What is the recommended dose of Valacyclovir (Valacyclovir) for adults with normal renal function and impaired renal function?

Valacyclovir Dosing Recommendations

For adults with normal renal function (CrCl ≥50 mL/min), valacyclovir dosing varies by indication: 1 gram three times daily for herpes zoster, 500 mg-1 gram twice daily for genital herpes episodes, and 500 mg-1 gram daily for suppressive therapy; dose adjustments are mandatory in renal impairment to prevent neurotoxicity. 1

Standard Dosing for Normal Renal Function (CrCl ≥50 mL/min)

Herpes Zoster (Shingles)

• 1 gram orally every 8 hours for 7 days 1
• Initiate therapy within 48 hours of rash onset for maximum efficacy 1

Genital Herpes - First Episode

• 1 gram orally twice daily for 7-10 days 2
• Most effective when started within 48 hours of symptom onset 2
• May extend beyond 10 days if healing is incomplete 2

Genital Herpes - Recurrent Episodes

• 500 mg orally twice daily for 5 days 3, 1
• Alternative: 1 gram once daily for 5 days 3
• Start at first sign of prodrome or lesions 3

Genital Herpes - Suppressive Therapy (Immunocompetent)

• 1 gram orally once daily for patients with ≥10 recurrences per year 3, 1
• 500 mg orally once daily for patients with <10 recurrences per year 3, 1
• Alternative: 500 mg twice daily 3
• Note: 500 mg once daily is less effective in patients with very frequent recurrences (≥10 episodes/year) 3

Genital Herpes - Suppressive Therapy (HIV-Infected)

• 500 mg orally twice daily 3, 1
• This is the recommended regimen specifically for HIV-infected persons, not once-daily dosing 3

Cold Sores (Herpes Labialis)

• 2 grams orally twice daily for 1 day (12 hours apart) 1
• For patients ≥12 years of age 1

Orolabial HSV in HIV-Infected Patients

• Oral valacyclovir for 5-10 days (specific dose not detailed in guidelines, but typically 500 mg-1 gram twice daily) 3

Dose Adjustments for Renal Impairment

Renal function assessment is mandatory before initiating therapy and periodically during treatment to prevent accumulation and neurotoxicity. 4, 5

CrCl 30-49 mL/min

• Herpes zoster: 1 gram every 12 hours 4, 1
• Genital herpes (recurrent): 500 mg every 12 hours (no reduction needed) 1
• Genital herpes (suppressive): 500 mg-1 gram every 24 hours 4, 1
• Cold sores: 1 gram every 24 hours 1

CrCl 10-29 mL/min

• Herpes zoster: 1 gram every 24 hours 4, 1
• Genital herpes (recurrent): 500 mg every 24 hours 4, 1
• Genital herpes (suppressive): 500 mg every 24 hours 4, 1
• Cold sores: 500 mg every 24 hours 1

CrCl <10 mL/min (Including ESRD)

• Herpes zoster: 500 mg every 24 hours 4, 1
• Genital herpes (recurrent): 500 mg every 24 hours 4, 1
• Genital herpes (suppressive): 500 mg every 24 hours or every 48 hours (for patients with ≤9 recurrences/year) 1
• Cold sores: 500 mg every 24 hours 1

Hemodialysis Patients

• Administer the recommended dose after hemodialysis 1
• Approximately one-third of acyclovir is removed during a 4-hour hemodialysis session 1
• In severe neurotoxicity cases, emergent hemodialysis should be utilized for rapid drug excretion 5

Peritoneal Dialysis

• No supplemental doses required after CAPD or CAVHD 1
• Acyclovir removal is less pronounced than with hemodialysis 1

Critical Safety Considerations

Neurotoxicity Risk

• Valacyclovir neurotoxicity (VAN) is a common and preventable adverse effect in patients with renal dysfunction 5
• The half-life of valacyclovir can extend up to 14 hours in ESRD patients 5
• Failure to adjust doses appropriately can result in severe neurological manifestations requiring hospitalization 5
• Central nervous system toxicity is frequently observed with high doses but regresses upon withdrawal 6

High-Dose Toxicity Warning

• Avoid valacyclovir 8 grams per day in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) 2, 7
• TTP/HUS has been reported in HIV-infected patients on high-dose therapy but not at standard HSV treatment doses 3

Monitoring Requirements

• No routine laboratory monitoring needed for patients with normal renal function receiving episodic or suppressive therapy 3, 4
• Renal function monitoring is mandatory in patients with substantial renal impairment 3

Treatment Duration Considerations

When to Continue vs. Discontinue

• Episodic therapy: Continue until lesions completely heal 3
• Suppressive therapy: After 1 year of continuous therapy, discuss discontinuation to reassess recurrence frequency 3
• Severe disease: IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days is preferred over oral valacyclovir for hospitalized patients 3, 2

Treatment Failure

• Suspect acyclovir resistance if lesions do not begin to resolve within 7-10 days 3
• All acyclovir-resistant HSV strains are also resistant to valacyclovir 2
• IV foscarnet 40 mg/kg every 8 hours is the treatment of choice for resistant HSV 2

Special Population Notes

HIV-Infected Patients

• Use twice-daily regimens (500 mg twice daily) for suppressive therapy, not once-daily dosing 3
• Short-course therapy (1-3 days) should not be used 3
• Treatment duration for acute episodes: 5-14 days 3

Elderly Patients

• Exposure to acyclovir is enhanced in elderly patients due to decreased glomerular filtration 6
• Dose adjustment based on creatinine clearance is essential 3

Hepatic Impairment

• No dose adjustment needed for hepatic failure, as acyclovir exposure is not significantly altered 6