What are the standard adult dosing regimens for valacyclovir?

Valacyclovir Dosing Guidelines

Standard Adult Dosing Regimens

For genital herpes first episode, administer valacyclovir 1 gram orally twice daily for 7-10 days, or alternatively 500 mg twice daily for 10 days. 1, 2, 3

Genital Herpes – First Episode

• Valacyclovir 1 gram orally twice daily for 7-10 days is the preferred regimen for initial genital herpes infection 1, 2, 3
• Alternative dosing: 500 mg twice daily for 10 days achieves comparable clinical control 2
• Initiate therapy as soon as infection is suspected; laboratory confirmation may be deferred 2
• Treatment is most effective when started within 48 hours of symptom onset 4

Genital Herpes – Recurrent Episodes (Episodic Treatment)

• Valacyclovir 500 mg orally twice daily for 5 days is the standard episodic regimen 1, 4, 3
• Alternative: 1 gram once daily for 5 days 4
• Start treatment during prodromal phase or within 24 hours of lesion onset for maximal benefit 2

Genital Herpes – Suppressive Therapy (Immunocompetent Adults)

• For patients with ≥10 recurrences per year: 1 gram once daily 1, 2, 4, 3
• For patients with <10 recurrences per year: 500 mg once daily 1, 2, 4, 3
• Suppressive therapy reduces recurrence frequency by ≥75% 1, 2
• After 1 year of continuous suppressive therapy, discuss trial discontinuation to reassess recurrence frequency 1, 2, 4

Genital Herpes – Suppressive Therapy (HIV-Infected Adults)

• Use valacyclovir 500 mg twice daily in HIV-infected patients with CD4 ≥100 cells/mm³ 1, 2, 4, 3
• Once-daily dosing does not achieve adequate viral suppression in this population 1, 2
• Continuous suppressive therapy reduces HIV-RNA concentrations in plasma and genital secretions 1

Herpes Labialis (Cold Sores)

• Valacyclovir 2 grams orally twice daily for 1 day (doses taken 12 hours apart) 1, 2, 3
• Initiate during prodromal symptoms (tingling, burning, itching) or within 24 hours of lesion appearance 1, 2
• This single-day regimen shortens median episode duration by approximately 1 day versus placebo 2

Herpes Zoster (Shingles) – Immunocompetent Adults

• Valacyclovir 1 gram orally three times daily for 7 days 5, 1, 2, 3
• Start within 72 hours of rash onset for greatest benefit 1
• Continue therapy until all lesions have fully scabbed, rather than stopping at a fixed 7-day interval 1
• Valacyclovir shortens the duration of acute zoster pain and reduces the incidence of post-herpetic neuralgia compared to acyclovir 1

Herpes Zoster – Immunocompromised Adults (Uncomplicated)

• Prefer acyclovir 800 mg orally four times daily over high-dose valacyclovir 1
• Valacyclovir doses ≥8 grams/day carry risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) 1, 4, 6

Severe VZV Disease (Acute Retinal Necrosis)

• Intravenous acyclovir 10 mg/kg every 8 hours for 10-14 days, followed by oral valacyclovir 1 gram three times daily for 4-6 weeks 1, 2

Renal Dose Adjustments

All patients with renal impairment require mandatory dose reduction based on creatinine clearance to prevent neurotoxicity and nephrotoxicity. 5, 2, 4, 3

Herpes Zoster Dosing with Renal Impairment

• CrCl 30-49 mL/min: 1 gram every 12 hours 5, 4, 3
• CrCl 10-29 mL/min: 1 gram every 24 hours 5, 4, 3
• CrCl <10 mL/min: 500 mg every 24 hours 5, 3

Genital Herpes (Recurrent Episodes) with Renal Impairment

• CrCl 30-49 mL/min: 500 mg every 12 hours (no reduction needed) 5, 3
• CrCl 10-29 mL/min: 500 mg every 24 hours 5, 4, 3
• CrCl <10 mL/min: 500 mg every 24 hours 5, 3

Suppressive Therapy with Renal Impairment (Immunocompetent)

• CrCl 30-49 mL/min: No dose reduction needed for 500 mg daily 2, 3
• CrCl <30 mL/min: 500 mg every 24 hours (instead of 1 gram) 5, 1, 3
• Alternative for patients with <10 recurrences/year and CrCl <30 mL/min: 500 mg every 48 hours 3

Suppressive Therapy with Renal Impairment (HIV-Infected)

