Trade names Valtrex MedlinePlus a695010 Molar mass 324.336 g/mol CAS ID 124832-27-5 Formula C13H20N6O4 | AHFS/Drugs.com Monograph Routes ofadministration Oral Bioavailability 55% License data US FDA: Valacyclovir ATC code J05AB11 (WHO) | |
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Pregnancycategory AU: B3US: B (No risk in non-human studies) Legal status AU: S4 (Prescription only)UK: POM (Prescription only)US: ℞-onlyIn general: ℞ (Prescription only) |
Valaciclovir, also spelled valacyclovir, is an antiviral drug used in the management of herpes simplex, herpes zoster (shingles), and herpes B.
Contents
It is a prodrug, being converted in vivo to aciclovir.
Valaciclovir was approved for medical use in 1995. 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.
Medical use
Valaciclovir is indicated for the treatment of HSV and VZV infections, including:
It has shown promise as a treatment for infectious mononucleosis, and is preventively administered in suspected cases of herpes B virus exposure.
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.
Mechanism of action
Valaciclovir belongs from a family of molecules first described and patented by P.Cornaglia Ferraris in 1982 (patents EP0077460 A2, CA1258149A1, DE3273785D1, EP0077460A3, EP0077460B1, US4567182). 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.
Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity:
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. Although it can prevent the establishment of viral latency, acyclovir therapy has not proven effective at eradicating 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.
It also is used for herpes B virus postexposure prophylaxis.
Chemistry
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.