Valaciclovir

What is valaciclovir?

Valaciclovir is an oral antiviral drug that belongs to the class of nucleoside analogue DNA polymerase inhibitors.

What is valaciclovir used for?

Valaciclovir is commonly approved for use in the treatment and prevention of infections caused by herpes simplex virus and varicella zoster virus (which causes chickenpox and shingles).


Adult patients:

• Herpes labialis (cold sores)
• Genital herpes
• Herpes zoster (shingles), including herpes zoster ophthalmicus.

Pediatric patients:

• Herpes labialis (cold sores) in patients aged 12 years and over
• Varicella (chickenpox) in patients aged 2 to 18 years.

While not FDA-approved, valaciclovir is approved in several other regions (eg, UK, EU, Australia, and NZ) for the prophylaxis of cytomegalovirus (CMV) infection and disease following solid organ transplantation in adults and adolescents aged 12 years or older.

The monomorphic erosions and crusted lesions of eczema herpeticum, a common reason for the use of valaciclovir. 

Chickenpox in a toddler, an indication for the use of valaciclovir 

What are the contraindications and precautions with valaciclovir?

Contraindications:

Valaciclovir is contraindicated in patients with a known hypersensitivity to valaciclovir, aciclovir, or any component of the drug formulation.

Precautions:

• Renal impairment — dose reductions are required
• Elderly population
  • More susceptible to CNS adverse effects
  • Ensure adequate hydration and consider the need for dose reduction due to impaired renal function
• Immunocompromised patients — increased dose and duration of therapy are typically recommended on specialist advice
• Hepatic impairment — caution is advised when administering high doses (≥4 g per day)
• Pregnancy and lactation — limited safety data; use with caution when the benefits of treatment outweigh risks.

Tell me more about valaciclovir

Valaciclovir is a prodrug of aciclovir and inhibits DNA replication in herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV).

Following oral administration, valaciclovir is rapidly metabolised to aciclovir and L-valine by first-pass metabolism in the gastrointestinal tract and liver. Intracellularly, aciclovir is first converted to aciclovir monophosphate by a virus-encoded enzyme called thymidine kinase, making aciclovir activity specific to virus-infected cells.

Aciclovir monophosphate is then converted by cellular enzymes to its active form, aciclovir triphosphate, which acts as a competitive inhibitor of viral DNA polymerase. By inhibiting viral DNA polymerase, further viral replication is halted, thereby reducing the length and severity of outbreaks.

Aciclovir is eliminated by renal clearance and, therefore, dose reductions of valaciclovir are required in patients with renal impairment.

What is the dosage for valaciclovir?

Typical dosing recommendations for valaciclovir depend on the indication. Dose adjustments are needed for individuals with renal impairment or who are immunocompromised.

Genital herpes

• First episode: 500 mg twice daily for 5–10 days
• Episodic treatment: 500 mg twice daily for 3–5 days, administered at the earliest sign/symptom
• Suppressive treatment: 500 mg once daily

Herpes labialis (cold sores)

2 g twice daily for 1 day, administered at the earliest symptom eg, tingling, burning, or itching


Herpes zoster (shingles)

1 g three times daily for 7 days, administered at the earliest sign/symptom

CMV prophylaxis after solid organ transplantation

2 g four times a day for 90 days

Varicella (chickenpox)

20 mg/kg (up to 1 g) three times daily for 5–7 days in children aged 2–18 years

What are the benefits of valaciclovir?

• Generally well tolerated and efficacious across its approved indications.
• Pharmacokinetic profile offers three- to fivefold greater bioavailability than aciclovir and allows for less frequent dosing, which may improve patient adherence.
• Evidence suggests greater efficacy than aciclovir in relieving pain associated with herpes zoster when started early (within 72 hours of rash onset).
• Can be used in both immunocompromised and immunocompetent patients.
• Can be given with or without a meal, as food does not significantly affect its bioavailability.

What are the side effects and risks of valaciclovir?

Common side effects:

• Headache
• Nausea and vomiting
• Diarrhoea
• Constipation.

Uncommon but serious adverse effects:

• Cases of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome have been reported in immunosuppressed patients taking high doses or a prolonged course of valaciclovir.
• Reversible neurological adverse reactions have been reported in both adults and children, including dizziness, agitation, confusion, hallucinations, seizures, and others.
• Acute renal failure may occur in patients with underlying kidney disease receiving doses higher than recommended for their level of renal function; elderly patients are also at increased risk.
• Drug reaction with eosinophilia and systemic symptoms (DRESS), a severe and potentially life-threatening condition, has been associated with valaciclovir.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).