Valaciclovir

Valaciclovir, also known as valacyclovir, is an antiviral drug used for treating viral infections including herpes simplex, herpes zoster (shingles), and herpes B. This medication is a prodrug, meaning it is metabolically converted within the body into the active drug aciclovir, along with the amino acid valine. Marketed under the brand names Valtrex and Zelitrex by GlaxoSmithKline, valaciclovir is synthesized using the natural proteinogenic amino acid L-valine.

Valacyclovir Structural Formulae

Pharmacology

Mechanism of Action

Valaciclovir has a higher oral bioavailability (around 55%) compared to aciclovir (10–20%), due to its esterified form. Once in the body, it is metabolized by esterases into active aciclovir and the amino acid valine, mainly through hepatic first-pass metabolism. The active drug, aciclovir, is then further converted into its monophosphate form by viral thymidine kinase. This enzyme is significantly more effective at phosphorylating aciclovir than the corresponding cellular enzyme. This monophosphate form is then further phosphorylated into its active triphosphate form, aciclo-GTP, by cellular kinases.

Microbiology

Aciclovir, the active metabolite of valaciclovir, is effective against most species in the herpesvirus family, including:

Herpes simplex virus type I (HSV-1) Herpes simplex virus type II (HSV-2) Varicella zoster virus (VZV) Epstein–Barr virus (EBV) Cytomegalovirus (CMV) Valaciclovir is primarily active against HSV, and to a lesser extent VZV. While it shows limited efficacy against EBV and CMV, it has shown promise in reducing or eliminating the presence of EBV in individuals afflicted with acute mononucleosis.

Indications

Valaciclovir is used for the treatment and prevention of various herpes infections including oral and genital herpes simplex, and herpes zoster (shingles). It is also used for the reduction of HSV transmission, prevention of cytomegalovirus following organ transplantation, prophylaxis against herpesviruses in immunocompromised patients, and as postexposure prophylaxis for herpes B virus.

Adverse Effects

Common side effects associated with valaciclovir use include nausea, vomiting, diarrhea, and headache. Less common but possible side effects include agitation, vertigo, confusion, dizziness, edema, arthralgia, sore throat, constipation, abdominal pain, and rash. Infrequently, patients may also experience weakness, renal impairment, coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic symptoms, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis.

Resistance

To date, clinical resistance to valaciclovir has been infrequent. Resistance mechanisms in HSV include a deficiency in viral thymidine kinase and mutations to viral thymidine kinase and/or DNA polymerase that alter substrate sensitivity.

Ingredients and Dosage

Valaciclovir is available as Valtrex in 250 mg, 500 mg, and 1 gram tablets. The active ingredient is valacyclovir hydrochloride, combined with inactive ingredients including 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.

Summary

Valaciclovir is a potent antiviral medication used in the management of several herpesvirus infections. As a prodrug, it offers improved oral bioavailability compared to aciclovir, and its safety and efficacy are well-documented in clinical settings. It is crucial for healthcare professionals to understand the mechanisms, indications, and potential side effects associated with this drug to ensure its appropriate use and to optimize patient care.

• Dailymed label info on Valaciclovir
• FDA Valaciclovir