Introduction
Valtrex (valacyclovir hydrochloride) is an oral antiviral prescription medication used primarily for the treatment of herpes virus infections. It is a prodrug of acyclovir that offers improved bioavailability compared to its parent compound. Valacyclovir is converted to acyclovir in the body, which then exerts potent antiviral activity against herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV).
Mechanism of Action
Valtrex is rapidly converted to acyclovir by first-pass intestinal and hepatic metabolism. Acyclovir is subsequently phosphorylated by viral thymidine kinase to acyclovir monophosphate, which is then converted to acyclovir triphosphate by cellular enzymes. Acyclovir triphosphate inhibits viral DNA replication through two mechanisms: competitive inhibition of viral DNA polymerase and incorporation into the growing viral DNA chain, causing premature chain termination.
Indications
- Treatment of herpes zoster (shingles) in immunocompetent adults
- Treatment of initial and recurrent genital herpes in immunocompetent adults
- Suppression of recurrent genital herpes in immunocompetent adults
- Treatment of cold sores (herpes labialis) in immunocompetent adults and children (age ≥12 years)
- Reduction of transmission of genital herpes in immunocompetent adults
- Treatment of chickenpox in immunocompetent children (age ≥2 years)
Dosage and Administration
Herpes Zoster: 1 g orally three times daily for 7 days Genital Herpes (initial episode): 1 g orally twice daily for 10 days Recurrent Genital Herpes: 500 mg orally twice daily for 3 days Suppressive Therapy: 1 g orally once daily (500 mg once daily in patients with <9 recurrences/year) Cold Sores: 2 g orally twice daily for 1 day (doses 12 hours apart) Chickenpox: 20 mg/kg orally three times daily for 5 days (maximum 1 g three times daily) Renal Impairment Dosing Adjustments:CrCl 30-49 mL/min: Adjust dose frequency to twice daily CrCl 10-29 mL/min: Adjust dose frequency to once daily CrCl <10 mL/min: 500 mg every 24-48 hours
Administration: May be taken with or without foodPharmacokinetics
Absorption: Rapidly absorbed and converted to acyclovir; bioavailability of acyclovir from valacyclovir is 54.5% (significantly higher than oral acyclovir) Distribution: Acyclovir distributes widely into tissues and body fluids, including cerebrospinal fluid Metabolism: Converted to acyclovir and L-valine by first-pass metabolism in intestine and liver Elimination: Primarily renal excretion via glomerular filtration and tubular secretion; half-life 2.5-3.3 hours in adults with normal renal functionContraindications
- Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation
- Patients with demonstrated hypersensitivity to famciclovir
Warnings and Precautions
Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS): Has occurred in patients with advanced HIV disease and in bone marrow transplant and renal transplant recipients Acute Renal Failure: Has been reported in elderly patients and those with underlying renal disease; dosage adjustment required for renal impairment Neurological Symptoms: Agitation, hallucinations, confusion, coma, and seizures may occur; more common in elderly patients and those with renal impairment CNS Effects: Use with caution in patients with pre-existing neurological disorders Hepatic Impairment: Use with caution; dosage adjustment may be necessary in severe hepatic impairment Elderly Patients: Increased risk of neurological and renal adverse effects; require dosage adjustment based on renal functionDrug Interactions
Probenecid: Increases acyclovir AUC and half-life by reducing renal clearance Nephrotoxic Drugs: Increased risk of renal toxicity when used with other nephrotoxic agents (aminoglycosides, cyclosporine, NSAIDs, etc.) Cimetidine: May increase acyclovir AUC Mycophenolate Mofetil: May increase concentrations of both drugsAdverse Effects
Common (>10%): Headache, nausea, diarrhea, dizziness Less Common (1-10%): Abdominal pain, vomiting, fatigue, rash, arthralgia Serious (<1%): Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute renal failure, neurological symptoms (agitation, hallucinations, confusion, seizures), anaphylaxis, hepatitis, Stevens-Johnson syndromeMonitoring Parameters
- Renal function (serum creatinine, BUN, CrCl) at baseline and during treatment
- CBC with platelets in immunocompromised patients
- Neurological status, especially in elderly patients and those with renal impairment
- Signs of thrombotic microangiopathy (fever, bruising, bleeding, fatigue)
- Hepatic function in patients with pre-existing liver disease
- Hydration status, particularly in elderly patients
Patient Education
- Complete the full course of treatment as prescribed
- Maintain adequate hydration during therapy
- Report any signs of neurological symptoms (confusion, hallucinations, seizures) immediately
- Notify healthcare provider of any unusual bruising or bleeding
- This medication does not prevent transmission of herpes; use appropriate barrier protection
- For genital herpes suppression, continue daily therapy as prescribed
- Store at room temperature, away from moisture and heat
- Do not share medication with others
References
1. GlaxoSmithKline. Valtrex (valacyclovir hydrochloride) prescribing information. 2021. 2. Kimberlin DW, Rouse DJ. Clinical practice: Genital herpes. N Engl J Med. 2004;350(19):1970-1977. 3. Tyring SK, Baker D, Snowden W. Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir. J Infect Dis. 2002;186 Suppl 1:S40-S46. 4. Beutner KR, Friedman DJ, Forszpaniak C, et al. Valacyclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546-1553. 5. Lexicomp Online. Valacyclovir monograph. Wolters Kluwer Clinical Drug Information. Accessed 2023. 6. Micromedex Solutions. Valacyclovir. Truven Health Analytics. Accessed 2023.