Valacyclovir

• Herpes Zoster (Shingles)
• Genital Herpes
• Cold Sores
• Chickenpox

Valacyclovir is an antiviral prodrug of acyclovir used to treat herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Its enhanced oral bioavailability compared to acyclovir allows for less frequent dosing while achieving higher antiviral levels.

Mechanism of Action

Valacyclovir is converted to acyclovir, which inhibits viral DNA synthesis:

• Prodrug conversion: Rapidly converted to acyclovir by intestinal and hepatic esterases
• Viral thymidine kinase activation: Acyclovir is phosphorylated by viral thymidine kinase to acyclovir monophosphate
• Cellular kinase conversion: Host cell kinases convert to acyclovir triphosphate (active form)
• DNA polymerase inhibition: Acyclovir triphosphate competitively inhibits viral DNA polymerase
• Chain termination: Incorporation into viral DNA causes chain termination

Selective toxicity results from preferential activation in infected cells.

Available Formulations

Valacyclovir is available as tablets:

• 500 mg, 1000 mg (1 g) tablets (Valtrex)

Medical Uses

FDA-Approved Indications:

• Herpes zoster (shingles) in immunocompetent adults
• Initial and recurrent genital herpes in immunocompetent adults
• Suppression of recurrent genital herpes in immunocompetent and HIV-infected adults
• Reduction of transmission of genital herpes
• Cold sores (herpes labialis) in immunocompetent adults and pediatric patients ≥12 years
• Chickenpox in immunocompetent pediatric patients (2-18 years)

Dosing Guidelines

Herpes Zoster:

• 1 g three times daily for 7 days
• Start within 72 hours of rash onset

Genital Herpes (Initial):

• 1 g twice daily for 10 days

Genital Herpes (Recurrent):

• 500 mg twice daily for 3 days, OR
• 1 g once daily for 5 days

Genital Herpes Suppression:

• 1 g once daily (or 500 mg once daily if <9 recurrences/year)

Cold Sores:

• 2 g twice daily for 1 day (doses 12 hours apart)

Renal Impairment: Significant dose adjustments required based on CrCl.

Important Safety Information

Contraindications:

• Known hypersensitivity to valacyclovir, acyclovir, or any component

Warnings and Precautions:

• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): Reported in advanced HIV disease and transplant patients at high doses
• Acute renal failure: May occur, especially with pre-existing renal impairment or dehydration
• CNS adverse reactions: Confusion, hallucinations, agitation, seizures (more common in elderly or renal impairment)

Drug Interactions

• Nephrotoxic drugs: May increase risk of renal toxicity
• Probenecid, cimetidine: Reduce acyclovir clearance; monitor for toxicity
• Mycophenolate mofetil: Concurrent use may increase exposure of both drugs
• Vaccines: Avoid live vaccines during active infection

Special Populations

• Hepatic Impairment: No adjustment for mild to moderate
• Renal Impairment: Significant dose adjustments required
• Elderly: Reduce dose based on renal function; monitor for CNS effects
• Pregnancy: Category B; may be used when benefit outweighs risk
• Lactation: Acyclovir is excreted in milk; use with caution
• Pediatric: Approved for cold sores ≥12 years; chickenpox 2-18 years