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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]

Pharmacology

Mechanism of action

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.^[2]

Microbiology

Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity:^[3]

Herpes simplex virus type I (HSV-1)
Herpes simplex virus type II (HSV-2)
Varicella zoster virus (VZV)
Epstein–Barr virus (EBV)
Cytomegalovirus (CMV)

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.^[4]^[5]^[6] 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.^[7]

It also is used for herpes B virus postexposure prophylaxis.^[8]

Ingredients and dosage

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.^[9]

Clinical use

Indications

Valtrex brand valaciclovir 500mg tablets

Valaciclovir is indicated for the treatment of HSV and VZV infections, including:^[10]

Oral and genital herpes simplex (treatment and prophylaxis)
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. ^[11]

Prevention of cytomegalovirus following organ transplantation
Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy)^[12]

It has shown promise as a treatment for infectious mononucleosis,^[4]^[13]^[6] and is preventively administered in suspected cases of herpes B virus exposure.^{[citation needed]}

Adverse effects

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.^[10]

References

^ Ahmed, Rumman (2009-11-27). "Ranbaxy Launches Generic Valtrex in U.S.". The Wall Street Journal. Retrieved 2010-01-16.
^ http://www.uscnk.us/protein-antibody-elisa/Valaciclovir-%28VCV%29-V511.htm
^ 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.
^ ^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
^ "Adverse Effects Caused by Regular Use of Valacyclovir". Retrieved February 1, 2015.
^ ^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.
^ Sweetman, Sean C., ed. (2005). Martindale: the complete drug reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4. OCLC 56903116. ^{[page needed]}
^ CDC - Herpes B virus: First Aid and Treatment
^ "Valtrex Prescribing Information" (PDF). GlaxoSmithKline. September 2008. Retrieved 7 May 2009.
^ ^a ^b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3^{[page needed]}
^ 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.
^ 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.
^ 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" (PDF). International Pediatrics 18 (3): 164–169. ^{[dead link]}

UpToDate Contents

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1. バラシクロビル：概要 valacyclovir an overview
2. HIV感染患者における2型性器単純ヘルペスウイルスの治療 treatment of genital herpes simplex virus type 2 in hiv infected patients
3. 性器単純ヘルペスウイルス感染の治療 treatment of genital herpes simplex virus infection
4. 免疫正常患者における帯状疱疹の治療 treatment of herpes zoster in the immunocompetent host
5. HIV感染患者における薬剤抵抗性性器単純ヘルペスウイルス感染の治療 treatment of drug resistant genital herpes simplex virus infection in hiv infected patients

English Journal

Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men.

Cattamanchi A, Saracino M, Selke S, Huang ML, Magaret A, Celum C, Corey L, Wald A, Casper C.SourceDepartment of Medicine, University of Washington, Seattle, Washington.
Journal of medical virology.J Med Virol.2011 Oct;83(10):1696-703. doi: 10.1002/jmv.22194.
Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually in
PMID 21837785

Marine organisms as a therapeutic source against herpes simplex virus infection.

Vo TS, Ngo DH, Ta QV, Kim SK.SourceDepartment of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2011 Sep 18;44(1-2):11-20. Epub 2011 Jul 12.
Herpes simplex virus (HSV) is a member of the Herpesviridae family that causes general communicable infections in human populations throughout the world, the most common being genital and orolabial disease. The current treatments for HSV infections are nucleoside analogs such as acyclovir, valacyclo
PMID 21782018

Japanese Journal

バラシクロビル投与後にアシクロビル脳症および急性腎障害を発症した高齢糖尿病患者の1例

佐川尚子,鶴谷悠也,野村和至 [他],奥山朋子,近藤真衣,佐田晶,宮尾益理子,水野有三
日本老年医学会雑誌 51(6), 581-585, 2014
症例は83歳男性．29年来の2型糖尿病で当院通院中であり，グリメピリド0.5 mg内服にてHbA1c 6.0%前後，腎症1期で推移し，入院7日前の採血結果では，血清Cre 0.8 mg/dl（eGFR 69.67 ml/分/1.73 m2）であった．入院5日前に右眼瞼および結膜の炎症にて近医眼科を受診し，帯状疱疹が疑われ，バラシクロビル3,000 mgが処方され，頭痛が出現したため2日前にロキソプ …
NAID 130004917189

