| Systematic (IUPAC) name | |
|---|---|
| (S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl-2-amino-3-methylbutanoate | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | B3 (Au), B (U.S.) |
| Legal status | S4 (Au), POM (UK), ℞-only (U.S.) |
| Routes | 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 number | 124832-26-4 |
| ATC code | J05AB11 |
| PubChem | CID 60773 |
| DrugBank | APRD00697 |
| ChemSpider | 54770 |
| UNII | MZ1IW7Q79D |
| KEGG | D00398 |
| ChEBI | CHEBI:35854 |
| ChEMBL | CHEMBL1349 |
| Chemical data | |
| Formula | C13H20N6O4 |
| Mol. mass | 324.336 g/mol |
| SMILES | eMolecules & PubChem |
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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. As of November 25, 2009[update], valacyclovir is marketed in generic form in the United States by Ranbaxy Laboratories.[1]
Contents |
Valaciclovir is prepared starting from the natural proteinogenic amino acid L-valine.
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. Acyclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation 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.
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.
To date, 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]
Valtrex is offered in 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, polysorbateJ 80, povidone, and titanium dioxide.[8]
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][12] and is preventively administered in suspected cases of herpes B virus exposure.
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]
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