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Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). Severe side effects may include kidney problems. Valaciclovir is a therapeutic alternative on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 98th most commonly prescribed medication in the United States, with more than 7million prescriptions.
Medical uses
thumb|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)
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.
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.
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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.