|Trade names||Valtrex, Zelitrex, others|
|Metabolism||Liver (to aciclovir)|
|Elimination half-life||<30 minutes (valaciclovir);|
2.5–3.6 hours (aciclovir)
|Excretion||Kidney 40–50% (aciclovir),|
faecal 47% (aciclovir)
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||324.336 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
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.
Common side effects include headache and vomiting. Severe side effects may include kidney problems. Use in pregnancy appears to be safe. It is a prodrug, which works after being converted to aciclovir in a person's body.
Valaciclovir was patented in 1987 and came into medical use in 1995. It is available as a generic medication. A month supply in the United Kingdom costs the NHS about £3 as of 2019. In the United States the wholesale cost of this amount is about US$2.80. In 2016 it was the 168th most prescribed medication in the United States with more than 3 million prescriptions.
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
- Prophylaxis against herpesviruses in immunocompromised patients (such as patients undergoing cancer chemotherapy)
Common adverse drug reactions (≥1% of people) associated with valaciclovir 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 to a family of molecules. 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.
- 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, 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.
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, altering substrate sensitivity.
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.
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