塩酸バラシクロビルにより急性腎障害とアシクロビル脳症を生じた水痘の1例 (特集ウイルス感染症)

小原宏哉,上田喬士,佐藤直哉 [他]
皮膚科の臨床 54(8), 1064-1066, 2012-08
NAID 40019404415

健康成人に発症した汎発性帯状疱疹を伴うハント症候群の1例

溝上大輔,田中伸明,栗田昭宏,松延毅,塩谷彰浩
Otology Japan 22(1), 53-57, 2012-02-29
Ramsay Hunt症候群 (以下、ハント症候群) は膝神経節に潜伏感染した水痘・帯状疱疹ウイルスvaricella-zoster virus (VZV) の再活性化により引き起こされる、1) 耳介・外耳道の帯状疱疹、2) 顔面神経麻痺、3) 耳鳴、難聴、めまいなどの内耳症状を３徴候とする症候群である。VZVによる疱疹が汎発化した場合、通常は初感染か免疫不全を疑うが、今回、生来健康な自衛官のハ …
NAID 10030285519

Related Pictures

★リンクテーブル★

リンク元	「バラシクロビル」「valaciclovir」

「バラシクロビル」

Valaciclovir
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 names	Valtrex
AHFS/Drugs.com	monograph
MedlinePlus	a695010
Licence data	US FDA:link
Pregnancy; category	AU: B3; US: B (No risk in non-human studies);
Legal status	AU: Prescription Only (S4); UK: Prescription-only (POM); US: ℞-only; ℞ (Prescription only);
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	55%
Protein binding	13–18%
Metabolism	Hepatic (to aciclovir)
Half-life	<30 minutes (valaciclovir);; 2.5–3.6 hours (aciclovir)
Excretion	Renal 40–50% (aciclovir),; faecal 47% (aciclovir)
Identifiers
CAS Registry Number	124832-26-4
ATC code	J05AB11
PubChem	CID 60773
DrugBank	DB00577
ChemSpider	54770
UNII	MZ1IW7Q79D
KEGG	D00398
ChEBI	CHEBI:35854
ChEMBL	CHEMBL1349
NIAID ChemDB	070982
Chemical data
Formula	C13H20N6O4
Molecular mass	324.336 g/mol
	SMILES O=C(OCCOCn1c2N\C(=N/C(=O)c2nc1)N)[C@@H](N)C(C)C;
	InChI 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 ; Key:HDOVUKNUBWVHOX-QMMMGPOBSA-N ;
(what is this?) (verify)

　　[★]

英: valacyclovir、valaciclovir
化: 塩酸バラシクロビル, valaciclovir hydrochloride
商: バルトレックス
関: 抗ウイルス薬

適応

単純疱疹、帯状疱疹、性器ヘルペスの再発抑制、(水痘)

「valaciclovir」

　　[★] バラシクロビル valacyclovir

[1] Ahmed, Rumman (2009-11-27). "Ranbaxy Launches Generic Valtrex in U.S.". The Wall Street Journal. Retrieved 2010-01-16.

[2] ttp://www.uscnk.us/protein-antibody-elisa/Valaciclovir-%28VCV%29-V511.htm

[OBrien1989-3] 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.

[balfour2005-4] 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

[5] "Adverse Effects Caused by Regular Use of Valacyclovir". Retrieved February 1, 2015.

[pmid17369082-6] 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.

[Martindale34-7] Sweetman, Sean C., ed. (2005). Martindale: the complete drug reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4. OCLC 56903116. ^{[page needed]}

[8] CDC - Herpes B virus: First Aid and Treatment

[9] "Valtrex Prescribing Information" (PDF). GlaxoSmithKline. September 2008. Retrieved 7 May 2009.

[AMH2006-10] Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3^{[page needed]}

[11] 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.

[Cancer-12] 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.

[simon2003-13] 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" (PDF). International Pediatrics 18 (3): 164–169. ^{[dead link]}

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