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| Trade names | Valtrex, Zelitrex, others |
| Other names | valacyclovir, valacyclovir hydrochloride (USANUS) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a695010 |
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| Routes of administration | By mouth |
| Drug class | Antiviral |
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| Pharmacokinetic data | |
| Bioavailability | 55% |
| Protein binding | 13–18% |
| Metabolism | Liver (toaciclovir) |
| Eliminationhalf-life | <30 minutes (valaciclovir); 2.5–3.6 hours (aciclovir) |
| Excretion | Kidney 40–50% (aciclovir), faecal 47% (aciclovir) |
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| ECHA InfoCard | 100.114.479 |
| Chemical and physical data | |
| Formula | C13H20N6O4 |
| Molar mass | 324.341 g·mol−1 |
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Valaciclovir, also spelledvalacyclovir, is anantiviral medication used to treat outbreaks ofherpes simplex orherpes zoster (shingles).[2] It is also used to preventcytomegalovirus following akidney transplant in high risk cases.[2] It is takenby mouth.[2]
Common side effects includeheadache andvomiting.[2] Severe side effects may includekidney problems.[2] Use inpregnancy appears to be safe.[2] It is aprodrug, which works after being converted toaciclovir in a person's body.[2]
Valaciclovir was patented in 1987 and came into medical use in 1995.[3][4] Valaciclovir is a therapeutic alternative on theWorld Health Organization's List of Essential Medicines.[5] It is available as ageneric medication.[6] In 2023, it was the 98th most commonly prescribed medication in the United States, with more than 7 million prescriptions.[7][8]
Valaciclovir is used for the treatment of HSV and VZV infections, including:[9]
It has shown promise as a treatment forinfectious mononucleosis[12][13][14] and is preventively administered in suspected cases of herpes B virus exposure.[15]
Bell's palsy does not seem to benefit from using valaciclovir as its only treatment.[16][17]
Commonadverse drug reactions (≥1% of people) associated with valaciclovir are the same as foraciclovir, 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/orrenal 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/oranaphylaxis.[9]
Valaciclovir is a prodrug, anesterified version ofaciclovir that has greater oralbioavailability (about 55%) than aciclovir.[1] It is converted byesterases to the active drug,aciclovir, and theamino acidvaline viahepaticfirst-pass metabolism.Aciclovir is selectively converted into a monophosphate form by viralthymidine kinase, which is more effective (3000 times) inphosphorylation ofaciclovir 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 cellularkinases.[1]
Aciclo-GTP, the active triphosphate metabolite of aciclovir, is a very potent inhibitor ofviralDNA replication. Aciclo-GTP competitively inhibits and inactivates theviralDNA polymerase.[1] Its monophosphate form also incorporates into the viral DNA, resulting inchain 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 cellularphosphatases.[18]
Aciclovir is active against most species in theherpesvirus family. In descending order of activity:[19]
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.[12][13][14] 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.[20] Acyclovir therapy does preventviral latency, but has not proven effective at eradicating latent viruses innerve ganglia.[19]
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.[21]
It also is used forherpes B virus postexposure prophylaxis.[15][22]
Details of the synthesis of valaciclovir were first published by scientists from theWellcome Foundation.
Aciclovir was esterified with acarboxybenzylprotectedvaline, usingdicyclohexylcarbodiimide as thedehydrating agent. In the final step, the protecting group was removed byhydrogenation using a palladium on alumina catalyst.[23][24]
Valaciclovir was patented in 1987 and came into medical use in 1995.[3][4] It is available as ageneric medication.[6] In 2022, it was the 113th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[25][8]
It is marketed byGlaxoSmithKline under the brand names Valtrex[1] and Zelitrex. Valaciclovir has been available as ageneric drug in the US since November 2009.[26]
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