valaciclovir valaciclovir valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). it is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. it is taken by mouth. valaciclovirclinical datatrade namesvaltrex, zelitrex, othersother namesvalacyclovir, valacyclovir hydrochloride (usan us)ahfs/drugs.commonographmedlineplusa695010license data us dailymed: valacyclovir us fda: valacyclovir pregnancycategory au: b3 routes ofadministrationby mouthatc codej05ab11 (who) legal statuslegal status au: s4 (prescription only) uk: pom (prescription only) us: ℞-only in general: ℞ (prescription only) pharmacokinetic databioavailability55%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 iupac name 2-ethyl (2s)-2-amino-3-methylbutanoate cas number124832-26-4 yas hcl: 124832-27-5pubchem cid135398742as hcl: 135398741iuphar/bps4824drugbankdb00577 yas hcl: dbsalt000289chemspider54770 yuniimz1iw7q79das hcl: g447s0t1vckeggd08664 yas hcl: d00398chebichebi:35854 yas hcl: chebi:9919chemblchembl1349 yas hcl: chembl1201110niaid chemdb070982comptox dashboard (epa)dtxsid1023732 echa infocard100.114.479 chemical and physical dataformulac13h20n6o4molar mass324.341 g·mol−13d model (jsmol)interactive image smiles o=c(occocn1c2n\c(=n/c(=o)c2nc1)n)(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 ykey:hdovuknubwvhox-qmmmgpobsa-n y ny (what is this?) (verify) common side effects include headache and vomiting. severe side effects may include kidney problems. use in pregnancy appears to be safe. it is a prodrug, which works after being converted to aciclovir in a person's body. valaciclovir was patented in 1987 and came into medical use in 1995. it is on the world health organization's list of essential medicines. it is available as a generic medication. in 2020, it was the 119th most commonly prescribed medication in the united states, with more than 5 million prescriptions. medical uses valtrex brand valaciclovir 500mg tablets valaciclovir is used for the treatment of hsv and vzv infections, including: 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. prevention of cytomegalovirus following organ transplantation prevention of herpesviruses in immunocompromised people (such as those undergoing cancer chemotherapy) chickenpox in children (ages 2–18) it has shown promise as a treatment for infectious mononucleosis and is preventively administered in suspected cases of herpes b virus exposure. bell's palsy does not seem to benefit from using valaciclovir as its only treatment. adverse effects common adverse drug reactions (≥1% of people) associated with valaciclovir are the same as for aciclovir, its active metabolite. they 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. pharmacology valaciclovir is a prodrug, an esterified version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir. it is converted by esterases to the active drug, aciclovir, and the amino acid valine via hepatic 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. mechanism of action aciclo-gtp, the active triphosphate metabolite of aciclovir, is a very potent inhibitor of viral dna replication. aciclo-gtp competitively inhibits and inactivates the viral dna 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 metabolized within the cell, possibly by cellular phosphatases. aciclovir is active against most species in the herpesvirus family. in descending order of activity: 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, 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. 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. acyclovir therapy does prevent viral latency, but has not proven effective at eradicating latent viruses in nerve ganglia. 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. it also is used for herpes b virus postexposure prophylaxis. chemistry details of the synthesis of valaciclovir were first published by scientists from the wellcome foundation. aciclovir was esterified with a carboxybenzyl protected valine, using dicyclohexylcarbodiimide as the dehydrating agent. in the final step, the protecting group was removed by hydrogenation using a palladium on alumina catalyst. history valaciclovir was patented in 1987 and came into medical use in 1995. it is available as a generic medication. in 2019, it was the 110th most commonly prescribed medication in the united states, with more than 5 million prescriptions. society and culture brand names it is marketed by glaxosmithkline under the brand names valtrex and zelitrex. valaciclovir has been available as a generic drug in the u.s. since november 2009.