• CrCl 30-49 mL/min: 500 mg every 12 hours (no reduction) 3
• CrCl <30 mL/min: 500 mg every 24 hours 5, 1, 3

Cold Sores with Renal Impairment

• CrCl 30-49 mL/min: 1 gram every 12 hours for 1 day (no reduction) 3
• CrCl 10-29 mL/min: 1 gram every 24 hours 3
• CrCl <10 mL/min: 500 mg every 24 hours 3
• Do not exceed 1 day of treatment 3

Hemodialysis Patients

• Administer the recommended dose of valacyclovir after hemodialysis 5, 3
• During hemodialysis, approximately one-third of acyclovir is removed during a 4-hour session 3

Peritoneal Dialysis Patients

• Supplemental doses of valacyclovir should not be required following CAPD or CAVHD 3
• Pharmacokinetic parameters closely resemble those in ESRD patients not receiving hemodialysis 3

Pediatric Dosing

Cold Sores (Age ≥12 Years)

• Valacyclovir 2 grams twice daily for 1 day (12 hours apart) 1, 3
• Initiate at earliest symptom (tingling, itching, burning) 3

Chickenpox (Age 2 to <18 Years, Immunocompetent)

• Valacyclovir 20 mg/kg three times daily for 5 days (maximum 1 gram per dose) 1, 3
• Initiate at earliest sign or symptom 3

Chickenpox (Immunosuppressed Children)

• Mild-to-moderate immunosuppression: Acyclovir 20 mg/kg orally four times daily (max 800 mg per dose) for 7-10 days 1
• Severe immunosuppression: Intravenous acyclovir 10 mg/kg every 8 hours 1

Herpes Zoster (Adolescents ≥12 Years)

• Valacyclovir 1 gram three times daily for 7 days (if able to tolerate adult dosing) 1

Herpes Zoster (Children <12 Years)

• Acyclovir 20 mg/kg orally four times daily (maximum 800 mg per dose) 1

Monitoring Requirements

No routine laboratory monitoring is needed for patients with normal renal function receiving episodic or suppressive therapy. 5, 4

• Assess baseline renal function before initiating therapy 1, 4
• For patients receiving high-dose IV acyclovir, monitor renal function once or twice weekly during treatment 5, 1
• Patients with substantial renal impairment require renal function monitoring 5, 4
• Check BMP if clinical deterioration occurs or new symptoms suggest renal dysfunction 4
• Maintain adequate hydration throughout therapy to minimize nephrotoxicity 1, 2

Critical Safety Warnings

Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of TTP/HUS. 1, 4, 6

• TTP/HUS has been reported in HIV-infected patients on high-dose therapy (8 g/day) but not at standard HSV treatment doses 5, 4
• High-dose valacyclovir (8 g/day for approximately 30 weeks) in advanced HIV disease was associated with increased gastrointestinal complaints and increased risk of death, leading to premature study termination 6
• Close monitoring for TMA symptoms is indicated in all immunocompromised patients receiving high-dose valacyclovir 6

Antiviral Resistance

If lesions do not begin to resolve within 7-10 days of appropriate therapy, suspect antiviral resistance. 1, 2, 4

• Obtain viral culture with susceptibility testing to confirm drug resistance 5, 1, 2
• All acyclovir-resistant strains are also resistant to valacyclovir 1, 2
• Resistance rates: <0.5% in immunocompetent patients and 5-7% in immunocompromised patients 1, 2
• Treatment of choice for confirmed resistant HSV or VZV: Intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution 1, 2, 4

Common Pitfalls to Avoid

• Do not use once-daily valacyclovir 500 mg in patients with ≥10 recurrences per year; this results in inadequate dosing 1, 2
• Do not use once-daily dosing for suppressive therapy in HIV-infected patients; twice-daily 500 mg is required 1, 2, 4
• Do not delay antiviral initiation in suspected herpes zoster while awaiting laboratory confirmation; start within 72 hours of rash onset 1
• Do not use short-course (1-3 day) regimens designed for genital herpes to treat herpes zoster 1
• Do not fail to adjust doses in renal impairment; this increases risk of neurotoxicity 2, 4
• Topical acyclovir alone is substantially less effective than systemic therapy 1, 2
• Initiating therapy after the first 24 hours markedly reduces efficacy 2

Transmission and Patient Counseling

• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding; transmission risk persists 2
• Patients remain contagious until all lesions are fully crusted 2
• Counsel patients to avoid direct contact (kissing, sexual activity) during active lesions or prodromal symptoms 2
• Use barrier protection with uninfected partners 2