To date,[when?] resistance to valaciclovir has not been clinically significant. Mechanisms of resistance in HSV include deficient viral thymidine kinase, and mutations to viral thymidine kinase and/or DNA polymerase, altering substrate sensitivity.[6]

It also is used for herpes B virus postexposure prophylaxis.[7]

Ingredients and dosage[edit]

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.[8]

Clinical use[edit]

Indications[edit]

Valtrex brand valaciclovir 500mg tablets

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

It has shown promise as a treatment for infectious mononucleosis,[3][4][5] and is preventively administered in suspected cases of herpes B virus exposure.[citation needed]

Adverse effects[edit]

Common adverse drug reactions (≥1% of patients) associated with valaciclovir therapy 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.[9]

References[edit]

  1. ^ Ahmed, Rumman (2009-11-27). "Ranbaxy Launches Generic Valtrex in U.S.". The Wall Street Journal. Retrieved 2010-01-16. 
  2. ^ 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. 
  3. ^ 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
  4. ^ a b Simon, Michael W.; Robert G. Deeter and Britt Shahan (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.  [dead link]
  5. ^ 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. 
  6. ^ Sweetman, Sean C., ed. (2005). Martindale: the complete drug reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4. OCLC 56903116. [page needed]
  7. ^ CDC - Herpes B virus: First Aid and Treatment
  8. ^ "Valtrex Prescribing Information". GlaxoSmithKline. September 2008. Retrieved 7 May 2009. 
  9. ^ a b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3[page needed]
  10. ^ Lille, H. Martina; Wassilew, Sawko W. (2006). "Antiviral therapies of shingles in dermatology". In Gross, Gerd; Doerr, H.W. 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 1 January 2012. 
  11. ^ 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.