Valacyclovir
Valacyclovir is an oral nucleoside antiviral prodrug of acyclovir used in adults for herpes simplex, varicella-zoster and cytomegalovirus infections. Its higher oral bioavailability allows less frequent dosing than acyclovir.
- Chemical formula
- C13H20N6O4
- CAS number
- 124832-26-4
- ATC code
- J05AB11
- Molecular weight
- 324.34 g/mol
- Drug class
- Nucleoside antiviral prodrug
- Also known as
- Valaciclovir, BW-256U87
What is it?
Valacyclovir is the L-valyl ester prodrug of acyclovir, approved for clinical use in 1995. It is supplied as oral tablets at 500mg and 1000mg. Valacyclovir is dispensed only on prescription and is one of the most prescribed antivirals worldwide for herpesvirus infections. Multiple authorised generics are now widely available. The molecule is part of the World Health Organization List of Essential Medicines.
Mechanism of action
Valacyclovir is rapidly and almost completely converted to acyclovir during first-pass intestinal and hepatic metabolism by valacyclovir hydrolase. Acyclovir is then selectively phosphorylated by viral thymidine kinase to its triphosphate form, which inhibits viral DNA polymerase and causes chain termination. The prodrug strategy substantially improves oral bioavailability over acyclovir itself, supporting less frequent dosing.
Pharmacokinetics
Oral valacyclovir bioavailability is approximately 55%, three to five times higher than oral acyclovir. The prodrug itself has a very short plasma half-life because it is rapidly converted to acyclovir, which has a plasma half-life of 2.5 to 3 hours. The active drug is excreted predominantly unchanged in urine via glomerular filtration and active tubular secretion. Renal impairment requires substantial dose reduction.
Indications
Valacyclovir is approved in adults for the treatment of herpes simplex virus infections, including genital herpes (initial episodes, recurrent episodes and suppressive therapy), herpes labialis (single-day high-dose regimen), reduction of transmission in heterosexual immunocompetent adults, herpes zoster (shingles) and prophylaxis of cytomegalovirus disease following solid organ transplantation. According to international guidelines, valacyclovir is preferred over acyclovir when adherence is a concern, with the choice made by the prescriber.
Safety profile
Common adverse effects include headache, nausea, abdominal pain and dizziness. High doses (used for cytomegalovirus prophylaxis) have been associated with thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome in advanced immunocompromise. Acute kidney injury, particularly with crystalluria, can occur with inadequate hydration. Central nervous system effects (confusion, hallucinations) are reported in older adults and renal impairment. According to the prescribing information, dose adjustment is required in renal impairment.
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Frequently asked questions
How is valacyclovir different from acyclovir? ▾
Valacyclovir is a prodrug of acyclovir with much higher oral bioavailability (around 55%) than acyclovir (15-30%), allowing twice or three times daily dosing instead of up to five times daily. The active drug is identical, so efficacy is comparable at equivalent acyclovir exposures. According to international guidelines, valacyclovir is preferred when adherence is a concern, with the choice made by the prescriber.
When is valacyclovir indicated for cold sores? ▾
Valacyclovir is approved for herpes labialis (cold sores) at a high single-day dose of 2000mg twice on the same day, taken at the earliest signs of recurrence (tingling, redness). According to the prescribing information, this short regimen reduces healing time and pain duration compared with placebo. Patients with frequent severe recurrences may benefit from chronic suppressive therapy at lower daily doses.
Can valacyclovir reduce transmission of genital herpes? ▾
Yes. Daily valacyclovir 500mg has been shown in randomised trials to reduce transmission of genital herpes simplex type 2 in serodiscordant heterosexual immunocompetent couples by approximately 50%. According to the prescribing information, suppressive therapy is offered in addition to safer-sex practices, which remain essential. The prescriber should review the relative benefits and risks for each patient.
Why must the dose be reduced in kidney disease? ▾
Valacyclovir is converted to acyclovir, which is excreted predominantly unchanged in urine, so renal impairment substantially increases acyclovir concentrations and the risk of adverse effects, including neurotoxicity (confusion, hallucinations) and crystalluria. According to the prescribing information, the dose is reduced based on creatinine clearance, including in patients on dialysis where supplemental doses are given after sessions. Adequate hydration is essential.
What are the main contraindications for valacyclovir? ▾
Valacyclovir is contraindicated in known hypersensitivity to valacyclovir, acyclovir or any excipient. Caution is required in renal impairment (with mandatory dose adjustment), in older adults, in advanced HIV disease (risk of thrombotic microangiopathy at high doses), in dehydration and during pregnancy and breastfeeding. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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