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.][
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Common side effects include headache and vomiting.[ Use in pregnancy appears to be safe.][ It is a prodrug, which works after being converted to aciclovir in a person's body.][
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Valaciclovir was patented in 1987 and came into medical use in 1995.
Medical uses
Valaciclovir is used for the treatment of HSV and VZV infections, including:[Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ]
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Oral and genital herpes simplex (treatment and prophylaxis)
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Reduction of HSV transmission from people with recurrent infection to uninfected individuals
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Herpes zoster (shingles): the typical dosage for treatment of herpes is 1,000 mg orally three times a day for seven consecutive days.
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Prevention of cytomegalovirus following organ transplantation
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Prevention of herpesviruses in immunocompromised people (such as those undergoing cancer chemotherapy)
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Chickenpox in children (ages 2–18)
It has shown promise as a treatment for infectious mononucleosis
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 version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir.
Mechanism of action
Aciclo-GTP, the active triphosphate metabolite of aciclovir, is a very potent inhibitor of Viral disease DNA replication. Aciclo-GTP competitively inhibits and inactivates the Virus DNA polymerase.
Aciclovir is active against most species in the herpesvirus family. In descending order of activity:
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Herpes simplex virus type I (HSV-1)
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Herpes simplex virus type II (HSV-2)
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Varicella zoster virus (VZV)
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Epstein–Barr virus (EBV)
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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.
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 protecting group 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.
Society and culture
Brand names
It is marketed by GlaxoSmithKline under the brand names Valtrex
