What is the dosage and treatment regimen for Valacyclovir (valacyclovir) in treating herpes simplex virus infections, including genital herpes and cold sores, as well as varicella-zoster virus infections, such as shingles?

Valacyclovir Dosing and Treatment Regimens

Herpes Simplex Virus (HSV) Infections

Genital Herpes - First Episode

For initial genital herpes episodes, valacyclovir 1 gram orally twice daily for 7-10 days is the recommended treatment, with therapy most effective when initiated within 48 hours of symptom onset. 1

• Treatment may be extended beyond 10 days if healing remains incomplete 1
• Approximately 5-30% of first-episode genital herpes cases are caused by HSV-1, though clinical recurrences are much less frequent for HSV-1 compared to HSV-2 1

Genital Herpes - Recurrent Episodes

Valacyclovir 500 mg orally twice daily for 5 days is the CDC-recommended episodic treatment for recurrent genital herpes, initiated at the first sign of prodrome or lesions. 2

• Patients should be provided with medication or a prescription in advance to enable immediate treatment initiation 2
• Treatment must begin at the first sign of prodrome or genital lesions for maximum efficacy 2
• Alternative regimen: 1 gram once daily for 5 days is equally effective 3, 4
• Treatment initiated more than 24 hours after symptom onset has reduced effectiveness 5

Genital Herpes - Suppressive Therapy

For patients with normal immune function, valacyclovir 1000 mg once daily is recommended for suppressive therapy, reducing recurrence frequency by ≥75%. 2

• For patients with <10 recurrences per year, 500 mg once daily is sufficient 6
• For patients with ≥10 recurrences per year, 1 gram once daily or 500 mg twice daily is more effective 6
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding, and transmission can occur even during asymptomatic periods 2
• Safety and effectiveness data beyond 1 year of continuous suppressive therapy in immunocompetent patients is limited 5

Genital Herpes in HIV-Infected Patients

For HIV-infected patients with CD4+ count ≥100 cells/mm³, valacyclovir 500 mg twice daily is recommended for suppressive therapy. 1

• Safety and effectiveness data beyond 6 months of continuous suppressive therapy in HIV-infected patients is limited 5
• Higher dosing may be required for immunocompromised patients due to potentially more severe and frequent recurrences 1

Cold Sores (Herpes Labialis)

For cold sores in patients ≥12 years, valacyclovir 2 grams orally twice daily for 1 day (two doses taken 12 hours apart) is the recommended treatment. 5

• Therapy should be initiated at the earliest symptom of a cold sore (tingling, itching, or burning) 5
• There are no data on effectiveness when treatment is initiated after development of clinical signs (papule, vesicle, or ulcer) 5
• Treatment should not exceed 1 day (2 doses total) 5

Varicella-Zoster Virus (VZV) Infections

Herpes Zoster (Shingles) - Immunocompetent Adults

For uncomplicated herpes zoster, valacyclovir 1 gram orally three times daily for 7-10 days is the recommended first-line treatment, with therapy most effective when initiated within 72 hours of rash onset. 7, 5

• Treatment should continue until all lesions have scabbed, not just for an arbitrary 7-day period 7
• Valacyclovir is significantly more effective than acyclovir in reducing the duration of zoster-associated pain and postherpetic neuralgia 8
• Treatment initiated within 48 hours of symptom onset provides optimal efficacy, though the 72-hour window is the maximum timeframe for benefit 2, 7
• For facial herpes zoster, treatment urgency is particularly critical given the risk of ophthalmic and cranial nerve complications 7

Herpes Zoster - Immunocompromised Patients

Severely immunocompromised patients with herpes zoster require intravenous acyclovir 5-10 mg/kg every 8 hours for 7-10 days or until clinical resolution, rather than oral valacyclovir. 2, 7

• This includes patients on active chemotherapy, those with disseminated infection, or those with multi-dermatomal involvement 7
• Immunocompromised patients may require treatment extension well beyond 7-10 days as lesions continue to develop over longer periods (7-14 days) and heal more slowly 7
• A temporary reduction in immunosuppressive medication should be considered in these patients 7
• Without adequate antiviral therapy, some immunocompromised patients develop chronic ulcerations with persistent viral replication 7

Chickenpox (Varicella) - Pediatric Patients

For chickenpox in immunocompetent pediatric patients aged 2 to <18 years, valacyclovir 20 mg/kg orally three times daily for 5 days is recommended, with a maximum dose of 1 gram three times daily. 5

• Therapy should be initiated at the earliest sign or symptom 5

Critical Dosing Adjustments and Precautions

Renal Impairment

Dose adjustments are mandatory for patients with creatinine clearance <50 mL/min to prevent acute renal failure. 7, 5

For herpes zoster:

• CrCl 30-49 mL/min: 1 gram every 12 hours 5
• CrCl 10-29 mL/min: 1 gram every 24 hours 5
• CrCl <10 mL/min: 500 mg every 24 hours 5

For recurrent genital herpes:

• CrCl 30-49 mL/min: No reduction needed 5
• CrCl 10-29 mL/min: 500 mg every 24 hours 5
• CrCl <10 mL/min: 500 mg every 24 hours 5

For suppressive therapy (immunocompetent):

• CrCl 30-49 mL/min: No reduction needed 5
• CrCl 10-29 mL/min: 500 mg every 24 hours 5
• CrCl <10 mL/min: 500 mg every 24 hours 5

Hemodialysis

Patients requiring hemodialysis should receive the recommended dose of valacyclovir after hemodialysis. 5

• About one-third of acyclovir is removed during a 4-hour hemodialysis session 5
• Supplemental doses are not required following peritoneal dialysis 5

High-Dose Therapy Warnings

The CDC advises against valacyclovir doses of 8 grams per day in immunocompromised patients due to the risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). 2, 1

• This potentially fatal complication has been reported in immunocompromised patients receiving high-dose prophylactic valacyclovir therapy (8 g/day) for CMV disease for prolonged periods 9
• The risk appears highest in patients with advanced HIV disease 9
• Close monitoring for symptoms of TTP/HUS is indicated in all immunocompromised patients receiving high-dose valacyclovir 9

Severe Disease Requiring Hospitalization

For any severe HSV or VZV infection with complications (disseminated infection, pneumonitis, hepatitis, or CNS involvement), intravenous acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution is recommended instead of oral valacyclovir. 2

• Monitor renal function closely during IV acyclovir therapy, with dose adjustments as needed for renal impairment 7
• Assess for TTP/HUS in immunocompromised patients receiving high-dose therapy 7

Antiviral Resistance

If lesions persist despite appropriate valacyclovir treatment, consider HSV resistance; all acyclovir-resistant HSV strains are also resistant to valacyclovir. 2, 1

• For acyclovir-resistant HSV or VZV, intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice 2, 1, 7

Important Clinical Considerations

Patient Counseling

• Valacyclovir is not a cure for HSV or VZV infections 5
• Patients should maintain adequate hydration during therapy 5
• For genital herpes, patients should avoid contact with lesions or intercourse when lesions/symptoms are present 5
• Transmission can occur even during asymptomatic periods through asymptomatic viral shedding 5
• Patients with shingles should avoid contact with susceptible individuals until all lesions have crusted 7

Vaccination

• The recombinant zoster vaccine (Shingrix) is recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes 7
• Vaccination should ideally occur before initiating immunosuppressive therapies 7